New Drugs & Biologics Approved in 2019
Presented by: Pharmacy Residents
Supervised by: Ryan Garst, Sr Director of Clinical Services, NHIA Financial Disclosure
1. None of the residents in this presentations have any financial relationships to disclose.
2. None of the residents in this presentation will discuss off label and/or investigational use in their presentations. Quzyttir™ (Cetirizine hydrochloride)
Charlie Nguyen, PharmD Option Care Health Quzyttir™ (Cetirizine hydrochloride)
• Class: Histamine-1 (H1) Receptor Antagonist • Approved on October 4, 2019 • Indications: Treatment of acute urticaria in adults and children 6 months of age and older
• MOA: Selective inhibition of peripheral (H1) receptors • Dosing (IV only): • Adults and adolescents ≥ 12 years of age and older: 10 mg • Children 6 to 11 years: 5 mg or 10 mg • Children 6 months to 5 years: 2.5 mg • Adverse reactions: • Incidence less than 1%: dysgeusia, headache, paresthesia, presyncope, dyspepsia, feeling hot, and hyperhidrosis. Quzyttir™ (Cetirizine hydrochloride)
• Supplied as 2 mL size amber glass vials for single use (10mg/mL) • AWP Cost: $360 • Storage: Stored at 20°-25°C (68°-77°F), excursions permitted to 15°-30°C (59°-86°F) • Preparation and Administration: • Administer as IV push (over 1 to 2 mins) once every 24 hrs as needed for acute urticaria. • Education and Nursing considerations: • Not recommended in pediatric patients < 6 years of age with impaired renal or hepatic function • Somnolence - exercise caution when operating a car or potentially dangerous machinery. • Avoid use of alcohol or other CNS depressants Quzyttir™ (Cetirizine hydrochloride) Clinical Trials
Berger W, Blaiss M, Stiell I, et al. 2 • 262 Patients randomly assigned QUZYTTIR 10 mg or diphenhydramine 50 mg injection for the treatment of acute urticaria. • Pre-specified non-inferiority margin is 0.50 for the difference between treatment groups. • Primary Efficacy: Quzyttir™ (Cetirizine hydrochloride) Clinical Trials
Secondary Efficacy: Quzyttir™ (Cetirizine hydrochloride) References: • QUZYTTIR. New Drug Application Approval Letter. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2019/211415Orig1s000ltr.pdf. Accessed January 13, 2020. • QUZYTTIR [package insert]. TerSera Therapeutics LLC, Lake Forest, IL USA • Cetirizine. In: Drugdex system (Micromedex 2.0) Greenwood Village, CO: Truven Health Analytics; c1974-2018. Accessed January 13, 2020. • Cetirizine. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed January 13, 2020. • Berger W, Blaiss M, Stiell I, et al. Intravenous (IV) cetirizine shows greater overall benefit to IV diphenhydramine for acute urticaria. Ann Allergy Asthma Immunol. 2018;121(5):S34. doi: 10.1016/j.anai.2018.09.109. Givlaari™ (givosiran)
Ashley W McCracken, PharmD Johns Hopkins Home Care Group Givlaari™ (givosiran)1
Drug Class: Aminolevulinate synthase 1 (ALAS1)-directed small interfering RNA (siRNA)
Indication: treatment of adults with acute hepatic porphyria (AHP)
MOA • Double stranded siRNA that causes degradation of ALAS1 mRNA in hepatocytes through RNA interface • Lower ALAS1 leads to reduced neurotoxic intermediates (ALA and PBG) that are associated with attacks and other disease manifestations of AHP
Dosing: 2.5 mg/kg subcutaneous injection once monthly Givlaari™ (givosiran)1 Givlaari™ (givosiran)1 Givlaari™ (givosiran)1
Contraindications • Known severe hypersensitivity Common ADRs (>20% of patients) • Nausea and injection site reactions
Warnings, Precautions and Monitoring • Anaphylaxis (<1%) - healthcare supervision for minimum of 30 minutes post injection • Hepatic Toxicity (15%) –liver function tests before treatment for first 6 months • Renal Toxicity (15%) - renal function tests • Injection Site Reactions (25%) - healthcare supervision for minimum of 30 minutes post injection Givlaari™ (givosiran)1
• Supplied: clear colorless-to-yellow ready-to-use solution in single-dose vial of 189mg/mL (NDC: 71336-1001-01)
• Storage: 2°C to 25°C (36°F to 77°F)
• Cost: $46,800 per single use vial (AWP)
• Patient Counseling • Common injection site reactions Givlaari™ (givosiran)1 References:
1. Alnylam Pharmaceuticals. GIVLAARI (givosiran) [package intsert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/0212194s000lbl.pdf. Revised November 2019. Accessed February 14, 2020.
2. Kothadia JP, LaFreniere K, Shah JM. Acute Hepatic Porphyria. [Updated 2019 Dec 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537178/
3. Alnylam Pharmaceuticals. ENVISION: A Study to Evaluate the Efficacy and Safety of Givosiran (ALN-AS1) in Patients With Acute Hepatic Porphyrias (AHP). Clinical Trials identifier NCT03338816. https://clinicaltrials.gov/ct2/show/NCT03338816
4. AWP based on McKesson Pricing Zolgensma™ (onasemnogene abeparvovec-xioi)
Ashley W McCracken, PharmD Johns Hopkins Home Care Group Zolgensma® (onasemnogene abeparvovec-xioi)1
Drug Class: adeno-associated virus vector-based (AAV9) gene therapy Indication: treatment of patients <2 years of age with spinal muscular atrophy (SMA) with bi-allelic mutations in survival motor neuron 1 (SMN1) gene MOA • SMA is caused by bi-allelic mutation of SMN1 gene which results in insufficient SMN protein expression • Zolgensma ® is a AAV9-based gene therapy designed to deliver a functioning copy of the gene encoding human SMN1 protein Prior to Treatment: test for anti-AAV9 antibodies Zolgensma® (onasemnogene abeparvovec-xioi)1
• Dosing: 1.1 x 1014 vector genomes (vg) per kg of body weight administered over 60 minutes
• Pre- and post-treatment with oral systemic corticosteroid Zolgensma® (onasemnogene abeparvovec-xioi)2-5 Zolgensma® (onasemnogene abeparvovec-xioi)2 Zolgensma® (onasemnogene abeparvovec-xioi)1
Boxed Warning Warnings and Precautions Acute Serious Liver Injury Thrombocytopenia • Monitor LFTs before and 3 months post • Monitor platelet counts before and on regular infusion bases for 3 months post infusion • Oral prednisolone day prior and at least 60 Elevated Troponin-1 days after • Monitor troponin-1 before and on regular Common ADRs (≥5% of patients) bases for 3 months post infusion • Elevated aminotransferases • Vomiting Zolgensma® (onasemnogene abeparvovec-xioi)1
Supplied: provided as a weight standardized dose kit to meet dosing requirements for each patient. Kit contains: • 2-9 vials of Zolgensma® • One alcohol wipe per vial based on kit size and dosing specific National Drug Codes (NDC)
Dosing example: Johns Hopkins most recent Zolgensma® patient was a one month old infant who had the following dosing overview: • Dosing weight: 3.8 kg • Product: Zolgensma® 3.6 – 4 kg kit (NDC: 718-0122-03) • Dose volume: 22 mL • Dose unit: 4.4 x 1014 vector genomes Zolgensma® (onasemnogene abeparvovec-xioi)1
Storage • Shipped frozen (≤ -60°C [-76°F]) in clear vials • Upon receipt, immediately place the kit in a refrigerator at 2°C to 8°C (36°F to 46°F) and is stable • Must be used within 14 days or receipt Cost: $2.125 million (WAC) Patient Counseling • Vector shedding in feces • Vaccine adjustment due to corticosteroid use Zolgensma® (onasemnogene abeparvovec-xioi)1 References: 1. AveXis, Inc. ZOLGENSMA (onasemnogene abeparvovec-xioi) [package intsert]. U.S. Food and Drug Administration website. https://www.fda.gov/media/126109/download. Revised May 2019. Accessed February 14, 2020. 2. AveXis, Inc. Gene Replacement Therapy Clinical Trial for Patients with Spintal Muscular Atorphy Type 1. Clinical Trials identifier NCT03306277;. https://clinicaltrials.gov/ct2/show/NCT03306277 3. AveXis, Inc. Gene Transfer Clinical Trial for Spintal Muscular Atrophy Type 1. Clinical Trials identifier NCT02122952;. https://clinicaltrials.gov/ct2/show/NCT02122952 4. AveXis, Inc. Long-Term Follow-up Study for patients from AVXS-101-CL-101 (START). Clinical Trials identifier NCT03421977;. https://clinicaltrials.gov/ct2/show/NCT03421977 5. AveXis, Inc. Pre-Symptomatic Study of Intravenous onasemnogene abeparvovec-xioi in spintal muscular atrophy (SMA) for patient with multiple copies of SMN2 (SPR1NT). Clinical Trials identifier NCT03505099;. https://clinicaltrials.gov/ct2/show/NCT03505099 Myxredlin® (Insulin Human in Normal Saline)
Neel Patel, PharmD Coram/CVS Specialty Infusion Services ® Myxredlin (Insulin Human in Normal Saline)
• Approved 07/22/2019 • Common adverse reactions: • Indicated for glycemic control in • Hypoglycemia patients with diabetes mellitus • Weight gain • Symptoms include blurred vision, • Serious adverse reactions: fatigue, confusion, fruity smelling • Heart failure breath, and excessive thirst • Arrhythmias • IV Dosing: ~0.1 unit/kg/hr • Hypoglycemia • Hypokalemia • Hypersensitivity reaction ® Myxredlin (Insulin Human in Normal Saline)
• 100 units/100 mL single-dose • Storage plastic container • $42.00 / container (AWP) • Clear, colorless • Refrigerate • Nursing Considerations: • Infusion time varies • Protect from light • Monitor patient frequently during • No preparation needed infusion ® Myxredlin (Insulin Human in Normal Saline)
• Submitted as Type 5 NDA
• Pharmacokinetics and pharmacodynamics studies ® Myxredlin (Insulin Human in Normal Saline) References: 1. Accessdata.fda.gov. (2019). Highlights of Prescribing Information - Myxredlin. [online] Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208157s000lbl.pdf [Accessed 8 Feb. 2020].
2. Baxter.com. (2019). Baxter Announces U.S. FDA Approval of Myxredlin, the First and Only Ready-To -Use Insulin for IV Infusion. [online] Available at: https://www.baxter.com/baxter-newsroom/baxter-announces-us- fda-approval-myxredlin-first-and-only-ready-use-insulin-iv [Accessed 8 Feb. 2020]. 3. Kitabchi, A., Umpierrez, G., Miles, J. and Fisher, J. (2009). Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care, [online] 32(7), pp.1335-1343. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699725/#!po=66.2500 [Accessed 8 Feb. 2020]. 4. Myxredlin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com [Accessed 8 Feb. 2020]. ® Fetroja (cefiderocol)
Neel Patel, PharmD Coram/CVS Specialty Infusion Services ® Fetroja (cefiderocol)
• Approved 11/14/2019 • Indicated for complicated urinary • Common adverse reactions: tract infections • Nausea • Cephalosporin and siderophore • Diarrhea • IV Dosing • Skin rash
• Serious adverse reactions: • Hypersensitivity reaction • Clostridium difficile-associated diarrhea • Increased mortality ® Fetroja (cefiderocol)
• 1,000mg/vial • Stability of reconstituted drug • $TBD / container (AWP) • Clear, colorless • Refrigerate • Protect from light • Nursing Considerations: • Preparation • 3 hour infusion • Reconstitute vial with 10mL of NS • Home mix or D5W • Add to 100mL of NS or D5W ® Fetroja (cefiderocol) ® Fetroja (cefiderocol) References: 1. Accessdata.fda.gov. (2019). Highlights of Prescribing Information - Fetroja. [online] Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/209445s000lbl.pdf [Accessed 8 Feb. 2020].
2. FDA approves new antibacterial drug to treat complicated urinary tract infections as part of ongoing efforts to address antimicrobial resistance. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda- approves-new-antibacterial-drug-treat-complicated-urinary-tract-infections-part-ongoing-efforts. [Accessed 8 Feb. 2020].
3. Fetroja. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com [Accessed 8 Feb. 2020].
4. Portsmouth S, van Veenhuyzen D, Echols R et al. Cefiderocol versus imipenem-cilastatin for the treatment of complicated urinary tract infections caused by Gram-negative uropathogens: a phase 2, randomised, double-blind, non-inferiority trial. The Lancet Infectious Diseases. 2018;18(12):1319-1328. doi:10.1016/s1473-3099(18)30554-1 [Accessed 8 Feb. 2020].
5. Sato T, Yamawaki K. Cefiderocol: Discovery, Chemistry, and In Vivo Profiles of a Novel Siderophore Cephalosporin. Clinical Infectious Diseases. 2019;69(Supplement_7):S538-S543. doi:10.1093/cid/ciz826 [Accessed 8 Feb. 2020]. Vyondys 53TM (golodirsen)
Susan Chhen, PharmD Fairview Pharmacy Services Vyondys 53TM (golodirsen)
• Approved: December 12, 2019 under FDA accelerated approval program • Drug Class: Antisense oligonucleotide • Indication: treatment of Duchenne muscular dystrophy (DMD) in patients with confirmed mutation of the DMD gene amenable to exon 53 skipping • Gene mutation leads to minimal or no production of dystrophin • Dystrophin is an essential protein that keeps muscle cells intact • DMD occurs in 1 in every 3,500 to 5,000 males born worldwide – 8% have mutations responsive to treatment with Vyondys 53 • MOA: binds to exon 53 of dystrophin pre-mRNA excluding the exon during mRNA processing and thereby allowing for production of shortened, partially functional dystrophin protein • Dosing: 30 mg/kg IV infusion over 35 – 60 minutes once weekly • Monitor GFR prior to initiation and during treatment • Administer within 4 hours of dilution Vyondys 53TM (golodirsen) Vyondys 53TM (golodirsen)
• Warning and Precautions • Hypersensitivity reactions – consider slowing infusion • Renal toxicity – based on animal data; creatinine may not be reliable in DMD patients • Monitoring • GFR – baseline and during treatment • Urinalysis – monthly • Serum cystatin C – every 3 months Vyondys 53TM (golodirsen) Storage and Cost • Supplied: 100 mg/2 mL (2 mL) single-dose vial • Storage • Refrigerate in original container (2-8°C), protect from light • Diluted product may be stored in the refrigerator for up to 24 hours (2-8°C) • Cost: $1,920 per 100 mg/2 mL vial (AWP) Vyondys 53TM (golodirsen) References:
1. Vyondys 53 [package insert]. Cambridge, MA: Sarepta Therapeutics, Inc.; 2019. 2. Muscular Dystrophy Association. MDA celebrates FDA approval of Vyondys 53 for treatment of DMD amenable to exon 53 skipping. Accessed February 13, 2020. 3. National Center for Advancing Translational Sciences and Genetic and Rare Diseases Information Center. Duchenne muscular dystrophy. National Institute of Health. February 2020. 4. Golodirsen: drug information. In: UpToDate, Waltham, MA, 2020. Evenity ® (romosozumab-aqqg)
Nita Vorn, PharmD Option Care Health Evenity ® (romosozumab-aqqg)
• Monoclonal Antibody; Sclerostin Inhibitor • FDA Approved: April 9th, 2019 • Indication: treatment of osteoporosis in postmenopausal women at high risk for fracture • MOA: inhibits sclerostin, increases bone formation and decreases bone resorption • Boxed Warning: Potential risk of myocardial infarction, stroke and cardiovascular death • Adverse Reactions: • >10 %: Joint pain • 1% to 10%: Headache, peripheral edema, muscle spasm, hypersensitivity reactions • <1%: Angioedema, hypocalcemia, femur fracture, osteonecrosis of the jaw Evenity ® - Clinical Trials Evenity ® (romosozumab-aqqg)
• Dosing: SubQ: 2 consecutive injections (105 mg each) for a total dose of 210 mg once monthly • No dosage adjustments for renal or hepatic impairments • Monitored closely for hypocalcemia if eGFR <30 mL/minute/1.73 m 2 or receiving dialysis
• Preparation and Administration: • Allow to sit at room temp for at least 30 minutes before injecting • Sites of injection: abdomen, thigh or outer area of upper arm • Should only be administered by a health care professional
• Must be dispensed with Medication Guide, https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761062s000lbl.pdf#page=19
• Nursing consideration/Monitoring: Signs/symptoms of hypersensitivity; cardiovascular events; patient’s weight; serum calcium; bone mineral density Evenity ® (romosozumab-aqqg)
• Storage/Stability: 2°C to 8°C & protect from light. May store at ≤ 25°C for up to 30 days. Do not expose to temp >25°C. Do not freeze. Do not shake. • Supplied: clear, colorless to light yellow solution; a single-use prefilled syringe • Cost: each syringe contains 105mg/1.17mL • WAC: $912.50, AWP: $1,095.00
• Patient Education: • Supplemental calcium and vitamin D should be taken if dietary intake is inadequate • If a dose is missed, administer as soon as it can be rescheduled; subsequent doses should be scheduled every month from the date of last dose • Counsel patients about good mouth care and hygiene Evenity ® (romosozumab-aqqg) References:
1. Evenity (romosozumab-aqqg) [prescribing information]. Thousand Oaks, CA: Amgen; April 2019. 2. Evenity. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed April 3, 2020. 3. Saag KG, Petersen J, Brandi ML, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med. 2017;377(15):1417-1427. 4. Langdahl BL, Libanati C, Crittenden DB, et al. Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet. 2017;390(10102):1585-1594. Xembify® (immune globulin subcutaneous, human- klhw)
Eric Slayton, PharmD Coram/CVS Specialty Infusion Services Xembify® (immune globulin subcutaneous, human- klhw)
• Drug Class: Immune globulin (IgG)
• Indication: primary humoral immunodeficiency (PI)
• Mechanism of Action: • immune support via IgG pathway • Detailed mechanisms unknown Xembify® (immune globulin subcutaneous, human- klhw)
• Dosing: • From IVIG • Multiply IVIG dose by 1.37 • Divide this result by number of weeks between IVIG infusions • From SCIG • Maintain same weekly dose • Dose Adjustments: • Check IgG troughs as early as 5 weeks after initiating therapy • Adjust dose according to manufacturer provided guidelines Xembify® (immune globulin subcutaneous, human- klhw) Clinical Trial Xembify® (immune globulin subcutaneous, human- klhw)
• Administration • Subcutaneous • Doses may be weekly or divided throughout week • 25 mL per site with 25 mL/hr/site maximum rate • Maximum number of site per infusion – 6 Xembify® (immune globulin subcutaneous, human- klhw)
• Warnings • Thrombosis • Aseptic Meningitis Syndrome • Hemolysis • Transfusion-related Acute Lung Injury (TRALI) • Monitoring • IgG levels • Renal function • Blood counts Xembify® (immune globulin subcutaneous, human- klhw)
• Supplied: • Single use vials – 1 gram per 5 mL • 1 g, 2 g, 4 g, 10 g • Storage: • Refrigerate at 2-8°C • May be stored at up to 25°C for no more than six months prior to expiration
• AWP: $41 per mL ($205 per gram) Xembify® (immune globulin subcutaneous, human- klhw) References:
1. Xembify [package insert]. Triangle Park, NC: Grifols Therapeutics, Inc.; 2019.
2. Sleasman JW, Lumry WR, Hussain I, et al. Immune globulin subcutaneous, human - klhw 20% for primary humoral immunodeficiency: an open-label, Phase III study. Immunotherapy. 2019;11(16):1371-1386. Recarbrio™ Imipenem, Cilastatin, and Relebactam
Shelby Dick, PharmD Option Care Health Recarbrio™ (Imipenem, Cilastatin, and Relebactam)
Classification: • Combination of imipenem (carbepenem antibiotic), cilastatin (renal dehydropeptidase inhibitor), and relebactam (beta-lactamase inhibitor) • Approved July 17th, 2019 Indications: • Complicated urinary tract infections including pyelonephritis (cUTI), complicated intra-abdominal infections (cIAI) Mechanism of Action: • Imipenem: binds to PBP2 and PBP1B in Enterobacteriaceae and P. Aeruginosa and subsequently inhibits penicillin-binding proteins, leading to the disruption of bacterial cell wall synthesis • Cilastatin: limits renal metabolism of imipenem via renal dehydropeptidase inhibitor • Relebactam: Beta-lactamase inhibitor that protects imipenem from degradation by serine beta-lactamases Recarbrio™ (Imipenem, Cilastatin, and Relebactam)
Dosing: • 1.25grams (imipenem 500mg, cilastatin 500mg, relebactam 250mg) IV over 30 minutes every 6 hours in patients 18 years and older with creatinine clearance >90mL/min Recarbrio™ (Imipenem, Cilastatin, and Relebactam)
• Preparation: 1 • Withdraw 20mL (in 10mL aliquots) from appropriate 100mL infusion bag (NS, D5W, D5NS, D5 /2NS, or 1 D5 /4NS). • Reconstitute vial with one 10mL aliquot. Shake well and transfer to infusion bag. • Transfer remaining 10mL aliquot to empty vial and shake well to ensure complete transfer of all vial contents. • Transfer remaining 10mL to infusion bag for a total volume of 100mL. • Refer to PI for reconstitution instructions for renal adjustment dosing • Solutions range from colorless to yellow
• Storage: • Intact vials: 20⁰C-25⁰C (68⁰F-77⁰F) • Reconstituted and diluted solution: 2 hrs room temperature, <24hrs refrigerated, do not freeze Recarbrio™ (Imipenem, Cilastatin, and Relebactam)
Adverse Reactions: • Headache (4%), Diarrhea (6%), vomiting (3%) • Increased AST/ALT (3%) • Phlebitis, infusion site pain, erythema (<2%) Precautions: • CNS reactions, seizures reported with imipenem-cilastatin • Clostridium difficile- associated diarrhea • Hypersensitivity reactions reported in patients with beta-lactam allergies Interactions: • Avoid use with ganciclovir, valproic acid, divalproex sodium due to seizure potential Cost (AWP): • $321/vial Recarbrio™ (Imipenem, Cilastatin, and Relebactam)
Initial determination of efficacy and safety of Recarbrio™ was supported by previous findings of the safety and efficacy of imipenem/cilastatin for the treatment of cIAI and cUTI • Contribution of relebactam was assessed through in vitro and in animals with infection Recarbrio™ (Imipenem, Cilastatin, and Relebactam) References: 1.Recarbrio (Imipenem, Cilastatin, Relebactam) [package insert]. Whitehouse Station, NJ: Merck & Co., Inc; 2019. 2.Imipenem, Cilastatin, Relebactam. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed February 8, 2020. 3.Motsch J, Murta de Oliveira C, Stus V, et al. RESTORE-IMI 1: A Multicenter, Randomized, Double-blind Trial Comparing Efficacy and Safety of Imipenem/Relebactam vs Colistin Plus Imipenem in Patients With Imipenem-nonsusceptible Bacterial Infections [published online ahead of print, 2019 Aug 10]. Clin Infect Dis. 2019;ciz530. doi:10.1093/cid/ciz530 4.Center for Drug Evaluation and Research. (n.d.). Drug Trial Snapshot: RECARBRIO. Retrieved February 8, 2020, from https://www.fda.gov/drugs/resources-information- approved-drugs/drug-trial-snapshot-recarbrio Xenleta™ (Lefamulin)
Shelby Dick, PharmD Option Care Health Xenleta™ (Lefamulin)
Classification: Pleuromutilin antibiotic • Approved August 19th, 2019 Indication: community-acquired bacterial pneumonia
Mechanism of Action: • Inhibits bacterial protein synthesis through interactions with the A- and P- sites of the peptidyl transferase center in domain V of the 23s Ribosomal RNA of the 50S subunit • The binding pocket of the bacterial ribosome closes around the mutilin core for an induced fit that prevents correct positioning of transfer RNA
Spectrum of activity: • S pneumonia, S aureus (MSSA), H Influenzae, Legionella, Mycoplasma Pneumoniae, Chlamydophila Pneumoniae • Not approved for CABP caused by MRSA Xenleta™ (Lefamulin)
Dosing: • IV: 150mg every 12 hours • Severe hepatic impairment (Child-Pugh class C): 150mg every 24 hours • Oral: 600mg every 12 hours • Not recommended for use in moderate-severe hepatic impairment (Child-Pugh class B or C)
Treatment Duration: • Total duration is a minimum of 5 days and varies based on disease severity and response to therapy; patients should remain afebrile and stable >48 hours prior to discontinuing therapy
Intravenous Preparation: • Dilute entire 15mL lefamulin vial into the provided diluent bag (250mL of 10mM citrate buffered NS). Mix thoroughly • Solutions should be clear, discard if particulate matter/discoloration is visible Xenleta™ (Lefamulin)
Adverse Reactions: • Injection: site reactions, hepatic enzyme elevation, nausea, hypokalemia, headache, insomnia • Tablets: diarrhea, nausea, vomiting, hepatic enzyme elevation
Precautions: • QT prolongation: monitor ECG in patients at risk • Superinfection including clostridium difficile infections • Hepatic impairment • Embryo-fetal harm
Interactions: • CYP3A4 substrate • Use caution with strong CYP3A4 inducers/inhibitors Xenleta™ (Lefamulin)
Administration • IV: infuse over 60 minutes • Oral: administer >1 hour before a meal or 2 hours after a meal; swallow whole with 6-8 ounces of water; do not crush/divide tablet
Storage: • Vials for Injection: 2⁰C-8⁰C (36⁰F- 46⁰F), do not freeze • Diluent Bags: stored at room temperature 20⁰C-25⁰C (68⁰F-77⁰F) • Diluted Product: <24 hrs at room temperature, <48 hours refrigerated • Tablets: stored at room temperature 20⁰C-25⁰C (68⁰F-77⁰F)
Cost (AWP): • 150mg/15mL (per mL): $8.20 ($246/day) • 600mg tablet: $165 each ($330/day) Xenleta™ (Lefamulin) Xenleta™ (Lefamulin)
1. Xenleta (lefamulin) [package insert]. Dublin, Ireland: Nabriva Therapeutics US, Inc; 2019.
2. Lefamulin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed February 8, 2020.
3. File TM, Goldberg L, Das A, et al. Efficacy and Safety of Intravenous-to-oral Lefamulin, a Pleuromutilin Antibiotic, for the Treatment of Community-acquired Bacterial Pneumonia: The Phase III Lefamulin Evaluation Against Pneumonia (LEAP 1) Trial. Clin Infect Dis. 2019;69(11):1856–1867. doi:10.1093/cid/ciz090
4. Alexander E, Goldberg L, Das AF, et al. Oral Lefamulin vs Moxifloxacin for Early Clinical Response Among Adults With Community-Acquired Bacterial Pneumonia: The LEAP 2 Randomized Clinical Trial [published online ahead of print, 2019 Sep 27]. JAMA. 2019;322(17):1661–1671. doi:10.1001/jama.2019.15468
5. Center for Drug Evaluation and Research. (n.d.). Drug Trials Snapshots: XENLETA. Retrieved February 8, 2020, from https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-xenleta
6. Lefamulin (Xenleta) for Community-Acquired Bacterial Pneumonia: The Medical Letter, Inc. (2019, September 23). Retrieved February 8, 2020, from https://secure.medicalletter.org/w1581a Bonsity (teriparatide)
Kristina Nguyen, PharmD Coram/CVS Specialty Infusion Services Bonsity (teriparatide)
• Class: parathyroid hormone analog (PTH1-34) • FDA approved: October 7, 2019 • Indication: • Treatment of postmenopausal women with osteoporosis at high risk for fracture • Increase of bone mass in men with primary or hypogonadal osteoporosis at high risk for fracture • Treatment of men and women with osteoporosis associated with sustained systemic glucocorticoid therapy at high risk for fracture • Dosing: 20 mg SQ daily for up to 2 years Bonsity (teriparatide) Clinical Trials Bonsity (teriparatide)
• BBW: potential risk of osteosarcoma • ADR: arthralgia, pain, nausea • Warnings/precautions: transient orthostatic hypotension, urolithiasis exacerbation • Monitoring: • Serum and urinary calcium • Bone mineral density Bonsity (teriparatide)
• Supplied: 620 mcg/2.48 mL (250 mcg/mL) • Storage: refrigeration at all times • Administration: SQ into thigh or abdominal wall • Initial injection should occur when a patient can sit or lie down • Patients and caregivers administering should receive appropriate training and instruction • AWP: awaiting therapeutic equivalence study Bonsity (teriparatide) References:
1. Bonsity [package insert]. San Diego, CA: Pfenex, Inc.; 2019. 2. Teriparatide. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed February 8, 2020. Vyleesi (bremelanotide)
Kristina Nguyen, PharmD Coram/CVS Specialty Infusion Services Vyleesi (bremelanotide)
• Drug class: melanocortin receptor agonist • FDA approval: June 21, 2019 • Indication: • Treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD) • Dosing: • 1.75mg SQ prn • At least 45 mins before anticipated sexual activity
https://www.vyleesi.com/wp-content/uploads/2019/08/AboutVyleesi_HandHoldingBox2.png Vyleesi (bremelanotide) Clinical Trials Vyleesi (bremelanotide) • ADR: nausea, flushing, injection site reactions, headache, vomiting • Warnings/precautions: transient increase in blood pressure, and decrease in heart rate • CI: uncontrolled hypertension or known cardiovascular disease • Counseling: • Use effective contraception, d/c use if pregnancy is suspected • Focal hyperpigmentation Vyleesi (bremelanotide) • Supplied: 1.75mg in 0.3mL solution in a single-dose, disposable prefilled autoinjector • Storage: refrigeration, protect from light • Administration: SQ in the abdomen or thigh • No more than 1 dose in 24 hours • More than 8 doses per month is not recommended • AWP: $270 (1.75mg/0.3mL) Vyleesi (bremelanotide) References:
1. Vyleesi [package insert]. Waltham, MA: AMAG Pharmaceuticals, Inc.; 2019. 2. Vyleesi. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Available at: http://online.lexi.com. Accessed February 8, 2020. 3. Kingsberg SA, et al. Obstet Gynecol. 2019 Nov;134(5):899-908. doi: 10.1097/AOG.0000000000003500. Reblozyl® (Luspatercept)
Dustin Lee, PharmD, PGY-1 Option Care Health Reblozyl® (Luspatercept)
•Approved November 2019
•Indications *Treatment of anemia in adults with beta thalassemia who require regular red blood transfusion •Dosing *Starting dose 1 mg/kg once every 3 weeks via subcutaneous injection *If no reduction in RBC transfusion burden after 2 doses, may increase dose to 1.24 mg/kg *Review hemoglobin results give when ≤ 11g/ dL •Serious adverse reactions *Thrombosis/Thromboembolism *Embryo-Fetal Toxicity Reblozyl® (Luspatercept)
• Average Wholesale Price • 25mg vial : $4,129 • 75mg vial : $12,388 • Appearance • Colorless to slightly yellow solution free of particulate matter • Storage • Store vials under refrigeration (2-8⁰)C protected from light. Do not freeze • Preparation • Mixed with sterile water, allow to stand for one minute, gently swirl vial for 30 seconds and let vial sit upright for • 30 seconds, repeat until in solution. • Stable for 8 hours at room temperature, 24 hours refrigerated • Nursing Considerations • Monitoring • Signs and symptoms of thromboembolic events • Hypertension Reblozyl® (Luspatercept)
• Response was defined as a reduction of at least 2 units for 3 consecutive doses • Patients with beta-thalassemia getting blood transfusions with no break longer than 5 weeks • No antiemetics or other pre-medications are recommended Reblozyl® (Luspatercept) References: • Markham, Anthony. "Luspatercept: First Approval." Drugs (2020): 1-6. • Platzbecker U, Germing U, Gotze KS, et al. Luspatercept for the treatment of anaemia in patients with lower-risk myelodysplastic syndromes (PACE-MDS): a multicentre, open-label phase 2 dose- finding study with long-term extension study. Lancet Oncol. 2017;18(10):1338–47. • Luspatercept . In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2020 [updated 15 Jan 2020; cited 27 Jan 2020]. Available from: http://online.lexi.com. Subscription required to view. • https://media.celgene.com/content/uploads/reblozyl-pi.pdf ® Enhertu (fam-trastuzumab deruxtecan-nxk)
Dustin Lee, PharmD, PGY-1 Option Care Health Enhertu® (fam-trastuzumab deruxtecan- nxk)
• Approved December 2019 • Indications • HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting • Dosing • IV use only • 5.4mg/kg once every 3 weeks • First dose over 90 minutes • Serious adverse reactions • Neutropenia, Left ventricular dysfunction • BBW Interstitial lung disease & embryo-fetal harm Enhertu® (fam-trastuzumab deruxtecan- nxk)
• Average Wholesale Price • 100 mg (per vial): $2,755 • Appearance • The solution should be clear and colorless to light yellow • Storage • Vials are stored under refrigeration in original carton protected from light • Do not shake • Preparation • Use sterile water for injection (5ml) to make concentration of 20mg/mL • Nursing Considerations • Reconstituted solution is stable for 24 hours under refrigeration • Administer with 0.2 micron in-line filter Enhertu® (fam-trastuzumab deruxtecan- nxk)
• The most common adverse reactions (≥20%) were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anemia, neutropenia, diarrhea, leukopenia, and respiratory tract infections Enhertu® (fam-trastuzumab deruxtecan- nxk) References:
• https://dsi.com/prescribing-information- portlet/getPIContent?productName=Enhertu&inline=true
• BioPharmaceuticals, Josie Afolabi, and Craig Marks Finance. "Enhertu (trastuzumab deruxtecan) approved in the US for HER2- positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based regimens.“
• Viña, Gonzalo, et al. "Enhertu (trastuzumab deruxtecan) approved in the US for HER2-positive unresectable or metastatic breast cancer following two or more prior anti-HER2 based regimens." ® Zulresso (Brexanolone)
Jordan Mendkoff, PharmD Fairview Pharmacy Services Zulresso® (Brexanolone)
• Approved: March 2019 • Drug Class: Gamma-aminobutyric acid (GABA) A Receptor Positive Modulator • Indication: Postpartum depression • MOA: Not fully understood, but thought to be related to its positive allosteric modulation of GABA A Receptors Zulresso® (Brexanolone)
• Boxed warning: Excessive sedation and sudden loss of consciousness • Monitoring: • Excessive sedation every 2 hours during planned, non-sleep periods • Continuous pulse oximetry monitoring • Specific populations: • Safe for breastfeeding, avoid in end stage renal disease • Zulresso® REMS Program • Facility, Pharmacy, Wholesaler, and Patient requirements Zulresso® (Brexanolone) • 0 to 4 hours: Start at 30 mcg/kg/hr • 4 to 24 hours: Increase to 60 mcg/kg/hr • 24 to 52 hours: Increase to 90 mg/kg/hr • Consider 60 mcg/kg/hr if not tolerating • 52 to 56 hours: Decrease to 60 mcg/kg/hr • 56 to 60 hours: Decrease to 30 mcg/kg/hr Zulresso® (Brexanolone)
Lancet. 2018 Sep 22;392(10152):1058-1070 Zulresso® (Brexanolone)
Lancet. 2018 Sep 22;392(10152):1058-1070 Zulresso® (Brexanolone) • Supplied: 100 mg/20 mL single-dose vial • Must be diluted before administration • Storage: • Refrigerate product (2-8ºC), protect from light • Diluted product can be refrigerated for up to 96 hours • Diluted product can be used for only 12 hours room temp • Cost: $8,940/vial (AWP) • Nursing Considerations: • Must use a PVC, non-DEHP, nonlatex infusion set • Must use programmable pump with a dedicated line Zulresso® (Brexanolone) References:
• Zulresso (brexanolone) [prescribing information]. Cambridge, MA: Sage Therapeutics, Inc; March 2019. • Meltzer-Brody S, Colquhoun H, Riesenberg R, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo- controlled, phase 3 trials Lancet. 2018;392(10152):1058-1070. ® Adakveo (crizanlizumab-tnca)
Sofia Shrestha, PharmD Fairview Pharmacy Services Adakveo® (crizanlizumab-tnca)
• Selectin-targeted monoclonal antibody • Approval: November 15, 2019 • Indication: Sickle cell disease − Reduce frequency of vasoocclusive crises in patients 16 years of age and older • MOA: Binds to p-selectin on the surface of activated endothelium and platelets, blocking interactions between endothelial cells, platelets, red blood cells, and leukocytes • Dosing: 5mg/kg intravenously over 30 minutes − Initial Dose: Week 0 − Loading Dose: Week 2 − Maintenance Dose: Week 6 and every 4 weeks thereafter Adakveo® Preparation & Administration
• 5mg/kg - Dose based on patient’s actual body Administration weight −0.2 micron filter • May be given with or without hydroxyurea −Do not co-administer or mix with other drugs through • Stability of prepared product same IV line −After administration, flush line with 25mL NS or D5W Missed dose −If administered within 2 weeks after missed dose, continue original schedule −If administered more than 2 weeks after missed dose, continue dosing every 4 weeks thereafter Adakveo® SUSTAIN Clinical Trial Adakveo® Safety Considerations
• Warnings and precautions: − Infusion-Related Reactions: 3% in clinical trials → Monitor for signs and symptoms of reactions − Laboratory Test Interference: Interference with automated platelet counts (platelet clumping) has been observed • Most common adverse reactions (>10%): − Headache, back pain, nausea, vomiting, arthralgia, UTI, upper respiratory tract infection, pruritis, chest pain
• Use in special populations: − Pregnancy: May cause fetal harm − Safety and efficacy in pediatric patients <16 years of age not established Adakveo® Storage & Cost
• Available as 100mg/10mL solution in single-dose vial • Store under refrigeration (2°C to 8°C) and protect from light • Cost: $2,829/vial (AWP) • Annualized cost: $113,143 (assuming 80kg patient) Adakveo® References:
1. Ataga KI, Kutlar A, Kanter J, et al: Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med 2017; 376(5):429-439. 2. ADAKVEO(R) intravenous injection, crizanlizumab-tmca intravenous injection. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2019. 3. Crizanlizumab. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (Accessed on February 14, 2019.) 4. Crizanlizumab, Voxelotor, and L-Glutamine for Sickle Cell Disease: Effectiveness and Value. Draft Evidence Report. Institute for Clinical and Economic Review. January 23, 2020. ® Asceniv (immune globulin intravenous, human - slra)
Sofia Shrestha, PharmD Fairview Pharmacy Services Asceniv®
• Plasma-derived, polyclonal, immune globulin intravenous (human) 10% liquid • Approval: April 1, 2019 • Indication: Primary humoral immunodeficiency (PI) in adults and adolescents (12-17 years of age) • MOA: Replacement therapy for immunodeficiencies • Broad spectrum of neutralizing IgG antibodies against bacterial and viral pathogens and their toxins help to avoid recurrent serious opportunistic infections Asceniv Dosage & Administration
• Dose adjustments → Patients who fail to maintain trough total IgG of at least 500mg/dL • Renal insufficiency: − Ensure patients are not volume-depleted − Administer at minimum infusion rate practicable and discontinue if renal function deteriorates • Administration: − Intravenous use only − Bring to room temperature before use − Do not shake, dilute, or mix with other IG products − Monitor vital signs throughout the infusion and slow or stop infusion if reactions occur Asceniv Clinical Trial Asceniv Safety
Adverse Reactions (>5%) Additional Warnings and Precautions
− Headache − Hypoproteinemia, hyponatremia, ↑ serum viscosity − Sinusitis − Aseptic Meningitis Syndrome − Diarrhea − Hemolysis − GI and respiratory tract infections − Transfusion-Related Acute Lung Injury − Transmissible Infectious Agents Asceniv Safety
Monitoring Special populations −Geriatric patients >65 years: if at risk − Renal function, BUN, creatinine before and for renal insufficiency, do not exceed during therapy recommended dose and infusion rate − Consider baseline blood viscosity test −Pregnancy/Lactation: No known harm Interactions − Passive transfer of antibodies may transiently interfere with immune response to live virus vaccines Asceniv Other Considerations
• Available as 5g/50mL single-use vial • Store under refrigeration (2 to 8°C); do not freeze or heat • Cost: $5,454/vial (AWP) Asceniv References
1. Asceniv (immune globulin intravenous [human]) [prescribing information]. Boca Raton, FL: ADMA Biologics; April 2019. 2. Immune globulin (Intravenous, subcutaneous, and intramuscular). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com (Accessed on February 14, 2019.) 3. Asceniv. Vaccines, Blood & Biologics. U.S. Food & Drug Administration. (Accessed on February 14, 2019.) Esperoct (turoctocog alfa pegol, N8-GP)
Rachel Dellevar, PharmD Coram/CVS Specialty Infusion Services Esperoct (turoctocog alfa pegol, N8-GP)
Coagulation Factor VIII concentrate, conjugated to a 40-kDa polyethylene glycol molecule to increase the half-life and decrease rate of clearance • Approval date: 2/19/2019 • Manufacturer: Novo Nordisk • Indication: Treatment of adults and children with hemophilia A for: • On-demand treatment and control of bleeding episodes • Perioperative management of bleeding • Routine prophylaxis to reduce the frequency of bleeding episodes Esperoct (turoctocog alfa pegol, N8-GP)
Dosing*: • Control Bleeding Episodes: • Age ≥12 yrs: 40 IU/kg (minor/moderate); 50 IU/kg (major) • Age <12 yrs: 65 IU/kg • Perioperative Management: • Age ≥12 yrs: 50 IU/kg • Age <12 yrs: 65 IU/kg • Routine Prophylaxis: • Age ≥12 yrs: 50 IU/kg every 4 days • Age <12 yrs: 65 IU/kg twice weekly
*May also be dosed to achieve a specific target Factor VIII activity level: Dosage (IU) = Body Weight (kg) × Desired Factor VIII Increase (IU/dL or % normal) × 0.5 Esperoct (turoctocog alfa pegol, N8-GP)
• Supplied as: single-dose vials (500, 1000, 1500, 2000, or 3000 IU) • AWP: $2.68 per each • Storage: protect from light, powder stored under refrigeration • Powder: 30 month refrigerated; 12 months room temperature • Reconstituted: 24 hrs refrigerated; 4 hrs room temperature • Administration: IV only • Comes with prefilled diluent syringe to reconstitute vial • Infuse IV slowly over 2 minutes Esperoct (turoctocog alfa pegol, N8-GP) Esperoct (turoctocog alfa pegol, N8-GP) References: • Esperoct [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2019. • Tiede A, Brand B, Fischer R, et al. Enhancing the pharmacokinetic properties of recombinant factor VIII: first-in-human trial of glycoPEGylated recombinant factor VIII in patients with hemophilia A. J Thromb Haemost. 2013;11(4):670-678. • Giangrande P, Andreeva T, Chowdary P, et al. Clinical evaluation of glycoPEGylated recombinant FVIII: efficacy and safety in severe haemophilia A. Thromb Haemost. 2017;117(2):252-261. • Esperoct. Micromedex Solutions. Truven Health Analytics, Inc. Ann Arbor MI. Available at http://www.micromedexsolutions.com. Accessed 2/11/2020. Other Biologics & Biosimilars
Rachel Dellevar, PharmD Coram/CVS Specialty Infusion Services