44 Rare Exposure 18 Executive Corner

44 Rare Exposure Three rare diseases and novel therapeutic developments 18 Executive Corner: The Need for Health System Specialty Pharmacies by Willis Chandler 52 Special Advertorial Key Considerations for Biosimilars 65 Updated Product Catalog Want more time for your patients?

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rancis Bacon, a 16th century Beyond Stereotypes on page 30 exam- philosopher whom many ines sickle cell disease, including the regard as the father of scien- misconceptions of afflicted patients F tific methods of inquiry, said and the impact of substandard care. “Knowledge is power.” For health- Rare Exposure, which begins on page care professionals, Bacon’s quote may 44, further dispels preconceived easily extend to “Knowledge is our notions while examining three rare power to heal.” diseases — hemophagocytic lymphohistiocytosis, hereditary ATTR amyloi- Empowering health systems toward dosis and chronic inflammatory demy- exceptional patient care is a goal at elinating polyneuropathy — as well as AmerisourceBergen, as evidenced in the development of novel therapeutics. Executive Corner on page 18. Senior Vice President and President of Health For quick reads on interesting health- Systems and Services Willis Chandler care developments, turn to Medical examines The Need for Health System Minute on page 25. New Products Specialty Pharmacies while providing offered by ASD Healthcare are found on strategies for implementation. page 62, followed by New Indications for existing FDA-approved medications Washington Update offers insight on page 64. Our updated Product on the FDA’s Guidance on Medical Catalog starts on page 65. Product Manufacturer Communications and Compounding Policy Plan, as well as Right to Try Legislation and Trump’s Drug Pricing Plan. Begin reading on page 14. We sincerely admire the hard work and dedication embodied in healthcare professionals. It is an honor to serve you.

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ASD Healthcare Order Flyer 2018 072618.indd 1 8/1/18 10:49 AM While Adacel® is indicated for patients 10-64 years of age…1

BOOSTRIX is indicated for the widest range of patients (10 years of age and older).1,2 BOOSTRIX is the ONLY Tdap vaccine approved by the FDA for adults 65 years of age and older.1,2 BOOSTRIX is a vaccine indicated for active booster immunization against tetanus, diphtheria, and pertussis. BOOSTRIX is approved for use as a single dose in individuals 10 years of age and older. Severe allergic reaction after a previous dose of any tetanus toxoid-, diphtheria toxoid-, or pertussis antigen-containing vaccine, or to any component of BOOSTRIX, or encephalopathy within 7 days of a previous pertussis antigen-containing vaccine is a contraindication.

Features of BOOSTRIX • BOOSTRIX is available in 0.5-mL single-dose vials and disposable prefilled Tip-Lok® syringes (packaged without needles) • The tip caps of the prefilled syringes for BOOSTRIX contain natural rubber latex, which may cause allergic reactions. The vial stoppers are not made with natural rubber latex • BOOSTRIX comes with a 2D barcode

Please see accompanying Brief Summary for Boostrix. Please see additional Important Safety Information on the following pages.

CPT® Code: 907153

Tdap=tetanus, diphtheria, and acellular pertussis. FDA=US Food and Drug Administration.

821111R0_Boostrix_JournalAd_BriefSummary.indd 1 8/11/17 2:50 PM Indication

BOOSTRIX is a vaccine indicated for active booster immunization against tetanus, diphtheria, and pertussis. BOOSTRIX is approved for use as a single dose in individuals 10 years of age and older.

Important Safety Information for BOOSTRIX (cont’d)

• The tip caps of the prefilled syringes for BOOSTRIX contain natural rubber latex, which may cause allergic reactions • The decision to give BOOSTRIX should be based on benefits and risks if Guillain-Barré syndrome occurred within 6 weeks of receipt of a prior tetanus toxoid-containing vaccine • Syncope (fainting) can occur in association with administration of injectable vaccines. Procedures should be in place to avoid falling injury and to restore cerebral perfusion following syncope • Progressive or unstable neurologic conditions are reasons to defer vaccination with a pertussis- containing vaccine, including BOOSTRIX • Persons who experienced an Arthus-type hypersensitivity reaction following a prior dose of tetanus toxoid-containing vaccine should not receive BOOSTRIX unless 10 years have elapsed since the last dose of a tetanus toxoid-containing vaccine • In clinical studies, common adverse reactions were pain, redness, and swelling at the injection site, increase in arm circumference of injected arm, headache, fatigue, gastrointestinal symptoms, and fever • Vaccination with BOOSTRIX may not result in protection in all vaccine recipients

References: 1. Prescribing Information for Adacel. 2. Prescribing Information for BOOSTRIX. 3. American Medical Association. Current Procedural Terminology 2016: Standard Edition. Abraham M, Ahlman JT, Boudreau AJ, et al, eds. Chicago, IL: AMA Press; 2015.

www.BOOSTRIX.com

Please see accompanying Brief Summary for BOOSTRIX.

www.GSKSource.com BOOSTRIX and Tip-Lok are registered trademarks of the GSK group of companies. Adacel is a registered trademark of the sanoﬁ pasteur group, and its subsidiaries. CPT is a registered trademark of the American Medical Association.

821111R0_Boostrix_JournalAd_BriefSummary.indd 6 8/11/17 2:50 PM BRIEF SUMMARY Studies (14.4) of full prescribing information]. A total of 860 adults 19 years of age and older BOOSTRIX® (Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis received concomitant vaccination with BOOSTRIX and influenza vaccines in a coadministration Vaccine, Adsorbed) Suspension for Intramuscular Injection study [see Drug Interactions (7.1), Clinical Studies (14.5) of full prescribing information]. An additional 1,092 adolescents 10 to 18 years of age received a non-U.S. formulation of BOOSTRIX The following is a brief summary only; see full prescribing information for complete product (formulated to contain 0.5 mg aluminum per dose) in non-U.S. clinical studies. In a randomized, information. observer-blinded, controlled study in the U.S., 3,080 adolescents 10 to 18 years of age received 1 INDICATIONS AND USAGE a single dose of BOOSTRIX and 1,034 received the comparator Td vaccine, manufactured by BOOSTRIX® is indicated for active booster immunization against tetanus, diphtheria, and pertussis. MassBioLogics. There were no substantive differences in demographic characteristics between BOOSTRIX is approved for use as a single dose in individuals 10 years of age and older. the vaccine groups. Among BOOSTRIX and comparator vaccine recipients, approximately 75% were 10 to 14 years of age and approximately 25% were 15 to 18 years of age. Approximately 2 DOSAGE AND ADMINISTRATION 98% of participants in this study had received the recommended series of 4 or 5 doses of either 2.1 Preparation for Administration: Shake vigorously to obtain a homogeneous, turbid, Diphtheria and Tetanus Toxoids and Pertussis Vaccine Adsorbed (DTwP) or a combination of DTwP white suspension before administration. Do not use if resuspension does not occur with vigorous and DTaP in childhood. Subjects were monitored for solicited adverse events using standardized shaking. Parenteral drug products should be inspected visually for particulate matter and diary cards (Day 0-14). Unsolicited adverse events were monitored for the 31-day period following discoloration prior to administration, whenever solution and container permit. If either of these vaccination (Day 0-30). Subjects were also monitored for 6 months post-vaccination for non- conditions exists, the vaccine should not be administered. For the prefilled syringes, attach a routine medical visits, visits to an emergency room, onset of new chronic illness, and serious sterile needle and administer intramuscularly. For the vials, use a sterile needle and sterile syringe adverse events. Information regarding late onset adverse events was obtained via a telephone to withdraw the 0.5-mL dose and administer intramuscularly. Changing needles between drawing call 6 months following vaccination. At least 97% of subjects completed the 6-month follow-up vaccine from a vial and injecting it into a recipient is not necessary unless the needle has been evaluation. In a study conducted in Germany, BOOSTRIX was administered to 319 children 10 damaged or contaminated. Use a separate sterile needle and syringe for each individual. Do not to 12 years of age previously vaccinated with 5 doses of acellular pertussis antigen-containing administer this product intravenously, intradermally, or subcutaneously. vaccines; 193 of these subjects had previously received 5 doses of INFANRIX® (Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed). Adverse events were recorded on 2.2 Dose and Schedule: BOOSTRIX is administered as a single 0.5-mL intramuscular injection diary cards during the 15 days following vaccination. Unsolicited adverse events that occurred into the deltoid muscle of the upper arm.There are no data to support repeat administration within 31 days of vaccination (Day 0-30) were recorded on the diary card or verbally reported to of BOOSTRIX. Five years should elapse between the last dose of the recommended series of the investigator. Subjects were monitored for 6 months post-vaccination for physician office visits, Diphtheria and Tetanus Toxoids and Acellular Pertussis Vaccine Adsorbed (DTaP) and/or Tetanus emergency room visits, onset of new chronic illness, and serious adverse events. The 6-month and Diphtheria Toxoids Adsorbed For Adult Use (Td) vaccine and the administration of BOOSTRIX. follow-up evaluation, conducted via telephone interview, was completed by 90% of subjects. The 2.3 Additional Dosing Information: Primary Series: The use of BOOSTRIX as a primary series U.S. adult (19 to 64 years of age) study, a randomized, observer-blinded study, evaluated the or to complete the primary series for diphtheria, tetanus, or pertussis has not been studied. Wound safety of BOOSTRIX (N = 1,522) compared with ADACEL® (Tetanus Toxoid, Reduced Diphtheria Management: If tetanus prophylaxis is needed for wound management, BOOSTRIX may be given Toxoid and Acellular Pertussis Vaccine Adsorbed) (N = 762), a Tdap vaccine manufactured by if no previous dose of any Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Sanofi Pasteur SA. Vaccines were administered as a single dose. There were no substantive Vaccine, Adsorbed (Tdap) has been administered. differences in demographic characteristics between the vaccine groups. Subjects were monitored 4 CONTRAINDICATIONS for solicited adverse events using standardized diary cards (Day 0-14). Unsolicited adverse events were monitored for the 31-day period following vaccination (Day 0-30). Subjects were also 4.1 Hypersensitivity: A severe allergic reaction (e.g., anaphylaxis) after a previous dose of any monitored for 6 months post-vaccination for serious adverse events, visits to an emergency room, tetanus toxoid-, diphtheria toxoid-, or pertussis antigen-containing vaccine or any component hospitalizations, and onset of new chronic illness. Approximately 95% of subjects completed the of this vaccine is a contraindication to administration of BOOSTRIX [see Description (11) of full 6-month follow-up evaluation. The U.S. elderly (65 years of age and older) study, a randomized, prescribing information]. Because of the uncertainty as to which component of the vaccine might observer-blinded study, evaluated the safety of BOOSTRIX (N = 887) compared with DECAVAC® be responsible, none of the components should be administered. Alternatively, such individuals (Tetanus and Diphtheria Toxoids Adsorbed) (N = 445), a U.S.-licensed Td vaccine, manufactured may be referred to an allergist for evaluation if immunization with any of these components is by Sanofi Pasteur SA. Vaccines were administered as a single dose. Among all vaccine recipients, considered. the mean age was approximately 72 years; 54% were female and 95% were white. Subjects 4.2 Encephalopathy: Encephalopathy (e.g., coma, decreased level of consciousness, prolonged were monitored for solicited adverse events using standardized diary cards (Day 0-3). Unsolicited seizures) within 7 days of administration of a previous dose of a pertussis antigen-containing adverse events were monitored for the 31-day period following vaccination (Day 0-30). Subjects vaccine that is not attributable to another identifiable cause is a contraindication to administration were also monitored for 6 months post-vaccination for serious adverse events. Approximately of any pertussis antigen-containing vaccine, including BOOSTRIX. 99% of subjects completed the 6-month follow-up evaluation. Solicited Adverse Events in the 5 WARNINGS AND PRECAUTIONS U.S. Adolescent Study: Table 1 presents the solicited local adverse reactions and general adverse events within 15 days of vaccination with BOOSTRIX or Td vaccine for the total vaccinated cohort. 5.1 Latex: The tip caps of the prefilled syringes contain natural rubber latex which may cause The primary safety endpoint was the incidence of Grade 3 pain (spontaneously painful and/or allergic reactions. prevented normal activity) at the injection site within 15 days of vaccination. Grade 3 pain was 5.2 Guillain-Barré Syndrome and Brachial Neuritis: If Guillain-Barré syndrome occurred reported in 4.6% of those who received BOOSTRIX compared with 4.0% of those who received within 6 weeks of receipt of a prior vaccine containing tetanus toxoid, the risk of Guillain-Barré the Td vaccine. The difference in rate of Grade 3 pain was within the pre-defined clinical limit for syndrome may be increased following a subsequent dose of tetanus toxoid-containing vaccine, non-inferiority (upper limit of the 95% CI for the difference [BOOSTRIX minus Td] ≤4%). including BOOSTRIX. A review by the Institute of Medicine (IOM) found evidence for a causal Table 1. Rates of Solicited Local Adverse Reactions or General Adverse Events within relationship between receipt of tetanus toxoid and both brachial neuritis and Guillain-Barré the 15-daya Post-vaccination Period in Adolescents 10 to 18 Years of Age (Total syndrome. Vaccinated Cohort) 5.3 Syncope: Syncope (fainting) can occur in association with administration of injectable vaccines, including BOOSTRIX. Syncope can be accompanied by transient neurological signs such BOOSTRIX Td as visual disturbance, paresthesia, and tonic-clonic limb movements. Procedures should be in (N = 3,032) (N = 1,013) place to avoid falling injury and to restore cerebral perfusion following syncope. % % 5.4 Progressive or Unstable Neurologic Disorders: Progressive or unstable neurologic Local conditions (e.g., cerebrovascular events and acute encephalopathic conditions) are reasons to defer vaccination with a pertussis-containing vaccine, including BOOSTRIX. It is not known whether Pain, anyb 75.3 71.7 administration of BOOSTRIX to persons with an unstable or progressive neurologic disorder might Pain, Grade 2 or 3b 51.2 42.5 hasten manifestations of the disorder or affect the prognosis. Administration of BOOSTRIX to Pain, Grade 3c 4.6 4.0 persons with an unstable or progressive neurologic disorder may result in diagnostic confusion between manifestations of the underlying illness and possible adverse effects of vaccination. Redness, any 22.5 19.8 Redness, >20 mm 4.1 3.9 5.5 Arthus-Type Hypersensitivity: Persons who experienced an Arthus-type hypersensitivity Redness, ≥50 mm 1.7 1.6 reaction following a prior dose of a tetanus toxoid-containing vaccine usually have a high serum tetanus antitoxin level and should not receive BOOSTRIX or other tetanus toxoid-containing Swelling, any 21.1 20.1 vaccines unless at least 10 years have elapsed since the last dose of tetanus toxoid-containing Swelling, >20 mm 5.3 4.9 vaccine. Swelling, ≥50 mm 2.5 3.2 5.6 Altered Immunocompetence: As with any vaccine, if administered to immunosuppressed Arm circumference increase, >5 mmd 28.3 29.5 persons, including individuals receiving immunosuppressive therapy, the expected immune Arm circumference increase, >20 mmd 2.0 2.2 response may not be obtained. Arm circumference increase, >40 mmd 0.5 0.3 5.7 Prevention and Management of Acute Allergic Reactions: Prior to administration, the healthcare provider should review the immunization history for possible vaccine sensitivity and General previous vaccination-related adverse reactions to allow an assessment of benefits and risks. Headache, any 43.1 41.5 Epinephrine and other appropriate agents used for the control of immediate allergic reactions Headache, Grade 2 or 3b 15.7 12.7 must be immediately available should an acute anaphylactic reaction occur. Headache, Grade 3 3.7 2.7 6 ADVERSE REACTIONS Fatigue, any 37.0 36.7 6.1 Clinical Trials Experience: Because clinical trials are conducted under widely varying Fatigue, Grade 2 or 3 14.4 12.9 conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly Fatigue, Grade 3 3.7 3.2 compared to rates in the clinical trials of another vaccine, and may not reflect the rates observed in practice. As with any vaccine, there is the possibility that broad use of BOOSTRIX could reveal Gastrointestinal symptoms, anye 26.0 25.8 adverse reactions not observed in clinical trials. In clinical studies, 4,949 adolescents (10 to 18 Gastrointestinal symptoms, Grade 2 or 9.8 9.7 years of age) and 4,076 adults (19 years of age and older) were vaccinated with a single dose of 3e Gastrointestinal symptoms, Grade 3e 3.0 3.2 BOOSTRIX. Of these adolescents, 1,341 were vaccinated with BOOSTRIX in a coadministration study with meningococcal conjugate vaccine [see Drug Interactions (7.1), Clinical Studies (14.5) of full prescribing information]. Of these adults, 1,104 were 65 years of age and older [see Clinical Continued on next page.

821111R0_Boostrix_JournalAd_BriefSummary.indd 2 8/11/17 2:50 PM Table 1. Rates of Solicited Local Adverse Reactions or General Adverse Events within Table 3. Rates of Solicited Local Adverse Reactions or General Adverse Events within the 15-daya Post-vaccination Period in Adolescents 10 to 18 Years of Age (Total the 15-daya Post-vaccination Period in Adults 19 to 64 Years of Age (Total Vaccinated Vaccinated Cohort) (cont’d) Cohort) (cont’d) General General Fever, ≥99.5°F (37.5°C)f 13.5 13.1 Fatigue, any 28.1 28.9 Fever, >100.4°F (38.0°C)f 5.0 4.7 Fatigue, Grade 2 or 3 9.1 9.4 Fever, >102.2°F (39.0°C)f 1.4 1.0 Fatigue, Grade 3 2.5 1.2 Td = Tetanus and Diphtheria Toxoids Adsorbed For Adult Use manufactured by MassBioLogics. Gastrointestinal symptoms, anyb 15.9 17.5 N = Number of subjects in the total vaccinated cohort with local/general symptoms sheets Gastrointestinal symptoms, Grade 2 or 3b 4.3 5.7 completed. Gastrointestinal symptoms, Grade 3b 1.2 1.3 Grade 2 = Local: painful when limb moved; General: interfered with normal activity. Grade 3 = Local: spontaneously painful and/or prevented normal activity; General: prevented Fever, ≥99.5°F (37.5°C)c 5.5 8.0 normal activity. Fever, >100.4°F (38.0°C)c 1.0 1.5 c a Day of vaccination and the next 14 days. Fever, >102.2°F (39.0°C) 0.1 0.4 b Statistically significantly higher P( <0.05) following BOOSTRIX as compared with Td vaccine. Tdap = Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed, a c Grade 3 injection site pain following BOOSTRIX was not inferior to Td vaccine (upper limit of Tdap vaccine manufactured by Sanofi Pasteur SA. two-sided 95% CI for the difference [BOOSTRIX minus Td] in the percentage of subjects ≤4%). N = Number of subjects in the total vaccinated cohort with local/general symptoms sheets d Mid-upper region of the vaccinated arm. completed. e Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain. Grade 2 = Local: painful when limb moved; General: interfered with normal activity. f Oral temperatures or axillary temperatures. Grade 3 = Local/General: prevented normal activity. a Day of vaccination and the next 14 days. Unsolicited Adverse Events in the U.S. Adolescent Study: The incidence of unsolicited adverse b Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain. events reported in the 31 days after vaccination was comparable between the 2 groups (25.4% c Oral temperatures. and 24.5% for BOOSTRIX and Td vaccine, respectively). Solicited Adverse Events in the German Adolescent Study: Table 2 presents the rates of solicited local adverse reactions and fever within Unsolicited Adverse Events in the U.S. Adult (19 to 64 Years of Age) Study: The incidence of 15 days of vaccination for those subjects who had previously been vaccinated with 5 doses of unsolicited adverse events reported in the 31 days after vaccination was comparable between INFANRIX. No cases of whole arm swelling were reported. Two individuals (2/193) reported large the 2 groups (17.8% and 22.2% for BOOSTRIX and Tdap vaccine, respectively). Solicited Adverse injection site swelling (range 110 to 200 mm diameter), in one case associated with Grade 3 Events in the U.S. Elderly (65 Years of Age and Older) Study: Table 4 presents solicited local pain. Neither individual sought medical attention. These episodes were reported to resolve without adverse reactions and general adverse events within 4 days of vaccination with BOOSTRIX or the sequelae within 5 days. comparator Td vaccine for the total vaccinated cohort. a Table 4. Rates of Solicited Local Adverse Reactions or General Adverse Events within 4 Table 2. Rates of Solicited Adverse Events Reported within the 15-day Post-vaccination a Period following Administration of BOOSTRIX in Adolescents 10 to 12 Years of Age Who Days of Vaccination in the Elderly 65 Years of Age and Older (Total Vaccinated Cohort) Had Previously Received 5 Doses of INFANRIX BOOSTRIX Td % % BOOSTRIX (N = 193) Local (N = 882) (N = 444) % Pain, any 21.5 27.7 Pain, any 62.2 Pain, Grade 2 or 3 7.5 10.1 Pain, Grade 2 or 3 33.2 Pain, Grade 3 0.2 0.7 Pain, Grade 3 5.7 Redness, any 10.8 12.6 Redness, any 47.7 Redness, >20 mm 1.4 2.5 Redness, >20 mm 15.0 Redness, ≥50 mm 0.6 0.9 Redness, ≥50 mm 10.9 Swelling, any 7.5 11.7 Swelling, any 38.9 Swelling, >20 mm 2.2 3.4 Swelling, >20 mm 17.6 Swelling, ≥50 mm 0.7 0.7 Swelling, ≥50 mm 14.0 General (N = 882) (N = 445) Fever, ≥99.5°F (37.5°C)b 8.8 Fatigue, any 12.5 14.8 Fever, >100.4°F (38.0°C)b 4.1 Fatigue, Grade 2 or 3 2.5 2.9 Fever, >102.2°F (39.0°C)b 1.0 Fatigue, Grade 3 0.7 0.7 N = Number of subjects with local/general symptoms sheets completed. Headache, any 11.5 11.7 Grade 2 = Painful when limb moved. Headache, Grade 2 or 3 1.9 2.2 Grade 3 = Spontaneously painful and/or prevented normal activity. Headache, Grade 3 0.6 0.0 a Day of vaccination and the next 14 days. b Oral temperatures or axillary temperatures. Gastrointestinal symptoms, anyb 7.6 9.2 Gastrointestinal symptoms, Grade 2 or 3b 1.7 1.8 Solicited Adverse Events in the U.S. Adult (19 to 64 Years of Age) Study: Table 3 presents solicited Gastrointestinal symptoms, Grade 3b 0.3 0.4 local adverse reactions and general adverse events within 15 days of vaccination with BOOSTRIX or the comparator Tdap vaccine for the total vaccinated cohort. Fever, ≥99.5°F (37.5°C)c 2.0 2.5 Table 3. Rates of Solicited Local Adverse Reactions or General Adverse Events within Fever, >100.4°F (38.0°C)c 0.2 0.2 the 15-daya Post-vaccination Period in Adults 19 to 64 Years of Age (Total Vaccinated Fever, >102.2°F (39.0°C)c 0.0 0.0 Cohort) Td = Tetanus and Diphtheria Toxoids Adsorbed, a U.S.-licensed Td vaccine, manufactured by BOOSTRIX Td Sanofi Pasteur SA. (N = 1,480) (N = 741) N = Number of subjects with a documented dose. % % Grade 2 = Local: painful when limb moved; General: interfered with normal activity. Grade 3 = Local/General: prevented normal activity. Local a Day of vaccination and the next 3 days. b Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain. Pain, any 61.0 69.2 c Pain, Grade 2 or 3 35.1 44.4 Oral temperatures. Pain, Grade 3 1.6 2.3 Unsolicited Adverse Events in the U.S. Elderly (65 Years of Age and Older) Study: The incidence of unsolicited adverse events reported in the 31 days after vaccination was comparable between Redness, any 21.1 27.1 the 2 groups (17.1% and 14.4% for BOOSTRIX and Td vaccine, respectively). Serious Adverse Redness, >20 mm 4.0 6.2 Events (SAEs): In the U.S. and German adolescent safety studies, no serious adverse events were Redness, ≥50 mm 1.6 2.3 reported to occur within 31 days of vaccination. During the 6-month extended safety evaluation period, no serious adverse events that were of potential autoimmune origin or new onset and Swelling, any 17.6 25.6 chronic in nature were reported to occur. In non-U.S. adolescent studies in which serious adverse Swelling, >20 mm 3.9 6.3 events were monitored for up to 37 days, one subject was diagnosed with insulin-dependent Swelling, ≥50 mm 1.4 2.8 diabetes 20 days following administration of BOOSTRIX. No other serious adverse events of General potential autoimmune origin or that were new onset and chronic in nature were reported to occur in these studies. In the U.S. adult (19 to 64 years of age) study, serious adverse events were Headache, any 30.1 31.0 reported to occur during the entire study period (0-6 months) by 1.4% and 1.7% of subjects Headache, Grade 2 or 3 11.1 10.5 who received BOOSTRIX and the comparator Tdap vaccine, respectively. During the 6-month Headache, Grade 3 2.2 1.5 extended safety evaluation period, no serious adverse events of a neuroinflammatory nature or with information suggesting an autoimmune etiology were reported in subjects who received BOOSTRIX. In the U.S. elderly (65 years of age and older) study, serious adverse events were

821111R0_Boostrix_JournalAd_BriefSummary.indd 3 8/11/17 2:50 PM reported to occur by 0.7% and 0.9% of subjects who received BOOSTRIX and the comparator 8.1 Pregnancy: Pregnancy Category B. A developmental toxicity study has been performed in Td vaccine, respectively, during the 31-day period after vaccination. Serious adverse events were female rats at a dose approximately 40 times the human dose (on a mL/kg basis) and revealed no reported to occur by 4.2% and 2.2% of subjects who received BOOSTRIX and the comparator evidence of harm to the fetus due to BOOSTRIX. Animal fertility studies have not been conducted Td vaccine, respectively, during the 6-month period after vaccination. Concomitant Vaccination with BOOSTRIX. There are no adequate and well-controlled studies in pregnant women. Because with Meningococcal Conjugate Vaccine in Adolescents: In a randomized study in the U.S., 1,341 animal reproduction studies are not always predictive of human response, BOOSTRIX should be adolescents (11 to 18 years of age) received either BOOSTRIX administered concomitantly given to a pregnant woman only if clearly needed. In a developmental toxicity study, the effect of with MENACTRA® (Meningococcal (Groups A, C, Y, and W-135) Polysaccharide Diphtheria BOOSTRIX on embryo-fetal and pre-weaning development was evaluated in pregnant rats. Animals Toxoid Conjugate Vaccine), (Sanofi Pasteur SA), or each vaccine administered separately 1 were administered INFANRIX by intramuscular injection once prior to gestation and BOOSTRIX by month apart [see Drug Interactions (7.1), Clinical Studies (14.5) of full prescribing information]. intramuscular injection during the period of organogenesis (gestation Days 6, 8, 11, and 15), 0.1 Safety was evaluated in 446 subjects who received BOOSTRIX administered concomitantly mL/rat/occasion (approximately 40-fold excess relative to the projected human dose of BOOSTRIX with meningococcal conjugate vaccine at different injection sites, 446 subjects who received on a body weight basis). The antigens in INFANRIX are the same as those in BOOSTRIX, but BOOSTRIX followed by meningococcal conjugate vaccine 1 month later, and 449 subjects who INFANRIX is formulated with higher quantities of these antigens. No adverse effects on pregnancy, received meningococcal conjugate vaccine followed by BOOSTRIX 1 month later. Solicited local parturition, lactation parameters, and embryo-fetal or pre-weaning development were observed. adverse reactions and general adverse events were recorded on diary cards for 4 days (Day 0-3) There were no vaccine-related fetal malformations or other evidence of teratogenesis. Pregnancy following each vaccination. Unsolicited adverse events were monitored for the 31-day period Registry: GlaxoSmithKline maintains a surveillance registry to collect data on pregnancy following each vaccination (Day 0-30). Table 5 presents the percentages of subjects experiencing outcomes and newborn health status outcomes following vaccination with BOOSTRIX during local reactions at the injection site for BOOSTRIX and solicited general events following BOOSTRIX. pregnancy. Women who receive BOOSTRIX during pregnancy should be encouraged to contact The incidence of unsolicited adverse events reported in the 31 days after any vaccination was GlaxoSmithKline directly or their healthcare provider should contact GlaxoSmithKline by calling similar following each dose of BOOSTRIX in all cohorts. 1-888-452-9622. Table 5. Rates of Solicited Local Adverse Reactions or General Adverse Events Reported 8.3 Nursing Mothers: It is not known whether BOOSTRIX is excreted in human milk. Because within the 4-day Post-vaccination Period following Administration of BOOSTRIX in many drugs are excreted in human milk, caution should be exercised when BOOSTRIX is Individuals 11 to 18 Years of Age (Total Vaccinated Cohort) administered to a nursing woman. 8.4 Pediatric Use: BOOSTRIX is not indicated for use in children younger than 10 years of age. BOOSTRIX+MCV4a BOOSTRIX→MCV4b MCV4→BOOSTRIXc Safety and effectiveness of BOOSTRIX in this age group have not been established. (N = 441) (N = 432-433) (N = 441) 8.5 Geriatric Use: In clinical trials, 1,104 subjects 65 years of age and older received BOOSTRIX; % % % of these subjects, 299 were 75 years of age and older. In the U.S. elderly (65 years and older) study, immune responses to tetanus and diphtheria toxoids following BOOSTRIX were non-inferior Local (at injection site for BOOSTRIX) to the comparator Td vaccine. Antibody responses to pertussis antigens following a single dose of BOOSTRIX in the elderly were non-inferior to those observed with INFANRIX administered as Pain, any 70.1 70.4 47.8 a 3-dose series in infants [see Clinical Studies (14.4) of full prescribing information]. Solicited adverse events following BOOSTRIX were similar in frequency to those reported with the Redness, any 22.7 25.7 17.9 comparator Td vaccine [see Adverse Reactions (6.1)]. Swelling, any 17.7 18.1 12.0 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility: BOOSTRIX has not been General (following administration of BOOSTRIX) evaluated for carcinogenic or mutagenic potential, or for impairment of fertility. Fatigue 34.0 32.1 20.4 17 PATIENT COUNSELING INFORMATION Headache 34.0 30.7 17.0 See FDA-Approved Patient Labeling. Gastrointestinal d 15.2 14.5 7.7 BOOSTRIX, FLUARIX, INFANRIX, and TIP-LOK are registered trademarks of the GSK group symptoms of companies. The other brands listed are trademarks of their respective owners and are not trademarks of the GSK group of companies. The makers of these brands are not affiliated with Fever, ≥99.5°F 5.2 3.5 2.3 and do not endorse the GSK group of companies or its products. (37.5°C)e MCV4 = MENACTRA (Meningococcal (Groups A, C, Y, and W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine), Sanofi Pasteur SA. N = number of subjects in the total vaccinated cohort with local/general symptoms sheets completed. a BOOSTRIX+MCV4 = Concomitant vaccination with BOOSTRIX and MENACTRA. b BOOSTRIX→MCV4 = BOOSTRIX followed by MCV4 1 month later. c MCV4→BOOSTRIX = MCV4 followed by BOOSTRIX 1 month later. d Gastrointestinal symptoms included nausea, vomiting, diarrhea, and/or abdominal pain. e Oral temperatures. 6.2 Postmarketing Experience: In addition to reports in clinical trials, worldwide voluntary Manufactured by GlaxoSmithKline Biologicals reports of adverse events received for BOOSTRIX in persons 10 years of age and older since Rixensart, Belgium, U.S. License 1617, and market introduction of this vaccine are listed below. This list includes serious events or events that have causal connection to components of this or other vaccines or drugs. Because these GSK Vaccines GmbH events are reported voluntarily from a population of uncertain size, it is not possible to reliably Marburg, Germany, U.S. License 1617 estimate their frequency or establish a causal relationship to the vaccine. Blood and Lymphatic Distributed by GlaxoSmithKline System Disorders: Lymphadenitis, lymphadenopathy. Immune System Disorders: Allergic reactions, including anaphylactic and anaphylactoid reactions. Cardiac Disorders: Myocarditis. Research Triangle Park, NC 27709 General Disorders and Administration Site Conditions: Extensive swelling of the injected limb, ©2016 the GSK group of companies. All rights reserved. injection site induration, injection site inflammation, injection site mass, injection site pruritus, BTX:29BRS injection site nodule, injection site warmth, injection site reaction. Musculoskeletal and Connective Tissue Disorders: Arthralgia, back pain, myalgia. Nervous System Disorders: Convulsions (with Revised: 10/2016 and without fever), encephalitis, facial palsy, loss of consciousness, paraesthesia, syncope. Skin and Subcutaneous Tissue Disorders: Angioedema, exanthem, Henoch-Schönlein purpura, rash, ©2017 GSK group of companies. urticaria. All rights reserved. Printed in USA. 821111R0 July 2017 7 DRUG INTERACTIONS 7.1 Concomitant Vaccine Administration: BOOSTRIX was administered concomitantly with MENACTRA in a clinical study of subjects 11 to 18 years of age [see Clinical Studies (14.5) of full prescribing information]. Post-vaccination geometric mean antibody concentrations (GMCs) to pertactin were lower following BOOSTRIX administered concomitantly with meningococcal conjugate vaccine compared to BOOSTRIX administered first. It is not known if the efficacy of BOOSTRIX is affected by the reduced response to pertactin. BOOSTRIX was administered concomitantly with FLUARIX® (Influenza Virus Vaccine) in a clinical study of subjects 19 to 64 years of age [see Clinical Studies (14.5) of full prescribing information]. Lower GMCs for antibodies to the pertussis antigens filamentous hemagglutinin (FHA) and pertactin were observed when BOOSTRIX was administered concomitantly with FLUARIX as compared with BOOSTRIX alone. It is not known if the efficacy of BOOSTRIX is affected by the reduced response to FHA and pertactin. When BOOSTRIX is administered concomitantly with other injectable vaccines or Tetanus Immune Globulin, they should be given with separate syringes and at different injection sites. BOOSTRIX should not be mixed with any other vaccine in the same syringe or vial. 7.2 Immunosuppressive Therapies: Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs, and corticosteroids (used in greater than physiologic doses), may reduce the immune response to BOOSTRIX. 8 USE IN SPECIFIC POPULATIONS

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FDA Finalizes Guidance on Medical Product Manufacturer Communications by Stacie Heller, Vice President, Policy, AmerisourceBergen

In June, the FDA finalized two guidances payors [sic],” as outlined in the Trump the life cycle of their products. Notably, to clarify the agency’s current thinking administration’s drug pricing blueprint the guidance creates an expanded safe on communicating medical product in- released in May (more information ap- harbor for preapproval communications formation to payers and to inform indus- pears in Trump Administration Releases to cover new uses of legally marketed try on how to communicate information Drug Pricing Plan), and stated that it “can products, allowing more flexibility in the about products not contained in product help nurture this change by providing information manufacturers can provide labeling. Specifically, the guidance docu- clear guidance to pharmaceutical com- about the value of their products. ments outline the agency’s position with panies about open, responsible com- According to Gottlieb, the additional respect to (1) manufacturer communica- munication with payors [sic], formulary flexibility provided in the guidance could tions with payers, formulary committees, committees and others.” Gottlieb further speed coverage decisions for new medi- and similar entities, Final Guidance on stated that the “ultimate goal is to help cal products by enabling payers to review Payer Communications, and (2) manu- facilitate a market that is more competi- relevant information about unapproved facturer communications consistent with tive” and benefits patients. products before they enter the market. FDA-required labeling, Consistent with the Labeling Guidance. The final guid- Final Guidance on Payer Consistent with the ances include changes from the draft Communications FDA-Required Labeling versions released in January 2017 and The FDA’s Final Guidance on Payer The second guidance, Medical Product attempt to spell out the agency's policies Communications includes questions and Communications That are Consistent with toward communicating medical product answers (beyond those included in the the FDA-Required Labeling, provides information that doesn't fall within ap- draft guidance) regarding communicat- the FDA’s views—through a set of 11 proved labeling in a truthful and non- ing information about unapproved prod- questions and answers—on manufactur- misleading way. ucts or unapproved uses of approved ers’ communication of information that An accompanying press release products to payers, formulary commit- is consistent with—but not in—the FDA- from FDA Commissioner Scott Gottlieb tees and similar entities. approved labeling. referenced Health and Human Services In a change from the draft version, the Gottlieb mentioned that “[t]his infor- (HHS) Secretary Azar’s goal of “linking final payer communications guidance mation, such as data from post-market payments for drugs to their value and discusses how drug and device makers studies and surveillance of a product’s [is] committed to removing regulatory can communicate “truthful, non-mislead- approved uses, or additional information obstacles to value-based purchasing by ing, and appropriate” information across form the pre-market studies that were used to support approval of the product, may help inform decision-making regarding patient care.” The agency clarified in the final guidance that it does not intend to rely on such communications as the basis for establishing a new intended use for a product different from its legally marketed use(s), provided the communication is consistent with required labeling. As envisioned by the FDA, the final guidances may help broaden communications between payers and manufacturers and establish how the value of medicines can facilitate a shift toward value-based payment arrangements.

14 | InsideOut FDA Advances Compounding Policy Priorities Plan for 2018 by Beth Mitchell, Director, Government Affairs, AmerisourceBergen

In March, the FDA issued new draft guid- (3) stipulates that even if a bulk substance is to the guidance. Manufacturers, sterile ance, Evaluation of Bulk Drug Substances approved for inclusion on the list, it may not be to sterile compounders and public Nominated for Use in Compounding used in all circumstances. health groups are generally supportive Under Section 503B of the Federal Food, of the guidance but have urged FDA to Drug, and Cosmetic Act, outlining ap- In relation to financial incentives to strengthen some aspects. propriate use of bulk drug substances by purchase compounded products that Significant questions remain concern- outsourcing facilities that provide com- originate from bulk powders instead of ing the draft guidance and its impacts on pounded preparations for patients who from the FDA-approved vial, the draft healthcare: When will FDA finalize the receive therapeutic IVs administered in guidance notes, “Finally, compound- guidance and what changes will they hospitals, health systems, ambulatory ing a drug product from a bulk drug make to the current draft? How will FDA surgery centers and physician offices. substance that is a component of an enforce and communicate the final guid- The draft guidance was released as approved drug when there is no clinical ance to the vast healthcare marketplace part of FDA’s Compounding Priorities need to do so, perhaps because of eco- (including critical care personnel of hos- Plan, unveiled earlier this year, and is a nomic incentives, undermines the drug pital clinicians, pharmacists, physicians, significant policy component of FDA’s approval process.” purchasers, administrators and CEOs)? implementation of the Drug Quality and Once finalized, the draft guidance may And what actions will FDA take until the Security Act (DQSA). DQSA is federal initiate a new process to ensure there is guidance is finalized and enforced to legislation enacted in 2013 following the a legitimate clinical need for each bulk communicate appropriate use of bulk New England Compounding Center drug substance approved for use in substances in 503B compounding? fungal meningitis outbreak, which caused compounding. To access the FDA new draft guidance, more than 60 deaths and 750 cases of Until FDA finalizes the draft guidance please visit fda.com/guidance503b. infection throughout the U.S. Section 503B and releases more explicit communica- of DQSA created the outsourcing facility tion to ensure clarity in the marketplace, category and requires such facilities to FDA’s current guidance and interim meet more stringent FDA requirements policies remain in place: final guidance than traditional 503A compounding issued in January 2018, Compounded pharmacies. Drug Products That Are Essentially DQSA clearly restricts the use of bulk Copies of Approved Drug Products, and drug substances for compounding by the Interim Policy on Compounding Using 503B outsourcing facilities, except when Bulk Drug Substances, which includes clinically necessary or if a drug is in open-ended enforcement discretion for shortage. Section 503B specifies FDA- a list of nearly 200 Bulk Drug Substances. approved products or sterile to sterile The majority of the substances on Bulk compounded products originating from Drug Substances list are a component of an FDA-approved vial should be used for an FDA-approved drug. patients whenever possible. Consistent Comments on the draft guidance were with the statute, the new guidance: due May 25. FDA received approximately 70 unique letters, reflecting the variety of (1) articulates the risk and higher potential for viewpoints on the guidance, disharmony errors associated with compounding from bulk in the marketplace and the need for FDA powders; to clarify and communicate their position with respect to appropriate use of bulk (2) outlines the factors and procedures FDA pro- drug substances. Several outsourcing poses to use to evaluate if a bulk drug substance facilities who compound from bulk pow- should be used in compounding by outsourcing ders (instead of from the FDA-approved facilities; and sterilized vial) are urging major changes

ASD Healthcare | 15 Federal Right to Try Legislation Enacted by Madison Malsch, Legislative Intern and Stacie Heller, Vice President, Policy, AmerisourceBergen

After a year’s long, protracted legislative with a life-threatening disease and must such clinical outcomes are “critical to debate, President Trump signed into have considered all applicable FDA- determining the safety” of the product. law S 204, The Trickett Wendler, Frank approved treatment options before Opponents of the new law suggest Mongiello, Jordan McLinn, and Matthew seeking an eligible investigational drug. it poses too many risks for patients, Bellina Right to Try Act of 2017 (Right to Eligible drugs must have completed a i.e., adverse side effects, patients were Try). Amending the Food, Drug, and Phase 1 study; have not been approved misdiagnosed, or patients’ current condi- Cosmetic Act, Right to Try creates a new or licensed for any use; be subject to tions could worsen due to investigational framework for access to investigational a filed New Drug Application (NDA) drugs. Numerous patient advocacy drugs in limited situations outside of a or Biologics License Application (BLA); groups, including the National Organi- clinical trial. This new federal legislation and continue to undergo the trial zation for Rare Disorders and Friends comes after state legislatures implement- process for the duration of the eligible of Cancer Research, are concerned the ed Right to Try laws in 38 states over the patient’s treatment. If a sponsor sup- new law could weaken FDA’s authority last several years. plies the drug, the sponsor must submit by rolling back the agency’s oversight of Right to Try aims to provide an ac- annual reports to the FDA regarding investigational treatments. Others assert celerated alternative to investigational doses, patients, intended use of the Right to Try just speeds up access to treat- use pathways currently in place, includ- drug and any adverse event. ments already available in clinical trials ing the FDA’s current program known Similar to Expanded Access, Right to and pose no additional risks to patients. as Expanded Access (also known as Try does not require sponsors to provide While the new law was clearly written Compassionate Use). Expanded Access access to investigational drugs. The new to cut FDA out of the process, the agency requires doctors to apply to the FDA, out- law exempts sponsors from any litigation expects to play a role in Right to Try lining their intended use and treatment related to refusing to provide an investi- implementation. At last month’s annual of the appropriate investigational drugs. gational drug and protects the sponsor meeting of the American Society of Right to Try intentionally reduces the and physician from most litigation. While Clinical Oncology, FDA Commissioner regulatory burden of including FDA in the the law mitigates the risk that a negative Gottlieb said, “The compassionate use process, leaving eligibility determination clinical outcome would impact the prod- program will sit alongside ‘Right To Try’… to the investigational drug sponsor. uct’s ultimate development or approval, nothing’s going to change about our cur- To qualify, several criteria must be the law does allow FDA to use negative rent approach.” met: eligible patients must be diagnosed outcomes if the agency determines that

16 | InsideOut ★ ★ ★ Washingtondate Trump Administration Releases Drug Pricing Plan by Ashley O’Sullivan, Manager, Legislation and Policy, AmerisourceBergen

In May, the Trump administration released »» Medicare B to D: Proposes moving some removing regulatory barriers to value-based its long-awaited drug pricing plan, Medicare Part B drugs to Part D, allowing payment as outlined in the blueprint. “American Patients First,” a 44-page more treatments to fall under Part D's price “blueprint to lower drug prices and negotiation process. President Trump also indicated drug reduce out-of-pocket costs.” The blue- companies would be voluntarily lower- print identifies four central challenges: »» Part D Rebates: Proposes reducing or end- ing drug prices, stating, “Some of the high list prices for drugs; seniors and ing rebates in the Part D prescription drug big drug companies in two weeks… government programs overpaying for program. HHS believes it has the regulatory they are going to announce — because drugs due to lack of negotiation; high and authority to modify the statute that provides of what we did — they are going to rising out-of-pocket costs for consumers; safe harbor for rebates. announce voluntary massive drops and foreign governments “free-riding” in prices.” However, in a June Senate of American investment in innovation. Since its release in May, the adminis- Health, Education, Labor, and Pensions President Trump and the Department tration has advanced several immediate Committee hearing, HHS Secretary of Health and Human Services (HHS) actions identified in the blueprint: Alex Azar said that while there are “sev- pinpointed four key strategies for reform: eral drug companies that are looking at improve competition, increase nego- »» CMS Administrator Seema Verma sent a letter substantial, material decreases in drug tiation, provide incentives for lower list to all Part D plan sponsors warning them that prices,” he indicated it could take time prices and lower out-of-pocket costs. any form of “gag clauses” (which prevent for cost reductions. The blueprint does not provide pharmacists from telling patients when While the timeline for implementing detailed legislative or regulatory pro- alternatives to billing their insurance would policy changes is uncertain, the blue- posals but provides a range of policy be cheaper than the co-pay) in pharmacy print and HHS request for information options that are under active consider- contracts are unacceptable to CMS. (RFI) from stakeholders are first steps ation by HHS. Not all proposals in the toward substantive reforms that are likely blueprint can be implemented through »» The FDA posted a list on its website of more implemented through a formal rulemak- administrative action and may require than three dozen drug companies that may ing process. With RFI comments due by future congressional involvement. be engaging in “gaming” tactics to delay July 16, AmerisourceBergen joins indus- The plan encompasses two phases: generic competition; FDA later released two try and provider stakeholders by actively the first contains immediate actions guidance documents relating to medical assessing the impact the blueprint pro- President Trump may direct to HHS; the product manufacturer communications posals may have on patient and provider second includes actions HHS is actively (more information appears in FDA Finalizes access to pharmaceutical therapies considering. For the second phase, Guidance on Medical Product Manufacturer across the healthcare continuum. HHS requested stakeholder feedback Communications) and reiterating its goals of on more than 100 detailed questions that cover almost every aspect of federal prescription drug policy. Three proposals of significant interest/concern to healthcare stakeholders include:

»» Part B Competitive Acquisition Program (CAP): Through its Center for Medicare and Medicaid Innovation (CMMI, also known as the “Innova- tion Center”) authority, HHS may update CAP for immediate action to “support better negotiation of drug discounts through government insurance programs.”

ASD Healthcare | 17 Executiveone Trends and innovations influencing specialty pharmaceuticals’ delivery

The Need for Health System Specialty Pharmacies Unmatched coordination of patient care and services throughout the patient journey by Willis Chandler

In less than two decades, precision medi- complex, especially for patients with nu- With these opportunities in mind, health cine has evolved from theory to research merous providers and discrete electronic systems should give careful evaluation to actual launch of novel therapeutics. medical records. of how an in-house specialty pharmacy From January 2015 through May 2018, Health systems housing specialty could advance their goals for enhanced the FDA approved 128 novel drugs, pharmacies possess the unique ability patient care. many of which are considered specialty to facilitate comprehensive patient pharmaceuticals. Specialty medications care — from inpatient to ambulatory ser- A Strategic Approach frequently provide remarkable outcomes vices — improving the time to fill specialty Well before implementing an in-house for patients who need them; these life- therapeutics and the quality of care with specialty pharmacy, health systems saving therapeutics, however, add layers increased clinical coordination. In-house should evaluate the volume of patients of complexities to patient care, often specialty pharmacies also provide access with complex diseases who require requiring genetic and molecular profiles to new revenue streams. Industry experts specialty drugs, then compare those to determine best treatment for patients estimate pharmacy revenues will reach patients with the organization’s centers of with complex cancers and rare diseases. approximately $576 billion by 2022 excellence. Additional key considerations Given the comorbid complexities of the and specialty drugs will account for a should include prescriber networks, diseases, coordination of care grows projected 47 percent of those revenues. payer contracts, technology capacities,

18 | InsideOut existing pharmacies, physical footprint holders included in the implementation to offer individual services as the health and capital reserves. Many health process may not have a complete un- system’s capabilities increase. Also systems seek consultative partners to derstanding of the nuances of a specialty consider the transparency a partner compare their unique capabilities with pharmacy’s operations and financials; as provides during transfer of health system industry benchmarks, develop assump- such, robust education is important during prescriptions; some partners work more tions for financial modeling and reveal strategic development and throughout seamlessly to ensure continuity of care for potential opportunities. each stage of the implementation patients. Once initial steps are taken, developing processes. Manufacturers and payers alike are strategic planning is imperative. Strategic more willing to open their networks to development of a compelling business Access to Specialty Drugs specialty pharmacies that demonstrate case will ease internal alignment and Limited distribution networks and payer improvements in patient adherence buy in. In addition, by prioritizing contracts can challenge health system and outcomes. An ability to capture and specialty pharmacy services based on specialty pharmacies, yet options exist report comprehensive data through- patient needs, the health system can to overcome such potential barriers. out the continuum of patient care in the manage initial investments while creating During early stages, many health systems health system contributes to demon- a viable roadmap for future expansion. benefit from working with a specialty strating value. Consultative partners For example, health systems with an pharmacy partner that offers access to who assist with manufacturer and payer ambulatory or 340B pharmacy can specialty therapies and payer contracts. negotiations, who also collect the most model the design of a specialty phar- While evaluating specialty partners, pertinent data and package the data macy to leverage existing infrastructure consider if they initially provide a full appropriately, empower a health system and reduce initial costs. Selecting targeted complement of services and the flexibility for immediate and continued successes. disease states for specialty pharmacy services, projecting financials at the therapy level and determining how to maximize existing resources are key elements of the strategy.

Detailed Plans Aid Implementation Detailed plans that encompass a range of areas will benefit specialty pharmacy implementation and patients. For example, a layout and design may be needed for the pharmacy facility. New technologies may require selection and implementation. Workflow design, policies and procedures and specialty pharmacy accreditation are essential. Establishing payer contracts and aligning specialty product access to targeted disease states are also imperative. Staffing may require recruiting and deploying clinicians and other personnel. Ensuring patient out- reach programs, including programs for comprehensive medication management and prior authorizations, will contribute to pharmacy growth, patient satisfaction and the health system’s reputation in the community. Health systems often leverage partners that deliver project management and oversight needed to ensure strategic alignment and completion of steps within each implementation stage. All stake-

ASD Healthcare | 19 FPO Graphic

Health systems can further leverage scribers. These choices, coupled with About the author their distributor partnership as a channel an increasingly competitive market, As senior vice president for engaging the manufacturers — most compel prudent health systems to and president, health notably, those with longstanding manu- recognize the need to educate patients systems and specialty facturer relationships and an understand- and prescribers on enhanced patient services, Willis leads ing of the complexities faced by health care and outcomes delivered in a co- AmerisourceBergen’s systems. Distributors committed to ordinated care model — a model health full line and specialty quality patient care frequently serve as systems currently provide. distribution businesses for health system the health system’s advocate to broaden To mobilize the resources required for customers, driving sales strategy within health access to specialty pharmaceuticals. By a successful specialty pharmacy, health systems and integrated delivery networks. providing services well beyond drug systems need a deliberate, well-planned Willis joined AmerisourceBergen from CVS distribution, the right distributor may implementation process and continuous Health, where he most recently served as the also help health systems retain patients organizational alignment. The selection of vice president, health system alliances — a long after discharge from their facilities. key partners and their subsequent level role in which he led and developed a national of collaboration can inhibit or greatly commercial team focused on developing C-suite Unique Patient Care and Outcomes enhance a specialty pharmacy build-out relationships with hospitals and health systems. Specialty drugs inarguably changed and success. Ultimately, the integration of His team represented all of CVS capabilities in the healthcare industry’s landscape, the patient care team with a health system retail, specialty, infusion, post-acute care, PBMs, and that landscape remains dynamic. specialty pharmacy requires a strong 340B and Medicare Part D for health systems Sophisticated technologies and commitment and clear goals. Regardless and ACOs. research continue to evolve develop- of complexities, implementing a health Willis earned a BS in history and American ment of novel specialty drugs; within system specialty pharmacy enhances studies from Brandeis University and an MBA that evolution, more choices become patient care while improving patient in healthcare from the Wharton School of the available to patients and their pre- outcomes. University of Pennsylvania.

20 | InsideOut Exposure of high risk patients to varicella is unpredictable—treatment requires quick action. Are you prepared?

VARIZIG is indicated, and the Centers for Disease Control (CDC) recommends VARIZIG, for postexposure prophylaxis of varicella for persons at high risk for severe disease who lack evidence of immunity to varicella.1,2,3 VARIZIG administration is intended to reduce the severity of varicella. Administer VARIZIG as soon as possible following varicella zoster virus (VZV) exposure, ideally within 96 hours for greatest effectiveness.

Summary of incidence of varicella in subjects treated with VARIZIG through an Expanded Access Protocol (EAP)1: 4.5%, n = 12 (269 doses) in immunocompromised patients 7.3%, n = 10 (137 doses) in pregnant women 11.4%, n = 12 (105 doses) in infants

SELECTED IMPORTANT SAFETY INFORMATION The most serious adverse drug reactions observed in clinical trials for all subjects and patients include pyrexia, nausea, and vomiting. The most common adverse events observed in clinical trials for all subjects and patients were injection site pain, headache, chills, fatigue, rash, and nausea.

References: 1. VARIZIG Prescribing Information, August 2016. 2. CDC. Updated Recommendations for Use of VariZIG—United States, 2013. MMWR. 2013;62:574-576. 3. American Academy of Pediatrics. Varicella-zoster infections. In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book®: 2012 Report of the Committee on Infectious Diseases. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012:774–89.

VARIZIG® [Varicella Zoster Immune Globulin (Human)] and all Saol brand, product, service and feature names, logos, and slogans are trademarks or registered trademarks of Saol in the United States and/or other countries. © 2018 Saol Therapeutics Inc. All rights reserved. ST-203-1006-01

Please see VARIZIG Important Safety Information and full Prescribing Information at www.varizig.com.

Saol Thera Varzig Ad_05092018.indd 1 8/1/18 11:34 AM Transmissible Infectious Agents Because VARIZIG is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The plasma donors are screened for the presence VARIZIG® [Varicella Zoster Immune Globulin (Human)] of certain infectious agents and the manufacturing process for VARIZIG includes measures for intramuscular administration only. to inactivate and remove certain viruses. Despite these measures, products derived from human plasma can still potentially transmit diseases. No cases of transmission of viral Sterile Solution for Injection diseases, vCJD or CJD have been associated with the use of VARIZIG. Brief Summary of Prescribing Information: Please see full Report all infections thought by a physician to have been transmitted by VARIZIG to prescribing information for details. Aptevo BioTherapeutics at 1-844-859-6675. Discuss the risks and benefits of this product with the patient before administering it to the patient. INDICATIONS AND USAGE ADVERSE REACTIONS VARIZIG® [Varicella Zoster Immune Globulin (Human)] is indicated for post-exposure The most serious adverse drug reactions observed in clinical trials for all subjects and prophylaxis of varicella in high risk individuals. High risk groups include: patients (n=601) include pyrexia, nausea, and vomiting. • immunocompromised children and adults, The most common adverse drug reactions (reported by ≥ 1% of subjects) observed in • newborns of mothers with varicella shortly before or after delivery, clinical trials for all subjects and patients (n=601) are the following: • premature infants, • injection site pain (3%), • neonates and infants less than one year of age, • headache (2%), • adults without evidence of immunity, • rash (including terms pruritus, rash, rash erythematous, rash vesicular and urticaria) (1%), • pregnant women. • fatigue (1%), VARIZIG administration is intended to reduce the severity of varicella. Administer VARIZIG as • chills (1%), soon as possible following varicella zoster virus (VZV) exposure, ideally within 96 hours for • nausea (1%). greatest effectiveness. All other adverse drug reactions occurred in less than 1%. • There is no convincing evidence that VARIZIG reduces the incidence of chickenpox infection after exposure to VZV. Clinical Trial Experience • There is no convincing evidence that established infections with VZV can be modified by Because clinical trials are conducted under widely varying conditions, adverse reaction rates VARIZIG administration. observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials • There is no indication for the prophylactic use of VARIZIG in immunodeficient children of another drug and may not reflect the rates observed in practice. or adults when there is a past history of varicella, unless the patient is undergoing bone Six hundred and one (n=601) high risk individuals received VARIZIG intramuscularly in two marrow transplantation. clinical trials which included pregnant women, infants and immunocompromised pediatric CONTRAINDICATIONS and adult patients. The highest incidence of adverse reactions occurred in pregnant women (n=166), including injection site pain (7%), rash (including terms pruritus, rash, • Individuals known to have anaphylactic or severe systemic (hypersensitivity) reactions rash erythematous, and rash vesicular) (4%), headache (3%), and fatigue (2%). All other to human immune globulin preparations should not receive VARIZIG. adverse reactions occurred in 1% or less of clinical trial subjects within each high risk • IgA-deficient patients with antibodies against IgA and a history of hypersensitivity may group. A single incidence of serum sickness (approximately one in 600 patients treated with have an anaphylactoid reaction. VARIZIG) was observed in an immunocompromised adolescent patient. • VARIZIG contains less than 40 micrograms per milliliter of IgA. There were eight reported adverse events associated with the coagulation system including, WARNINGS AND PRECAUTIONS deep vein thrombosis (n=1), disseminated intravascular coagulation (n=1), intracranial Thrombotic Events hemorrhage (n=2), coagulopathy (n=2), intraventricular hemorrhage (n=1), and pulmonary hemorrhage (n=1) in 621 subjects in the open-label, Expanded Access Protocol Thrombotic events may occur during or following treatment with immune globulin (EAP); the study was not designed to differentiate between adverse events attributed to the products (1, 2, 3). Patients at risk include those with a history of atherosclerosis, multiple underlying medical condition and adverse reactions to VARIZIG. cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known/suspected hyperviscosity. Consider USE IN SPECIFIC POPULATIONS baseline assessment of blood viscosity in patients at risk for hyperviscosity including those Pregnancy with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), Pregnancy category C. Animal reproduction studies have not been conducted with VARIZIG. or monoclonal gammopathies. It also is not known whether VARIZIG can cause fetal harm when administered to a pregnant Coagulation Disorders woman or can affect reproduction capacity. VARIZIG should be given to a pregnant woman only if clearly needed. Administer VARIZIG intramuscularly only. In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, only The safety and effectiveness of VARIZIG have been evaluated for post-exposure prophylaxis administer VARIZIG if the expected benefits outweigh the potential risks. in clinical trials in 166 pregnant women [see ADVERSE REACTIONS and CLINICAL STUDIES]. Hypersensitivity Nursing Mothers Severe hypersensitivity reactions may occur following VARIZIG administration. Administer It is not known whether VARIZIG is excreted in human milk. Because many drugs are excreted VARIZIG in a setting with appropriate equipment, medication and personnel trained in the in human milk, caution should be exercised when VARIZIG is administered to a nursing mother. management of hypersensitivity, anaphylaxis and shock. In the case of hypersensitivity, Pediatric Use discontinue administration of VARIZIG immediately and provide appropriate treatment. The dosing recommendations in the treatment of pediatric patients are by body weight. VARIZIG contains trace amounts of IgA (less than 40 micrograms per milliliter). Patients with known antibodies to IgA have a greater risk of severe hypersensitivity and anaphylactic The safety and effectiveness of VARIZIG have been evaluated for post-exposure prophylaxis reactions. VARIZIG is contraindicated in IgA deficient patients with antibodies against IgA in the VARIZIG expanded access clinical trial in 374 pediatric patients, including and history of hypersensitivity reactions [see CONTRAINDICATIONS] . immunocompromised pediatric patients:

Saol Thera Varzig Ad_05092018.indd 2 8/1/18 11:34 AM • 94 preterm newborns and infants, adult (Table 1). Clinical varicella was more common after prolonged VZV exposure. The • 53 term newborns, • 45 infants and toddlers, comparison of the incidence of varicella based on treatment window revealed that treatment • 176 children and, • 43 adolescents. Table 1 Comparison of Varicella Incidence in Subjects Treated with VARIZIG to Historical Incidence of Varicella in Untreated Individuals – Interim analysis In the EAP, follow up data were available for 110 VARIZIG treatments in infants (including newborns, pre-term infants, and infants <1 year old). Three severe infections were Historical Incidence reported, all three with pox count >100, one of which also had pneumonia and another one Incidence of Varicella 95% High Risk also developed probable varicella encephalitis. of Varicella n1 in VARIZIG- p-value2 Population in Untreated treated Interval Geriatric Use Individuals Subjects Clinical studies of VARIZIG administered intramuscularly for post-exposure prophylaxis 6.8% (2.2- Pregnant Women 70% 74 <0.0001* (n=5) 15.1%) Immunocompromised 8.4% (4.6- 88% 154 <0.0001* Use caution when administering VARIZIG to patients age 65 and over who are judged to be patients (n=13) 14.0%) at increased risk of thrombotic events [see WARNINGS AND PRECAUTIONS]. Do not exceed 14.8% (7.9- Infants 50% 81 <0.0001* recommended doses and administer VARIZIG intramuscularly only. (n=12) 24.5%) Immunocompromised Patients 1 In the EAP, both adult (n=37) and pediatric immunocompromised subjects (n=235) were 2 One sample two-sided exact binomial test. treated. Twelve immunocompromised subjects developed clinical varicella and none developed

acyclovir and due to incomplete reporting, it is not known if others also received acyclovir. Table 2 Updated Summary of Incidence of Varicella in Subjects Treated with CLINICAL STUDIES VARIZIG - Final Report

Pregnant Women Exposed to Varicella Zoster Virus All VARIZIG Treated Subjects A randomized, open-label, multicenter, active controlled clinical trial was conducted in Incidence of 95% High Risk Population Varicella in n1 VARIZIG-treated Interval • one to four days post-exposure and, Subjects

Pregnant Women 137 7.3% (n=10) (3.6%-13.0%) The women were randomized into one of three study arms as follows: Immunocompromised • a single intravenous dose of 125 IU/10 kg body weight to a maximum dose of 625 IU of VARIZIG, 269 4.5% (n=12) (2.3%-7.7%) • a single intramuscular dose of 125 IU/10 kg body weight to a maximum dose of 625 IU of patients VARIZIG or, Infants including newborns, • a single intramuscular dose of 125 IU/10 kg body weight to a maximum dose of 625 IU of pre-term infants and infants 105 11.4% (n=12) (6.1%-19.1%) <1 year VZIG (licensed comparator product). 1 Patients were followed for 42 days. Incidence of clinical varicella was similar across all treatment groups with an overall REFERENCES incidence of 33%; however, in the subset of 28 subjects with more than 24 hours exposure 1. D alakas MC. High-dose intravenous immunoglobulin and serum viscosity: risk of to varicella, the incidence of clinical varicella in the combined treatment groups was 64%. precipitating thromboembolic events. Neurology. 1994; 44:223-6. 2. irkin FC, Smith IL. Fatal thrombotic events during treatment of Mean weighted constitutional illness scores (CIS) (4) were similar across all groups and none autoimmune thrombocytopenia with intravenous immunoglobulin in elderly patients. of the subjects had serious complications of varicella. The small number of subjects in each Lancet. 1986; 2:217-8. 3. Wolberg AS, Kon RH, Monroe DM, H formal statistical comparisons between groups. intravenous immunoglobulin preparations. Am J Hematol. 2000; 65:30-4. High Risk Patients Exposed to Varicella Zoster Virus 4. Koren G, Money D, Boucher M, Aoki F, Petric M, Innocencion G et al. Serum concentrations,

An open-label, Expanded Access Protocol (EAP) conducted in the United States of America globulin in pregnant women. J Clin Pharmacol. 2002; 42(3):267-74. was designed to provide VARIZIG to high risk individuals who were exposed to varicella

injection of VARIZIG in the prevention or reduction of severity of complications from varicella infections in the indicated high risk populations. Initially, enrolment was limited Manufactured by: to allow treatment with VARIZIG only within 96 hours of exposure, but the protocol was Saol Therapeutics LLC amended to expand the treatment window to 10 days post-exposure. U.S.Distributed License byNo. Saol XXXX Therapeutics, Inc.

reference rates. The incidence of severe varicella complications, including pneumonia, AprilJune 2018 encephalitis, severe varicella with pox counts >100 pox, mortality and all complications was also evaluated. The overall incidence of clinical varicella was evaluated in an interim analysis, where 10% (31/311) of high risk individuals exposed to VZV and treated with VARIZIG for

varicella was observed in 8.4% (13/154) of immunocompromised pediatric and adult patients, in 6.8 % (5/74) of pregnant women, in 14.8% (12/81) of infants and one healthy

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33684-15-308850_ABC_HS_Discharged_8.375x10.875_BHR_4C_r1.indd 1 5/11/17 9:46 PM Medicalinte The latest facts, stats and stories making headlines in health

Middle School Kids Invent for Community Health

A Kentucky middle school won a residue left on the barrel of a used 3 inches wide and a few inches nationwide competition for creating heroin syringe could contaminate a longer than a needle — using 3D a device that can safely pick up used person with carfentanil. Carfentanil, printers from their school. The needles and other drug parapher- an analogue of fentanyl with an anal- students also developed an online nalia. The students’ invention was gesic potency 10,000 times that of database, which allows people to in response to used heroin needles morphine, is used to sedate large report locations of syringes and littering their Ashland, Kentucky animals. Drug dealers mix it with other types of drug paraphernalia community. heroin for a more powerful high, but for safe removal. In addition to first responders find- the drug can be absorbed through Participating in Samsung’s Solve for ing “dirty” needles when arriving an unsuspecting person’s skin or Tomorrow contest, an annual event on the scene of drug overdoses, eyes and enter the bloodstream. designed to boost interest and pro- teachers found them on elementary Ashland police officer Troy Patrick, ficiency in science, technology, en- school playgrounds and routinely who serves as Ashland Middle gineering, art and math (STEAM) to searched for syringes before re- School’s resource officer, pitched the improve their community, the Ashland leasing kindergarten classes for idea of inventing a device to pick up Middle School won $150,000 in elec- recess. The concern was so great, needles to Ashland Middle School tronics from Samsung. Students hope adults within the community wanted science and technology teacher their invention will be patented and to organize needle pickups. But even Mike Polley last fall. Polley’s class of mass-produced. cautious adults faced danger. In addi- middle-schoolers developed their tion to needle pricks that may spread award-winning product — a hollow Source: Will Wright, Dirty needles litter the playground. So these Kentucky students invented a solution, March 19, 2018, accessed April diseases such as hepatitis C and HIV, plastic box with plastic teeth, about 2018 at kentucky.com

ASD Healthcare | 25 Genetic Mutation Linked to ALS Kinesin family member 5A (KIF5A), with funding provided by the NIH to the bottom of the spine, forming a gene previously linked to two and several public and private sector some of the longest single cellular rare neurodegenerative disorders, organizations. pathways in the body,” said Traynor. has been definitively connected to More than 125,000 samples were “KIF5A helps to move key proteins amyotrophic lateral sclerosis (ALS), used in this study, making it by and organelles—specialized parts also known as Lou Gehrig’s disease, far the largest such study of ALS of cells—up and down that axonal by an international team from several performed to date. transport system, controlling the of the world’s top ALS research labs. KIF5A regulates part of the kine- engines for the nervous system’s The findings identify how mutations sin family of proteins that serve as long-range cargo trucks. This muta- in KIF5A disrupt transport of key tiny intracellular motors. Problems tion disrupts that system, causing proteins up and down long, thread- with these proteins are connected the symptoms we see with ALS.” like axons that connect nerve to ALS, Parkinson’s disease and Traynor cautioned that the dis- cells between the brain and the Alzheimer’s disease. KIF5A muta- covery, while exciting, still leaves spine, eventually leading to the tions were previously known to much more work to be done. neuromuscular symptoms of ALS. be connected to two other rare Next steps for the project include The discovery, published in the neurodegenerative diseases with further study of the frequency and March 21, 2018, issue of Neuron, was muscle weakening, stiffening and location of mutations within KIF5A led by Bryan Traynor, MD, PhD, of spasticity symptoms similar to ALS: and determining what cargos are the Intramural Research Program at hereditary spastic paraplegia type being disrupted. He and his team the National Institute on Aging (NIA) 10 (SPG10) and Charcot-Marie- hope this will help reveal what as- at the NIH and John Landers, PhD, Tooth Type 2 (CMT2). Scientists pect of axonal transport is essential of the University of Massachusetts suspected KIF5A might be associ- to maintain the cell. Medical School, Worcester. Genetic ated with ALS but lacked definite data collected by teams of scientists proof until now. Source: National Institute of Neurological Disorders and Stroke, New Genetic Mutation Linked to ALS, April 12, 2018, accessed April 2018 worldwide contributed to the project, “Axons extend from the brain at dddmag.com

Preventive HIV Pill Under Prescribed A drug approved by the FDA in 2012 Americans and nearly 300,000 Latinos including military health to prevent HIV is not reaching those across the nation could have poten- plans, or managed care who could potentially benefit from tially benefited from PrEP. However, consortia that operate it most. Truvada (Gilead Sciences, only 7,000 prescriptions were filled at their own prescription Inc.), commonly referenced as PrEP retail pharmacies or mail order ser- drug programs. Previous (abbreviation for pre-exposure vices for African-Americans and just studies suggest commercial pharma- prophylaxis), can reduce the risk 7,600 for Latinos during a similar time cies account for roughly 85 percent to of contracting the virus that causes period (September 2015 – August 90 percent of all PrEP prescriptions. AIDS by 90 percent. However, a 2016). While racial and ethnic data CDC is leading efforts to build new CDC analysis suggests that of were not available for one-third of the awareness and help ensure PrEP an estimated 1.1 million Americans prescription data, the analysis found a is available to everyone who could who are at substantial risk for HIV, substantial unmet prevention need. potentially benefit from it. Efforts commercial pharmacies filled only The gap was smaller among whites, include issuing step-by-step check- 90,000 PrEP prescriptions. In the yet still considerable. Of approxi- lists and interview guides for clinical first detailed analysis by race and by mately 300,000 whites, only 42,000 use, as well as providing targeted risk group, CDC researchers also PrEP prescriptions were filled at retail funding to help health departments found that while two-thirds of people pharmacies or mail order services. and community-based organizations are African-American or Latino, they CDC said the actual PrEP use is expand PrEP access for all people account for the smallest percentage somewhat higher than estimates at risk. Additional information is of prescriptions to date. because some Americans obtain available at cdc.gov/hiv/risk/prep. Study results indicate that in 2015, PrEP through demonstration projects Source: Sharon Begley, U.S. lifts moratorium on funding controversial, high-risk virus research, December 19, 2017, accessed January 2018 at approximately 500,000 African- or non-commercial pharmacies, statnews.com

26 | InsideOut Precision Education: DNA IQ Test Ready for a world in which a $50 DNA read the DNA of a young child and to quantify anyone’s genetic IQ from test can predict your odds of earning get a notion of how intelligent he or a spit sample. Others are holding back. a PhD or forecast which toddler gets she will be, says Plomin, an American The largest company offering direct- into a selective preschool? Robert based at King’s College London, to-consumer DNA health reports, Plomin, a behavioral geneticist, says where he leads a long-term study 23andMe, says it’s not telling people that’s exactly what’s coming. of 13,000 pairs of British twins. their brain rating out of concern For decades, genetic researchers Plomin outlined the DNA IQ test the information would be poorly have sought the hereditary factors scenario in January in a paper titled received. And that’s not because behind intelligence, with little luck. “The New Genetics of Intelligence,” 23andMe doesn’t have the data. It But now, gene studies have finally making a case that parents will use does. Because it surveys customers gotten big enough — and hence direct-to-consumer tests to predict on how long they stayed in school, a powerful enough — to zero in on kids’ mental abilities and make proxy for intelligence, the Google- genetic differences linked to IQ. In schooling choices, a concept he calls backed company has been playing May 2017, a Dutch-led study of the ge- precision education. a supporting role in the search for netic makeup of 78,308 people who’d As of now, the predictions are not intelligence genes by contributing its taken tests zeroed in on variations highly accurate. The DNA variations customers’ DNA data to the largest of in 22 genes linked to IQ scores. By that have been linked to test scores the gene hunts. March 2018, the tally had rapidly risen explain less than 10 percent of the Several educators reacted with to 199,000 people and 500 genes. intelligence differences between the alarm to the new developments, Plomin says a forthcoming report will people of European ancestry who’ve saying DNA tests should not be used establish links to 1,000 genes, and been studied. to evaluate children’s academic results from an experiment correlating Aspects of Plomin’s testing scenario prospects. one million people’s DNA with their are already happening. At least three academic success are due at any time. online services, including GenePlaza Source: Antonio Regalado, DNA tests for IQ are coming, but it might not be smart to take one, April 2, 2018, accessed April 2018 at The discoveries mean we can now and DNA Land, have started offering technologyreview.com

ASD Healthcare | 27 Dangerous Drug Combination Prescribed for Opioid Use Disorder Despite being well aware that patients depressants commonly prescribed increased overdose and mortality who take benzodiazepines while on for treating anxiety and sleep disor- risk for patients taking both drugs. buprenorphine are at increased risk ders. Combining buprenorphine with The surveys were part of the for overdose and death, more than CNS depressants, including alcohol, Buprenorphine-Containing half of doctors surveyed still pre- can cause an overdose or death. Transmucosal Products for Opioid scribed the two together, according to Researchers reviewed surveys Dependence Treatment (BTOD) Risk a study presented at the 49th Annual conducted from 2014 to 2016 taken Evaluation and Mitigation Strategy Conference of the American Society by 1,214 doctors who prescribed (REMS) program issued by the FDA in of Addiction Medicine in April. buprenorphine. Among surveyed 2013 to reduce the risks of accidental Buprenorphine, buprenorphine/nal- physicians who prescribed buprenor- overdose and death from buprenor- oxone and methadone are partial opi- phine in 2015, almost 54 percent said phine-containing agents, as well as oid receptor agonists used to prevent they had also prescribed a benzodi- raise awareness of the risks among acute opioid withdrawal and reduce azepine to the same patient. In 2016, patients, clinicians and pharmacists. opioid cravings. Common side effects slightly over 61 percent said they Researchers also examined health- include nausea, vomiting, constipa- had prescribed the two together. The care utilization data from a cohort tion, muscle aches and cramps, and vast majority of doctors prescribing of 43,118 U.S. patients treated with sleep problems. Benzodiazepines buprenorphine (97 to slightly more buprenorphine who were followed are central nervous system (CNS) than 98 percent) were aware of the for four years. This data revealed that an alarming number of patients had prescriptions for the two drugs that overlapped (ranging from more than 33 percent in 2014 to close to 47 percent in 2016). Overall, simul- taneous use of the two drugs for four months or longer occurred in 26 to 44 percent of patients studied. Remarkably, the physicians are following FDA guidance. When the FDA first approved buprenorphine in 2002, benzodiazepines were contraindicated. In September 2017, however, the FDA issued a Drug Safety Communication that, while ac- knowledging risks with the combination, advised it could be legitimately prescribed due to increased risks of untreated opioid use. FDA said expanded guidance will be added to the Warnings and Precautions section on how to manage patients in methadone treatment in Opioid Treatment Programs who are also taking CNS depressants. For the buprenorphine products, FDA will expand and revise an existing statement in the Warnings and Precautions section to provide more detailed guidance on managing patients in buprenorphine treatment who are also taking CNS depressants.

Source: Ian Ingram, Despite OD Risks, Opioid-Benzo Rx Continues, April 15, 2018, accessed April 2018 at medpagetoday.com

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PHS is a market leader for ambulatory, specialty and transitional care solutions. For more information, call 877-892-1254, email [email protected] or visit pharmhs.com. 30 | InsideOut ASD Healthcare | 31 Sickle cell disease is a term used to describe a group of disorders called hemoglobinopathies. These disorders cause abnormal hemoglobin (Hb), a substance in red blood cells that carries oxygen from the lungs to tissues throughout the body and returns carbon dioxide from the tissues to the lungs. Abnormal hemoglobin in sickle cell disease causes red blood cells — which are typically round and pliable — to change shape, resulting in inflexible sickle (or crescent) shaped cells. Because of their shape and rigidity, sickle hemoglobin, or Hb type S (HbS), break apart and are easily trapped in small blood vessels, blocking the flow of blood and oxygen to tissues and causing intense pain. Sickle cells are also prone to hemolysis, or early cell destruction. Due to this and the disruption of oxygen, patients with sickle cell disease develop anemia. Anemia is not caused by lack of iron; in fact, iron is contraindicated for patients with sickle cell disorders.1 The disease can affect every system in the body. Most patients experience both chronic and episodic pain, and acute pain crisis is the most common reason for emergency department use by patients. Other complications include susceptibility to infection, stroke (more common in children than adults), acute chest syndrome, fatigue, difficulty concentrating, leg ulcers, priapism (unwanted painful erection), delayed growth and sexual maturation, and pregnancy complications. Over time, blood vessel damage and reduced blood and oxygen flow can lead to avascular necrosis, pulmonary hypertension, vision and hearing problems, kidney dysfunction, cardiovascular diseases and other morbidities. The impact of sickle cell disease varies from person to person. Some patients have frequent crises and severe disability, while others are able to lead relatively normal lives.2

Common Types sickle cell “S” genes, one from each Approximately one in 13 African- and Misconceptions parent. HbSS is commonly called American babies are born with An autosomal recessive disease, sickle cell anemia and is usually the sickle cell trait, which occurs when sickle cell is the most common he- most severe form. HbSS is also the a person inherits one sickle cell “S” reditary hematologic disorder in the most common type of sickle cell gene from one parent and one nor- world. Although it primarily affects disease in the U.S. mal “A” gene from the other. People Black Africans and Americans, it People with sickle cell HbS beta with sickle cell trait usually do not also occurs in people of Mediter- thalassemia inherit one sickle cell “S” have any signs of sickle cell disease, ranean, East Indian, Saudi Arabian gene from one parent and one gene but they can pass the trait to their and Central and Latin American for beta thalassemia, another type children. If both parents carry the heritage. of anemia, from the other. There are sickle cell trait, there is a 25 percent In the U.S., sickle cell disorder af- two types of beta thalassemia: 0 and +. chance — or one in four — that their fects approximately 100,000 Ameri- Those with HbS beta 0-thalassemia child will inherit sickle cell disease. cans, occurs in about one out of every (HbSβ0 thalassemia) usually have Complications, however, can occur in 365 Black or African-American births a severe form of sickle cell disease. people with sickle cell trait, including and about one out of every 16,300 People with HbS beta +-thalassemia vaso-occlusive crisis.1 Hispanic-American births. (HbSβ+ thalassemia) tend to have a Vaso-occlusive crisis, or acute pain People with type HbSS inherit two milder form. crisis, is the hallmark of sickle cell

32 | InsideOut disease and the most common cause sickle cell anemia. Silent infarcts in damage liver, heart, pancreas and of hospitalization. The pain crisis, children are known to be associated other organs, leading to diseases which can appear suddenly and last with long-term cognitive problems such as diabetes mellitus. Iron chela- from hours to days, is caused by the and poor academic performance. tion therapy to reduce excess iron entrapment of sickle hemoglobin- Previous studies demonstrated levels should start in patients who containing red blood cells (HbS) in that blood transfusions are effective receive regular blood transfusions. the microcirculation. Vaso-occlusive in preventing stroke in patients with crisis can lead to ischemia (an HbSS; transfusions of healthy blood Impact of Disease in Adults inadequate blood supply to an organ cells increase the number of normal In high-income and developed coun- or part of the body, especially the red blood cells and reduce the oc- tries, such as the U.S., life expectancy heart muscles) and reperfusion currence of blocked blood vessels. for a person with sickle cell disease is injury (tissue damage caused when Study authors recommend children between 40 to 60 years old, or 20 to blood supply returns to the tissue). with HbSS receive monthly blood 30 years less than the U.S. average Early alleviation of the pain associ- transfusions.5 mortality rate. ated with an acute episode is vital in Blood transfusions are also indicat- Few treatment options are available preventing further tissue damage.3 ed for adults who experience severe to prevent complications and lengthen anemia. Multiple blood transfusions, the lives of those with sickle cell Disease Impact in Children however, might cause health prob- disease; of those few, efficacy of treat- Newborns do not present sickle cell lems due to the iron content of blood. ment is highly subjective and con- at birth — fetal hemoglobin protects Hemosiderosis, or iron overload, can tingent on an individual’s symptoms, the infant’s red blood cells from sickling. Symptoms typically appear between four to five months of age, when the body replaces fetal hemoglobin with sickle hemoglobin (HbS). Swelling of the hands and feet (hand-foot syndrome) due to sickle cell entrapment are symptoms An autosomal of onset. Children with sickle cell disease recessive disease, are prone to viral and bacterial sickle cell is the infections. To prevent or limit infections, children should receive all most common routine childhood immunizations, including both pneumococcal con- hereditary jugate and pneumococcal polysac- hematologic charide, as well as a prophylactic antibiotic administered daily until disorder in the child reaches five years of age.1 Sadly, a recent study conducted by the world. the University of Michigan Medical School revealed only 18 percent of children with sickle cell disease receive prophylactic antibiotic therapy.4 A 2014 study funded by the NIH indicated approximately one-third of children with HbSS experience silent cerebral infarcts, or strokes. Silent cerebral infarcts do not cause obvious symptoms; a silent stroke is visible only with magnetic resonance imaging (MRI), yet the study’s researchers noted MRIs are not routinely conducted in people with

ASD Healthcare | 33 severity of disease and tolerance for hydroxyurea in storage, and ASTN- incidence of acute chest syndrome. therapy.1 rated gloves with a protective gown Endari is the first FDA-approved Hydroxyurea, an antimetabolite when manipulating tablets/capsules treatment for sickle cell disease in that selectively inhibits ribonucleo- to prepare for oral suspension.7, 8 20 years.9 side disphosphate reductase, is CDC says the treatment is safe Stem cell transplant (also known commonly prescribed for sickle cell when administered by medical as a bone marrow transplant) is the disease. In plain terms, hydroxyurea specialists experienced in caring for only cure for some individuals with is a chemotherapy indicated for patients with sickle cell disease; the sickle cell disease. Although stem cell patients with chronic myelogenous side effects of taking hydroxyurea transplants are increasingly used, the leukemia (a cancer of the white during pregnancy or over lengthy procedure requires a matched donor, blood cells) to slow the growth of periods are not completely known.1 which is why many patients are not cancerous cells. It’s also indicated In July 2017, the FDA approved eligible candidates. Transplants may for patients with HbSS to reduce Endari (L-glutamine oral powder, cause severe side effects, including the production of sickle hemoglobin Emmaus Medical, Inc.) to reduce occasional life-threatening illness and increase the production of fetal the acute complications of sickle or death.1 hemoglobin, as well as reduce the cell disease in adult and pediatric Many sickle cell patients practice frequency of painful crises and blood patients five years of age and older. holistic care to reduce symptoms of transfusions.6, 7 Efficacy was established during a their disease. Alternative therapies Hydroxyurea carries two black randomized, double-blind, placebo- include cupping, massage therapy, box warnings due to its carcinogenic controlled, multi-center clinical trial heat therapy and topical oils to treat properties. The National Institute of patients with HbSS or HbSβ0 line incisions. Ensuring adequate for Occupational Safety and Health thalassemia. Patients treated with hydration is key, and many consume (NIOSH) recommends healthcare Endari experienced fewer hospital- eight to 10 glasses of water daily. workers wear single-use gloves when izations due to sickle cell pain, fewer Nutritional intake is important; their receiving, unpacking and placing cumulative hospital days and a lower diet typically includes plenty of green vegetables and fruits, with avoid- ance of iron-rich foods and sodium. People also avoid extreme temperatures, high altitudes and strenuous Since 1976, mortality physical training due to impacts on rates for adults circulation and potential triggers for vaso-occlusive crisis. In addition to increased 1 percent folic acid, they regularly take multivi- tamins, with additional supplements each year. such as dandelion tea, vitamin B-12 for energy, and amino acids such as L-arginine and L-methionine.2

Barriers to Care The systemic effects of sickle cell disease and its debilitating pain affects all aspects of a person’s life. Complex treatment needs limit a person’s ability to perform well in school, pursue a career, have a family and maintain relationships. The disease takes an emotional toll as patients face challenges in healthcare systems, stigma within society, financial hardships and concerns for the future. Few effective treatments to combat sickle cell pain crisis exist beyond opioids. Yet when sickle

34 | InsideOut cell patients seek pain relief from Stat News reported in September large reductions in the time to ill-informed medical staff in emer- 2017 that inadequate training of resolve pain crisis, use of opioids to gency departments and hospitals, doctors and nurses is one underly- treat pain and the length of hospital the majority face unnecessary ob- ing cause for the inadequate treat- stays in clinical trials. Estimated stacles — especially now due to the ment of sickle cell patients. Racism, primary completion date for a Phase current opioid epidemic. unfortunately, is another. Healthcare III clinical trial is November 9, Sickle cell pain grows in intensity professionals, consciously or not, 2018. Voxelotor (previously called as a person ages, and because pain frequently suspect sickle cell pa- GBT440, in development from Global frequently develops in the first year tients are looking to “score opiates.” Blood Therapeutics Inc.) is designed of life, people with sickle cell disease Research shows sickle cell patients to help Hb cells hold more oxygen to have adapted to pain levels intol- are typically treated by generalists maintain cell flexibility and shape erable to most people. When they who know little about the disease and reduce episodes of vaso-occlu- present to an emergency department and the patient’s desperate need for sion. And crizanlizumab (SEG101, during a pain crisis, patients typical- pain relief. At one hospital, research formerly SelGA, in development from ly do not appear uncomfortable. They indicated sickle cell patients waited Novartis) is a monoclonal antibody may play games on cell phones, sit an average of 60 percent longer to re- intended to inhibit P-selectin — an quietly or use meditation to distract ceive pain medication in emergency adhesion molecule that contributes their minds. They are well versed departments than other patients who to blood vessel occlusion, inflam- in opioid dosing and drug types and reported less severe pain and were mation and pain crisis — and help will frequently name the medication triaged into a less serious category. maintain normal blood flow. and dosage that delivers relief. High mortality rates among Gene therapies using viral vectors Healthcare staff, however, fre- sickle cell patients are the results and CRISPR-Cas9, also in develop- quently attribute sickle cell patients’ of chronic substandard healthcare. ment, promise a one-time therapeu- demeanors and knowledge to drug- Since 1976, mortality rates for adults tic with cure. LentiGlobin BB305 seeking behaviors. increased 1 percent each year, with (bluebird bio) showed encouraging Wally Smith, MD, a professor of people succumbing to vaso-occlusive interim results from the ongoing sickle cell disease at Virginia Com- crisis, organ failure, chronic kidney Phase I clinical trial investigation. monwealth University in Richmond, disease and a host of other sickle cell LengiGlobin uses an autologous said contrary to popular belief, the related complications.11 process to reengineer a patient’s he- vast majority of sickle cell patients Sickle cell patients seek more than matopoietic stem cell (an immature are not opioid addicts and charac- pain relief and therapies that treat cell that can develop into any type terizing patients as habitual drug symptoms, what they call “down- of cell) to produce the human beta- seekers is unfair. He believes the stream” effects. They want thera- A-T87Q globin protein and prohibit prevailing fear of opioid addiction peutics that address the “upstream” development of HbSS. and overdoses has led a growing causes of sickle cell disease — they Vertex Pharmaceuticals is part- number of doctors to withhold ap- want a cure.2 nering with Crispr Therapeutics to propriate therapeutics from sickle develop CTX001 for HbSS and HbSβ0 cell patients. Dr. Smith has a special Developing Therapeutics thalassemia. CTX001 is also an ex term for it: opio-phobia. He acknowl- Several drugs in development aim vivo therapy in which autologous edges that opio-phobia was common to reduce vaso-occlusion events in cells are removed from the patient, among physicians prior to the exist- patients. Rivipansel (GMI-1070, in reengineered and returned to the ing opioid crisis, but the existing development from GlycoMimetics in patient. Clinical trials located in the epidemic has made it much worse.10 partnership with Pfizer) has shown U.S. are set to begin in late 2018.12

Sources: 1 CDC, Sickle Cell Disease, reviewed and updated April 24, 2018, accessed April 2018 at cdc.gov 2 Center for Drug Evaluation and Research, Center for Biologics and Research and U.S. FDA, The Voice of the Patient, October 2014, accessed April 2018 at fda.gov/sicklecelldisease 3 Amani Mahdi, MD, MBBS, Pain Management in Vaso-occlusive Sickle Cell Crisis, April 11, 2017, accessed April 2018 at emra.org 4 Beata Mostafavi, Most Children with Sickle Cell Anemia Not Receiving Key Medication, February 13, 2018, accessed April 2018 at labblog.uofmhealth.org 5 NIH, Monthly blood transfusions reduce sickle cell anemia-related brain injury in children, August 20, 2014, accessed April 2018 at nih.cog 6 Cara Clayton, P4 student at University of Texas at Austin College of Pharmacy, The Pharmacist Guide to Sickle Cell Disease, accessed April 2018 at tldrpharmacy.com 7 NIH, MedlinePlus, Hydroxyurea, last revised April 15, 2017, accessed April 2018 at medlineplus.gov 8 HHS, CDC, NIOSH, NIOSH list of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2016, last revised April 19, 2018, accessed April 2018 at cdc.gov 9 FDA, FDA approved L-glutamine powder for the treatment of sickle cell disease, July 7, 2017, accessed April 2018 at fda.gov 10 NIH, National Heart, Lung and Blood Institute, Opioid crisis adds to pain of sickle cell patients, September 15, 2017, accessed April 2018 at nhib.nih.gov 11 Sharon Begley, ‘Every time it’s a battle’: In excruciating pain, sickle cell patients are shunted aside, September 18, 2017, accessed April 2018 at statnews.com 12 Emma Court, This could be the next $1 billion drug, if patients get on board, March 6, 2018, accessed April 2018 at marketwatch.com

ASD Healthcare | 35 Keep Antivirals on Hand this Flu Season

Getting a flu vaccine is the best protection against influenza. But when flu strains drift — as is expected this season — the CDC says clinical trials and observational data show that early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of complications from influenza.

For hospitalized patients, including those with confirmed and suspected influenza, the CDC says: • Administering antivirals early reduces deaths • Early antiviral treatment in hospitalized children shortens the duration of hospitalization • Clinical benefit is greatest when antiviral treatment is administered early, especially within 48 hours of onset of influenza illness

CDC recommends antiviral treatment as early as possible for any patient with confirmed or suspected influenza who: • is hospitalized; • has severe, complicated, or progressive illness; or • is at higher risk for influenza complications.

Source: Centers for Disease Control, Influenza Antiviral Medications: Summary for Clinicians, October 26, 2017, accessed December 2017 at cdc.gov © ASD Healthcare 2017 121

ASD Healthcare Ad_Flu Antivirials 122017.indd 1 12/27/17 1:09 PM Keep Antivirals on Hand this Flu Season

Source: Centers for Disease Control, Influenza Antiviral Medications: Summary for Clinicians, October 26, 2017, accessed December 2017 at cdc.gov © ASD Healthcare 2017 121

The persons depicted are models used for illustrative purposes only. FAST-MOVING LIVES DEMAND THE FASTEST SERIES COMPLETION

ASD Healthcare Ad_Flu Antivirials 122017.indd 1 12/27/17 1:09 PM 816247R0_LetterSize_Ad_singles.indd 4 8/11/17 1:40 PM BRIEF SUMMARY Reports of all serious adverse events, medically attended adverse events and Non-serious Adverse Events BEXSERO is a registered trademark of the GSK group of companies. BEXSERO® (Meningococcal Group B Vaccine) adverse events leading to premature withdrawal were collected throughout the In the 3 controlled studies1,2,3 (BEXSERO N=2221, control N=2204), non-serious Suspension for intramuscular injection study period for the studies conducted in Chile (12 months), UK (12 months), US/ unsolicited adverse events that occurred within 7 days of any dose were reported Poland (8 months), and Canada/Australia (2 months). by 439 (20%) BEXSERO and 197 (9%) control recipients. Unsolicited adverse The following is a brief summary only; see full prescribing information for Solicited Adverse Reactions events that were reported among at least 2% of participants and were more complete product information. frequently reported in BEXSERO recipients than in control recipients were injection Manufactured by gSK Vaccines, Srl The reported rates of local and systemic reactions among participants 10 through site pain, headache, and injection site induration unresolved within 7 days, and Bellaria-Rosia 53018, Sovicille (SI), Italy 1 InDICATIOnS AnD USAGE 25 years of age following each dose of BEXSERO administered 2 months apart or nasopharyngitis. ® control in the US/Polish study1 are presented in Table 1. US License No. 1617 BEXSERO is a vaccine indicated for active immunization to prevent invasive Serious Adverse Events disease caused by Neisseria meningitidis serogroup B. BEXSERO is approved for Table 1: Percentage of US and Polish Participants 10 through 25 Years of Age Overall, in clinical studies, among 3,058 participants 10 through 25 years of Distributed by glaxoSmithKline use in individuals 10 through 25 years of age. Reporting Solicited Local and Systemic Adverse Reactions within 7 Days after age who received at least 1 dose of BEXSERO, 66 (2.1%) participants reported Research Triangle Park, NC 27709 Approval of BEXSERO is based on demonstration of immune response, as measured BEXSERO or Control, by Dose serious adverse events at any time during the study. In the 3 controlled studies1,2,3 by serum bactericidal activity against three serogroup B strains representative ©2016 the GSK group of companies. All rights reserved. Dose 1 Dose 2b (BEXSERO N=2716, Control N=2078), serious adverse events within 30 days after of prevalent strains in the United States. The effectiveness of BEXSERO against any dose were reported in 23 (0.8%) BEXSERO recipients and 10 (0.5%) control BXS:1BRS diverse serogroup B strains has not been confirmed. BEXSERO Placebo BEXSERO Menveo Solicited Reactiona recipients. 4 COnTRAInDICATIOnS (Saline) 6.2 Additional Pre-licensure Safety Experience ©2017 GSK group of companies. Hypersensitivity, including severe allergic reaction, to any component of the N=110-114 N= 94-96 N=107-109 N=90-92 In response to outbreaks of serogroup B meningococcal disease at two universities All rights reserved. Printed in USA. 816247R0 January 2017 in the US, BEXSERO was administered as a 2 dose series at least 1 month apart. vaccine, or after a previous dose of BEXSERO. [see Description (11) of full Local Adverse Reactions prescribing information] Information on serious adverse events was collected for a period of 30 days after Pain Any 90 27 83 43 each dose from 15,351 individuals 16 through 65 years of age who received 5 WARnInGS AnD PRECAUTIOnS Mild 27 20 18 26 at least 1 dose. Overall 50 individuals (0.3%) reported serious adverse events, 5.1 Preventing and Managing Allergic Reactions including one event considered related to vaccination, a case of anaphylaxis within Moderate 44 5 37 9 30 minutes following vaccination. Appropriate observation and medical treatment should always be readily available in case of an anaphylactic event following the administration of the vaccine. Severe 20 2 29 8 6.3 Postmarketing Experience 5.2 Syncope Erythema Any 50 13 45 26 Adverse event reports received for BEXSERO marketed outside the US are listed below. Because these events are reported voluntarily from a population of uncertain Syncope (fainting) can occur in association with administration of BEXSERO. Ensure 1-25 mm 41 11 36 13 size, it is not always possible to estimate reliably their frequency, or to establish a procedures are in place to avoid injury from falling associated with syncope. >25-50 mm 6 1 5 6 causal relationship to vaccination. This list includes serious events or events which 5.3 Latex have suspected causal association to BEXSERO. The tip caps of the pre-filled syringes contain natural rubber latex which may cause >50-100 mm 3 0 5 4 allergic reactions in latex sensitive individuals. General disorders and Blisters at or around the injection site. >100 mm 0 0 0 2 administration site conditions: 5.4 Limitation of vaccine effectiveness Induration Any 32 10 28 23 Immune System Disorders: Allergic reactions (including anaphylactic BEXSERO may not protect all vaccine recipients. BEXSERO may not provide 1-25 mm 24 9 22 16 reactions), rash, eye swelling. protection against all meningococcal serogroup B strains [see Clinical Nervous System Disorders: Syncope, vasovagal responses to injection. Pharmacology (12.1) of full prescribing information]. >25-50 mm 7 0 4 0 5.5 Altered Immunocompetence > 50-100 mm 1 1 2 4 7 Drug INtErActIoNS Sufficient data are not available to establish the safety and immunogenicity of Individuals with altered immunocompetence may have reduced immune responses > 100 mm 0 0 0 2 to BEXSERO. concomitant administration of BEXSERO with recommended adolescent vaccines. Systemic Adverse Reactions 6 ADVERSE REACTIOnS 8 uSE IN SPEcIfIc PoPulAtIoNS Fatigue Any 37 22 35 20 The most common solicited adverse reactions observed in clinical trials were pain 8.1 Pregnancy at the injection site (≥83%), myalgia (≥48%), erythema (≥45%), fatigue (≥35%), Mild 19 17 18 11 Pregnancy Category B: headache (≥33%), induration (≥28%), nausea (≥18%), and arthralgia (≥13%). Moderate 14 5 10 7 Reproduction studies have been performed in rabbits at doses up to 15 times the 6.1 Clinical Trials Experience Severe 4 0 6 2 human dose on a body weight basis and have revealed no evidence of impaired Because clinical trials are conducted under widely varying conditions, adverse fertility in females or harm to the fetus due to BEXSERO. There are, however, reaction rates observed in clinical trials of a vaccine cannot be directly compared to Nausea Any 19 4 18 4 no adequate and well controlled studies in pregnant women. Because animal rates in the clinical trials of another vaccine and may not reflect the rates observed Mild 12 3 10 3 reproduction studies are not always predictive of human response, BEXSERO in practice. should be used during pregnancy only if clearly needed. Moderate 4 1 5 1 In four clinical trials, 3058 individuals 10 through 25 years of age received at least Pregnancy Registry for BEXSERO one dose of BEXSERO, 1436 participants received only BEXSERO, 2089 received Severe 4 0 4 0 GlaxoSmithKline maintains a surveillance registry to collect data on pregnancy only placebo or a control vaccine, and 1622 participants received a mixed regimen Myalgia Any 49 26 48 25 outcomes and newborn health status outcomes following exposure to BEXSERO (placebo or control vaccine and BEXSERO). during pregnancy. Women who receive BEXSERO during pregnancy should be In a randomized controlled study1 conducted in US and Poland, 120 participants Mild 21 20 16 14 encouraged to contact GlaxoSmithKline directly or their healthcare provider should 10 through 25 years of age received at least one dose of BEXSERO, including 112 Moderate 16 5 19 7 contact GlaxoSmithKline by calling 1-877-413-4759. participants who received 2 doses of BEXSERO 2 months apart; 97 participants Severe 12 1 13 4 8.3 Nursing Mothers received saline placebo followed by Menveo [Meningococcal (Groups A, C, Y, and It is not known whether BEXSERO is excreted in human milk. Because many W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine]. Across groups, Arthralgia Any 13 4 16 4 drugs are excreted in human milk, caution should be exercised when BEXSERO is median age was 13 years, males comprised 49% and 60% were White; 34% were Mild 9 3 8 2 administered to a nursing woman. Hispanic, 4% were Black,<1% were Asian, and 2% were other. 8.4 Pediatric use In a second randomized controlled study2 conducted in Chile, all subjects Moderate 3 1 6 2 (N=1,622) 11 through 17 years of age received at least one dose of BEXSERO. Severe 2 0 2 0 Safety and effectiveness of BEXSERO have not been established in children younger This study included a subset of 810 subjects who received 2 doses of BEXSERO than 10 years of age. 1 or 2 months apart. A control group of 128 subjects received at least 1 dose of Headache Any 33 20 34 23 8.5 geriatric use placebo containing aluminum hydroxide. A subgroup of 128 subjects received 2 Mild 19 15 21 8 Safety and effectiveness of BEXSERO have not been established in adults older doses of BEXSERO 6 months apart. In this study, median age was 14 years, males than 65 years of age. comprised 44%, and 99% were Hispanic. Moderate 9 4 6 12 In a third randomized controlled study3 conducted in the United Kingdom (UK), Severe 4 1 6 3 15 rEfErENcES 974 university students 18 through 24 years of age received at least 1 dose of Fever ≥38°C 1 1 5 0 1. NCT01272180 (V102_03) BEXSERO, including 932 subjects who received 2 doses of BEXSERO 1 month 38.0-38.9°C 1 1 4 0 2. NCT00661713 (V72P10) apart. Comparator groups received 1 dose of Menveo followed by 1 dose of 3. NCT01214850 (V72_29) placebo containing aluminum hydroxide (N=956) or 2 doses of IXIARO (Japanese 39.0-39.9°C 0 0 1 0 Encephalitis Vaccine, Inactivated, Adsorbed) (N=947). Across groups, median age 4. NCT01423084 (V72_41) was 20 years, males comprised 46%, and 88% were White, 5% were Asian, 2% ≥40°C 0 0 0 0 5. Wang X, et al. Vaccine. 2011; 29:4739-4744. were Black, <1% were Hispanic, and 4% were other. Clinicaltrials.gov Identifier NCT01272180. 6. Hosking J, et al. Clin Vaccine Immunol. 2007;14:1393-1399. In an uncontrolled study4 conducted in Canada and Australia, 342 participants a Erythema, and induration: Any (≥ 1 mm). Pain and systemic reactions: mild 11 through 17 years of age received at least 1 dose of BEXSERO, including 338 (transient with no limitation in normal daily activity); moderate (some limitation 17 PAtIENt couNSElINg INforMAtIoN participants who received 2 doses of BEXSERO 1 month apart. The median age was in normal daily activity); severe (unable to perform normal daily activity) See FDA-Approved Patient Labeling. 13 years, males comprised 55%, and 80% were White, 10% were Asian, 4% were b Administered 2 months after Dose 1 Native American/Alaskan, and 4% were other. Solicited adverse reaction rates were similar among participants 11 through 24 Local and systemic reactogenicity data were solicited from all participants in the studies years of age who received BEXSERO in the other three clinical studies,2,3,4 except conducted in Chile, US/Poland, Canada/Australia, and in a subset of participants in for severe myalgia which was reported by 3-7% of subjects. Severe pain was the UK study. Reports of unsolicited adverse events occurring within the first 7 days reported by 8% of university students in the UK3. after each vaccination were collected in all studies. In the US/Poland study, reports of unsolicited adverse events were collected up to one month after the second vaccination. (continued on next page)

816247R0_LetterSize_Ad_singles.indd 2 8/11/17 1:40 PM 816247R0_LetterSize_Ad_singles.indd 3 8/11/17 1:40 PM Non-serious Adverse Events BEXSERO is a registered trademark of the GSK group of companies. In the 3 controlled studies1,2,3 (BEXSERO N=2221, control N=2204), non-serious unsolicited adverse events that occurred within 7 days of any dose were reported by 439 (20%) BEXSERO and 197 (9%) control recipients. Unsolicited adverse events that were reported among at least 2% of participants and were more frequently reported in BEXSERO recipients than in control recipients were injection Manufactured by gSK Vaccines, Srl site pain, headache, and injection site induration unresolved within 7 days, and Bellaria-Rosia 53018, Sovicille (SI), Italy nasopharyngitis. US License No. 1617 Serious Adverse Events Overall, in clinical studies, among 3,058 participants 10 through 25 years of Distributed by glaxoSmithKline age who received at least 1 dose of BEXSERO, 66 (2.1%) participants reported Research Triangle Park, NC 27709 1,2,3 serious adverse events at any time during the study. In the 3 controlled studies ©2016 the GSK group of companies. All rights reserved. (BEXSERO N=2716, Control N=2078), serious adverse events within 30 days after any dose were reported in 23 (0.8%) BEXSERO recipients and 10 (0.5%) control BXS:1BRS recipients. 6.2 Additional Pre-licensure Safety Experience ©2017 GSK group of companies. In response to outbreaks of serogroup B meningococcal disease at two universities All rights reserved. Printed in USA. 816247R0 January 2017 in the US, BEXSERO was administered as a 2 dose series at least 1 month apart. Information on serious adverse events was collected for a period of 30 days after each dose from 15,351 individuals 16 through 65 years of age who received at least 1 dose. Overall 50 individuals (0.3%) reported serious adverse events, including one event considered related to vaccination, a case of anaphylaxis within 30 minutes following vaccination. 6.3 Postmarketing Experience Adverse event reports received for BEXSERO marketed outside the US are listed below. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency, or to establish a causal relationship to vaccination. This list includes serious events or events which have suspected causal association to BEXSERO. General disorders and Blisters at or around the injection site. administration site conditions: Immune System Disorders: Allergic reactions (including anaphylactic reactions), rash, eye swelling. Nervous System Disorders: Syncope, vasovagal responses to injection. 7 Drug INtErActIoNS Sufficient data are not available to establish the safety and immunogenicity of concomitant administration of BEXSERO with recommended adolescent vaccines. 8 uSE IN SPEcIfIc PoPulAtIoNS 8.1 Pregnancy Pregnancy Category B: Reproduction studies have been performed in rabbits at doses up to 15 times the human dose on a body weight basis and have revealed no evidence of impaired fertility in females or harm to the fetus due to BEXSERO. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, BEXSERO should be used during pregnancy only if clearly needed. Pregnancy Registry for BEXSERO GlaxoSmithKline maintains a surveillance registry to collect data on pregnancy outcomes and newborn health status outcomes following exposure to BEXSERO during pregnancy. Women who receive BEXSERO during pregnancy should be encouraged to contact GlaxoSmithKline directly or their healthcare provider should contact GlaxoSmithKline by calling 1-877-413-4759. 8.3 Nursing Mothers It is not known whether BEXSERO is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when BEXSERO is administered to a nursing woman. 8.4 Pediatric use Safety and effectiveness of BEXSERO have not been established in children younger than 10 years of age. 8.5 geriatric use Safety and effectiveness of BEXSERO have not been established in adults older than 65 years of age. 15 rEfErENcES 1. NCT01272180 (V102_03) 2. NCT00661713 (V72P10) 3. NCT01214850 (V72_29) 4. NCT01423084 (V72_41) 5. Wang X, et al. Vaccine. 2011; 29:4739-4744. 6. Hosking J, et al. Clin Vaccine Immunol. 2007;14:1393-1399. 17 PAtIENt couNSElINg INforMAtIoN See FDA-Approved Patient Labeling.

816247R0_LetterSize_Ad_singles.indd 3 8/11/17 1:40 PM ONLY BEXSERO CAN HELP PROTECT YOUR PATIENTS FROM MenB IN AS FAST AS 1 MONTH WITH 2 DOSES 1,2

COMPONENTS 4 1 that may be present on the surface of MenB are distinctly targeted by BEXSERO. 2 DOSES 1 of BEXSERO are administered, each as a 0.5-mL prefilled syringe.

AS FAST AS1MONTH The dosing schedule for BEXSERO allows your patients to complete 1 the series within the span of 1 typical summer break.

Talk with your adolescent patients about vaccinating against MenB Visit www.ChooseBEXSERO.com

Indication for BXSRO BEXSERO is a vaccine indicated for active immunization to prevent invasive disease caused by Neisseria meningitidis serogroup B. BEXSERO is approved for use in individuals 10 through 25 years of age. Approval of BEXSERO is based on demonstration of immune response, as measured by serum bactericidal activity against three serogroup B strains representative of prevalent strains in the United States. The e ectiveness of BEXSERO against diverse serogroup B strains has not been conﬁ rmed. Important Safety Information for BXSRO • BEXSERO is contraindicated in cases of hypersensitivity, including severe allergic reaction, to any component of the vaccine, or a er a previous dose of BEXSERO • Appropriate observation and medical treatment should always be readily available in case of an anaphylactic event following the administration of the vaccine • The tip caps of the preﬁ lled syringes contain natural rubber latex, which may cause allergic reactions in latex-sensitive individuals • Syncope (fainting) can occur in association with administration of BEXSERO. Ensure procedures are in place to avoid injury from falling associated with syncope • The most common solicited adverse reactions observed in clinical trials were pain at the injection site (≥83%), myalgia (≥48%), erythema (≥45%), fatigue (≥35%), headache (≥33%), induration (≥28%), nausea (≥18%), and arthralgia (≥13%) • Vaccination with BEXSERO may not provide protection against all meningococcal serogroup B strains • Vaccination with BEXSERO may not result in protection in all vaccine recipients

Please see accompanying rief summary of full Prescriing Information for BXSRO.

References: 1. Prescribing Information for BEXSERO. 2. Prescribing Information for TRUMENBA.

BEXSERO is a registered trademark of the GSK group of companies.

816247R0_LetterSize_Ad_singles.indd 1 8/11/17 1:40 PM Convenient Connection to New Products

Check out the most up-to-date New Products available from ASD Healthcare at asdhealthcare.com/products/new-products.

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ASD Healthcare Flu Order Ad_Spread 062118.indd All Pages 6/21/18 10:23 AM Rare Exposure Three rare diseases and novel therapeutic developments

44 | InsideOut Many associate rare diseases with inherited disorders that manifest within the first year of life. Some rare diseases, however, can appear at any age. A few rare diseases thought to be solely caused by genetic mutations are now recognized as acquired infections. And some rare diseases are not inherited but result from acquired and unknown sources.

Diseases such as hemophagocytic lymphohistiocytosis, hereditary ATTR amyloidosis and chronic inflammatory demyelinating polyneuropathy are rare diseases that defy common beliefs. Dedicated researchers spent decades exposing and understanding the nuanced and multi-layered complexities of these rare diseases, resulting in novel and targeted therapeutic development. Their tenacious work is now reaching fruition with novel biologics that provide meaningful outcomes for patients, families and healthcare providers.

autosomal recessive manner (known easy bruising and abnormal bleed- as familial HLH) or acquired from ing. The brain may also be affected. non-genetic causes (known as Affected individuals may experience 1 secondary HLH).1 irritability, delayed closure of the bones of the skull in infants, neck Inherited & Acquired: Signs and Symptoms stiffness, abnormal muscle tone, im- Familial HLH occurs in approxi- paired muscle coordination, paraly- Hemophagocytic mately one in 50,000 individuals sis, blindness, seizures and coma. In worldwide and is caused by muta- addition to neurological problems, Lymphohistiocytosis tions in genes that provide instruc- familial HLH can cause abnormali- tions for making proteins to destroy ties of the heart, kidneys and other or deactivate lymphocytes no longer organs and tissues. Affected individ- Hemophagocytic lymphohistiocytosis needed. Symptoms usually appear uals also have an increased risk of (HLH) is a rare syndrome that within the first months or years of developing cancers of blood-forming causes the body to develop too many life; in ultra-rare situations, symp- cells (leukemia and lymphoma).2 activated lymphocytes (white blood toms appear in older ages. Signs Researchers identified mutations cells composed of T cells, natural and symptoms include fever and found in five separate genes and sub- killer cells, B cells and macrophages enlarged liver and spleen. typed those mutations as familial that attack infectious pathogens) The syndrome destroys blood pro- HLH types 1–5. Currently, the ge- and excessive amounts of cytokines ducing cells in the bone marrow, a netic mutation of HLH type 1 is (small proteins important for cell process called hemophagocytosis. As unknown. Types 2–5 are caused signaling). Overactivation of the a result, affected individuals present by mutations in the PRF1 gene, the immune system causes multiple anemia (low numbers of red blood UNC13D gene, the STX11 gene and issues, including inflammation cells) and a reduction in platelets the STXBP2 gene, respectively. and damage to vital organs. The (involved in blood clotting func- Familial HLH can also result from syndrome may be inherited in an tions). Platelets reduction may cause an inappropriate immune response

ASD Healthcare | 45 to Epstein-Barr virus and caused by may have triggered the exaggerated a separate genetic condition known immune response, clearing up the as X-linked lymphoproliferative acquired form of HLH. disease (XLP). XLP originates in a mutation in the SH2DIA or XIAP Prognosis gene and is inherited in an X-linked All forms of HLH, including ad- manner (typically affects males). equately treated forms, have high Researchers learned approximately mortality rates. Prognosis without 40 to 60 percent of familial HLH is treatment is extremely poor for caused by mutations in the PRF1 infants and children with familial gene (type 2) and the UNC13D gene HLH, with median survival of less (type 3). Genetic testing is available than two to six months after diagno- for HLH subtypes 2–5. sis. The course of the disease and life Since initial symptoms mimic expectancy are not well studied in illnesses caused by common infec- adults with familial HLH. tions, familial HLH can be challeng- The prognosis for people with ing to diagnose. Treatment depends acquired HLH varies. For example, on a number of factors, including the mortality rate is reportedly lower the severity of symptoms, the age of when HLH is associated with autoim- onset and type of genetic mutation mune diseases (8 to 22 percent) and involved. Currently, allogenic hema- greater when it is associated with topoietic cell transplantation (bone tumors (especially T-cell lymphoma).1, 2 marrow transplant)—which uses stem cells harvested from a donor Novel Therapeutic “matched” to the patient—is the Novimmune, a Swiss biophar- only known cure for familial HLH. maceutical company founded by Multiple risks exist, including the renowned immunologist Dr. Bernard patient’s body rejecting the donated Mach, discovered and developed a cells and graft-versus-host disease, biotherapeutic that targets inter- where the donor’s cells begin making feron-gammon (IFNy), a cytokine immune cells that attack the re- secreted by immune system cells cipient’s body. Prior to the allogenic to help regulate immune functions. hematopoietic cell transplantation, Abnormal levels of IFNy are as- patients receive chemotherapy and/ sociated with autoinflammatory or immunotherapy to destroy exist- and autoimmune diseases, including immune cells, which may cause ing lupus, arthritis and HLH. The life-threatening inflammation. biotherapeutic, emapalumab (also Acquired HLH primarily affects known as NI-0501), is a fully human HLH is a rare syndrome that adults and is caused by infections, monoclonal antibody that works medications that suppress the as a potent inhibitor of IFNy. FDA causes the body to develop too immune system, autoimmune dis- awarded Rare Pediatric Orphan eases, immunodeficiencies, certain Disease Designation to Novimmune’s many activated lymphocytes and types of cancer and/or metabolic emapalumab in 2017. In March 2018, diseases. This type of HLH often Novimmune submitted a biologics li- excessive amounts of cytokines. necessitates treating the underlying cense application to the FDA; in May condition. For example, antibiotics 2018, the FDA accepted the biologics or antiviral medications can be used application and granted emapalumab to treat or prevent infections that priority review.3

46 | InsideOut controls involuntary body functions such as blood pressure, heart rate, 2 and digestion, may also be affected by amyloidosis. In some cases, the Adult Onset: Hereditary central nervous system (brain and spinal cord) are affected. Other ATTR Amyloidosis areas impacted by hereditary ATTR amyloidosis include the heart, kidneys, eyes and gastrointestinal tract. Hereditary ATTR amyloidosis, also Three major forms of transthyre- known as hereditary transthyretin tin amyloidosis exist and are distin- amyloidosis, is a rare and progres- guished by their symptoms and the sively debilitating disease charac- body systems they affect. terized by abnormal deposits of a The neuropathic form of trans- protein—called amyloid—in the thyretin amyloidosis primarily affects body’s organs and tissues. Amyloid is the peripheral and autonomic ner- produced in the liver and functions vous systems, resulting in peripheral to deliver substances such as vita- neuropathy and difficulty control- min A throughout the body.4 ling bodily functions. Impairments in Hereditary ATTR amyloidosis is bodily functions can include sexual caused by genetic mutations in the impotence, diarrhea, constipation, TTR gene. These genetic mutations problems with urination and a sharp cause the amyloid protein to misfold drop in blood pressure upon stand- and subsequently gather and build ing (orthostatic hypotension). Some in the nervous, cardiac and gastroin- people experience heart and kidney testinal systems. Inheritance is au- problems as well. Various eye prob- tosomal dominant (genetic mutation lems may occur, such as cloudiness from one parent), but not all people of the clear gel that fills the eyeball with a TTR gene mutation will de- (vitreous opacity), dry eyes, in- velop hereditary ATTR amyloidosis. creased pressure in the eyes (glau- Approximately 50,000 suffer from coma), or pupils with an irregular this rare disease worldwide. The or “scalloped” appearance. Some age of symptom onset varies widely people with this form of transthyre- among individuals and occurs tin amyloidosis develop carpal tunnel between ages 20 and 70. syndrome, which is characterized by numbness, tingling and weakness in Major Forms and Impacts the hands and fingers. Amyloidosis occurs most frequently The leptomeningeal form of in the peripheral nervous system, transthyretin amyloidosis primarily Not all people with a TTR gene which is made up of nerves con- affects the central nervous system. necting the brain and spinal cord In people with this form, amyloi- mutation will develop hereditary to muscles and sensory cells that dosis occurs in the leptomeninges, detect sensations such as touch, which are two thin layers of tissue ATTR amyloidosis. pain, heat and sound. Protein that cover the brain and spinal deposits in these nerves result in cord. A buildup of protein in this peripheral neuropathy (a loss of tissue can cause stroke and bleed- sensation in the extremities). The ing in the brain, an accumulation of autonomic nervous system, which fluid in the brain (hydrocephalus),

ASD Healthcare | 47 difficulty coordinating movements Promise of Novel (ataxia), muscle stiffness and weak- RNAi Therapeutic ness (spastic paralysis), seizures, Patisiran, an investigational RNA and loss of intellectual function interface (RNAi) therapeutic (dementia). Eye problems similar to developed by Alnylam, is designed those in the neuropathic form may to target and silence specific mes- also occur. When people with lepto- senger RNA, potentially blocking the meningeal transthyretin amyloidosis production of TTR protein before it have associated eye problems, they is made. RNAi is a natural pathway are said to have the oculoleptomen- involved in regulation of gene ex- ingeal form. pression in all mammalian cells and The cardiac form of transthyretin is mediated by small interfering RNA amyloidosis affects the heart. People (siRNA) molecules. By harnessing with cardiac amyloidosis may have this natural biologic pathway, RNAi an abnormal heartbeat (arrhythmia), therapeutics can be readily designed an enlarged heart (cardiomegaly), to be highly selective and bind to or orthostatic hypertension. These proteins involved in disease. abnormalities can lead to pro- Results from the APOLLO Phase gressive heart failure and death. III clinical trial, the largest clinical Occasionally, people with the cardi- study conducted on patients with ac form of transthyretin amyloidosis the neuropathic form of hereditary have mild peripheral neuropathy. ATTR amyloidosis, revealed an approximately 50 percent decrease Current Treatment in the composite rate of all-cause Treatment depends on the tissues hospitalization and mortality over 18 affected and may include liver months in patisiran-treated patients, transplantation (which removes the relative to placebo, based upon hospi- source of the deposits), heart and/or talizations and deaths designated as kidney transplantation, vitrectomy serious adverse events (SAEs) within (surgical removal of the vitreous — 28 days after last dose of study drug. the gel that surrounds the inside A similar finding was observed with of the eye), and/or various medica- the composite rate of cardiac hos- tions. Life expectancy depends on pitalization and all-cause mortality, many factors and may range from showing an approximately 45 per- several years to decades after symp- cent decrease with patisiran, relative toms begin. to placebo; cardiac hospitalization Liver transplantation is the “gold events were defined as any hospital- standard” for treatment because it izations designated as SAEs within The APOLLO Phase III clinical replaces the main source of abnor- the system organ class designation mal amyloid. It may slow or halt of cardiac disorder. trial revealed an approximately progression of sensory, motor and Based on a quartile analysis of autonomic neuropathy; however, the baseline Neurologic Impairment 50 percent decrease in the rate disease often progresses in other Score (NIS), patisiran demonstrat- organs. Transplantation ideally ed halting or improvement in the of all-cause hospitalization and should be done as early as possible, modified NIS+7 (mNIS+7) primary before there is severe neurologic dis- endpoint in patients regardless mortality over 18 months in ability. Diuretics are typically used of baseline neuropathy severity, to manage congestive heart failure in contrast to the progression in patisiran-treated patients. associated with the disease.5 mNIS+7 seen in placebo-treated

48 | InsideOut patients. While treatment benefit neurological disorder that causes was observed across all stages of progressive weakness and impaired disease, these results support the sensory function in the legs and rationale for early treatment with arms. Symptoms often include tin- patisiran to potentially halt or im- gling or numbness (first in the toes prove neuropathy progression or and fingers), weakness of the arms impairment, respectively. Overall, and legs, loss of deep tendon reflexes, there were 13 deaths in the APOLLO fatigue and abnormal sensations.8 study; none were considered related The disorder can appear at any to study drug and the frequency of age, with 47.6 years the mean age deaths was lower in the patisiran of onset and a higher incidence in group (4.7 percent) as compared with men than women. Prevalence ranges placebo (7.8 percent). The most com- from 1 to 7.7 per 100,000, with no- monly reported adverse events (AEs) table increases in advancing ages that occurred more frequently in pa- and a peak incidence between ages tisiran-treated patients were periph- 40–60 years.9 eral edema and infusion-related reac- The underlying cause of CIDP is tions (IRRs) and were generally mild unknown, but many suggest CIDP to moderate in severity. AEs leading is an autoimmune disorder caused to treatment discontinuation were by the immune system mistakenly lower in patisiran-treated patients attacking and damaging the myelin (4.7 percent) compared with placebo- sheath (protective cover of nerve treated patients (14.3 percent).6 fibers) of the peripheral nerves. The FDA granted Fast Track Closely related to Guillain-Barre Designation, Breakthrough Therapy syndrome (GBS), CIDP is consid- Designation and an expanded Orphan ered the “chronic counterpart” of Drug Designation to Alnylam’s inves- GBS. GBS is a subacute disorder tigational RNAi therapeutic for ATTR that progresses during 3–4 weeks, amyloidosis. In February 2018, then plateaus and usually improves the FDA granted Priority Review over months and does not recur. and set a Prescription Drug User In contrast to GBS, most patients Fee ACT (PDUFA) action date of with CIDP cannot identify a preced- August 11, 2018.7 ing viral or infectious illness. CIDP characteristically presents ongoing symptoms for more than eight weeks and usually does not improve unless continuous treatment is given.10 Left untreated, 30 percent of people with CIDP will progress to The underlying cause of CIDP is wheelchair dependence.8 3 unknown, but many suggest CIDP Diagnosis and Acquired with Origin Standard Therapies is an autoimmune disorder caused CIDP can be difficult to diagnose. Unknown: CIDP Symptoms must be present for by the immune system mistakenly at least two months; symmetric proximal and distal weakness with attacking and damaging the Chronic inflammatory demyelinat- reduced or absent tendon reflexes ing polyneuropathy (CIDP) is a rare are highly suggestive of CIDP. myelin sheath.

ASD Healthcare | 49 Diagnostic tests include nerve require continued intermittent conduction testing and electro- treatments.10 myography for very slow nerve In March 2018, the FDA ap- conduction velocities, lumbar punc- proved Hizentra (Immune Globulin ture looking for elevated spinal fluid Subcutaneous [Human] 20% liquid), protein without many inflammatory manufactured by CSL Behring, as cells and MRI imaging of the nerve the first and only subcutaneous roots for enlargement and signs of immunoglobulin (SCIg) for the inflammation. treatment of CIDP as maintenance Glucocorticoid drugs such as therapy to prevent relapse of neuro- prednisone have proven effective in muscular disability and impairment. treating individuals with CIDP. In The approval was based on data from many cases, individuals with CIDP the Phase III PATH study, which is may respond to corticosteroid treat- the largest controlled clinical study ment alone. However, individuals re- in CIDP patients to date. quiring high doses of corticosteroid The PATH study demonstrated drugs may experience side effects the percentage of patients experi- that deter long-term therapy. encing CIDP relapse or withdrawal Plasma exchange (PE) has also for any other reason during SCIg been shown to be of benefit in treatment was significantly lower chronic inflammatory demyelinating with Hizentra (38.6 percent on low- polyneuropathy. This procedure re- dose Hizentra [0.2 g/kg weekly]; moves unwanted substances (toxins, 32.8 percent on high-dose Hizentra metabolic substances and plasma [0.4 g/kg weekly]; p values = 0.007 parts) from the blood. Blood is re- and <0.001 respectively) than with moved from an affected individual placebo (63.2 percent). Additionally, and blood cells are separated from the PATH study demonstrated that plasma. The plasma is then replaced patients on Hizentra reported fewer with other human plasma and the systemic adverse reactions (ARs) patient’s blood cells are transfused per infusion compared to IVIG treat- The PATH study demonstrated back into the affected individual, ment (2.7 percent versus 9.8 per- thus removing only the plasma and cent, respectively); 93 percent of the that patients on Hizentra reported its constituents. 4,225 total Hizentra infusions were Intravenous immunoglobulin free of any ARs. In addition to fewer fewer systemic ARs per infusion (IVIG) can enhance the immune adverse reactions, the novel deliv- system and is often used as a treat- ery of SCIg enables more freedom compared to IVIG treatment. ment for CIDP. Very high doses for CIDP patients, who now have the are usually used for initial treat- option of self-infusing in the com- ment of CIDP and most patients fort of their homes.11

Sources: 1 NIH, NCATS, GARD, Hemophagocytic lymphohistiocytosis, last updated September 11, 2017, accessed June 2018 at rarediseases.info.nih.gov 2 Genetics Home Reference, NLM, NIH, Familial hemophagocytic lymphohistiocytosis, June 19, 2018, accessed June 2018 at ghr.nlm.nih.gov 3 Cordis, Final Report Summary — FIGHT-HLH (First Targeted Therapy to Fight Hemophagocytic Lymphohistiocytosis (HLH): A novel approach to HLH), last updated May 5, 2018, accessed June 2018 at cordis.europa.eu 4 The Bridge, What causes hereditary ATTR (hTTR) amyloidosis? 2018, accessed June 2018 at hattrbridge.com 5 NIH, NCATS, GARD, Familial transthyretin amyloidosis, last updated October 23, 2017, accessed June 2018 at rarediseases.info.nih.gov 6 Business Wire, Alnylam Reports New Clinical Results from the APOLLO Phase 3 Study of Patisiran at the American Academy of Neurology 2018 Annual Meeting, April 24, 2018, accessed June 2018 at businesswire.com 7 Mathew Shanley, Patisiran NDA Accepted, hATTR Drug Granted Priority Review, February 1, 2018, accessed June 2018 at raredr.com 8 NIH, NCATS, GARD, Chronic inflammatory demyelinating polyneuropathy, last updated February 27, 2017, accessed June 2018 at rarediseases.info.nih.gov 9 Mazen M. Dimachkie, MD and Richard J. Barohn, MD, Chronic Inflammatory Demyelinating Polyneuropathy, June 15, 2013, accessed June 2018 at ncbi.nlm.nih.gov 10 National Organization for Rare Disorders (NORD), Chronic Inflammatory Demyelinating Polyneuropathy, 2015, accessed June 2018 at rarediseases.org 11 CSL Behring, FDA Approves Hizentra (Immune Globulin Subcutaneous [Human] 20% Liquid) for the Treatment of Patients With Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), March 16, 2018, accessed June 2018 at prnewswire.com

50 | InsideOut Clinicalials The latest research making therapies available to patients.

University of Texas Southwestern will then receive an AlloSCT from either and assessment of safety & tolerability Medical Center is sponsoring an a partially matched family member or of repeated administration of Anti-SAP interventional Phase 2 study to deter- an unrelated adult stem cell transplant treatment, including compatibility with mine the safety and therapeutic potential donor. The transplanted cells will allow chemotherapy treatment in patients of a new transplant approach in patients all the normal parts of the patient's blood with AL systemic amyloidosis. Eligibility with severe sickle cell disease and system to recover. The experimental requirements include, but are not limited thalassemia. The study requires portion of this treatment involves the to, 30 patients between the ages of 18 participation of a sibling donor — spe- use of a Miltenyi CliniMacs CD34+ and 80 years and older willing to comply cifically, a human lymphocyte antigen selection device to remove T-cells from with contraception requirements who (HLA)-matched donor. Primary outcomes the peripheral blood stem cell transplant meet diagnostic criteria for cardiac measures are defined as full donor type in order to decrease the risk of acute amyloidosis. Estimated study completion hemoglobin on hemoglobin electro- and chronic GVHD. Primary outcome is October 2021. NCT03044353 phoresis for patients with sickle cell measure is to determine the incidence disease and transfusion-independence and severity of acute GVHD. Eligibility St. Jude Children’s Research for patients with thalassemia. Recipient requirements include, but are not limited Hospital, in collaboration with University (patient) eligibility requirements include, to, patients up to 40 years of age (at least of Tennessee Health Science Center, but are not limited to, patients 18 to 45 two years old for patients with sickle cell is sponsoring a Phase 2 clinical trial years of age with high risk factors for disease) with non-malignant diseases. evaluating the efficacy of virtual reality high mortality and morbidity, defined by Estimated study completion is December technology when added to standard having irreversible end-organ damage 2019. NCT01966367 pain management for patients with or potentially reversible complication(s) sickle cell disease who are experiencing not ameliorated by hydroxyurea. Donor The Cleveland Clinic is sponsoring vaso-occlusive crisis (VOC) in an eligibility requirements include, but are an observational study to monitor ambulatory care setting. After consenting not limited to, 6/6 HLA identical family early disease progression in patients with to participate, patients will be random- donor. Estimated study completion is hereditary transthyretin amyloi- ized to receive either standard care January 2022. NCT02038478 dosis (MED-hATTR). Primary outcome therapy for VOC or receive standard measure for the five-year longitudinal care therapy plus a 15-minute virtual Diane George, MD, Columbia study will average the percentage reality (VR) session. Patients will be University is sponsoring an early Phase change in oligomers in patients with new additionally randomized into strata by 1, open label, clinical trial that tests an onset TTR amyloid symptoms. Eligibility age: six to 11 years, 12 to 18 years, and experimental treatment involving requirements include, but are not limited 19 to 25 years. At the end of therapy or the use of the CliniMACS® Reagent to, patients with known hereditary therapy plus the VR session, patients System (Miltenyi Biotec, Germany), a ATTR amyloidosis genetic mutations as will be asked to complete a five-minute CD34+ selection device to remove T-cells identified by genetic testing. Estimated satisfaction survey. Information will also from the peripheral blood stem cell study completion is February 15, 2024. be collected from the medical record transplant in order to decrease the risk NCT03431896 about the pain episode, including pain of acute and chronic graft versus host scores, medicines administered and disease (GVHD) in patients. A periph- GlaxoSmithKline is sponsoring an time needed for pain to lessen. Eligibility eral blood stem cell transplant using the open label, non-randomized, three-group, requirements include, but are not limited experimental treatment for patients with monthly repeat Anti-SAP treatment study to, patients between the ages of six and non-malignant diseases, including bone in systemic amyloidosis patients with 25 with sickle cell disease documented marrow failure syndrome, severe aplastic cardiac dysfunction caused by cardiac in the St. Jude medical record. Estimated anemia, severe congenital neutropenia, amyloidosis. The multiple treatment study completion is February 2021. primary immunodeficiency session Phase 2 investigational trial NCT03353584 syndromes, familial hemophagocytic will assess whether monthly repeat lymphocytosis, sickle cell disease courses of GSK2398852 administered To get information quickly and sickle cell-beta-thalassemia. following and along with GSK2315698 Some patients will receive an allogenic is associated with improved cardiac on the studies, access stem cell transplant (AlloSCT) from a function. Primary objectives for the Tip! ClinicalTrials.gov matched-related donor. If a patient does study are assessment of reduction in and type in the identifier not have a matched related donor, a bone cardiac amyloid load after repeated marrow search will be conducted in all administrations of Anti-SAP treatment as number. i.e., NCT01850004 global bone-marrow banks. The patient evaluated by CMR in all study groups

ASD Healthcare | 51 Integrated ealt Systems

Advertorial from AmerisouceBergen Biosimilars: Key Considerations

Executive Summary As biosimilars launch, they are shaping the treatment landscape. These new options are also creating new opportunities for health system pharmacy leaders to expand their influence on patient outcomes and the total cost of care. Pharmacy teams who understand the requirements for biosimilar approval, as well as the key components for biosimliars, will be prepared to guide their health system on how to evaluate biosimilars for formulary inclusion. This white paper outlines those key components and provides specific questions that will facilitate the health system pharmacy team's partnership with the P&T Committee. Pharmacy teams will find our actionable comparison tool particularly helpful when discussing similarities between reference products and associated biosimilars with physician stakeholders.

52 | InsideOut

Biosimilar Paper ISO Advetorial 080318.indd 1 8/8/18 12:45 PM Advertorial from AmerisouceBergen Biosimilars: Key Considerations

Background In March 2010, President Obama signed the Patient Protection and Affordable Care Act (ACA), which included the development of a new approval pathway for biosimilar medicines, called the Biologics Price Competition and Innovation Act (BPCIA). BPCIA is an abbreviated licensure pathway for biologic products, referred to as biosimilars, that are demonstrated to be “highly similar” to the FDA-approved reference products. The purpose of the pathway is to improve access to biologic medicines and lower healthcare costs via improved competition. While approval pathways for generic products have existed for more than three decades before ACA, there was no pathway to bring highly similar copies of biologics to the market. The United States has approved 11 biosimilars, but only three products have launched into the market. The others remain unlaunched as they are in various stages of litigation with the makers of the reference products. By contrast, the European Union established an approval pathway for biosimilars in 2006 and now has more than 40 approved and marketed biosimilars with more than 15 in various stages of approval.1 Given that the EU approval pathway was established earlier than the U.S. pathway, the breadth of patient experience and safety data with biosimilars is significant. To date, the EU has more than 700 million patient days of experience with biosimilars with no significant differences in safety or efficacy identified.2

Requirements for Biosimilar Approval The FDA regulates biologic products used to treat a variety of chronic and acute diseases, including immunology, oncology and vaccines. Biologics are generally very large, complex molecules and are typically produced in a living system. The nature of biologic products is complex, and since the manufacturing process produces batch-to-batch variation, a dynamic not seen in small molecule drugs, a new approval approach and pathway was warranted. Since biologics are not chemically synthesized, there is no way to produce identical copies; not even the reference product is an exact copy of itself. As such, the FDA has built the approval pathway for biosimilars to be based on being “highly similar.” According to the FDA, to be approved as a biosimilar, a manufacturer must demonstrate similarity through extensive analytics to characterize both the reference and biosimilar products. The majority of evidence requirements by the FDA lie within the analytical portion of the pathway. There are additional requirements including animal studies and a clinical study in the most sensitive population as determined by the FDA. These two sets of data comprise the “totality of evidence” approach, which is how the FDA ultimately determines approval for a biosimilar product.3

“ According to the FDA, to be approved as a biosimilar, a manufacturer must demonstrate similarity through extensive analytics to characterize both the reference and biosimilar products.”

ASD Healthcare | 53

Biosimilar Paper ISO Advetorial 080318.indd 2 8/8/18 12:45 PM Advertorial from AmerisouceBergen Biosimilars: Key Considerations

As stakeholders — including manufacturers, payers, health systems, physicians and patients — seek to evaluate how biosimilars can be utilized, it is critical to understand the key components of biosimilars.

1. Indication Extrapolation Given that the approval pathway for biosimilars generally requires only one clinical study, indication extrapolation is a key component of the pathway. According to the FDA, if the totality of evidence for the biosimilar supports the demonstration of biosimilarity in one indication, then it can be scientifically justified that approval to other indications is warranted without clinical study. The FDA works closely with the biosimilar manufacturer during the product development process to assess what data are required to support extrapolation. While extrapolation answers the scientific question of indications, the patent question is considerably more complex. Orphan and pediatric patents, for example, carry different rules of exclusivity; therefore, biosimilars may not have all the reference product indications as a result of the patent landscape, not the FDA approval process.

2. Totality of Evidence As outlined above, the totality of evidence approach takes into account analytical, animal and clinical studies to develop the full body of evidence needed for biosimilar approval. While biosimilar manufacturers may opt to do additional clinical studies to further support the clinical value of their product, the pathway takes into account more analytical and animal data rather than clinical data. As stakeholders evaluate biosimilars for utilization, this is a critical understanding as the clinical evidence is the smallest component of data and is unlikely to show differences in safety or efficacy. If differences did occur that were meaningful, the biosimilar would not get approved by the FDA.

3. Interchangeability The designation of interchangeability for a biosimilar can be sought by a manufacturer with the addition of different data. The crux of interchangeability is that the biosimilar product is expected to produce the same clinical result as the reference product in any given patient. This is proven through additional data submitted to the FDA, including data from a clinical study focused on switching a patient between the reference and biosimilar product. When awarded, an interchangeable product may be substituted for the reference product without the involvement of the physician (subject to requirements outlined by state pharmacy laws). There have been no biosimilars awarded interchangeability as of March 2018, and only one biosimilar manufacturer has publicly stated they are undergoing a clinical study to support an interchangeability designation.

54 | InsideOut

Biosimilar Paper ISO Advetorial 080318.indd 3 8/8/18 12:45 PM Advertorial from AmerisouceBergen Biosimilars: Key Considerations

4. Post-Marketing Surveillance The FDA has not set forth biosimilar-specific post-marketing surveillance requirements. Any requirements for biosimilars will be consistent with those set forth by the FDA for the reference product. There are efforts outside the FDA to develop an ample amount of post-marketing data of biosimilars within the U.S. The most evolved is the Biologic and Biosimilars Collective Intelligence Consortium (BBCIC).4 The BBCIC was established in 2015 to address anticipated stakeholder needs for post-marketing evidence generation for novel biologics and their biosimilar counterparts. The BBCIC is a non-profit initiative that will monitor both the novel biologic and biosimilars for efficacy and safety, and its results will be utilized to build the confidence of both patients and providers.

Considerations for Formulary Inclusion As more biosimilars are FDA-approved, P&T Committees should develop a process to evaluate their utility as an addition to or replacement of the reference product. This assessment should incorporate many different factors including:

Efficacy and Manufacturer supply and hospital Economic impact based safety assessments operational considerations on cost and payer policies

Although it is standard for P&T Committees to assess safety and efficacy data for formulary reviews, there are unique considerations for evaluating biosimilar data. FDA guidance on review of biosimilar data states that clinical studies of biosimilars should include assessment of immunogenicity and pharmacokinetics / pharmacodynamics, and should be adequately designed “to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed.”3 Because of the abbreviated nature of the biosimilar approval pathway and the greater reliance on analytical characterization, fewer clinical studies are typically available than would be for branded products. Even with limited data, it is expected that the P&T Committee approach to evaluating biosimilars should be completed with similar detail and thoroughness as conventional medications or branded biologics.5

“ As more biosimilars are FDA-approved, P&T Committees should develop a process to evaluate their utility as an addition to or replacement of the reference product."

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Biosimilar Paper ISO Advetorial 080318.indd 4 8/8/18 12:45 PM Advertorial from AmerisouceBergen Biosimilars: Key Considerations

Key components for consideration when reviewing biosimilars for formulary inclusion are outlined below:

Regulatory status » Is the biosimilar FDA approved for the same indication(s) as reference product? If not, is the difference based on clinical studies or due to regulatory or patent exclusivity?

Clinical efficacy » What clinical data are available? Are there additional data beyond that which is FDA-required for approval? » Is the medical staff comfortable with using the biosimilar in indications for which it was extrapolated from the reference product without being studied for those indications? » Are there any data available assessing multiple switches between the biosimilar and reference product (e.g., an interchangeability or bridge study)? » Are there international studies with relevant clinical data available for review? » Based on available data, are the P&T Committee and medical staff comfortable implementing a therapeutic equivalence protocol for the biosimilar? If so, will patients taking the reference product at home be included in the protocol and how will they be managed?

Pharmaceutics » Are there any clinically meaningful differences in formulation or excipients of the biosimilar versus the reference product? » Are there any clinically meaningful differences in drug or lab compatibility between the biosimilar and the reference product?

Biosimilar availability » Does the manufacturer have experience in manufacturing biologics and/or biosimilars? » Does the manufacturer have a history of drug shortages? » Does the manufacturer have a process to guarantee a reliable supply of the biosimilar?

Operational considerations » Are there any differences in storage, handling or preparation between the biosimilar and reference product? » Are there any differences in commercially available dosage sizes or strengths between the biosimilar and reference product? » How do you handle multiple biosimilars for the same product? » If stocking the reference product and biosimilar, how will the electronic medical record be differentiated? » What impact will that decision have on order set maintenance?

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Biosimilar Paper ISO Advetorial 080318.indd 5 8/8/18 12:45 PM Advertorial from AmerisouceBergen Biosimilars: Key Considerations

Economic considerations » Are patient assistant programs available and similar to what is available for the reference product? If not, what is budget impact if added to the formulary? » Are there any differences between the biosimilar and reference product with respect to the 340B Drug Pricing Program? » Are there any differences between the biosimilar and reference product with respect to ease of access to the product based on payer requirements for preauthorization or limited distribution networks?6

Conclusion Biosimilars represent a new class of drugs and face even more challenges than generics did years ago. However, there are many considerations to including a biosimilar on formulary and ensuring provider comfort in prescribing these medications. Affordability will be an important factor for patients as they consider treatment options; therefore, the financial impact should also be evaluated by providers and payers. Physician familiarity with and confidence in using biosimilars is critical to a successful formulary implementation. To that end, the biosimilar comparison tool on page fifty-eight can be used to facilitate discussion with physician stakeholders and emphasize the similarities between reference products and associated biosimilars.

References 1 Adrian Van de Hoven, Biosimilar Medicines for Europe, presented to the Association for Accessible Medicines Annual Biosimilar Meeting, September 2017 2 European Medicines Agency – European Commision, Biosimilars in the EU – Information Guide for healthcare professionals, April 2017 3 FDA, Biosimilar Development, Review, and Approval, October 23, 2017, accessed February 2018 at fda.gov 4 BBCIC, Biologics and Biosimilars Collective Intelligence Consortium, accessed February 2018 at bbcic.org 5 C. Ventola, Evaluation of biosimilars for formulary inclusion: factors for consideration by P&T committees, Pharmacy and Therapeutics, Oct. 2015; 40(10):680-9 6 N.Griffith, A. McBride, J. Stevenson, et al., Formulary selection criteria for biosimilars: considerations for US health-system pharmacists. Hospital Pharmacy. Oct. 2014;49(9):813-25

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Biosimilar Paper ISO Advetorial 080318.indd 6 8/8/18 12:45 PM Advertorial from AmerisouceBergen Biosimilars: Key Considerations Biosimilar Comparison to Reference Product Tool

Parameter Reference Product Biosimilar for Comparison Domain 1: Regulatory Status What are the FDA-labeled indications for the reference product and biosimilar product?

Domain 2: Clinical Data For which disease states have the reference product and biosimilar product been studied?

What is the FDA approved dosing, by indication, for each product?

Domain 3: Safety Data What are the most commonly reported adverse effects and associated frequencies?

What are the most severe reported adverse effects and associated frequencies?

How common are serious immunogenic reactions or anti- drug antibody development during use of the biosimilar or reference product?

Domain 4: Pharmaceutics Are there any differences in commercially available dosage sizes or strengths between the biosimilar and reference product? If so, include. Are there any clinically significant differences in formulation or excipients of the biosimilar versus the reference product? If so, include.

58 | InsideOut

Biosimilar Paper ISO Advetorial 080318.indd 7 8/8/18 12:45 PM Advertorial from AmerisouceBergen Biosimilars: Key Considerations About the Authors

Molly Burich Director for Public Policy – Biosimilars, Pipeline and Reimbursement Boehringer Ingelheim Ms. Burich focuses on key federal and state policy issues impacting the franchises of Boehringer Ingelheim, with a specific focus on biosimilars, pipeline products and reimbursement for in-line and pipeline products. She has held a variety of senior level positions in the manufacturer and healthcare industries where she specialized in reimbursement and legislative and regulatory changes in healthcare reform.

Ashley Pappas, PharmD, MHA Asst. Dir. of Medication Use Policy and Analytics UNC Hospitals Department of Pharmacy Dr. Pappas oversees the Medication Use Policy and Analytics team with the mission of supporting data-driven best practices by providing actionable information and expert consultation. She is also responsible for facilitating the system pharmacy and therapeutics committee and developing the approach to standardize the formulary across all 11 hospitals within the UNC Health Care System.

Kristin Chambers Vice President, Strategic Development AmerisourceBergen Ms. Chambers has more than 25 years of sales, operations, marketing and executive management experience in the healthcare and consulting industries. She has held a variety of senior-level marketing positions at major pharmacy retailers and with healthcare providers. She brings unique perspectives in market strategies for patients, providers and suppliers, having worked with all three segments.

About IHOC The Integrated Health Systems Outcomes Coalition (IHOC) is committed to supporting and improving the access, value and delivery of quality care for patients with specialty diseases through a unique partnership between health systems, manufacturers, payers and supply chain partners. IHOC, an independent LLC created by AmerisourceBergen, believes actionable data may help all involved stakeholders demonstrate the value of specialty pharmaceuticals and the coordination of patient care services provided in health system settings. Visit ihocnetwork.com to learn more.

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Biosimilar Paper ISO Advetorial 080318.indd 8 8/8/18 12:45 PM

Important Safety Information Kcentra is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by Vitamin K antagonist (VKA—eg, warfarin) therapy in adult patients with acute major bleeding or the need for urgent surgery or other invasive procedure. Kcentra is for intravenous use only. WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS Patients being treated with Vitamin K antagonist therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the risk of thromboembolic events, especially in patients with history of such events. Resumption of anticoagulation therapy should be carefully considered once the risk of thromboembolic events outweighs the risk of acute bleeding. Both fatal and nonfatal arterial and venous thromboembolic complications have been reported in clinical trials and postmarketing surveillance. Monitor patients receiving Kcentra, and inform them of signs and symptoms of thromboembolic Single-dose Kcentra 4F-PCC—the only FDA-approved events. Kcentra was not studied in subjects who had a alternative to plasma for urgent warfarin reversal thromboembolic event, myocardial infarction, disseminated • Indicated for the urgent reversal of acquired coagulation factor deficiency intravascular coagulation, cerebral vascular accident, induced by VKA (eg, warfarin) therapy in adult patients with: transient ischemic attack, unstable angina pectoris, or – Need for urgent surgery/invasive procedure or severe peripheral vascular disease within the prior 3 months. Kcentra might not be suitable for patients with – Acute major bleeding In 2 head-to-head trials, Kcentra demonstrated superiority Kcentra is contraindicated in patients with known anaphylactic or severe systemic reactions to Kcentra or any of its components to plasma in 3 of 4 efficacy endpoints (including heparin, Factors II, VII, IX, X, Proteins C and S, Urgent Surgery/Invasive Acute Major Antithrombin III and human albumin). Kcentra is also Efficacy endpoint contraindicated in patients with disseminated intravascular Procedures trial1 Bleeding trial2 coagulation. Because Kcentra contains heparin, it is ectie centra and lasma contraindicated in patients with heparin-induced centra superior thrombocytopenia (HIT). hemostasis equally effective Hypersensitivity reactions to Kcentra may occur. If patient arly centra superior centra superior experiences severe allergic or anaphylactic type reactions, reuction discontinue administration and institute appropriate treatment. In clinical trials, the most frequent (≥2.8%) adverse reactions Effective hemostasis measured up to 24 hours for the Acute Major Bleeding trial and until the observed in subjects receiving Kcentra were headache, nausea/ end of procedure (up to 24 hours) for the Urgent Surgery/Invasive Procedures trial. vomiting, hypotension, and anemia. The most serious adverse Rapid INR reduction to ≤1.3 at 0.5 hours after end of infusion. reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis. • The relationship between INR values and clinical hemostasis in patients has not been established Kcentra is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the • Shorter time to surgery Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), – Median time to surgery was ~5 hours faster with Kcentra cannot be completely eliminated. (3.6 hours) vs plasma (8.5 hours)1 Please see brief summary of full prescribing information • Safety comparable to plasma on adjacent page. – Kcentra did not increase the risk of thromboembolic events compared to plasma

References: 1. Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015;385(9982):2077-2087. 2. Sarode R, Milling TJ, Refaai MA, et al. Efﬁcacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11):1234-1243. Kcentra® and Beriplex® are registered trademarks of CSL Behring GmbH. Biotherapies for Life® is a registered trademark of CSL Behring LLC. ©2017 CSL Behring LLC 1020 First Avenue, PO Box 61501, King of Prussia, PA 19406-0901 USA www.CSLBehring.com www.Kcentra.com KCT-0135-DEC17 Urgent Warfarin Reversal KCENTRA® (Prothrombin Complex Concentrate [Human]) Pre-treatment INR 2–< 4 4–6 > 6 For Intravenous Use, Lyophilized Powder for Reconstitution Initial U.S. Approval: 2013 Dose* of Kcentra (units† of 25 35 50 BRIEF SUMMARY OF PRESCRIBING INFORMATION Factor IX) / kg body weight These highlights do not include all the information needed to use Kcentra Maximum dose‡ (units of Not to ex- Not to exceed Not to exceed safely and effectively. See full prescribing information for Kcentra. Factor IX) ceed 2500 3500 5000 * Dosing is based on body weight. Dose based on actual potency is stated on the vial, which will vary from 20- WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS 31 Factor IX units/mL after reconstitution. The actual potency for 500 vial ranges from 400-620 units/vial. The actual potency for 1000 unit vial ranges from 800-1240 units/vial.

Patients being treated with Vitamin K antagonists (VKA) therapy have † Units refer to International Units. underlying disease states that predispose them to thromboembolic ‡ Dose is based on body weight up to but not exceeding 100 kg. For patients weighing more than 100 kg, maximum events. Potential benefits of reversing VKA should be weighed against dose should not be exceeded. Important Safety Information the potential risks of thromboembolic events, especially in patients with ------DOSAGE FORMS AND STRENGTHS------the history of a thromboembolic event. Resumption of anticoagulation • Kcentra is available as a white or slightly colored lyophilized concentrate in a single-use Kcentra is a blood coagulation factor replacement product vial containing coagulation Factors II, VII, IX and X, and antithrombotic Proteins C and S. indicated for the urgent reversal of acquired coagulation factor should be carefully considered as soon as the risk of thromboembolic ------CONTRAINDICATIONS ------deficiency induced by Vitamin K antagonist (VKA—eg, warfarin) events outweighs the risk of acute bleeding. Kcentra is contraindicated in patients with: therapy in adult patients with acute major bleeding or the need • Both fatal and non-fatal arterial and venous thromboembolic complications have been reported with Kcentra in clinical trials and • Known anaphylactic or severe systemic reactions to Kcentra or any components in for urgent surgery or other invasive procedure. Kcentra is for Kcentra including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and intravenous use only. post marketing surveillance. Monitor patients receiving Kcentra for signs and symptoms of thromboembolic events. human albumin. WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC • Kcentra was not studied in subjects who had a thromboembolic • Disseminated intravascular coagulation. COMPLICATIONS event, myocardial infarction, disseminated intravascular coagulation, • Known heparin-induced thrombocytopenia. Kcentra contains heparin. Patients being treated with Vitamin K antagonist therapy cerebral vascular accident, transient ischemic attack, unstable angina ------WARNINGS AND PRECAUTIONS------have underlying disease states that predispose them to pectoris, or severe peripheral vascular disease within the prior 3 • Hypersensitivity reactions may occur. If necessary, discontinue administration and thromboembolic events. Potential benefits of reversing months. Kcentra may not be suitable in patients with thromboembolic institute appropriate treatment. VKA should be weighed against the risk of thromboembolic events in the prior 3 months. • Arterial and venous thromboembolic complications have been reported in patients events, especially in patients with history of such events. receiving Kcentra. Monitor patients receiving Kcentra for signs and symptoms of thromboembolic events. Kcentra was not studied in subjects who had a thrombotic or Resumption of anticoagulation therapy should be carefully ------INDICATIONS AND USAGE------thromboembolic (TE) event within the prior 3 months. Kcentra may not be suitable in considered once the risk of thromboembolic events Kcentra, Prothrombin Complex Concentrate (Human), is a blood coagulation factor patients with thromboembolic events in the prior 3 months. outweighs the risk of acute bleeding. Both fatal and replacement product indicated for the urgent reversal of acquired coagulation factor • Kcentra is made from human blood and may carry a risk of transmitting infectious nonfatal arterial and venous thromboembolic complications deficiency induced by Vitamin K antagonist (VKA, e.g., warfarin) therapy in adult patients agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and theoretically, have been reported in clinical trials and postmarketing with: the Creutzfeldt-Jakob disease (CJD) agent. surveillance. Monitor patients receiving Kcentra, and • acute major bleeding or inform them of signs and symptoms of thromboembolic Single-dose Kcentra 4F-PCC—the only FDA-approved • need for an urgent surgery/invasive procedure. ------ADVERSE REACTIONS------• The most common adverse reactions (ARs) (frequency ≥ 2.8%) observed in subjects events. Kcentra was not studied in subjects who had a alternative to plasma for urgent warfarin reversal ------DOSAGE AND ADMINISTRATION------receiving Kcentra were headache, nausea/vomiting, hypotension, and anemia. (6) thromboembolic event, myocardial infarction, disseminated For intravenous use after reconstitution only. • Indicated for the urgent reversal of acquired coagulation factor deficiency • The most serious ARs were thromboembolic events including stroke, pulmonary intravascular coagulation, cerebral vascular accident, • Kcentra dosing should be individualized based on the patient’s baseline International induced by VKA (eg, warfarin) therapy in adult patients with: embolism, and deep vein thrombosis. transient ischemic attack, unstable angina pectoris, or – Need for urgent surgery/invasive procedure or Normalized Ratio (INR) value, and body weight. severe peripheral vascular disease within the prior 3 • Administer Vitamin K concurrently to patients receiving Kcentra to maintain factor To report SUSPECTED ADVERSE REACTIONS, contact CSL Behring at 1-866-915- months. Kcentra might not be suitable for patients with – Acute major bleeding levels once the effects of Kcentra have diminished. 6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. • The safety and effectiveness of repeat dosing have not been established and it is not In 2 head-to-head trials, Kcentra demonstrated superiority Kcentra is contraindicated in patients with known anaphylactic recommended. or severe systemic reactions to Kcentra or any of its components to plasma in 3 of 4 efficacy endpoints • Administer reconstituted Kcentra at a rate of 0.12 mL/kg/min (~3 units/kg/min) up to See 17 for PATIENT COUNSELING INFORMATION (including heparin, Factors II, VII, IX, X, Proteins C and S, a maximum rate of 8.4 mL/min (~210 units/min). Revised: August 2017 Urgent Surgery/Invasive Acute Major Antithrombin III and human albumin). Kcentra is also Efficacy endpoint contraindicated in patients with disseminated intravascular Procedures trial1 Bleeding trial2 coagulation. Because Kcentra contains heparin, it is ectie centra and lasma contraindicated in patients with heparin-induced centra superior thrombocytopenia (HIT). hemostasis equally effective Hypersensitivity reactions to Kcentra may occur. If patient arly centra superior centra superior experiences severe allergic or anaphylactic type reactions, reuction discontinue administration and institute appropriate treatment. In clinical trials, the most frequent (≥2.8%) adverse reactions Effective hemostasis measured up to 24 hours for the Acute Major Bleeding trial and until the observed in subjects receiving Kcentra were headache, nausea/ end of procedure (up to 24 hours) for the Urgent Surgery/Invasive Procedures trial. vomiting, hypotension, and anemia. The most serious adverse Rapid INR reduction to ≤1.3 at 0.5 hours after end of infusion. reactions were thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis. • The relationship between INR values and clinical hemostasis in patients has not been established Kcentra is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the • Shorter time to surgery Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), – Median time to surgery was ~5 hours faster with Kcentra cannot be completely eliminated. (3.6 hours) vs plasma (8.5 hours)1 Please see brief summary of full prescribing information • Safety comparable to plasma on adjacent page. – Kcentra did not increase the risk of thromboembolic events compared to plasma

ASD Healthcare is now an authorized distributor for several new products, which are described here. We continuously expand our product lines to make sure you have access to the products you need, when you need them. To verify a product is appropriate to order for your facility, simply call your sales representative. We’re always here to help you.

Andexxa® Braftovi™ Kedrab [Rabies Immune Globulin (Human)] is Manufactured by Portola Pharmaceuticals, Manufactured by Array BioPharma Inc., Braftovi indicated for passive, transient post-exposure Andexxa (coagulation factor Xa) [recombinant] (encorafenib) capsules, in combination with prophylaxis (PEP) against rabies infection, inactivated-zhzo) is the first and only antidote (+) Mektovi (binimetinib) tablets, is indicated when given immediately after contact with a indicated for patients treated with rivaroxaban for the treatment of patients with unresectable rabid or possibly rabid animal. Kedrab should and apixaban, when reverse-anticoagulation is or metastatic melanoma with a BRAFV600E be administered concurrently with a full course needed due to life-threatening or uncontrolled or BRAF600K mutation, as detected by an of rabies vaccines. Kedrab provides immediate bleeding. Andexxa was granted Orphan Drug and FDA-approved test. Braftovi is not indicated for passive rabies virus neutralizing antibody Breakthrough Therapy designations and approved the treatment of patients with wild-type BRAF protection until the patient’s immune system under the FDA's accelerated approval pathway melanoma. FDA approval of Braftovi + Mektovi is responds to vaccination by actively producing based on the change from baseline in anti-factor based on results from the Phase 3 COLUMBUS antibodies. The efficacy of Kedrab administered Xa activity in healthy volunteers. Continued trial. concurrently with rabies vaccine was studied in approval for this indication may be contingent For specific product ordering information, a single-center, randomized, comparator HRIG- on post-marketing study results to demonstrate please see page 73 in our Product Catalog. controlled clinical study. an improvement in hemostatsis in patients. For specific product ordering information, For specific product ordering information, Kedrab™ please see page 72 in our Product Catalog. please see page 70 in our Product Catalog. Manufactured by Kedrion Biopharma, Mektovi® Manufactured by Array BioPharma Inc., Mektovi (binimetinib) tablets, in combination with (+) Braftovi (encorafenib) capsules, is indicated for the treatment of patients with unresectable or metastatic melanoma with a BRAFV600E or BRAF600K mutation, as detected by an FDA-approved test. Mektovi is not indicated for the treatment of patients with wild-type BRAF melanoma. FDA approval of Braftovi + Mektovi is based on results from the Phase 3 COLUMBUS trial. For specific product ordering information, please see page 75 in our Product Catalog.

Miglustat (generic) Manufactured by Amerigen Pharmaceuticals, miglustat is a glucosylceramide synthase inhibitor indicated as monotherapy for the treatment of adult patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy is not a therapeutic option. FDA granted approval through the Abbreviated New Drug Application (ANDA) for miglustat 100 mg capsules. Filing the ANDA resulted from an exclusive collaboration between Amerigen

62 | InsideOut Newroct Available from ASD Healthcare Newroct

Pharmaceuticals and Dipharma, which supplies the active ingredient of miglustat to Amerigen. Dipharma holds two U.S. patents: one for a method of synthesis for miglustat and the second for a crystalline form of the same. FDA approved the brand name counterpart in July 2003. For specific product ordering information, please see page 81 in our Product Catalog.

Tavalisse™ Manufactured by Rigel Pharmaceuticals, Tavalisse (fostamatinib disodium hexahydrate) tablets are indicated for treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. FDA granted Tavalisse Orphan Drug Designation. For specific product ordering information, please see page 82 in our Product Catalog.

Yonsa® Manufactured by Sun Pharmaceutical Industries, Yonsa (abiraterone acetate) is a CYP17 inhibitor indicated in combination with methylprednisolone for the treatment of patients with metastatic castration-resistant prostate cancer (CRPC). Yonsa in combination with methylprednisolone was filed as a New Drug Application (NDA) under the 505(b)(2) regulatory pathway and will be promoted as a branded product in the U.S. For specific product ordering information, please see page 77 in our Product Catalog.

Zemdri™ Manufactured by Achaogen, Inc., Zemdri (plazomicin) is indicated for patients 18 years and older for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis caused by Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Enterobacter cloacae, who have limited or no alternative treatment options. Zemdri is an intravenous infusion, administered once daily. For specific product ordering information, please see page 83 in our Product Catalog.

ASD Healthcare | 63 Newicatio FDA approved Newicatio Keytruda® Keytruda (pembrolizumab), manufactured by Merck, received accelerated Find product ordering information on all approval from the FDA for the treatment of patients with advanced, PD-L1-positive cervical cancer with disease progression on or after ASD Healthcare products in our Product chemotherapy. The FDA based approval on data from the global, open- label, nonrandomized, multicohort, multicenter Phase II KEYNOTE-158 Catalog on page 65. trial, an ongoing study designed to evaluate the efficacy of Keytruda in more than 1,300 adults who have advanced solid tumors that progressed on chemotherapy. For a listing of all FDA indications, please refer to the Get recent updates to new products and prescribing information (PI) or visit fda.gov. For specific product ordering information, please see page 75 in our new indications at asdhealthcare.com/ Product Catalog. products/new-products. Opdivo® and Yervoy® Opdivo (nivolumab) and Yervoy (ipilimumab), both manufactured by Bristol-Myers Squibb, are approved as combination treatment for intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma. The FDA granted Breakthrough Therapy designation and Priority Review to the combination treatment. Approval was based on data from 847 intermediate- or poor-risk patients with previously untreated advanced renal cell carcinoma from the randomized open-label CheckMate-214 trial. For a listing of all FDA indications, please refer to the prescribing information (PI) or visit fda.gov. For specific product ordering information, please see page 76 and 77 in our Product Catalog.

Opdivo® and low-dose Yervoy® Opdivo (nivolumab) 3mg/kg plus low-dose Yervoy (ipilimumab) 1 mg/ kg (injections for intravenous use), both manufactured by Bristol-Myers Squibb, are approved as combination treatment in adult and pediatric patients 12 years and older with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin and irinotecan. Approval for this indication has been granted under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. For specific product ordering information, please see page 76 and 77 in our Product Catalog.

64 | InsideOut Productaao Our most popular products

Our ASD Healthcare Product Catalog is your convenient way to get quick updates for our most popular products, including oncology, plasma derivatives, pharmaceuticals, contrast media and nephrology.

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Consumer PD Plasma Derivatives Albumin 66 Products Showcase Antihemophilic 67 Check out Consumer Products available through Immunologic 70 ABC Order or ABC Passport ordering system! Hyper-Immune Globulin 72

Showcased products represent just a few of the O Oncology extensive line of consumer products available from Oncology/Supportive Care 73 AmerisourceBergen. AmerisourceBergen works with more than 600 manufacturers in areas of CPG, OTC products, diabetes and home healthcare, so you may P Pharmaceuticals easily order just about any consumer products for your Vaccines 79 pharmacy. Specialty 80 Biosurgery 83 In addition, AmerisourceBergen carries advanced wound, institutional diabetes, ostomy/catheter items, gravity sets, clean room and store supplies. CM Contrast Media Bracco 84

Not an AmerisourceBergen customer? N Nephrology 610.727.7000 or Nephrology Rx 85 [email protected] Medical / Surgical 89

ASD Healthcare | 65 PD Plasma Derivatives

Albumin CODE PRODUCT SIZE EQ. UNIT MFR. NDC # PK/CS P9045 Albuked™ 5% 250 mL 1 KED 76125-0790-25 vl P9045 Albuked™ 25% 50 mL KED 76125-0792-25 vl P9045 Albuked™ 25% 100 mL KED 76125-0792-10 vl P9045 Albumin 5% 250 mL 1 OCT 68982-0623-02 vl P9045 Albumin 5% 500 mL 1 OCT 68982-0623-03 vl P9047 Albumin 25% 50 mL 1 OCT 68982-0643-01 vl P9047 Albumin 25% 100 mL 1 OCT 68982-0643-02 vl P9047 Albuminar® 25% 50 mL 1 CSL 00053-7680-32 vl

NEW P9047 Albuminar® 25% 100 mL CSL 00053-7680-33 vl P9045 Albutein® 5% (Albumin) 50 mL 0.5 GFS 68516-5214-05 vl P9045 Albutein® 5% (Albumin) 250 mL 1 GFS 68516-5214-01 vl P9045 Albutein® 5% (Albumin) 500 mL 2 GFS 68516-5214-02 vl P9045 Albutein® 25% (Albumin) 20 mL 0.4 GFS 68516-5216-05 vl P9047 Albutein® 25% (Albumin) 50 mL 1 GFS 68516-5216-01 vl P9047 Albutein® 25% (Albumin) 100 mL 2 GFS 68516-5216-02 vl P9047 AlbuRx® 25% 50 mL 1 CSL 44206-0251-05 vl P9047 AlbuRx® 25% 100 mL 2 CSL 44206-0251-10 vl P9045 AlbuRx® 5% 250 mL 1 CSL 44206-0310-25 vl P9045 AlbuRx® 5% 500 mL 2 CSL 44206-0310-50 vl J3490 Flexbumin 5% 10 x 250 mL 1 BXLT 00944-0493-01 cs J3490 Flexbumin 25% 24 x 50 mL 1 BXLT 00944-0493-01 cs J3490 Flexbumin 25% 12 x 100 mL 2 BXLT 00944-0493-02 cs P9048 Plasmanate® 5% (PPF) 250 mL 1 GFS 13533-0613-25 vl

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Antihemophilic CODE PRODUCT SIZE MFR. NDC # PK/CS Factor VIIa (Recombinant) J7189 NovoSeven® RT with MixProTM 1.0 mg NOVO 00169-7201-01 vl J7189 NovoSeven® RT with MixProTM 2.0 mg NOVO 00169-7202-01 vl J7189 NovoSeven® RT with MixProTM 5.0 mg NOVO 00169-7205-01 vl J7189 NovoSeven® RT with MixProTM 8.0 mg NOVO 00169-7208-01 vl Factor VIII (Recombinant) J7192 Advate® w/Baxject III 250 iu BXLT 00944-3051-02 vl J7192 Advate® w/Baxject III 500 iu BXLT 00944-3052-02 vl J7192 Advate® w/Baxject III 1000 iu BXLT 00944-3053-02 vl J7192 Advate® w/Baxject III 1500 iu BXLT 00944-3054-02 vl J7192 Advate® w/Baxject III 2000 iu BXLT 00944-3045-10 vl J7192 Advate® w/Baxject III 3000 iu BXLT 00944-3046-10 vl J7192 Advate® w/Baxject III 4000 iu BXLT 00944-3047-10 vl J7027 Adynovate 250 iu BXLT 00944-4622-01 ea J7027 Adynovate 500 iu BXLT 00944-4623-01 ea J7027 Adynovate 750 iu BXLT 00944-4626-01 ea J7027 Adynovate 1250 iu BXLT 00944-4624-01 ea J7027 Adynovate 1500 iu BXLT 00944-4627-01 ea J7027 Adynovate 2000 iu BXLT 00944-4625-01 ea J7027 Adynovate 3000 iu BXLT 00944-4625-01 ea J7199 AFSTYLA® 250 iu CSL 69911-0474-02 vl J7199 AFSTYLA® 500 iu CSL 69911-0475-02 vl J7199 AFSTYLA® 1000 iu CSL 69911-0476-02 vl J7199 AFSTYLA® 1500 iu CSL 69911-0480-02 vl J7199 AFSTYLA® 2000 iu CSL 69911-0477-02 vl J7199 AFSTYLA® 2500 iu CSL 69911-0481-02 vl J7199 AFSTYLA® 3000 iu CSL 69911-0478-02 vl J7025 Eloctate™ Kit 250 iu BIOV 64406-0801-01 vl J7025 Eloctate™ Kit 500 iu BIOV 64406-0802-01 vl J7025 Eloctate™ Kit 750 iu BIOV 64406-0803-01 vl J7025 Eloctate™ Kit 1000 iu BIOV 64406-0804-01 vl J7025 Eloctate™ Kit 1500 iu BIOV 64406-0805-01 vl J7025 Eloctate™ Kit 2000 iu BIOV 64406-0806-01 vl J7025 Eloctate™ Kit 3000 iu BIOV 64406-0807-01 vl J7200 Eloctate™ Kit 4000 iu BIOV 64406-0808-01 vl J7201 Eloctate™ Kit 5000 iu BIOV 64406-0809-01 vl Eloctate™ Kit 6000 iu BIOV 64406-0810-01 vl J7192 Helixate® FS PDS 250 iu CSL 00053-8131-02 vl J7192 Helixate® FS PDS 500 iu CSL 00053-8132-02 vl J7192 Helixate® FS PDS 1000 iu CSL 00053-8133-02 vl J7192 Helixate® FS PDS 2000 iu CSL 00053-8134-02 vl J7192 Helixate® FS PDS 3000 iu CSL 00053-8135-02 vl

ASD Healthcare | 67 PD Plasma Derivatives

CODE PRODUCT SIZE MFR. NDC # PK/CS J7192 Kogenate® FS Adaptor PDS 250 iu BYR 00026-3782-25 vl J7192 Kogenate® FS Adaptor PDS 500 iu BYR 00026-3783-35 vl J7192 Kogenate® FS Adaptor PDS 1000 iu BYR 00026-3785-55 vl J7192 Kogenate® FS Adaptor PDS 2000 iu BYR 00026-3786-65 vl J7192 Kogenate® FS Adaptor PDS 3000 iu BYR 00026-3787-75 vl J7192 Kovaltry® w/ Vial Adapter 250 iu vl BYR 00026-3821-25 ea J7192 Kovaltry® w/ Vial Adapter 500 iu vl BYR 00026-3822-25 ea J7192 Kovaltry® w/ Vial Adapter 1000 iu vl BYR 00026-3824-25 ea J7192 Kovaltry® w/ Vial Adapter 2000 iu vl BYR 00026-3826-50 ea J7192 Kovaltry® w/ Vial Adapter 3000 iu vl BYR 00026-3828-50 ea J7182 Novoeight® 250 iu NOVO 00169-7825-01 vl J7182 Novoeight® 500 iu NOVO 00169-7850-01 vl J7182 Novoeight® 1000 iu NOVO 00169-7810-01 vl J7182 Novoeight® 1500 iu NOVO 00169-7815-01 vl J7182 Novoeight® 2000 iu NOVO 00169-7820-01 vl J7182 Novoeight® 3000 iu NOVO 00169-7830-01 vl J7209 Nuwiq® 200 iu LFP vl kit OCT 68982-0139-01 ea J7209 Nuwiq® 500 iu LFP vl kit OCT 68982-0141-01 ea J7209 Nuwiq® 1000 iu LFP vl kit OCT 68982-0143-01 ea J7209 Nuwiq® 2000 iu LFP vl kit OCT 68982-0145-01 ea NEW J7209 Nuwiq® 3000 iu LFP vial kit OCT 68982-0149-01 ea J7192 Recombinate® PDS 250 iu/5 mL vl BXLT 00944-2841-10 vl J7192 Recombinate® PDS 500 iu/5 mL vl BXLT 00944-2842-10 vl J7192 Recombinate® PDS 1000 iu/5 mL vl BXLT 00944-2843-10 vl J7192 Recombinate® PDS 1500 iu/5 mL vl BXLT 00944-2844-10 vl J7192 Recombinate® PDS 2000 iu/5 mL vl BXLT 00944-2845-10 vl J7185 Xyntha® Kit KS 250 iu PFZ 58394-0012-01 vl J7185 Xyntha® PDS Kit 500 iu PFZ 58394-0013-01 vl J7185 Xyntha® PDS Kit 1000 iu PFZ 58394-0014-01 vl J7185 Xyntha® Kit KS 2000 iu PFZ 58394-0015-01 vl J7185 Xyntha® PDS Solofuse SYR 250 iu PFZ 58394-0022-03 vl J7185 Xyntha® PDS Solofuse SYR 500 iu PFZ 58394-0023-03 vl J7185 Xyntha® PDS Solofuse SYR 1000 iu PFZ 58394-0024-03 vl J7185 Xyntha® PDS Solofuse SYR 2000 iu PFZ 58394-0025-03 vl J7185 Xyntha® PDS Solofuse SYR 3000 iu PFZ 58394-0016-03 vl Factor VIII (Immunoaffinity Purified. Derived from Human Plasma.) J7190 Hemofil® M PDS AHF 250 iu BXLT 00944-3940-02 vl J7190 Hemofil® M PDS AHF 500 iu BXLT 00944-3942-02 vl J7190 Hemofil® M PDS AHF 1000 iu BXLT 00944-3944-02 vl J7190 Hemofil® M PDS AHF 1700 iu BXLT 00944-3946-02 vl J7190 Monoclate-P® PDS 1000 iu CSL 00053-7656-04 vl J7190 Monoclate-P® PDS 1500 iu CSL 00053-7656-05 vl

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CODE PRODUCT SIZE MFR. NDC # PK/CS Factor VIII (Derived from Human Plasma. Contains von Willebrand Factor.) J7186 Alphanate® AHF 250 iu GFS 68516-4611-01 vl J7186 Alphanate® AHF 500 iu GFS 68516-4612-01 vl J7186 Alphanate® AHF 1000 iu GFS 68516-4613-02 vl J7186 Alphanate® AHF 1500 iu GFS 68516-4614-02 vl J7186 Alphanate® AHF 2000 iu GFS 68516-4615-02 vl J7187 Humate-P® PDS RCoF 500 RCoF CSL 00053-7615-05 vl J7187 Humate-P® PDS RCoF 1000 RCoF CSL 00053-7615-10 vl J7187 Humate-P® PDS RCoF 2000 RCoF CSL 00053-7615-20 vl J7190 Koate®-DVI PDS 250 iu Mix 2 vl KED 76125-0256-20 ea J7190 Koate®-DVI PDS 500 iu Mix 2 vl KED 76125-0668-30 ea J7190 Koate® PDS 1000 iu mix 2 vl KED 76125-0676-50 ea J3590 Wilate® PDS VW Kit 500 iu RCo/5 mL OCT 68982-0182-01 pds vw kit J3590 Wilate® PDS VW Kit 1000 iu RCo/10 mL OCT 68982-0182-02 pds vw kit Factor IX (Recombinant) J7199 Alprolix® Kit 250 iu BIOV 64406-0966-01 vl J7199 Alprolix® Kit 500 iu BIOV 64406-0911-01 vl J7199 Alprolix® Kit 1000 iu BIOV 64406-0922-01 vl J7199 Alprolix® Kit 2000 iu BIOV 64406-0933-01 vl J7199 Alprolix® Kit 3000 iu BIOV 64406-0944-01 vl J7199 Alprolix® Kit 4000 iu BIOV 64406-0977-01 vl J7195 BeneFIX®-RT PDS 250 iu PFZ 58394-0633-03 vl J7195 BeneFIX®-RT PDS 500 iu PFZ 58394-0634-03 vl J7195 BeneFIX®-RT PDS 1000 iu PFZ 58394-0635-03 vl J7195 BeneFIX®-RT PDS 2000 iu PFZ 58394-0636-03 vl J7195 BeneFIX®-RT PDS 3000 iu PFZ 58394-0637-03 vl J7202 Idelvion® 250 iu SDV CSL 69911-0864-02 ea J7202 Idelvion® 500 iu SDV CSL 69911-0865-02 ea J7202 Idelvion® 1000 iu SDV CSL 69911-0866-02 ea J7202 Idelvion® 2000 iu SDV CSL 69911-0867-02 ea Rebinyn® 500 iu NOVO 00169-7905-01 vl Rebinyn® 1000 iu NOVO 00169-7901-01 vl Rebinyn® 2000 iu NOVO 00169-7902-01 vl J7195 RIXUBIS Kit BAXJECT 250 iu BXLT 00944-3026-02 vl J7195 RIXUBIS Kit BAXJECT 500 iu BXLT 00944-3028-02 vl J7195 RIXUBIS Kit BAXJECT 1000 iu BXLT 00944-3030-02 vl J3490 RIXUBIS Kit BAXJECT 2000 iu BXLT 00944-3032-02 vl Factor IX (Prothrombin Concentrates. Derived from Human Plasma. Contains Factor II, VII, IX and X.) J7194 Bebulin® VH PDS 700 iu BXLT 64193-0445-02 vl J3590 Kcentra® 500 iu SDV CSL 63833-0386-02 ea C9132 Kcentra® 1000 iu SDV CSL 63833-0387-02 ea J7194 Profilnine® SD PDS 500 iu GFS 68516-3207-01 vl J7194 Profilnine® SD PDS 1000 iu GFS 68516-3208-02 vl J7194 Profilnine® SD PDS 1500 iu GFS 68516-3209-02 vl

ASD Healthcare | 69 PD Plasma Derivatives

CODE PRODUCT SIZE MFR. NDC # PK/CS Factor IX (Derived from Human Plasma) J7193 AlphaNine® SD PDS 500 iu GFS 68516-3607-02 vl J7193 AlphaNine® SD PDS 1000 iu GFS 68516-3608-02 vl J7193 AlphaNine® SD PDS 1500 iu GFS 68516-3609-02 vl J7193 Mononine® PDS 1000 iu CSL 00053-7668-04 vl Factor XIII (Derived from Human Plasma) J7199 Corifact® PDS 1000 - 1600 iu CSL 63833-0518-02 vl Factor Xa (Recombinant) NEW Andexxa® 4 x 10 mg PORT 69853-0101-01 vl Fibrinogen Concentrate J1680 RiaSTAP™ 1000 mg CSL 63833-0891-51 vl Anti-Inhibitor Coagulation Complexes (Derived from Human Plasma) J7198 Feiba® NF PDS 500 iu BXLT 64193-0426-02 vl J7198 Feiba® NF PDS 1000 iu BXLT 64193-0424-02 vl J7198 Feiba® NF PDS 2500 iu BXLT 64193-0425-02 vl Antithrombin III (Derived from Human Plasma) J7197 Thrombate III® PDS 500 iu GFS 13533-0602-50 vl Desmopressin Acetate (Useful in Disorders of Hemostasis) J2597 Stimate® (Nasal Spray) 1.5 mg SPY 2.5 mL CSL 00053-6871-00 ea Recombinate von Willebrand Factor J7179 Vonvendi 500 iu vl 5 mL BXLT 00944-7551-02 ea J7179 Vonvendi 1500 iu vl 10 mL BXLT 00944-7553-02 ea Immunologic CODE PRODUCT SIZE MFR. NDC # PK/CS Immune Globulin Intravenous (Human) Lyophilized J1566 Carimune® NF 6 gm CSL 44206-0417-06 vl J1566 Carimune® NF 12 gm CSL 44206-0418-12 vl J1566 Gammagard® 5% S/D Low IgA 5 gm BXLT 00944-2656-03 vl J1566 Gammagard® 5% S/D Low IgA 10 gm BXLT 00944-2658-04 vl Immune Globulin Intravenous (Human) Liquid J1572 Flebogamma® DIF 5% 2.5 gm GFS 61953-0004-02 vl J1572 Flebogamma® DIF 5% 5 gm GFS 61953-0004-03 vl J1572 Flebogamma® DIF 5% 10 gm GFS 61953-0004-04 vl J1572 Flebogamma® DIF 5% 20 gm GFS 61953-0004-05 vl J1572 Flebogamma® DIF 10% 5 gm GFS 61953-0005-01 vl J1572 Flebogamma® DIF 10% 10 gm GFS 61953-0005-02 vl J1572 Flebogamma® DIF 10% 20 gm GFS 61953-0005-03 vl J1569 Gammagard® 10% Liquid 1 gm BXLT 00944-2700-02 vl J1569 Gammagard® 10% Liquid 2.5 gm BXLT 00944-2700-03 vl J1569 Gammagard® 10% Liquid 5 gm BXLT 00944-2700-04 vl J1569 Gammagard® 10% Liquid 10 gm BXLT 00944-2700-05 vl

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CODE PRODUCT SIZE MFR. NDC # PK/CS J1569 Gammagard® Liquid 20 gm BXLT 00944-2700-06 vl J1569 Gammagard® Liquid 30 gm BXLT 00944-2700-07 vl J1561 Gammaked™ 10% 1 gm KED 76125-0900-01 vl J1561 Gammaked™ 10% 5 gm KED 76125-0900-50 vl J1561 Gammaked™ 10% 10 gm KED 76125-0900-10 vl J1561 Gammaked™ 10% 20 gm KED 76125-0900-20 vl J1557 Gammaplex® 5% 5 gm BPL 64208-8234-06 vl J1557 Gammaplex® 5% 10 gm BPL 64208-8234-07 vl J1557 Gammaplex® 5% 20 gm BPL 64208-8234-08 vl J1557 Gammaplex® 10% 5 gm BPL 64208-8235-05 vl J1557 Gammaplex® 10% 10 gm BPL 64208-8235-06 vl J1557 Gammaplex® 10% 20 gm BPL 64208-8235-07 vl J1561 Gamunex® -C 1 gm GFS 13533-0800-12 vl J1561 Gamunex® -C 2.5 gm GFS 13533-0800-15 vl J1561 Gamunex® -C 5 gm GFS 13533-0800-20 vl J1561 Gamunex® -C 10 gm GFS 13533-0800-71 vl J1561 Gamunex® -C 20 gm GFS 13533-0800-24 vl J1561 Gamunex® -C 40 gm GFS 13533-0800-40 vl J1568 Octagam® 5% 1 gm OCT 67467-0843-01 vl J1568 Octagam® 5% 2.5 gm OCT 67467-0843-02 vl J1568 Octagam® 5% 100 mL 5 gm OCT 68982-0840-03 vl J1568 Octagam® 5% 200 mL 10 gm OCT 68982-0840-04 vl J1568 Octagam® 10% 2 gm OCT 68982-0850-01 vl J1568 Octagam® 10% 5 gm OCT 68982-0850-02 vl J1568 Octagam® 10% 10 gm OCT 68982-0850-03 vl J1568 Octagam® 10% 20 gm OCT 68982-0850-04 vl J1459 Privigen® 10% 5 gm CSL 44206-0436-05 vl J1459 Privigen® 10% 10 gm CSL 44206-0437-10 vl J1459 Privigen® 10% 20 gm CSL 44206-0438-20 vl J1459 Privigen® 10% 40 gm CSL 44206-0439-40 vl Immune Globulin Subcutaneous (Human) Liquid J1559 Hizentra™ 1 gm CSL 44206-451-01 vl J1559 Hizentra™ 2 gm CSL 44206-452-02 vl J1559 Hizentra™ 4 gm CSL 44206-454-04 vl J1559 Hizentra™ 10 gm CSL 44206-454-10 vl J1575 HyQvia® 10% Liquid 2.5 gm BXLT 00944-2510-02 vl J1575 HyQvia® 10% Liquid 5 gm BXLT 00944-2511-02 vl J1575 HyQvia® 10% Liquid 10 gm BXLT 00944-2512-02 vl J1575 HyQvia® 10% Liquid 20 gm BXLT 00944-2513-02 vl J1575 HyQvia® 10% Liquid 30 gm BXLT 00944-2514-02 vl

ASD Healthcare | 71 PD Plasma Derivatives

Hyper-Immune Globulin CODE PRODUCT SIZE MFR. NDC # PK/CS Intramuscular Immune Globulins (Human) J1470 GamaSTAN® S/D 2 mL GFS 13533-0635-04 vl J1550 GamaSTAN® S/D 10 mL GFS 13533-0635-12 vl J9999 Varizig® Liquid 125 iu APVO 70504-0126-02 ea Rho(D) Immune Globulin J2788 HyperRHO® S/D Mini-Dose 250 iu GFS 13533-0661-06 10/pk J2790 HyperRHO® S/D 1500 iu GFS 13533-0631-02 syr J2790 HyperRHO® S/D 1500 iu GFS 13533-0631-10 10/pk J2788 MICRhoGAM® UF Plus 1 x 50 mcg KED 00562-7806-01 syr J2788 MICRhoGAM® UF Plus 5 x 50 mcg KED 00562-7806-05 syr J2788 MICRhoGAM® UF Plus 25 x 50 mcg KED 00562-7806-25 syr J2790 RhoGAM® UF Plus 1 x 300 ug KED 00562-7805-01 syr J2790 RhoGAM® UF Plus 5 x 300 ug KED 00562-7805-05 syr J2790 RhoGAM® UF Plus 25 x 300 ug KED 00562-7805-25 syr J2791 Rhophylac® 300 mcg CSL 44206-0300-01 syr J2791 Rhophylac® 300 mcg CSL 44206-0300-10 10/pk J2792 WinRho® SDF Liquid 1500 iu 300 mcg APVO 70504-3300-02 ea J2792 WinRho® SDF Liquid 2500 iu 500 mcg APVO 70504-3500-02 ea J2792 WinRho® SDF Liquid 5000 iu 1000 mcg APVO 70504-3100-02 ea J2792 WinRho® SDF Liquid 15000 iu 3000 mcg APVO 70504-3300-02 vl Hepatitis B Immune Globulin J1573 HepaGam B® 1 mL APVO 70504-0052-02 vl J1573 HepaGam B® 5 mL APVO 53270-0051-01 vl J1573 HepaGam B® NovoPlus 5 mL APVO 53270-0054-01 vl CPT-90371 HyperHEP B® S/D 0.5 mL GFS 13533-0636-03 syr CPT-90371 HyperHEP B® S/D 1 mL GFS 13533-0636-02 syr CPT-90371 HyperHEP B® S/D 5 mL GFS 13533-0636-05 vl CPT-90371 Nabi-HB® 1 mL BIOT 59730-4202-01 vl CPT-90371 Nabi-HB® 5 mL BIOT 59730-4203-01 vl Rabies Immune Globulin NEW HyperRAB® 300 iu/mL 1 mL GFS 13533-0318-01 vl NEW HyperRAB® 300 iu/mL 5 mL GFS 13533-0318-05 vl NEW KedRAB™ 2 mL KED 76125-0150-02 vl NEW KedRAB™ 10 mL KED 76125-0150-10 vl Tetanus Immune Globulin J1670 HyperTET® S/D 1 mL GFS 13533-0634-02 syr Cytomegalovirus Immune Globulin Intravenous (Human) J0850 CytoGam® 2.5 gm/50 mL CSL 44206-0532-11 vl

72 | InsideOut O Oncology

CODE PRODUCT SIZE MFR. NDC # PK/CS J9042 Adcetris® 50 mg SGEN 51144-0050-01 vl J8999 Afinitor® 2.5 mg/28 tabs NOV 00078-0594-51 pk J8999 Afinitor® 5 mg/28 tabs NOV 00078-0566-51 pk J8999 Afinitor® 7.5 mg/28 tabs NOV 00078-0620-51 pk J8999 Afinitor® 10 mg/28 tabs NOV 00078-0567-51 pk J8999 Afinitor Disperz® 2 mg/28 tabs NOV 00078-0626-51 pk J8999 Afinitor Disperz® 3 mg/28 tabs NOV 00078-0627-51 pk J8999 Afinitor Disperz® 5 mg/28 tabs NOV 00078-0628-51 pk Alecensa® 150 mg/240 caps GNT 50242-0130-01 ea J9305 Alimta® 100 mg inj ELI 00002-7640-01 vl J9305 Alimta® 500 mg inj ELI 00002-7623-01 vl Aliqopa™ 60 mg SDV BYR 50419-0385-01 vl J2469 Aloxi® .25 mg/5 mL SDV EISAI 62856-0797-01 ea Alunbrig™ 90 mg/7 tabs MILL 63020-0090-07 pk Alunbrig™ 90 mg/30 tabs MILL 63020-0090-30 pk Alunbrig™ 180 mg/30 tabs MILL 63020-0180-30 pk Alunbrig™ 30 mg/30 tabs MILL 63020-0113-30 pk Alunbrig™ 90/180 mg tabs copack MILL 63020-0198-30 pk J9035 Avastin® 100 mg GNT 50242-0060-01 vl J9035 Avastin® 400 mg GNT 50242-0061-01 vl J9025 Azacitidine 100 mg generic* vl Bavencio® 200 mg/10 mL EMD 44087-3535-01 vl J9032 Beleodaq® 500 mg/30 mL LYO SDV SPEC 68152-0108-09 vl Besponsa® 0.9 mg SDV PF 20 mL PFZ 00008-0100-01 vl J9039 Blincyto® 35 mcg SDV AMG 55513-0160-01 vl Bosulif® 100 mg/120 tabs PFZ 00069-0135-01 pk Bosulif® 400 mg/tab 30 PFZ 00069-0193-01 pk Bosulif® 500 mg/30 tabs PFZ 00069-0136-01 pk NEW Braftovi™ 50 mg 2 x 60 cap ARRAY 70255-0020-01 btl NEW Braftovi™ 75 mg 2 x 90 cap ARRAY 70255-0025-01 btl J8999 Cabometyx™ 20 mg/30 tabs EXEL 42388-0024-26 ea J8999 Cabometyx™ 40 mg/30 tabs EXEL 42388-0025-26 ea J8999 Cabometyx™ 60 mg/30 tabs EXEL 42388-0023-26 ea Calquence® 100 mg cap 60 ASTRA 00310-0512-60 ea J9120 Cosmegen® Injectable 0.5 mg REC 55292-0811-55 vl J8999 Cotellic™ 20 mg/63 tabs GNT 50242-0717-01 ea J9999 Cyramza® 100 mg/10 mL SDV ELI 00002-7669-01 ea J9999 Cyramza® 500 mg/50 mL SDV ELI 00002-7678-01 ea

* This generic product may be available from multiple manufacturers, depending on inventory availibility.

ASD Healthcare | 73 O Oncology

CODE PRODUCT SIZE MFR. NDC # PK/CS J0894 Dacogen® 50 mg SDV OTS 59148-0046-70 ea Darzalex™ 100 mg/5 mL SDV SOL JOM 57894-0502-05 ea Darzalex™ 400 mg/20 mL SDV SOL JOM 57894-0502-20 ea Empliciti™ 300 mg SDV LYO BMS 00003-2291-11 ea Empliciti™ 400 mg SDV LYO BMS 00003-4522-11 ea J9055 Erbitux® 100 mg/50 mL ELI 66733-0948-23 vl J9055 Erbitux® 200 mg/100 mL ELI 66733-0958-23 vl Erivedge® 150 mg/28 caps GNT 50242-0140-01 ea Erleada™ 60 mg tab 120 JOM 59676-0600-12 btl Farydak® 10 mg cap 6 UD NOV 00078-0650-06 pk Farydak® 15 mg cap 6 UD NOV 00078-0651-06 pk Farydak® 20 mg cap 6 UD NOV 00078-0652-06 pk J9395 Faslodex® 500 mg PF syr 2 x 5.0 mL AZP 00310-0720-10 pk J9999 Folotyn™ 20 mg ALLOS 48818-0001-01 vl J9999 Folotyn™ 40 mg ALLOS 48818-0001-02 vl J0641 Fusilev® (Levoleucovorin) Injectable 50 mg SPEC 68152-0101-00 vl J9999 Gazyva® 1000 mg/40 mL GNT 50242-0070-01 ea J8999 Gilotrif® 20 mg/30 tabs BIP 00597-0141-30 pk J8999 Gilotrif® 30 mg/30 tabs BIP 00597-0137-30 pk J8999 Gilotrif® 40 mg/30 tabs BIP 00597-0138-30 pk J9999 Halaven® 1 mg/2 mL SDV EISAI 62856-0389-01 vl J9355 Herceptin® 150 mg SDV GNT 50242-0132-01 ea J8999 Ibrance® 75 mg/21 caps PFZ 00069-0187-21 ea J8999 Ibrance® 100 mg/21 caps PFZ 00069-0188-21 ea J8999 Ibrance® 125 mg/21 caps PFZ 00069-0189-21 ea IDHIFA® 50 mg/30 tabs CEL 59572-0705-30 ea IDHIFA® 100 mg/30 tabs CEL 59572-0710-30 ea J8999 Imbruvica® 70 mg/28 caps PHA 57962-0070-28 btl J8999 Imbruvica® 140 mg/90 caps PHA 57962-0140-09 btl J8999 Imbruvica® 140 mg/120 caps PHA 57962-0140-12 btl NEW J8999 Imbruvica® 140 mg tab 28 UD PHA 57962-0014-28 pk NEW J8999 Imbruvica® 280 mg tab 28 UD PHA 57962-0280-28 pk NEW J8999 Imbruvica® 420 mg tab 28 UD PHA 57962-0420-28 pk NEW J8999 Imbruvica® 560 mg tab 28 UD PHA 57962-0560-28 pk J9999 Imfinzi™ 120 mg SDV AZP 00310-4500-12 vl J9999 Imfinzi™ 500 mg SDV AZP 00310-4611-50 vl J9325 Imlygic® 106 1 m PFU/mL 1 mL vl AMG 55513-0078-01 vl J9325 Imlygic® 108 100 m PFU/mL 1 mL vl AMG 55513-0079-01 vl J8999 Inlyta® 1 mg tab 180 PFZ 00069-0145-01 pk J8999 Inlyta® 5 mg tab 60 PFZ 00069-0151-11 pk J8565 Iressa® 250 mg/30 tabs AZP 00310-0482-30 btl J9315 Istodax® 10 mg Injection SOL Kit CEL 59572-0984-01 vl

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CODE PRODUCT SIZE MFR. NDC # PK/CS J9207 Ixempra® 15 mg RPHRM 70020-1910-01 ea J9207 Ixempra® 45 mg RPHRM 70020-1911-01 ea J8999 Jakafi® 5 mg/60 tabs INCY 50881-0005-60 ea J8999 Jakafi® 10 mg/60 tabs INCY 50881-0010-60 ea J8999 Jakafi® 15 mg/60 tabs INCY 50881-0015-60 ea J8999 Jakafi® 20 mg/60 tabs INCY 50881-0020-60 ea J8999 Jakafi® 25 mg/60 tabs INCY 50881-0025-60 ea J9354 Kadcyla® 100 mg/15 mL SDV GNT 50242-0088-01 vl J9354 Kadcyla® 160 mg/20 mL SDV GNT 50242-0087-01 vl J9271 Keytruda® 100 mg/4mL SDV SOL MERCK 00006-3026-02 ea C9485 Lartruvo™ 190 mg/19 mL SDV SOL ELI 00002-7190-01 ea C9485 Lartruvo™ 500 mg/50 mL SDV SOL ELI 00002-8926-01 ea J8999 Lenvima® 10 mg cap 30 UD EISAI 62856-0710-30 pk J8999 Lenvima® 10 mg/4 mg 18 mg DD 30 UD EISAI 62856-0718-30 pk J8999 Lenvima® 20 mg cap 30 UD EISAI 62856-0720-30 pk J8999 Lenvima® 10 mg/4 mg 24 mg DD 30 UD EISAI 62856-0724-30 pk J8999 Lenvima® 8 mg cap 30 UD EISAI 62856-0708-30 pk J8999 Lenvima® 10 mg/4 mg 14 mg DD 30 UD EISAI 62856-0714-30 pk J8999 Lonsurf® 15 mg/20 tabs TAIHO 64842-1025-01 btl J8999 Lonsurf® 20 mg/20 tabs TAIHO 64842-1020-01 btl J8999 Lonsurf® 15 mg/40 tabs TAIHO 64842-1025-02 btl J8999 Lonsurf® 20 mg/40 tabs TAIHO 64842-1020-02 btl J8999 Lonsurf® 15 mg/60 tabs TAIHO 64842-1025-03 btl J8999 Lonsurf® 20 mg/60 tabs TAIHO 64842-1020-03 btl Lynparza™ 50 mg caps 4 x 112 carton AZP 00310-0657-58 pk Lynparza™ 100 mg tab 60 AZP 00310-0668-60 pk Lynparza™ 100 mg tab 120 AZP 00310-0668-12 pk Lynparza™ 150 mg tab 60 AZP 00310-0679-60 pk Lynparza™ 150 mg tab 120 AZP 00310-0679-12 pk J8999 Mekinist™ 0.5 mg/30 tabs NOV 00078-0666-15 ea J8999 Mekinist™ 2 mg/30 tabs NOV 00078-0668-15 ea NEW Mektovi® 15 mg tab 180 ARRAY 70255-0010-02 ea J9300 Mylotarg™ 4.5 mg SDV PFZ 00008-4510-01 vl Nerlynx® 40 mg tab 180 PUMA 70437-0240-18 btl J2505 Neulasta® Onpro™ syringe 6 mg/0.6 mL AMG 55513-0190-01 ea Neulasta® Onpro™ Kit 6 mg/0.6 mL AMG 55513-0192-01 syr J8999 Nexavar® 200 mg/120 tabs BYR 50419-0488-58 btl J8999 Ninlaro® 2.3 mg caps 3/pk MILL 63020-0078-02 pk J8999 Ninlaro® 3 mg caps 3/pk MILL 63020-0079-02 pk J8999 Ninlaro® 4 mg caps 3/pk MILL 63020-0080-02 pk J2796 Nplate® 250 mcg SDV 0.5 mL AMG 55513-0221-01 vl J2796 Nplate® 500 mcg SDV 1.0 mL AMG 55513-0222-01 vl

ASD Healthcare | 75 O Oncology

CODE PRODUCT SIZE MFR. NDC # PK/CS J8999 Odomzo® 200 mg/30 caps SUN 47335-0303-83 btl J9266 Oncaspar® 750 iu/mL SDV 5 mL BXLT 00944-3810-01 vl J9205 Onivyde® 43 mg/10 mL SDV SOL IPSN 15054-0043-01 ea J9299 Opdivo® 40 mg/4 mL BMS 00003-3772-11 vl J9299 Opdivo® 100 mg/10 mL BMS 00003-3774-12 vl J9299 Opdivo® 240 mg/24 mL BMS 00003-3734-13 vl J9306 Perjeta® 420 mg/14 mL SDV GNT 50242-0145-01 ea J9295 Portrazza® 800 mg / 50 mL SDV SOL ELI 00002-7716-01 ea Q2043 Provenge® 250 mL VAL 30237-8900-06 ea J9310 Rituxan® 100 mg/10 mL GNT 50242-0051-21 vl J9310 Rituxan® 500 mg/50 mL GNT 50242-0053-06 vl Rituxan® Hycela 1400 mg SDV GNT 50242-0108-01 ea Rituxan® Hycela 1600 mg SDV GNT 50242-0109-01 ea J8999 Rubraca™ 200 mg/60 tabs CLVS 69660-0201-91 btl J8999 Rubraca™ 250 mg/60 tabs CLVS 69660-0202-91 btl J8999 Rubraca™ 300 mg/60 tabs CLVS 69660-0203-91 btl J1300 Soliris® 300 mg/30 mL ALX 25682-0001-01 vl J8999 Stivarga® 40 mg tabs BYR 50419-0171-03 btl J3490 SUSTOL® 10 mg/0.4 mL PFS kit 6/pk HRTX 47426-0101-06 pk J8999 Sutent® 12.5 mg/28 caps PFZ 00069-0550-38 btl J8999 Sutent® 25 mg/28 caps PFZ 00069-0770-38 btl J8999 Sutent® 37.5 mg/28 caps PFZ 00069-0830-38 btl J8999 Sutent® 50 mg/28 caps PFZ 00069-0980-38 btl J8999 Tafinlar® 50 mg/120 caps NOV 00078-0682-66 ea J8999 Tafinlar® 75 mg/120 caps NOV 00078-0681-66 ea J8999 Tagrisso™ 40 mg/30 tabs AZP 00310-1349-30 ea J8999 Tagrisso™ 80 mg/30 tabs AZP 00310-1350-30 ea J8999 Tarceva® 25 mg/30 tabs GNT 50242-0062-01 btl J8999 Tarceva® 100 mg/30 tabs GNT 50242-0063-01 btl J8999 Tarceva® 150 mg/30 tabs GNT 50242-0064-01 btl J3590 Targretin® 1% gel 60 gm VAL 00187-5525-60 ea J8999 Targretin® 75 mg SGC 100 VAL 00187-5526-75 ea NEW J8999 Tasigna® 50 mg/120 caps NOV 00078-0951-66 ea J8999 Tasigna® 150 mg/28 caps NOV 00078-0592-87 bx J8999 Tasigna® 200 mg/28 caps NOV 00078-0526-87 bx J9999 Tecentriq™ 1200 mg/20 mL SDV GNT 50242-0917-01 vl J1190 Totect® 500 mg SDV CBL 66220-0110-01 vl J9033 Treanda® 25 mg/8 mL TEVA 63459-0390-08 vl J9033 Treanda® 100 mg/20 mL TEVA 63459-0391-20 vl J8999 Tykerb® 250 mg/150 tabs NOV 00078-0671-19 ea J9999 Unituxin® 17.5 mg/5 mL SDV UNT 66302-0014-01 vl

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CODE PRODUCT SIZE MFR. NDC # PK/CS J8499 Venclexta™ 1 x 50 mg tab UD ABBV 00074-0566-11 ea J8499 Venclexta™ 1 x 100 mg tab UD ABBV 00074-0576-11 ea J8499 Venclexta™ 2 X 10 mg tab UD ABBV 00074-0561-11 ea J8499 Venclexta™ 7 X 50 mg tab wallet ABBV 00074-0566-07 ea J8499 Venclexta™ 14 X 10 mg tab wallet ABBV 00074-0561-14 ea J8499 Venclexta™ 100 mg/120 tabs ABBV 00074-0576-22 ea J8499 Venclexta™ Starter Pack ABBV 00074-0579-28 pk J9025 Vidaza® 100 mg CEL 59572-0102-01 vl J8999 Votrient® 200 mg/120 tabs NOV 00078-0670-66 ea J8999 Xalkori® 200 mg cap 60 PFZ 00069-8141-20 btl J8999 Xalkori® 250 mg cap 60 PFZ 00069-8140-20 btl J8999 Xtandi® 40 mg cap 120 AST 00469-0125-99 ea J9228 Yervoy® 50 mg/10 mL BMS 00003-2327-11 vl J9228 Yervoy® 200 mg/40 mL BMS 00003-2328-22 vl J9352 Yondelis® 1 mg PWD SDV JOM 59676-0610-01 ea NEW Yonsa® 125 mg tabs 120 SUN 47335-0401-81 ea J9400 Zaltrap® 100 mg/4 mL SDV SOL SANAV 00024-5840-01 vl J9400 Zaltrap® 200 mg/8 mL SDV SOL SANAV 00024-5841-01 vl J8999 Zelboraf® 240 mg/112 tabs GNT 50242-0090-02 ea J8999 Zydelig® 100 mg/60 tabs GIL 61958-1701-01 ea J8999 Zydelig® 150 mg/60 tabs GIL 61958-1702-01 ea Zykadia® 150 mg cap 70 NOV 00078-0640-70 ea J8999 Zytiga® 250 mg/120 tabs JOM 57894-0150-12 btl J8999 Zejula™ 100 mg cap 90 TSAR 69656-0103-90 btl

ASD Healthcare | 77 Your Patients. Your Purpose. Our Priority.

One-Stop Shop Make ASD Healthcare your one-source distributor for oncology and specialty pharmaceuticals.

Active Customers Oncology Market Share New Specialty Drugs

95% of U.S. hospitals 35% of health systems Contracted 98% of specialty drugs 88% of National 25% of specialty pharmacies launched within the Comprehensive Cancer past 12 months Network (NCCN) Centers

Convenient Connection ASD Healthcare makes it easy to order and reorder your inventory any time, any day, anywhere. Connect at asdhealthcare.com Customer Service 800.746.6273

ASD Oncology-Specialty Ad 100417.indd 1 10/4/17 12:58 PM P Pharmaceuticals

Vaccines CODE PRODUCT SIZE MFR. NDC # PK/CS Flu - Trivalent Vaccines CPT 90653 Fluad™ PFS 10 x 0.5 mL SEQ 70461-0018-03 syr CPT 90662 Fluzone® High-Dose PFS 10 x 0.5 mL SAN 49281-0403-65 syr Flu - Quadrivalent Vaccines Q2035 Afluria® Quadrivalent MDV 5 mL SEQ 33332-0418-10 vl CPT 90656 Afluria® Quadrivalent PFS 10 x 0.5 mL SEQ 33332-0318-01 syr CPT 90686 Fluarix® Quadrivalent PFS 10 x 0.5 mL GSK 58160-0898-52 syr CPT 90628 Flublok® Quadrivalent PFS 10 x 0.5 mL SAN 49281-0718-10 syr CPT 90674 Flucelvax® Quadrivalent MDV 5 mL SEQ 70461-0418-10 vl CPT 90661 Flucelvax® Quadrivalent PFS 10 x 0.5 mL SEQ 70461-0318-03 syr CPT 90688 FluLaval® Quadrivalent MDV 5 mL GSK 19515-0900-11 vl CPT 90686 FluLaval® Quadrivalent PFS 10 x 0.5 mL GSK 19515-0909-52 syr CPT 90688 Fluzone® Quadrivalent MDV 5 mL SAN 49281-0629-15 vl CPT 90686 Fluzone® Quadrivalent SDV 10 x 0.5 mL SAN 49821-0418-10 pk CPT 90686 Fluzone® Quadrivalent PFS 10 x 0.5 mL SAN 49281-0418-50 syr CPT 90685 Fluzone® Quadrivalent Pediatric 10 x 0.25 mL SAN 49281-0518-25 syr Haemophilus B Conjugate CPT 90647 Acthib® 5 SDV per pack SAN 49281-0545-03 pk Hepatitis A Havrix Pediatric Tip-Lok 10/pk GSK 58160-0825-52 pk CPT 90632 Havrix Adult 10 x 1 mL PF SDV GSK 58160-0826-11 pk Havrix Adult Tip-Lok 10/pk GSK 58160-0826-52 pk Japanese Encephalitis Ixiaro® 0.5 mL PFS VAL 42515-0002-01 ea Meningococcal Meningitis CPT 90734 Menactra 5 doses/pk SAN 49281-0589-05 pk MMR CPT 90707 MMR II SDV 10/box MERCK 00006-4681-00 bx Pneumococcal Conjugate for Bacterium Streptococcus Pneumoniae CPT 90670 Prevnar 13® 10 x 0.5 mL PFS PFZ 00005-1971-02 pk CPT 90670 Prevnar 13® 0.5 mL PFS PFZ 00005-1971-05 ea TDAP CPT 90715 Adacel® TDAP 10 x 0.5 mL vl SAN 49281-0400-10 pk CPT 90715 Adacel® TDAP PFS 5/ctn SAN 49281-0400-15 pk CPT 90715 Boostrix TDAP 10 x 0.5 mL SDV GSK 58160-0842-11 pk Tetanus and Diptheria CPT 90714 Tenivac® TD PFS 10/ctn 0.5 mL SAN 49281-0215-15 pk

ASD Healthcare | 79 P Pharmaceuticals

CODE PRODUCT SIZE MFR. NDC # PK/CS Tuberculosis CPT 86580 Aplisol® 5 TU 1 mL PAR 42023-0104-01 vl CPT 86580 Aplisol® 5 TU 5 mL PAR 42023-0104-05 vl CPT 86580 Tubersol® 5 TU 1 mL SAN 49281-0752-21 pk CPT 86580 Tubersol® 5 TU 5 mL SAN 49281-0752-22 pk Hepatitis A and Hepatitis B Twinrix® Tiploks 10/pk GSK 58160-0815-52 pk Specialty CODE PRODUCT SIZE MFR. NDC # PK/CS J3262 Actemra® Intravenous 80 mg/4 mL SDV GNT 50242-0135-01 vl J3262 Actemra® Intravenous 200 mg/10 mL SDV GNT 50242-0136-01 vl J3262 Actemra® Intravenous 400 mg/20 mL SDV GNT 50242-0137-01 vl J3490 Actemra® Subcutaneous 162 mg PFS 0.9 mL GNT 50242-0138-01 vl J2997 Activase® 50 mg GNT 50242-0044-13 vl J2997 Activase® 100 mg GNT 50242-0085-27 vl J2997 Activase® Cathflo 2 mg GNT 50242-0041-64 vl J3490 Ammonul® 50 mL VAL 00187-0010-50 vl J8499 Ampyra® 10 mg/60 tabs ACO 10144-0427-60 btl J0490 Benlysta® 120 mg SDV GSK 49401-0101-01 ea J0490 Benlysta® 400 mg SDV GSK 49401-0102-01 ea J0490 Benlysta® 200 mg auto-injector GSK 49401-0088-35 pk J0490 Benlysta® 200 mg PFS GSK 49401-0088-47 pk J0597 Berinert® 500 unit vl CSL 63833-0825-02 kit J7682 Bethkis® 300 mg/4 mL CHIE 10122-0820-56 bx J8499 Buphenyl® 500 mg tabs HRZN 75987-0060-08 btl J3490 Buphenyl® 250 g powder HRZN 75987-0070-09 btl J9120 Calcium Disodium Versenate 1000 mg/5 mL VAL 99207-0240-05 pk J2786 Cinqair® 100 mg/10 mL SDV TEVA 59310-0610-31 ea J0840 CroFab® 2 x 2 mL BTG 50633-0110-12 vl J0878 Cubicin® 500 mg MERCK 67919-0011-01 10/pk J0878 Cubicin® RF 500 mg MERCK 67919-0012-01 10/pk J0878 Daptomycin 500 mg/10 mL TEVA 00703-0125-01 vl Daraprim® 25 mg/30 tabs TUR 69413-0330-30 ea Daraprim® 25 mg/100 tabs TUR 69413-0330-10 ea J0894 Decitabine 50 mg PWD SDV DRE 55111-0556-10 vl J1162 DigiFab® 40 mg BTG 50633-0120-11 vl Endari™ 5 g powder 60/box EMM 42457-0420-60 box J3590 Entyvio® 300 mg/20 mL SDV TAK 64764-0300-20 ea

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CODE PRODUCT SIZE MFR. NDC # PK/CS J7503 Envarsus® XR 0.75 mg tab 30/btl VLX 68992-3075-03 btl J7503 Envarsus® XR 0.75 mg tab 100/btl VLX 68992-3075-01 btl J7503 Envarsus® XR 1 mg/30 tabs VLX 68992-3010-03 btl J7503 Envarsus® XR 1 mg/100 tabs VLX 68992-3010-01 btl J7503 Envarsus® XR 4 mg/30 tabs VLX 68992-3040-03 btl J7503 Envarsus® XR 4 mg/100 tabs VLX 68992-3040-01 btl Esbriet® 267 mg/270 caps GNT 50242-0121-01 ea Esbriet® 267 mg/270 tabs GNT 50242-0122-06 ea Esbriet® 801 mg/90 tabs GNT 50242-0123-01 ea J8499 Exjade® 125 mg/30 tabs NOV 00078-0468-15 btl J8499 Exjade® 250 mg/30 tabs NOV 00078-0469-15 btl J8499 Exjade® 500 mg/30 tabs NOV 00078-0470-15 btl C9484 Exondys 51™ 100 mg/2 mL SDV SRPT 60923-0363-02 vl C9484 Exondys 51™ 500 mg/10 mL SDV SRPT 60923-0284-10 vl Fasenra™ 30 mg PFS ASTRA 00310-1730-30 syr J3490 Gattex® 5 mg SDV NPS 68875-0103-01 vl J3490 Gattex® 30 mg vl kit NPS 68875-0102-01 vl kit Giapreza™ 2.5 mg/mL 1 mL vial LAJO 68547-0501-02 vl Hemlibra® 30 mg/mL SDV GNT 50242-0920-01 vl Hemlibra® 60 mg/0.4 mL SDV GNT 50242-0921-01 vl Hemlibra® 105 mg/0.7 mL SDV GNT 50242-0922-01 vl Hemlibra® 150 mg/mL SDV GNT 50242-0923-01 vl Ingrezza™ 40 mg cap 30/btl NEBSC 70370-1040-01 btl Ingrezza™ 80 mg cap 30/btl NEBSC 70370-1080-01 btl J1290 Kalbitor® 10 mg DYAX 47783-0101-01 vl J2840 Kanuma™ 20 mg/10 mL ALX 25682-0007-01 ea J3590 Kcentra® 500 iu SDV CSL 63833-0386-02 ea C9132 Kcentra® 1000 iu SDV CSL 63833-0387-02 ea J8499 Korlym® 300 mg/28 tabs COR 76346-0073-01 btl J9047 Kyprolis® 30 mg powder Lyo SDV AMG 76075-0102-01 ea J9047 Kyprolis® 60 mg powder SDV AMG 76075-0101-01 vl NEW Miglustat 100 mg cap 90 (15 x 6) AMER 43975-0310-83 pk CPT 96372 Natpara® 75 mcg dual cartridge NPS 68875-0204-02 ea CPT 96372 Natpara® 100 mcg dual cartridge NPS 68875-0205-02 ea J3490 Neoprofen® 10 mg/mL SDV 3 x 2 mL REC 55292-0122-52 vl J2182 Nucala® 100 mg GSK 00173-0881-01 ea Nuplazid™ 17 mg/60 tabs ACAD 63090-0170-60 btl J2941 Nutropin AQ® 5 mg/2 mL Nuspin inj GNT 50242-0075-01 ea J2941 Nutropin AQ® 10 mg/2 mL Nuspin inj GNT 50242-0074-01 ea J2941 Nutropin AQ® 20 mg/2 mL Nuspin inj GNT 50242-0076-01 ea J0587 Myobloc® 2500 units/0.5 mL SOL 10454-0710-10 vl J0587 Myobloc® 5000 units/1.0 mL SOL 10454-0711-10 vl J0587 Myobloc® 10000 units/2.0 mL SOL 10454-0712-10 vl

* This generic product may be available from multiple manufacturers, depending on inventory availibility.

ASD Healthcare | 81 P Pharmaceuticals

CODE PRODUCT SIZE MFR. NDC # PK/CS Ocrevus™ 300 mg/10 mL SDV GNT 50242-0150-01 vl Ofev® 100 mg/60 gel caps BIP 00597-0143-60 ea Ofev® 150 mg/60 gel caps BIP 00597-0145-60 ea C9447 Omidria™ 1%/0.3% SDV 4 x 4 mL OME 62225-0600-04 vl J2405 Ondansetron® 2 mg/mL SDV 2 mL PFZ 00409-4755-18 ea J1640 Panhematin® 350 mg REC 55292-0702-55 vial Panretin® 0.1% Gel 60 gm EISAI 62856-0601-22 ea J3490 Praxbind® 2.5 g/50 mL 1 x 2 mL BIP 00597-0197-05 ea J8499 Promacta® 12.5 mg/30 tabs NOV 00078-0684-15 ea J8499 Promacta® 25 mg/30 tabs NOV 00078-0685-15 ea J8499 Promacta® 50 mg/30 tabs NOV 00078-0686-15 ea J8499 Promacta® 75 mg/30 tabs NOV 00078-0687-15 ea J7336 Qutenza® single patch kit ACO 10144-0928-01 kit J7336 Qutenza® double patch kit ACO 10144-0929-01 kit J3490 Radicava™ 30 mg/100 mL x 2 bags/pk MTPA 70510-2171-02 pk J2547 Rapivab™ 200 mg/200 mL 1 x 3 vls BIOCY 61364-0181-03 vl J8499 Ravicti® 25 mL HRZN 75987-0050-06 vl SalivaMAX™ 351 mg 120/bx FORW 70275-0629-12 bx Sinuva™ sinus implant INTER 10599-0003-01 ea Sodium Phenylacetate and 50 mL SDV generic* 13811-0705-50 vl Sodium Benzoate Injection J1930 Somatuline® Depot 60 mg PFS IPSN 15054-1060-03 ea J1930 Somatuline® Depot 90 mg PFS IPSN 15054-1090-03 ea J1930 Somatuline® Depot 120 mg PFS IPSN 15054-1120-03 ea CPT 80299 Sotalol IV 150 mg/10 mL ALTA 69724-0112-10 vl J3357 Stelara® 45 mg PFS 0.5 mL JAN 57894-0060-03 ea J3357 Stelara® 90 mg PFS 1 mL JAN 57894-0061-03 ea Stelara® 45 mg SDV 0.5 mL JOM 57894-0060-02 vial J3357 Stelara® IV 130 mg SDV JAN 57894-0054-27 ea J3490 Strensiq® 18 mg/0.45 mL vls 12/pk ALX 25682-0010-12 pk J3490 Strensiq® 28 mg/0.7 mL vls 12/pk ALX 25682-0013-12 pk J3490 Strensiq® 40 mg/mL vls 12/pk ALX 25682-0016-12 pk J3490 Strensiq® 80 mg/0.8 mL vls 12/pk ALX 25682-0019-12 pk J2680 Sylvant® 100 mg Lyp Pwd SDV JOM 57894-0420-01 vl J2860 Sylvant® 400 mg Lyp Pwd SDV JOM 57894-0421-01 vl NEW Tavalisse 100 mg/60 tabs RIGEL 71332-0001-01 ea NEW Tavalisse 150 mg/60 tabs RIGEL 71332-0002-01 ea Triptodur™ 22.5 mg kit ARBR 24338-0150-20 kit J2323 Tysabri® 300 mg/15 mL BIOG 59075-0730-15 vl J3490 Varithena™ 18 mL/inj BIOCO 60635-0118-01 ea J3490 Varithena™ admin pack BIOCO 60635-0123-01 ea Q0181 Varubi™ 90 mg tab 2/pk TES 69656-0101-02 pk

* This generic product may be available from multiple manufacturers, depending on inventory availibility.

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CODE PRODUCT SIZE MFR. NDC # PK/CS Veltassa™ 8.4 gm 4/bx REL 53436-0084-04 bx Veltassa™ 8.4 gm 30/bx REL 53436-0084-30 bx Veltassa™ 16.8 gm 30/bx REL 53436-0168-30 bx Veltassa™ 25.2 gm 30/bx REL 53436-0252-30 bx C9293 Voraxaze® 1000 units/vl BTG 50633-0210-11 1 vl/cn J2357 Xolair® 150 mg GNT 50242-0040-62 vl NEW Zemdri™ 500 mg 10 mL SDV ACH 71045-0010-02 vial J0695 Zerbaxa® 10 x 1 g/0.5 g SDV MERCK 67919-0030-01 pk Zilretta™ 32 mg FLEX 70801-0003-01 vl

Biosurgery Products CODE PRODUCT SIZE MFR. NDC # PK/CS C9250 Artiss Fibrin Sealant PFS 2 mL BAX 00338-8503-02 ea C9250 Artiss Fibrin Sealant PFS 4 mL BAX 00338-8503-04 ea C9250 Artiss Fibrin Sealant PFS 10 mL BAX 00338-8503-10 ea 600038 Cannula DuploTip 20 g x 32 cm BAX 10/cs 934070 CoSeal™ 2 mL BAX vl 934071 CoSeal™ 4 mL BAX vl 934072 CoSeal™ 8 mL BAX vl 921022 Duplocath 25 BAX ea 600012 EasySpray Pressure Regulator BAX ea 600013 EasySpray Set BAX 10/cs 934057 FloSeal Matrix Hemostatic Sealant 6 x 5 mL BAX cs FloSeal NT Matrix Hemostatic 934050 6 x 5 mL BAX cs Sealant FloSeal Reusable Endoscopic 934055 BAX ea Applicator 1500181 FloSeal Endoscopic Applicator BAX 6/cs 934208 FloSeal Curved Applicator Tip 8 cm BAX ea 934210 FloSeal Curved Applicator Tip 10 cm BAX ea J3490 Tisseel Frozen 2 mL BAX 00338-8402-02 ea J3490 Tisseel Frozen 4 mL BAX 00338-8402-04 ea J3490 Tisseel Frozen 10 mL BAX 00338-8402-10 ea 921028 Tisseel VH 2 mL S/D kit BAX 00338-4301-02 ea 921029 Tisseel VH 4 mL S/D kit BAX 00338-4302-04 ea 921030 Tisseel VH 10 mL S/D kit BAX 00338-4303-10 ea

921051VP ValuPak 2 mL (1 cs TISSEEL Biologic-Only 6 x 2 mL BAX 00338-4210-02 cs and 1 cs DUPLOJECT EASY PREP)

921052VP ValuPak 4 mL (1 cs TISSEEL Biologic-Only 6 x 4 mL BAX 00338-4302-04 cs and 1 cs DUPLOJECT EASY PREP)

921053VP ValuPak 10 mL (1 cs TISSEEL Biologic-Only 6 x 10 mL BAX 00338-4212-10 cs and 1 cs DUPLOJECT EASY PREP)

ASD Healthcare | 83 CM Contrast Media

Bracco ASD # MFR # DESCRIPTION SIZE NDC # PK/CS Oral Contrast Agents - CT Barium 35357 7450 Readi-Cat Banana 450 mL 32909-0725-03 24/cs 48869 7150 Readi-Cat Berry 450 mL 32909-0711-03 24/cs 48887 7550 Readi-Cat Creamy Vanilla 450 mL 32909-0756-03 24/cs 48888 4503-07 Readi-Cat Mochaccino 450 mL 32909-0777-03 24/cs 48886 723 Readi-Cat2 Barium 2.1% 450 mL 32909-0724-03 24/cs 35369 4507-01 Volumen 0.1% 450 mL 32909-0945-03 24/cs Double Contrast Colon Examination 36703 L168 Liquid Polibar PLS 105% 1900 mL 32909-0168-02 4/cs Routine Upper GI Examination 36063 9021-01 E-Z Paste 16 oz 32909-0770-01 12/cs 36061 9019-01 E-Z Paque 6.2 oz 32909-0750-03 24/cs 36062 9028-01 E-Z Paque 12 oz 32909-0186-02 24/cs Double Contrast Examination of Esophagus, Stomach and Duodenum 35699 9017-02 E-Z HD 98% w/w susp 12 oz 32909-0764-01 24/cs Fluoroscopy 35997 9020-01 E-Z Gas II Granules 10361-0793-01 50/cs 38938 9021-02 E-Z Disc 10 Grain Tabs 10361-0778-31 100/cs Modified Barium Swallowing Studies 36719 9000-01 Varibar Barium Thin liquid 148 g 32909-0105-10 24/cs 36720 9000-02 Varibar Barium Nectar 240 mL 32909-0115-00 24/cs 36721 9000-04 Varibar Barium Thin Honey 250 mL 32909-0121-07 12/cs 36722 9000-05 Varibar Barium Honey 250 mL 32909-0122-07 12/cs 36723 9000-06 Varibar Barium Pudding 230 mL 32909-0125-22 12/cs Small Bowel/Enteroclysis Studies 36734 9014-07 Entero Vu 24% 600 mL 32909-0145-06 12/cs Ultrasound Gels and Disinfecting Towelettes 36307 6010-01 E-Z Gel Refill Bottle 8 oz 00270-6010-01 12/cs Stool Tagging Agent Tagitol Fecal Tag Agent 32909-0814-53 24/cs Fluid Collection Device Vinyl Retention Enema Ring 00270-9011-01 12/cs

84 | InsideOut N Nephrology

Nephrology Rx ASD # DESCRIPTION NDC # MANUFACTURER Antibiotics 24330 Amikacin Sulfate 250 mg 4 mL 00703-9040-03 Teva Pharmaceuticals USA 37063 Amikacin Sulfate 250 mL vl 10 x 2 mL 00703-9032-03 Teva Pharmaceuticals USA 40377 Cefazolin 1 gm SDV 25/10 mL 00143-9924-90 Pfizer Injectables 48447 Cefazolin 500 mg vl 25/pk 00143-9923-90 Westward 30605 Cefazolin Sod 1 mg IV adv 25/pk 00409-2585-01 Pfizer Injectables 37505 Ceftazidime 1 gm SDV 20 mL 25/pk 25021-0127-20 Sagent Pharmaceuticals 37506 Ceftazidime 2 gm 50 mL 25021-0128-50 Sagent Pharmaceuticals 26591 Ceftriaxone 1 gm 00409-7332-01 Pfizer Injectables 40401 Ceftriaxone 2 gm 00143-9856-25 Westward/Baxter 45652 Ciprofloxacin 400 mg SDV 40 mL ea 36000-0011-01 Claris Lifesciences Inc. 35066 Ciprofloxacin 750 mg Tab 50 16252-0516-05 Actavis/Watson Pharmaceuticals 47387 Daptomycin 500 mg vial 10 mL 00703-0125-01 Teva Pharmaceuticals USA 51574 Daptomycin 350 mg SDV 25021-0179-15 Sagent Pharmaceuticals 40751 Fortaz® 500 mg vl 10/pk 00173-0377-10 Teligent Pharma, Inc 26708 Gentamicin 40 mg/mL FTV 25 x 2 mL 00409-1207-03 Pfizer Injectables 13322 Gentamicin Top crm 15 gm 45802-0046-35 Perrigo Pharmaceuticals Co. 13321 Gentamicin Top 0.1% crm 15 gm 45802-0056-35 Perrigo Pharmaceuticals Co. 46098 Levofloxacin 500 mg 20 mL SDV 17478-0107-20 Akorn Inc. 27620 Tazicef™ 1 gm SDV 25 x 20 mL 00409-5082-16 Pfizer Injectables 32181 Tazicef™ 2 gm vl 10 x 60 mL 00409-5084-11 Pfizer Injectables 46438 Tazicef™ 1 gm ADV SDV 25 X 1 gm 00409-5092-16 Pfizer Injectables 46969 Tazicef™ 2 gm ADV SDV 10 X 2 gm 00409-5093-11 Pfizer Injectables 26111 Vancomycin 1 gm SDV FTV 10/bx 00409-6533-01 Pfizer Injectables 26216 Vancomycin 500 mg FTV 10/bx 00409-4332-01 Pfizer Injectables Calcimimetics 50043 Parsabiv™ 2.5 mg/0.5 mL SDV 10 x 0.5 mL 55513-0740-10 Amgen Inc. 50044 Parsabiv™ 5 mg/mL SDV 10 x 1 mL 55513-0741-10 Amgen Inc. 50045 Parsabiv™ 10 mg/2 mL SDV 10 x 2 mL 55513-0742-10 Amgen Inc. 24632 Sensipar® 30 mg tab 30 55513-0073-30 Amgen Inc. 24633 Sensipar® 60 mg tab 30 55513-0074-30 Amgen Inc. 24634 Sensipar® 90 mg tab 30 55513-0075-30 Amgen Inc. ESAs 28198 Aranesp® 25 mcg SDV 4 x 1 mL 55513-0002-04 Amgen Inc. 28199 Aranesp® 40 mcg SDV 4 x 1 mL 55513-0003-04 Amgen Inc. 28200 Aranesp® 60 mcg SDV 4 x 1 mL 55513-0004-04 Amgen Inc. 28201 Aranesp® 100 mcg SDV 4 x 1 mL 55513-0005-04 Amgen Inc. 28203 Aranesp® 200 mcg SDV 1 mL 55513-0006-01 Amgen Inc. 28204 Aranesp® 300 mcg SDV 1 mL 55513-0110-01 Amgen Inc. 44483 Aranesp® 10 mcg PFS 4 x 0.4 mL 55513-0098-04 Amgen Inc. 28191 Aranesp® 25 mcg PFS 4 x 0.42 mL 55513-0057-04 Amgen Inc. 28192 Aranesp® 40 mcg PFS 4 x 0.4 mL 55513-0021-04 Amgen Inc.

ASD Healthcare | 85 N Nephrology

ASD # DESCRIPTION NDC # MANUFACTURER 28193 Aranesp® 60 mcg PFS 4 x 0.3 mL 55513-0023-04 Amgen Inc. 28194 Aranesp® 100 mcg PFS 4 x 0.5 mL 55513-0025-04 Amgen Inc. 28195 Aranesp® 150 mcg PFS 4 x 0.3 mL 55513-0027-04 Amgen Inc. 28196 Aranesp® 200 mcg PFS 0.4 mL 55513-0028-01 Amgen Inc. 28197 Aranesp® 300 mcg PFS 0.6 mL 55513-0111-01 Amgen Inc. 28140 Aranesp® 500 mcg PFS 1 mL 55513-0032-01 Amgen Inc. 11230 Epogen® S3 3 M un/mL vl 10 x 1 mL 55513-0267-10 Amgen Inc. 11295 Epogen® S4 4 M un/mL vl 10 x 1 mL 55513-0148-10 Amgen Inc. 11294 Epogen® S2 2 M un/mL vl 10 x 1 mL 55513-0126-10 Amgen Inc. 11296 Epogen® S10 10 M un/mL vl 10 x 1 mL 55513-0144-10 Amgen Inc. 11177 Epogen® M10 20 M un/2mL MDV 10 x 2 mL 55513-0283-10 Amgen Inc. 11508 Epogen® M20 20 M un/mL MDV 10 x 1 mL 55513-0478-10 Amgen Inc. 30696 Procrit® 20 M un/mL MDV 4 x 1 mL 59676-0320-04 JOM Pharmaceutical 10982 Procrit® 40 M un/mL vl 4 x 1 mL 59676-0340-01 JOM Pharmaceutical 31310 Procrit® 10 M un/mL 2 mL MDV 4/pk 59676-0312-04 JOM Pharmaceutical 10510 Procrit® 10 M un/mL vl 6 x 1 mL 59676-0310-01 JOM Pharmaceutical 11190 Procrit® 10 M un/mL 1 mL 25/pk 59676-0310-02 JOM Pharmaceutical Vaccines, Hep. B 30326 Engerix-B® Adult 20 mcg SDV 10 X 1 mL 58160-0821-11 Glaxosmithkline Vaccines 30218 Engerix-B® Adult 20 mcg TIPLK 10/pk 58160-0820-11 Glaxosmithkline Vaccines 43204 Pneumovax® 23 PFS 10/pk 00006-4837-03 Merck & Co. 38983 Prevnar-13 PFS 10 x 0.5 mL 00005-1971-02 Pfizer 41022 Prevnar-13 PFS 0.5 mL 00005-1971-05 Pfizer 22353 Recombivax® DF 40 mcg/mL PF 1 mL 00006-4992-00 Merck & Co. 22719 Recombivax® 10 mcg 1 mL (pediatric) 00006-4995-00 Merck & Co. Heparin 36901 Heparin 1000 u/mL MDV 25 x 30 mL 25021-0400-30 Sagent Pharmaceuticals 33874 Heparin 5000 u/mL MDV 25 x 10 mL 00409-2723-02 Pfizer Injectables 36906 Heparin sod 5 M MDV vl 25 x 10 mL 25021-0402-10 Sagent Pharmaceuticals 37216 Heparin sod 10 M un MDV 25 x 1 mL 25021-0403-01 Sagent Pharmaceuticals 37217 Heparin sod 1 M un/mL MDV 25 x 10 mL 25021-0400-10 Sagent Pharmaceuticals 33873 Heparin sod 1 M un/mL MDV 25 x 30 mL 00409-2720-03 Pfizer Injectables 37215 Heparin sod 5 mL un MDV 25 x 1 mL 25021-0402-01 Sagent Pharmaceuticals 37218 Heparin sod 10 M un MDV 25 x 4 mL 25021-0403-04 Sagent Pharmaceuticals 40767 Heparin sod PF 1000 un/mL 25 x 2 mL 25021-0401-02 Sagent Pharmaceuticals 40765 Heparin sod 1000 un/mL 25 x 1 mL 25021-0400-01 Sagent Pharmaceuticals 11480 Heparin sod 10m un MDV 25 x 1 mL 63323-0542-01 Fresenius Kabi USA LLC 17773 Heparin 5000 u/mL MDV 25 x 10 mL 63323-0047-10 Fresenius Kabi USA LLC Iron 37769 Ferrlecit® 62.5 mg/5 mL vl 10 x 5 mL 00024-2792-10 Sanofi-Aventis US LLC 34408 Feraheme® 510 mg/17 mL SDV 59338-0775-01 Amag 34409 Feraheme® 510 mg/17 mL SDV 10/pk 59338-0775-10 Amag 22668 Infed® 50 mg/mL vl 10 x 2 mL 52544-0931-02 Allergan 41523 Injectafer® SDV 750 mg/15 mL 00517-0650-01 American Regent

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ASD # DESCRIPTION NDC # MANUFACTURER Sodium Ferric Gluconate Sucrose Injection 45094 00143-9570-10 Westward 62.5 mg x 5 mL 10/pk Triferic® 24 x 50 mL 57278-0314-02 Rockwell Medical 37214 Venofer® 50 mg SDV 10 x 2.5 mL 49230-0530-10 Fresenius Medical Services 33100 Venofer® 100 mg SDV 10 x 5 mL 49230-0534-10 Fresenius Medical Services 33101 Venofer® 100 mg SDV 25 x 5 mL 49230-0530-25 Fresenius Medical Services 39908 Venofer® 50 mg SDV 25 x 2.5 mL 49230-0530-25 Fresenius Medical Services Vitamin D 37547 Calcitriol 0.25 mcg caps 100/btl 64380-0723-06 Ranbaxy 37548 Calcitriol 0.5 mcg caps 100/btl 64380-0724-06 Ranbaxy 37813 Calcitriol Oral Solution 1 mcg 15 mL 00054-3120-41 Roxanne 38711 Calcitriol 1 mcg/mL amp 10 x 1 mL 17478-0931-01 Akorn Inc. 48858 Doxercalciferol 4 mcg MDV 50 x 2 mL 70121-1408-05 Amneal Biosciences 37299 Hectorol® 2 mcg SDV 50 x 1 mL 58468-0126-01 Sanofi Genzyme 33705 Hectorol® 4 mcg SDV 50 x 2 mL 58468-0123-01 Sanofi Genzyme 43059 Hectorol® 4 mcg MDV 50 x 2 mL 58468-0127-01 Sanofi Genzyme 46223 Paracalcitol 2 mcg MDV 25 x 1 mL 16729-0310-08 Accord Healthcare Inc 46224 Paracalcitol 5 mcg MDV 25 x 1 mL 16729-0311-08 Accord Healthcare Inc 46225 Paracalcitol 10 mcg MDV 25 x 2 mL 16729-0311-93 Accord Healthcare Inc 37232 Zemplar 1 mcg caps 30/btl 00074-4317-30 AbbVie Inc 37233 Zemplar 2 mcg caps 30/btl 00074-4314-30 AbbVie Inc 20967 Zemplar 2 mcg/mL vl 25 x 1 mL 00074-4637-01 AbbVie Inc 32194 Zemplar 4 mcg caps 30/btl 00074-4315-30 AbbVie Inc 10001 Zemplar 5 mcg/mL 25 x 1 mL FTV 00074-1658-01 AbbVie Inc 37381 Zemplar 10 mcg/2 mL MDV 25 x 2 mL 00074-1658-05 AbbVie Inc Other / Ancillary Rx 37180 Acetaminophen 325 mg tab 100 00904-1982-60 Major Pharm 28520 Acetaminophen 325 mg tab UD 100 00904-1982-61 Major Pharm 20363 Activase® Cathflo® 2 mg SDV 50242-0041-64 Genentech USA 45206 Antacid XS Fruit Chew 96/pk 00536-1049-22 Major Pharm 31843 Aplisol® 5TU 50 test vl 5 mL 42023-0104-05 Par Sterile Products LLC 31842 Aplisol® 5TU 10 test vl 1 mL 42023-0104-01 Par Sterile Products LLC 35293 Atropine AN syr .1 mg/mL 10 X 10 mL 00409-1630-10 Pfizer Injectables 32464 Atropine LFS syr 10 mL 0.1 mg/mL 00409-4911-34 Pfizer Injectables 40085 Atropine LJT syr 1 mg 10 x 10 mL 76329-3339-01 Intl Medication System Limited 21531 Atropine 1 mg/mL SDV PF 1 mL ea 00517-1010-25 American Regent 22203 Atropin Sul 1 mg/mL PF SDV 25 x 1 mL 00517-1010-25 American Regent 46119 Calcium Chloride 10% ls abj syringe 20 g x 10 00409-4928-34 Pfizer Injectables 27609 Calcium Chloride Ansyringe 10% 10 x 10mL 00409-1631-10 Pfizer Injectables 20490 Carnitor® 1 gm/5 mL SDV 5 x 5 mL 54482-0147-01 Leadiant Biosciences, Inc. 36583 Cefepime 1gm SDV 20 mL 10/pk 25021-0121-20 Sagent Pharmaceuticals 36584 Cefepime 2gm SDV 50 mL 10/pk 25021-0122-50 Sagent Pharmaceuticals 36226 Cefidinir 300 mg cap 60/btl 68180-0711-60 Lupin Pharma 49178 Cefotan 2 gm vl 10 x 20 mL 52565-0053-10 Teligent Pharma, Inc 10093 Clonidine 0.1 mg tab 100/btl 00228-2127-10 Actavis

ASD Healthcare | 87 N Nephrology

ASD # DESCRIPTION NDC # MANUFACTURER 46090 Clonidine 0.1 mg tab 500/btl 00228-2127-50 Actavis 10094 Clonidine .2 mg tab 100/btl 00228-2128-10 Actavis 50249 Cryodose Ta Mist Spray 115 mL Nuance Medical LLC 27537 Dextrose 50% ANSYR 25 gm/50 mL 00409-7517-16 Pfizer Injectables 27423 Dextrose 50% LFS SYG 50 mL 00409-4902-34 Pfizer Injectables 26223 Dextrose 50% vl 50 mL 00409-6648-02 Pfizer Injectables 10704 Diphenhydramine 25 mg cap 100/btl 00185-0648-01 Sandoz 38759 Diphenhydramine 25 mg UD 100/pk 00904-5306-61 Major Pharm 11153 Diphenhydramine 50 mg vl 25 x 1 mL 00641-0376-25 Westward 22253 Diphenhydramine 50 mg vl 25 x 1 mL 63323-0664-01 Fresenius Kabi USA LLC 46123 Epinep 1:1000 amp 25 x 1 mL 00409-7241-01 Pfizer Injectables 49324 Epinephrine 1 mg/mL pf sf 1 mL Amp Each 54288-0103-01 BPI Labs Inc 48229 Epinephrine 1 mL/mL pf sf 1 mL Amp 10/pk 54288-0103-10 BPI Labs Inc 27478 Epinep 1:10000 20 g abjct 10 mL X 10 00409-4921-34 Pfizer Injectables 34632 EpiPen adult 0.3 mg 2/pk 49502-0500-02 Mylan Specialty L.P. 34631 EpiPen Jr 0.15 mg 2/pk 49502-0501-02 Mylan Specialty L.P. 47931 Epinephrine 0.3 mg autoinj 2/pk (generic) 49502-0102-02 Mylan Specialty L.P. 27906 Gelfoam® 12-7 mm spg 12/pk 00009-0315-08 Pfizer Injectables 40021 Hydrogen Peroxide 3% Liq 16 oz ea 00869-0871-43 ABDC 10063 Insulin Hum R 100 u/mL vl 10 mL 00002-8215-01 Eli Lilly & Co 13685 Insulin Hum 100u/mL MDV 10 mL 00002-7510-01 Eli Lilly & Co 32794 Lidocaine 0.5% FTV 25 X 5 mL 00409-4275-01 generic* 27029 Lidocaine 1% ansyr syg 5 mL ea 00409-9137-05 generic* 46111 Lidocaine 1% FTV MDV 25 x 20 mL 00409-4276-01 Pfizer Injectables 26653 Lidocaine 1% FTV MDV 25 x 50 mL 00409-4276-02 Pfizer Injectables 26659 Lidocaine 2% FTV 25 x 50 mL 00409-4277-02 generic* 27452 Lido Ansyr 2% Syringe 10 x 5 mL 00409-1323-05 Pfizer Injectables 27319 Lido 2% Syringe 10 x 5 mL 00409-4903-34 Pfizer Injectables 37309 Lido/Prilo Cream 2.5% 30 gm 50383-0667-30 Akorn Inc. 20078 Loperamide 2 mg cap 100/btl 00093-0311-01 Teva Pharmaceuticals USA 36031 Mannitol 25% FTV 25 x 50 mL 00409-4031-01 Pfizer Injectables 11474 Mannitol 25% SDV 25 x 50 mL 63323-0024-25 Fresenius Kabi, LLC 40755 MaxipimeTM 1 gm FTV PWD 10/pk 00409-0219-01 Pfizer Injectables 40756 MaxipimeTM 2 gm FTV PWD 10/pk 00409-0220-01 Pfizer Injectables 48903 Metoclopram 10 mg/2 mL FTV 25 X 2 mL 00409-3414-18 Pfizer Injectables 17899 Metoclopramide 10 mg tab 100 00093-2203-01 Teva Pharmaceuticals USA Midodrine HCl 5 mg/100 tab *generic Mupirocin 30 gm 68462-0564-35 Glenmark Pharm Mupirocin 2% ointment 22 gm 45802-0112-22 Perrigo Pharmaceuticals Co 26843 Pain ease 3.5 oz spray 00386-0008-03 Gebauer Company 32320 Pain ease 3.5 oz spray mist 00386-0008-02 Gebauer Company 39202 Phenergan 25 mg 1 mL 25/pk 00641-6082-25 Westward/Baxter 32546 Phenytoin Sod 250 mg 5 mL vl 00641-2555-41 Westward/Baxter

* This generic product may be available from multiple manufacturers, depending on inventory availibility.

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ASD # DESCRIPTION NDC # MANUFACTURER 11151 Promethazine 25 mg/mL amp 25 x 1 mL 00641-1495-35 Westward/Baxter 28419 Promethazine 25 mg/mL SDV 25 x 1 mL 00641-0928-25 Westward/Baxter 10744 Promethazine HCL 25 mg 100/btl 00781-1830-01 Sandoz 24546 Promethazine 25 mg tab 100/btl 00591-5307-01 Actavis/Watson Pharmaceuticals 30170 Promethazine 25 mg tab 100/btl 68382-0041-01 Zydus Pharmaceuticals 27114 Sod Chl 0.9% ADV bag 24 x 250 mL 00409-7101-02 Pfizer Injectables 26191 Sod Chl 0.9% FTV PFV 25 x 10 mL 00409-4888-10 Pfizer Injectables 27706 Sod Chl 12 mL syr 10 mL 180/cs 08881-5701-21 Covidien Sales, LLC 46106 Sod Chl Bact 0.9% MDV 25 x 30 mL 00409-1966-07 Pfizer Injectables 28804 Sod Chl 23.4% INJ 25 x 10 mL 00409-1141-02 Pfizer Injectables 27615 Sod Bic 8.4% Ls syg 50 mL ea 00409-6637-34 Pfizer Injectables 26054 Sod Bic 8.4% FTV 25 x 50 mL 00409-6625-02 Pfizer Injectables 41958 Sod Thiosulfate Inj 12.5/50 mL 60267-0705-50 Hope Pharmaceuticals 37007 Triple Anti Oint Foil 144 x 0.9 gm Dynarex Corp 20609 Tubersol® 5 TU 10 test vl 1 mL 49281-0752-21 Sanofi Pasteur 19969 Tubersol® 5 TU 50 test vl 5 mL 49281-0752-22 Sanofi Pasteur 26656 Water Sterile FTV 25 x 10 mL 00409-4887-10 Pfizer Injectables 26552 Water Sterile FTV 25 x 20 mL 00409-4887-20 Pfizer Injectables 26193 Water Bact vl 25 x 30 mL 00409-3977-03 Pfizer Injectables 26701 Water Sterile FTV 25 x 50 mL 00409-4887-50 Pfizer Injectables 26657 Water Sterile FTV 25 x 100 mL 00409-4887-25 Pfizer Injectables Nephrology Medical / Surgical ASD # DESCRIPTION MANUFACTURER PK/CS Top Disposable Products 35009 Alcohol Prep Pad Med. (sterile) Dynarex 200/bx 27969 Alcohol Swabsticks 3'S Dynarex 25/bx 32474 Apron Gowns Disposable 28" x 46" (plastic) Busse 144/cs 32710 Catheter Cap (injectable) Latex Free Molded 100/bx 18784 Catheter Cap (dead end/non-injectable) B. Braun 100/bx 26860 Chloraprep® Single Swabstick Tacy Med 48/bx 37287 Cotton Tip Applicators 6" Sterile 2’s Hardwood 100/bx Dialysis Recliner – 6 Position Winco 1/ea 32475 Drape Sheet 18" x 26" (other sizes available) Busse 50/bx 26857 Drape Sheet 40" x 48" 2 ply TIDI 100/cs 36048 Drape Sheet 40" x 90" 3 ply TIDI 50/cs 34089 Emesis Basin 9" Medline 250/cs 32618 Fistula Pressure Clamps (plastic) Molded 1/ea 35908 Hemastix Test Strips Siemens 50/bx 32709 Hemoband® (non-sterile) Hemoband 1/ea 32761 Luer Lock End Caps – blue Molded 100/bx 18534 Mask – blue (ear loop) Dynarex 50/bx 14837 Mask – blue (molded) Dynarex 50/bx 18318 Medicine Cups 1 oz Dynarex 100/bx

ASD Healthcare | 89 N Nephrology

ASD # DESCRIPTION MANUFACTURER PK/CS 32538 Oxygen Mask Rebreather – adult Allied 1/ea 15184 Oxygen Nasal Cannula – adult Allied 1/ea 14844 Povidone/Iodine Prep Pads (PVP pads) Dynarex 100/bx 14840 Povidone/Iodine Swabsticks (1 per pack) Dynarex 50/bx 28053 Povidone/Iodine Swabsticks (3 per pack) Dynarex 75/bx 32754 Recirculating Connector (male to male) Molded 100/bx 32414 Shoe Covers – blue (one size fits all) Dynarex 150/pairs 26355 Skin Staple Remover Kits Busse 1/ea 20941 Suture Removal Kits Busse 1/ea 15598 Table Paper 21" x 225' Smooth TIDI 12/cs 20568 Towel 3 ply 13.5" x 18" White 500/cs Graham 500/cs 14815 Tape Remover Pads (sterile) Dynarex 100/bx 32643 Transducer Protector (w/luer lock) Molded 100/cs 32755 Tube Occluding Clamp – blue (hemostats) Molded 100/bag 25875 Underpad 17" x 24" (blue) Chux Dynarex 300/cs 33864 Urinals w/Cover (plastic disposable) Medline 1/ea 15601 Wash Cloths 10" x 13.5" – blue (disposable) Graham 500/cs Gloves 39657 Gloves PF Latex Small Tradex 100/bx 39658 Gloves PF Latex Medium Tradex 100/bx 39659 Gloves PF Latex Large Tradex 100/bx 39660 Gloves PF Latex X-Large Tradex 100/bx 39653 Gloves PF Vinyl Small Tradex 100/bx 39654 Gloves PF Vinyl Medium Tradex 100/bx 39655 Gloves PF Vinyl Large Tradex 100/bx 39656 Gloves PF Vinyl X-Large Tradex 100/bx 41762 Gloves PF Nitrile Small Tradex 200/bx 41763 Gloves PF Nitrile Medium Tradex 200/bx 41764 Gloves PF Nitrile Large Tradex 200/bx 41765 Gloves PF Nitrile X-Large Tradex 200/bx 32407 Gloves Sterile Latex Medium (Small and Large Available) Dynarex 50/pairs Lab Coats 39797 Lab Coat White No Pkt Small Dynarex 30/cs 39795 Lab Coat White No Pkt Medium Dynarex 30/cs 39794 Lab Coat White No Pkt Large Dynarex 30/cs 39796 Lab Coat White No Pkt X-Large Dynarex 30/cs 39836 Lab Coat White No Pkt XX-Large Dynarex 30/cs Sharps Containers 22352 Sharps Container 2 gallon – red (# 8970) Square Covidien 20/cs 36603 Sharps Container 3 gallon – red (# 852221) Square Covidien 10/cs 32727 Sharps Container 3 gallon – red (# 8964) Covidien 20/cs 23163 Sharps Container 8 gallon – red (# 8980) Square Covidien 10/cs 32042 Sharps Container 8 gallon – red (# 8980S) Slide Lid Covidien 10/cs 11973 Sharps Container 18 gallon – red Covidien 1/ea 32623 Sharps Container – brackets 2 and 3 gallon Covidien 1/ea

90 | InsideOut Go to www.asdhealthcare.com for pricing, ordering and more. Product availability subject to change.

ASD # DESCRIPTION MANUFACTURER PK/CS Thermometers 32742 Genius® Probe Covers Covidien 2100/cs 24456 Thermoscan® Sure Temp® Plus 690 Welch Allyn 1/ea 25572 Thermoscan® Sure Temp® Probe Covers Welch Allyn 800/bx 43632 Thermoscan® Probe Covers Welch Allyn 200/bx Tape 14137 DuraporeTM Tape 1" x 10 yards (cloth/silk) 3M 12/rolls 14138 DuraporeTM Tape 2" x 10 yards (cloth/silk) 3M 6/rolls 33234 DuraporeTM/Single Use 1" x 1.5 yards (cloth/silk) 3M 100/rolls 32338 Hypo-Pore Tape 1" x 10 yards (paper) Dukal 12/rolls 32577 Hypo-Silk Cloth Tape 1" x 10 yards Dukal 12/rolls 19140 MicroporeTM Tape 1" x 10 yards (paper) 3M 12/rolls 32535 MicroporeTM/Single Use 1" x 1.5 yards (paper) 3M 100/rolls 32536 TransporeTM Tape 1" x 1.5 yards (clear plastic) 3M 500/rolls 14151 TransporeTM Tape 1" x 10 yards (clear plastic) 3M 12/rolls Bandages 34440 Bandage Strip 1" x 3" (plastic) Dukal 100/bx 32553 Bandage Strip 3/4" x 3" (plastic) Dukal 100/bx 19216 Bandage Flex Strip 1" x 3" Dynarex 100/bx 19204 Bandage Sheer Strip 1" x 3" Dynarex 100/bx 32594 Gauze 2" x 2" (non-sterile) 8 Ply Dukal 5000/cs 32595 Gauze Pads 2" x 2" 8 Ply (sterile) 2's Dukal 1500/cs 32597 Gauze 4" x 4" 12 ply N/S 2000/cs Dukal 2000/cs 32693 Gauze 4" x 4" 12 ply (sterile) Dukal 100/bx 32796 Gauze 4" x 4" 8 Ply (sterile) 2's Dukal 1200/bx 24274 Gauze 2" x 2" 8 Ply (sterile) 2's Dynarex 100/bx 32578 Tegaderm 2 3/8" x 2 3/4" (compare to 3M brand) Dukal 100/bx 32741 Tegaderm 4" x 4 3/4" (compare to 3M brand) Dukal 50/bx 14163 Tegaderm™ 2 3/8" x 2 3/4" 3M brand 3M 100/bx 40159 Tegaderm™ 3 1/2" x 4 1/2" 3M Brand 3M 100/box 18528 Tegaderm™ 4" x 4 3/4" 3M brand 3M 50/bx 13275 TelfaTM Pads Sterile 2" x 3" Covidien 100/bx 32743 Topper Sponge Sterile 4" x 3" Dukal 50/bx 32357 Zorband™ (Large) 1" x 2 3/4" (compare to Sureseal) Exel 100/bx 32358 Zorband™ (XL) 1 1/4" x 2 3/4" (compare to Sureseal) Exel 100/bx Face Masks and Shields 34204 Face Shield (full length no visor) Precept 1/ea 18534 Mask – blue (ear loop) Dynarex 50/bx 14837 Mask – blue (molded) Dynarex 50/bx 18544 Mask – blue (ear loop w/Face Shield) Dynarex 50/bx

ASD Healthcare | 91 N Nephrology

ASD # DESCRIPTION MANUFACTURER PK/CS Test Strips 38945 Accuchek® Aviva Plus Strips Roche 50/bx 11265 Accuchek® Comfort Curve Control Solution Roche 1/bx 32328 Ascensia® Breeze Gluc. Blood Strips Bayer 50 strips 34128 Bicarb PH II Test Strips (100 per bottle) SerimResearch 5/btls 34124 Chlorine Test Strips (100 per bottle) SerimResearch 6/btls 21204 OneTouch® Ultra Test Strips Lifescan 100 strips 23596 OneTouch® Ultra Control Solution 4 mL Lifescan 2/vl 37537 Total Chlorine Hisense Test Kit Serim Research 1/kit 34131 Total Chlorine Hisense Refills 5 x 100 Serim Research 1/kit 34127 Peracetic Acid Reagant Strips (100 per bottle) Serim Research 6/btls 34126 Residual Peroxide Reagant Strips (100 per bottle) Serim Research 6/btls 34130 Water Hardness Reagent Strips (50 per bottle) SerimResearch 6/btls Needles 27525 Needles 18g x 1" Exel 100/bx 27558 Needles 18g x 1.5" Exel 100/bx 27528 Needles 20g x 1" Exel 100/bx 42271 Needles 21g x 1.5" Exel 100/bx 27518 Needles 23g x 1" Exel 100/bx 27678 Needles 25g x 5/8" Exel 100/bx Duopross Syringes 32571 1cc 22g x 1 x 1.5" Renal Max Duopross 100/bx 32570 1cc 22g x 1.5" Renal Safe safety syr Duopross 100/bx 32575 3cc 21g x 1.5" Low Dead Space safety syr Duopross 100/bx Syringes 32562 Insulin Syringe 1cc 29g x 1/2" Terumo 100/bx 32367 Safety Syringe 3cc 22g x 1" Exel 100/bx 22686 Syringe 1cc 27g x 1/2" Allergy (low dead space) Terumo 100/bx 27515 Syringe 1cc w/Luer Lock Exel 100/bx 27529 Syringe 3cc w/Luer Lock Exel 100/bx 18996 Syringe 3cc 20g x 1" w/Luer Lock Terumo 100/bx 27520 Syringe 3cc 21g x 1" w/Luer Lock Exel 100/bx 32367 Syringe 3cc 22g x 1" w/Luer Lock Exel 100/bx 11053 Syringe 3cc 23g x 1" Terumo 100/bx 11049 Syringe 3cc 25g x 5/8" Terumo 100/bx 27560 Syringe 5cc w/Luer Lock Exel 100/bx 27585 Syringe 10cc w/Luer Lock Exel 100/bx 27526 Syringe 10cc 21g x 1" Exel 100/bx 33579 Syringe 20cc w/Luer Lock Terumo 50/bx 27555 Syringe 30cc w/Luer Lock Exel 50/bx 27559 Syringe 50-60cc w/Luer Lock Exel 25/bx 27521 TB Syringe 1cc 25g x 5/8" Exel 100/bx 32352 TB Syringe 1cc 25g x 5/8" (zero dead space) Exel 100/bx

92 | InsideOut Go to www.asdhealthcare.com for pricing, ordering and more. Product availability subject to change.

ASD # DESCRIPTION MANUFACTURER PK/CS B/D – Syringes 10645 Syringe 10cc Luer Lock (BD# 309604) B/D 100/bx 10638 Syringe 10cc 21g x 1" (BD# 309642) B/D 100/bx 37116 Syringe 3cc Luer Lock (BD# 309657) B/D 200/bx 12791 Syringe 3cc 20g x 1.5" (BD# 309579) B/D 100/bx 12792 Syringe 3cc 20g x 1" (BD# 309578) B/D 100/bx 12794 Syringe 3cc 21g x 1" (BD# 309575) B/D 100/bx 12795 Syringe 3cc 22g x 1.5" (BD# 309574) B/D 100/bx 12796 Syringe 3cc 22g x 1" (BD# 309572) B/D 100/bx 12797 Syringe 3cc 23g x 1" (BD# 309571) B/D 100/bx 12799 Syringe 3cc 25g x 1" (BD# 309581) B/D 100/bx 12882 Syringe 30cc Luer Lock (BD# 309650) B/D 40/bx 12814 Syringe 5cc 21g x 1.5" (BD# 309633) B/D 100/bx 12786 TB Syringe 1cc 25g x 5/8" (BD# 309626) B/D 100/bx B/D – Safety Syringes 23970 BD IntegraTM 3cc 22g x 1.5" low dead space B/D 100/bx 23969 BD IntegraTM 3cc 23g x 1" low dead space B/D 100/bx 12782 Insulin Safety Syringe 1cc 29g x 1.5" (BD# 329464) B/D 500/cs 18735 Safety Syringe 10cc Luer Lock (BD# 305559) B/D 50/bx 19562 Safety Syringe 10cc 21g x 1.5" (BD# 305564) B/D 50/bx 12884 Safety Syringe 3cc Luer Lock (BD# 309606) B/D 100/bx 12808 Safety Syringe 3cc 21g x 1.5" (BD# 309595) B/D 100/bx 12789 Safety Syringe 3cc 22g x 1.5" (BD# 309593) B/D 100/bx 12811 Safety Syringe 3cc 25g x 5/8" (BD# 309592) B/D 100/bx 18734 Safety Syringe 5cc Luer Lock (BD# 305558) B/D 50/bx 19561 Safety Syringe 5cc 21g x 1.5" (BD# 305561) B/D 50/bx 12784 TB Safety Syringe 1cc 25g x 5/8" (BD#305554) B/D 100/bx 12785 TB Safety Syringe 1cc 27g x 1/2" (BD# 305553) B/D 100/bx Covidien – Safety Syringes 19521 Safety Syringe 1cc Insulin 29g x 1.5" Covidien 100/bx 19519 Safety Syringe 1cc 28g x 1/2" Covidien 100/bx 19518 Safety Syringe 1cc 25g x 5/8" Covidien 100/bx 19525 Safety Syringe 3cc 20g x 1 x 1.5" Covidien 100/bx 19302 Safety Syringe 3cc 21g x 1" Covidien 100/bx 20169 Safety Syringe 3cc 21g x 1 x 1.5" Covidien 100/bx 19528 Safety Syringe 3cc 22g x 1.5" Covidien 100/bx 19536 Safety Syringe 6cc 20g x 1.5" Covidien 50/bx 19308 Safety Syringe 6cc 21g x 1 x 1.5" Covidien 50/bx 19531 Safety Syringe 6cc Luer Lock Covidien 50/bx 19301 Safety Syringe 12cc 21g x 1 x 1.5" Covidien 50/bx

ASD Healthcare | 93 Consumer Products Showcase.

Check out Consumer Products available through ABC Order or ABC Passport ordering system!

You must order on your AmerisourceBergen Passport or ABC Ordering System. Non-AmerisourceBergen customers, please contact 610.727.7000 or [email protected] Resourceoeo Linking pharmacists to reliable sources & patient advocacy groups

Pharmacist Web Android IOS CDC Continuing Education for Health Professionals http://bit.ly/CDCLearn

CDC Flu Surveillance for Weekly Influenza Data http://bit.ly/FluLink

Clinical Trials for Comprehensive Investigational Studies https://clinicaltrials.gov

Clinical Trials Sponsored by National Cancer Institute http://bit.ly/CancerCTs

Expanded Access Navigator for non-FDA Approved Investigational http://navigator.reaganudall.org Drugs for Patients with Fatal Diseases

FDA Current and Resolved Drug Shortages and Discontinuations http://bit.ly/DrugShort

FDA MedWatch Volunteer Reporting Form for Adverse Events http://bit.ly/AdverseEvent

Federal Agency Disaster Preparation »»ASPR / Tracie https://asprtracie.hhs.gov/ »»CDC http://bit.ly/CDCDisaster »»FDA http://FDA.gov/emergencypreparedness »»FEMA http://fema.gov Federal Healthcare Proposed Rules, Notices, Laws and Regulations »»Federal Registry http://bit.ly/HealthHumanService

Kidney Community Emergency Response http://bit.ly/ESRDhelp

Level II HCPCS J-Codes for Injectable Drugs http://bit.ly/J-Code

National Drug Code (NDC) http://bit.ly/FDANDC

Orange Book for FDA Approved Drugs http://bit.ly/OrBook with Therapeutic Equivalence Evaluations

Patient Adocacy Web Android IOS Alpha 1 Foundation alpha-1foundation.org

Hemophilia »»Kelley kelleycom.com/projectshare »»Save One Life saveonelife.net Neuropathy »»Neuropathy Action Foundation neuropathyaction.org Oncology »»Family Reach familyreach.org »»The EVAN Foundation (pediatric neuroblastoma) theevanfoundation.org Primary Immune Diseases »»Immune Deficiency Foundation primaryimmune.org »»Jeffrey Modell Foundation info4pi.org Renal »»Bridge of Life bridgeoflifeinternational.org

ASD Healthcare | 95 HYPERRAB® ------DOSAGE FORMS AND STRENGTHS ------Rabies Immune Globulin (Human) 300 IU/mL solution for injection supplied in 1 mL and 5 mL single-dose vials. HIGHLIGHTS OF PRESCRIBING INFORMATION ------CONTRAINDICATIONS ------These highlights do not include all the None. information needed to use HYPERRAB® safely ------WARNINGS AND PRECAUTIONS ------and effectively. See full prescribing information • Severe hypersensitivity reactions, including for HYPERRAB. anaphylaxis, may occur with HYPERRAB. Have HYPERRAB [rabies immune globulin (human)] epinephrine available immediately to treat any solution for infiltration and intramuscular acute severe hypersensitivity reactions. injection • HYPERRAB is made from human blood, it may Initial U.S. Approval: 1974 carry a risk of transmitting infectious agents, ------INDICATIONS AND USAGE ------e.g., viruses, the variant Creutzfeldt-Jakob HYPERRAB is a human rabies immune globulin disease (vCJD) agent, and, theoretically, the indicated for postexposure prophylaxis, along with Creutzfeldt-Jakob disease (CJD) agent. rabies vaccine, for all persons suspected of ------ADVERSE REACTIONS ------exposure to rabies. The most common adverse reactions in >5% of Limitations of Use: subjects in clinical trials were injection site pain, Persons previously immunized with rabies vaccine headache, injection site nodule, abdominal pain, that have a confirmed adequate rabies antibody titer diarrhea, flatulence, nasal congestion, and oropha- should receive only vaccine. ryngeal pain. For unvaccinated persons, the combination of To report SUSPECTED ADVERSE REACTIONS, HYPERRAB and vaccine is recommended for both contact Grifols Therapeutics Inc. at 1-800-520- bite and nonbite exposures regardless of the time 2807 or FDA at 1-800-FDA-1088 or interval between exposure and initiation of post- www.fda.gov/medwatch. exposure prophylaxis. ------DRUG INTERACTIONS ------Beyond 7 days (after the first vaccine dose), • Repeated dosing after administration of rabies HYPERRAB is not indicated since an antibody vaccine may suppress the immune response to response to vaccine is presumed to have occurred. the vaccine. ------DOSAGE AND ADMINISTRATION ------• Defer live vaccine (measles, mumps, rubella) For infiltration and intramuscular use only. administration for 4 months. Administer HYPERRAB within 7 days after the first dose of rabies vaccine. Postexposure HYPERRAB • Administer as soon as prophylaxis, 20 IU/kg possible after along with body weight exposure, preferably at rabies OR the time of the first vaccine, after 0.0665 rabies vaccine dose. suspected mL/kg • Infiltrate the full dose exposure to body weight of HYPERRAB rabies thoroughly in the area Single dose around and into the wound(s), if anatom- ically feasible. • Inject the remainder, if Grifols Therapeutics Inc. Research Triangle Park, NC 27709 USA 3047927-BS any, intramuscularly. U.S. License No. 1871 R evised: 2/2018

ASD_HyperRAB_mech_ISI_BS.indd 2 3/26/18 11:01 AM Indication and Usage HYPERRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies. Limitations of Use Persons who have been previously immunized with rabies vaccine and have a confirmed adequate rabies antibody titer should receive only vaccine. For unvaccinated persons, the combination of HYPERRAB and vaccine is recommended for both bite and nonbite exposures regardless of the time interval between exposure and initiation of postexposure prophylaxis. Beyond 7 days (after the first vaccine dose), HYPERRAB is not indicated since an antibody response to vaccine is presumed to have occurred. Important Safety Information For infiltration and intramuscular use only. Severe hypersensitivity reactions may occur with HYPERRAB. Patients with a history of prior systemic allergic reactions to human immunoglobulin preparations are at a greater risk of developing severe hypersensitivity and anaphylactic reactions. Have epinephrine available for treatment of acute allergic symptoms, should they occur. HYPERRAB is made from human blood and may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The most common adverse reactions in >5% of subjects during clinical trials were injection-site pain, headache, injection-site nodule, abdominal pain, diarrhea, flatulence, nasal congestion, and oropharyngeal pain. Do not administer repeated doses of HYPERRAB once vaccine treatment has been initiated as this could prevent the full expression of active immunity expected from the rabies vaccine. Other antibodies in the HYPERRAB preparation may interfere with the response to live vaccines such as measles, mumps, polio, or rubella. Defer immunization with live vaccines for 4 months after HYPERRAB administration. Please see brief summary of Prescribing Information on adjacent page or visit HyperRAB.com for full Prescribing Information.

ASD_HyperRAB_mech_ISI_BS.indd 1 3/26/18 11:01 AM 3101 Gaylord Parkway Frisco, Texas 75034 www.asdhealthcare.com

An animal attack is traumatic enough… PROTECT HER FROM RABIES with the potential for fewer injections

NOW APPROVED! HyperRAB® (rabies immune globulin [human]) 300 IU/mL

The #1 prescribed human rabies immune globulin (HRIG) you’ve trusted for over 40 years is now available in a new high potency formulation

the volume of medication administered in a total dose

the concentration of rabies antibodies per mL at the wound site

Please see Important Safety Information and brief summary of Prescribing Information for HyperRAB on adjacent pages, or visit www.HyperRAB.com for full Prescribing Information.

HyperRAB® (rabies immune globulin [human]) is indicated for postexposure prophylaxis, along with rabies vaccine, for all persons suspected of exposure to rabies. HyperRAB is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent that can cause disease. There is also the possibility that unknown infectious agents may be present in such products.

ASD_HyperRAB_mech_backcover.indd 1 3/26/18 11:22 AM