October through December 2013

precautions about the risk of blood clots and severe Updated Warnings—Current Drugs narrowing of blood vessels, revise recommendations about dosage and administration of Iclusig, and update the patient Medication Guide. We are also requiring a risk Mass Destruction Muscle Growth—Safety Risk: The evaluation and mitigation strategy (REMS). In addition, FDA is advising consumers to immediately stop using a the manufacturer of Iclusig, ARIAD Pharmaceuticals, must product called Mass Destruction, marketed as a dietary conduct postmarket investigations to further characterize supplement for muscle growth. The product is labeled to the drug’s safety and dosing. contain at least one synthetic anabolic steroid and has been On October 31, 2013, FDA requested and ARIAD agreed to linked to at least one reported serious illness. The product’s voluntarily suspend marketing of Iclusig. FDA’s request ingredients are undergoing further analysis by the FDA. resulted from FDA’s investigation, which revealed a steady Liver injury is generally known to be a possible outcome of increase in the number of serious vascular occlusion events using products that contain anabolic steroids and steroid- identified through continued safety monitoring of the drug. like substances. In general, anabolic steroids may cause This observation represented a significant change in the other serious long-term consequences in women, men, and safety profile of Iclusig as the proportion of patients on the children. These include adverse effects on blood lipid lev- drug experiencing vascular occlusion events such as blood els, increased risk of heart attack and stroke, masculiniza- clots and severe narrowing of blood vessels was tion of women, shrinkage of the testicles, breast enlarge- significantly greater than the proportion reported at the ment, infertility in males, and short stature in children. time of its approval in December 2012 (see data summary). The FDA was alerted by the North Carolina Department of During the marketing suspension, Iclusig treatment has Health and Human Services of a serious injury associated been available through single patient or emergency with use of Mass Destruction. The report described a previ- investigational new drug applications (INDs). Patients ously healthy 28-year-old male with liver failure requiring should continue to receive Iclusig under their authorized transplant after several weeks of product use. Mass De- IND until marketing of Iclusig is resumed. FDA is working struction is manufactured for Blunt Force Nutrition in closely with ARIAD on the new safety measures and Sims, N.C. and sold in retail stores, fitness gyms, and on anticipates these will be in place by the end of January the Internet. An investigation is underway to identify the 2014. Once that process is complete, patients being treated product’s manufacturer. under these INDs can be transitioned back to receiving the Consumers who suspect they are experiencing problems marketed Iclusig product. (12/20/13) associated with Mass Destruction or other body building products should consult a health care professional, espe- Methylphenidate Medications for ADHD—Safety cially if they have experienced unexplained fatigue, ab- Risk: The FDA is warning that methylphenidate products, dominal or back pain, discolored urine, or any other unex- one type of stimulant drug used to treat attention deficit plained changes in their health. (12/23/13) hyperactivity disorder (ADHD), may in rare instances cause prolonged and sometimes painful erections known as New Safety Measures for Iclusig: The FDA is priapism. Based on a recent review of methylphenidate requiring several new safety measures for the leukemia products, the FDA updated drug labels and patient drug Iclusig (ponatinib) to address the risk of life- Medication Guides to include information about the rare threatening blood clots and severe narrowing of blood but serious risk of priapism. If not treated right away, vessels. Once these new safety measures are in place, the priapism can lead to permanent damage to the penis. manufacturer of Iclusig is expected to resume marketing to Priapism can occur in males of any age and happens when appropriate patients. Health care professionals should blood in the penis becomes trapped, leading to an review these additional safety measures and carefully abnormally long-lasting and sometimes painful erection. consider them when evaluating the risks and benefits of Another ADHD drug, Strattera (atomoxetine), has also Iclusig for each patient. been associated with priapism in children, teens, and The required safety measures involve label changes to adults. narrow the indication, provide additional warnings and

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For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 1 Priapism appears to be more common in patients taking care professionals carefully consider the timing of spinal atomoxetine than in those taking methylphenidate catheter placement and removal in patients taking products; however, because of limitations in available anticoagulant drugs, such as enoxaparin, and delay dosing information, FDA does not know how often priapism of anticoagulant medications for some time interval after occurs in patients taking either type of product. catheter removal to decrease the risk of spinal column Healthcare professionals should talk to male patients and bleeding and subsequent paralysis after spinal injections, their caregivers to make sure they know the signs and including epidural procedures and lumbar punctures. symptoms of priapism and stress the need for immediate These new timing recommendations, which can decrease medical treatment should it occur. Younger males, the risk of epidural or spinal hematoma, will be added to especially those who have not yet reached puberty, may not the labels of anticoagulant drugs known as low molecular recognize the problem or may be embarrassed to tell weight heparins, including Lovenox and generic anyone if it occurs. enoxaparin products and similar products. Encourage your patients to read the Medication Guide they Epidural or spinal hematomas are a known risk of receive with every filled prescription. Use caution when enoxaparin in the setting of spinal procedures and are considering switching patients from methylphenidate to already described in the Boxed Warning and the Warnings atomoxetine. Patients should not stop taking a and Precautions sections of the labels for Lovenox and methylphenidate product without first discussing it with generic enoxaparin products. However, these serious your health care professional. (12/17/13) adverse events continue to occur (see Data Summary). To address this safety concern, FDA worked with the Boxed Warning Revised for Hydroxyethyl Starch manufacturer of Lovenox, Sanofi-Aventis, to further Solutions: Hydroxyethyl starch solutions, indicated to evaluate this risk and to update the Warnings and treat hypovolemia in patients where plasma volume Precautions section of the Lovenox label with these expansion is desired, has had its boxed warning modified additional timing recommendations. The labels for generic by the FDA to include all of the following: enoxaparin products will also be revised accordingly, as • patients receiving open heart surgery associated with will those of other low molecular weight heparin-type cardiopulmonary bypass should be monitored for status products. of coagulation due to excessive bleeding being reported It is important to note that all anticoagulants carry the risk when hydroxyethyl starch products were used of causing spinal bleeding when used in conjunction with • patients who have severe liver disease should not use epidural/spinal anesthesia or spinal puncture. We are hydroxyethyl starch solutions continuing to evaluate the safety of other anticoagulants to • liver function should be monitored in patients receiving determine if additional label changes are needed. hydroxyethyl starch solutions Health care professionals and institutions involved in Recommendations from the FDA for medical professionals performing spinal/epidural anesthesia or spinal punctures also consisted of all of the following: should determine, as part of a preprocedure checklist, • adult patients who are severely ill (including patients whether a patient is receiving anticoagulants and identify with sepsis and patients who have been admitted into the appropriate timing of enoxaparin dosing in relation to the intensive care unit) should not be given catheter placement or removal. To reduce the potential risk hydroxyethyl starch products of bleeding, consider both the dose and the elimination • use should be avoided in patients who have preexisting half-life of the anticoagulant: renal dysfunction • For enoxaparin, placement or removal of a spinal • at the first sign of renal injury, hydroxyethyl starch catheter should be delayed for at least 12 hours after solutions should be discontinued administration of prophylactic doses such as those used • renal replacement therapy has been needed for some for prevention of deep vein thrombosis. Longer delays patients up to 90 days after administration of this (24 hours) are appropriate to consider for patients medication; continuation of renal monitoring for at least receiving higher therapeutic doses of enoxaparin (1 90 days in all patients is necessary mg/kg twice daily or 1.5 mg/kg once daily). • avoidance of use in patients having open heart surgery • A postprocedure dose of enoxaparin should usually be associated with cardiopulmonary bypass due to given no sooner than 4 hours after catheter removal. excessive bleeding • In all cases, a benefit-risk assessment should consider • at the first sign of coagulopathy, this drug should be both the risk for thrombosis and the risk for bleeding in discontinued the context of the procedure and patient risk factors. Voluven, a brand name of this drug manufactured by (11/6/13) Hospira, is also indicated for prophylaxis of hypovolemia if expansion of plasma volume is required. Hespan (brand Ofirmev (acetaminophen injection) Boxed name manufactured by B. Braun) is further indicated as Warning: Ofirmev (acetaminophen injection) has had a adjunctive therapy in leukapheresis to improve harvesting new boxed warning approved by the FDA added to its label. and increase the yield of granulocytes by centrifugal means. The first part of the boxed warning states to medical (11/27/13) professionals the risk of medication errors which could result in the accidental overdosing of patients. The second Low Molecular Weight Heparins Safety warning listed notifies providers about the risk of Communication: The FDA is recommending that health hepatotoxicity when using this medication. Ofirmev is For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 2 used for the management of mild to moderate pain and the Recalls/Suspensions reduction of fever. This drug is also indicated for managing mild to moderate severe pain in combination with other Any adverse events that may be related to the use of these products should be reported to the FDA's MedWatch Adverse Event Reporting Program (contact opioid analgesics. Ofirmev is manufactured by Cadence information located at the end of the bulletin). Pharmaceuticals. (11/4/13)

Entereg Boxed Warning Expanded: Entereg Abrams Royal Pharmacy Sterile Products: Abrams (alvimopan), manufactured by Cubist Pharmaceuticals, has Royal Pharmacy is voluntarily recalling all unexpired lots of had its boxed warning expanded by the FDA to include the sterile products dispensed nationwide due to concerns of potential risk of myocardial infarction when used long- lack of sterility assurance. All unexpired lots of sterile term. Entereg is approved to accelerate the time of upper compounded products are subject to the recall. Sterile and lower gastrointestinal recovery after partial small or products are injectable medications, IVs, eye drops, pellet large bowel resection surgery with primary anastomosis. implants, nasal sprays, inhalation solutions, and eye The medication is only available through the Risk and ointments. Evaluation and Mitigation Strategy (REMS) which restricts The recall was issued after a single, isolated report of an its use to a short-term duration. Due to this, Entereg is adverse event involving a patient in California who received dispensed with a medication guide. (10/23/13) a compounded medication from the pharmacy. If there is microbial contamination in products intended to be sterile, Iclusig (ponatinib): Drug Safety Communication – patients are at risk for serious, potentially life-threatening Increased Reports of Serious Blood Clots in infections. Arteries and Veins: The FDA is investigating an All recalled products have a label that includes Abrams increasing frequency of reports of serious and life- Royal Pharmacy’s name and phone as well as a lot number. threatening blood clots and severe narrowing of blood While not every label contains an expiration date, vessels (arteries and veins) of patients taking the leukemia consumers can call the pharmacy with the lot number and chemotherapy drug Iclusig (ponatinib). Data from clinical find out the expiration date. trials and postmarket adverse event reports show that The recalled products were distributed to health care serious adverse events have occurred in patients treated facilities, physicians, and patients from June 17, 2013, with Iclusig, including heart attacks resulting in death, through December 17, 2013. worsening coronary artery disease, stroke, narrowing of Abrams Royal Pharmacy is notifying its customers by mail large arteries of the brain, severe narrowing of blood and is arranging for the return of all recalled medication. vessels in the extremities, and the need for urgent surgical To return product or request assistance related to this procedures to restore blood flow. FDA is actively working recall, users should contact Abrams Royal at 214-349- to further evaluate these adverse events and will notify the 8000, Monday through Friday, between 9:00 a.m. and public when more information is available. 5:00 p.m. CST. Iclusig is a prescription medicine used to treat adults Customers that have product which is being recalled should diagnosed with chronic phase, accelerated phase, or blast stop using it and contact the pharmacy to arrange for phase chronic myeloid leukemia (CML) or Philadelphia return of unused product. (12/19/13) chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), who are no longer benefiting from previous Hydravax Dietary Supplement – Possible treatment or who did not tolerate other treatment. At the Undeclared Ingredient: IQ Formulations, of Sunrise, time of Iclusig’s approval in December 2012, the drug label Florida, is initiating a recall of all lots of its 45-capsule contained information about the risks of blood clots in the bottles of Hydravax due to potential inclusion of an Boxed Warning and Warnings and Precautions sections. In unlisted ingredient. The United States Food and Drug clinical trials conducted before approval, serious arterial Administration (FDA) has advised IQ Formulations that an blood clots occurred in 8 percent of Iclusig-treated analysis of a sample from one lot of Hydravax (Lot # 2458, patients, and blood clots in the veins occurred in 3 percent Exp # 07/16) revealed the presence of an undeclared of Iclusig-treated patients. In the most recent clinical trial ingredient (a diuretic). Diuretics are prescription drugs and data submitted by the manufacturer to FDA, at least 20 thus, are not listed on the packaging label for Hydravax. percent of all participants treated with Iclusig have Consumers are hereby notified not to use the product. developed blood clots or narrowing of blood vessels. Possible effects of using a diuretic include an electrolyte Health care professionals should consider for each patient, imbalance due to water loss. Symptoms include: polyuria, whether the benefits of Iclusig treatment are likely to nausea, vomiting, weakness, lassitude, fever, flushed face, exceed the risks of treatment. Patients taking Iclusig and hyperactive deep tendon reflexes. Fluid and electrolyte should seek immediate medical attention if they experience imbalances are the most important concern. Excessive symptoms suggesting a heart attack such as chest pain or doses of diuretics may elicit hyperkalemia, dehydration, pressure, pain in their arms, back, neck or jaw, or shortness nausea, vomiting and weakness, and possibly hypotension. of breath; or symptoms of a stroke such as numbness or Overdosing with a diuretic has been associated with weakness on one side of the body, trouble talking, severe hypokalemia, hypochloremia, hyponatremia, dehydration, headache, or dizziness. FDA is providing this information lethargy, and gastrointestinal irritation. People to patients and health care professionals while it continues experiencing these problems should seek immediate its investigation. (10/11/13) medical attention. For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 3 The product comes in a 45-capsule bottle. The recalled recalled, should stop using the product and return it to Hydravax was distributed nationwide in retail stores and place of purchase. mail order. Production of the product has been suspended Consumers with questions regarding this recall can contact while the company continues their investigation as to the Tendex by phone (800) 984-0341, from Monday to Friday, source of the potential unlisted ingredient. 9:00AM-5PM PST. Consumers should contact their All consumers who have purchased Hydravax 45-capsule physician or healthcare provider if they have experienced bottles are urged to return them to the place of purchase any problems that may be related to taking or using these for a full refund. Consumers and distributors with drug products. (11/20/13) questions regarding this recall should contact IQ Formulations Customer Service at RezzRX – Undeclared Drug Ingredients: Fossil Fuel [email protected] or by phone at 800-626-1022, Products, LLC, is recalling lots QL110714A102 and Monday through Friday from 9 am to 5 pm EST. (12/1/13) QL110408B046 of “RezzRX.” Laboratory analysis conducted by the FDA determined the RezzRX lot FreeStyle and FreeStyle Lite Test Strips: Abbott is QL110714A102 contains undeclared initiating a voluntary recall of 20 lots of FreeStyle and hydroxylthiohomosildenafil and aminotadalafil and FreeStyle Lite Blood Glucose Test Strips in the United RezzRX lot QL110408B046 contains undeclared States. These lots of test strips may produce erroneously hydroxylthiohomosildenafil. The products have been found low blood glucose results when used with both FreeStyle to contain active ingredients of FDA approved drugs used Blood Glucose Meters and FreeStyle Flash Blood Glucose to treat erectile dysfunction (ED), making “RezzRX” an Meters [neither of which have been in production since unapproved new drug. 2010], as well as the OmniPod Insulin Management These undeclared active ingredients pose a threat to System. consumers because use of these products have the potential When the test strips are used with the newer FreeStyle to interact with nitrates found in some prescription drugs brand meters including FreeStyle Freedom Blood Glucose such as nitroglycerin and may lower blood pressure to Meter, FreeStyle Lite Blood Glucose Meter, and FreeStyle unsafe levels. Additionally, these products may cause side Freedom Lite Blood Glucose Meter, the blood glucose test effects, such as headaches and flushing. results are not affected. Additionally, testing with the RezzRX is marketed as a natural supplement for sexual FreeStyle InsuLinx Blood Glucose Meter is not affected by enhancement. RezzRX was distributed nationwide through this action, as FreeStyle InsuLinx Blood Glucose Meters various websites and retail stores in Georgia. use FreeStyle InsuLinx Test Strips. Consumers, distributors and retailers that have product The affected test strips are from lots that hold expiration which is being recalled should stop using and return to dates between May 2014 and March 2015, and can be place of purchase. Consumers should contact their located in the Firm Press Release. physician or healthcare provider if they have experienced The company is notifying healthcare professionals, any problems that may be related to taking or using this pharmacies, distributors, and customers about the recall; drug product. Consumers with questions regarding this customers affected by this action are instructed to call recall can contact Fossil Fuel Products, LLC, by 1-877-773- Abbott's diabetes care customer service at 1-888- 736-9869 9979 or [email protected], Monday-Friday, 9:00 am- 5:00 for a replacement of the affected test strips at no charge. pm, EST. (11/19/13) (11/28/13) Rhino 5 Plus, Maxtremezen, and Extenzone: P-Boost and NatuRECT by Tendex: Tendex is Jobbers Wholesale is recalling Lot No. voluntarily recalling Lot# F51Q of P-Boost and Lot # F51Q KWAKPMC030505175957019 of Rhino 5 Plus, Lot No. of NatuRECT to the consumer level. The FDA laboratory JBP-L-1270-70 of Maxtremezen and Lot No. analysis on Lot# F51Q of P-Boost, which the firm also KWAKPMC03050517 of Extenzone. FDA analysis found labels as NatuRECT, has determined that this product these products to contain undeclared contains undeclared tadalafil. Tadalafil is an active desmethylcarbondenafil and dapoxetine, making these ingredient of FDA-approved prescription drugs used to products unapproved new drugs. Desmethylcarbondenafil treat erectile dysfunction (ED), making these products is a posphodiesterase (PDE-5) inhibitor which is a class of unapproved drugs. drugs used to treat male erectile dysfunction (ED). The undeclared active ingredient poses a threat to Dapoxetine is an active ingredient not approved by the consumers because tadalafil may interact with nitrates FDA. Chemically, dapoxetine belongs to a class of drugs found in some prescription drugs, such as nitroglycerin, known as selective serotonin reuptake inhibitors (SSRIs) and may lower blood pressure to unsafe levels. used to treat depression. These products are labeled and intended to be used as Desmethylcarbondenafil may pose a threat to consumers dietary supplements for sexual enhancement. They are because this PDE-5 inhibitor may interact with nitrates packaged in 1 capsule blister packs and 5, 10, 20, 40 found in some prescription drugs (such as nitroglycerin) capsule bottles. Both products are distributed nationwide and may lower blood pressure to dangerous levels that can to wholesale and retail customers and via the internet. be life threatening. Dapoxetine has not been approved by Tendex is notifying its distributors and customers by direct the FDA and therefore its safety or efficacy has not been mail or email and is arranging for return of all recalled established. Studies have shown that antidepressants products. Consumers, who have the product which is being increased the risk of suicidal thinking and behavior in For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 4 children, adolescents, and young adults when compared to to prevent further potential contamination. See the press placebo. Therefore, consuming these products presents a release for a listing of products affected by this recall. health risk which could be life threatening. Chloramphenicol is a prescription drug commonly used to Rhino 5 Plus, Maxtremezen and Extenzone are labeled and treat typhoid fever and eye infections around the world. It intended to be used as dietary supplements for sexual should only be used under medical supervision. It has been enhancement. All three products were distributed to associated with rare cases of aplastic anemia and allergic selected retail customers in California by Jobbers reactions in some people. Wholesale from June 1, 2013 to November 7, 2013. If you have purchased a product from any of the lot codes Consumers and retailers that have these products which affected by this recall, please call Vega for a full refund: 1- are being recalled should stop consumption or further 866-839-8863. (11/12/13) distribution and return to place of purchase or directly to Jobbers Wholesale, 16101 Garfield Avenue, Paramount, CA OxyElite Pro Dietary Supplements—Linked to 90723. Consumers should contact their physician or Liver Illnesses: The FDA announced today that USP healthcare provider if they have experienced any problems Labs LLC, of Dallas, Texas, is recalling certain OxyElite Pro that may be related to taking or using this product. dietary supplement products that the company markets. Consumers with questions regarding this recall can contact The company took this action after receiving a letter from Jobbers Wholesale by phone (562-331-0700), from the FDA stating that the products have been linked to liver Monday to Friday, 09:00-17:00. (11/19/13) illnesses and that there is a reasonable probability that the products are adulterated. Nature’s Pharmacy and Compounding Center In a review of 46 medical records submitted to the FDA by Sterile Products: Nature's Pharmacy and Compounding the Hawaii Department of Health, the records indicated Center of Asheville, NC is voluntarily recalling all lots of that 27 patients, or 58 percent, had taken a dietary sterile products compounded by the pharmacy that are not supplement labeled as OxyElite Pro prior to becoming ill. expired to the consumer level. The product will be in the Seventeen of the 27 patients (or 63 percent) reported that form of an injectable drug or an eye drop. The recall is OxyElite Pro was the only dietary supplement they were being initiated due to concerns associated with quality taking. One death has occurred among these patients, control procedures that present a potential risk to sterility another patient has required a liver transplant, and others assurance that were observed during a recent FDA await liver transplants. For a list of products affected please inspection. see the FDA News Release. This recall is being conducted as a result of an inspection By letter dated Nov. 6, 2013, the FDA notified USPlabs conducted by the North Carolina Board of Pharmacy. These about findings indicating a link between the use of OxyElite products were supplied to the offices of licensed medical Pro products and a number of liver illnesses reported in professionals and to patients by prescription within the Hawaii. The FDA also noted that cases of liver damage after pharmacy's local market area in North Carolina. They were use of these OxyElite Pro products had been found in a distributed from January 1, 2013 to present. Out of number of other states. abundance of caution and in the interest of the pharmacy's In a warning letter issued to USPlabs LLC on Oct. 11, 2013, patients, Nature's Pharmacy has decided to voluntarily the FDA informed the company that OxyElite Pro and proceed with this recall process and to cease production of another dietary supplement called VERSA-1 were deemed all sterile products. to be adulterated. The products contained aegeline, a new Medical professionals, clinics, or patients who have these dietary ingredient (i.e., an ingredient not marketed in the products should stop its use and return them to the place of United States before Oct. 15, 1994) that lacks a history of purchase. Clinics should contact any patient that has use or other evidence of safety. The letter stated that failure received treatment using any of these sterile products. to immediately cease distribution of all dietary Consumers or health care providers with questions supplements containing aegeline may result in regarding this recall may contact Nature's Pharmacy at enforcement action. 828-251-0094 or toll free at 800-645-8201 Monday In addition to the products being recalled, the FDA through Friday, 9:30 am to 6:00 pm EST or by e-mail: continues to advise consumers not to use any dietary [email protected]. (11/16/13) supplements labeled OxyElite Pro or VERSA-1. Consumers who believe they have been harmed by using a Vega One Nutritional Shakes and Vega Sport dietary supplement should contact their health care Performance: Sequel Naturals Inc., dba “Vega,” notified practitioner. If consumers think they have suffered a the public of a recall of its Vega One Nutritional Shakes and serious harmful effect or illness from a dietary supplement, Sports Performance Protein products due to finding trace healthcare professionals and patients are encouraged to amounts of chloramphenicol (CAP), an antibiotic. People report adverse events or side effects related to the FDA's who have severe sensitivity or allergies to chloramphenicol MedWatch Safety Information and Adverse Event may run the risk of an allergic reaction if they consume Reporting Program. (11/10/13) these products. Pregnant or lactating women should avoid this medication. Jimpness Beauty Fat Loss Capsules Contain Vega is withdrawing all of the listed products from the Hidden Drug Ingredients: The FDA is advising market and has taken steps to ensure all future products consumers not to purchase or use Jimpness Beauty Fat are CAP-free, including using a different source of enzymes For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 5 Loss Capsules, a product promoted and sold for weight loss Iclusig Marketing and Sales Suspended: The FDA on various websites, includingwww.jimpness.net. has asked the manufacturer of the leukemia chemotherapy FDA laboratory analysis confirmed that Jimpness Beauty drug Iclusig (ponatinib) to suspend marketing and sales of Fat Loss Capsules contain sibutramine, phenolphthalein, Iclusig because of the risk of life-threatening blood clots and sildenafil. and severe narrowing of blood vessels. We will continue to Sibutramine is a controlled substance that was removed evaluate the drug to further understand its risks and from the market in October 2010 for safety reasons. The potential patient populations in which the benefits of the product poses a threat to consumers because sibutramine drug may outweigh the risks. Patients currently receiving is known to substantially increase blood pressure and/or Iclusig should discuss with their health care professionals pulse rate in some patients and may present a significant the risks and benefits of continuing treatment with the risk for patients with a history of coronary artery disease, drug. congestive heart failure, arrhythmias, or stroke. This The drug manufacturer, Ariad Pharmaceuticals, has agreed product may also interact, in life-threatening ways, with to FDA’s request to suspend marketing and sales of Iclusig other medications a consumer may be taking. while we continue to evaluate the safety of the drug. At this Phenolphthalein was an ingredient in some over-the- time, patients and health care professionals should follow counter (OTC) laxative products until 1999, when FDA FDA’s new recommendations for the drug: reclassified the ingredient as “not generally recognized as Patients currently taking Iclusig who are not responding to safe and effective.” the drug should immediately discontinue treatment and Sildenafil is the active ingredient in the FDA approved discuss alternative treatment options with their health care prescription drug Viagra, used to treat erectile dysfunction professionals. (ED). This undeclared ingredient may interact with nitrates Patients who are currently taking Iclusig and responding to found in some prescription drugs such as nitroglycerin and the drug and whose health care professionals determine may lower blood pressure to dangerous levels. Men with that the potential benefits outweigh the risks should be diabetes, high blood pressure, high cholesterol, or heart treated under a single-patient Investigational New Drug disease often take nitrates. (IND) application or expanded access registry program Consumers should stop using this product immediately and while FDA’s safety investigation continues. FDA will work throw it away. Consumers who have experienced any with the manufacturer on a plan to quickly transition these negative side effects should consult a health care patients to a program that will allow access under an IND professional as soon as possible. (11/7/13) or expanded access registry program. Patients: For more information on access to treatment under an IND, please Perrigo Acetaminophen Infant Suspension Liquid: refer to the following website: Access to Investigational The Perrigo Company announced that it has initiated a Drugs Outside of a Clinical Trial (Expanded Access). voluntary, nationwide product recall to the retail level of 18 Health care professionals should not start treating new batches of its acetaminophen infant suspension liquid, 160 patients with Iclusig unless no other treatment options are mg/5 mL, sold in 2 oz. and 4 oz. bottles with syringes in a available and all other available therapies have failed. box under store brand products including Babies R Us, Upon the determination of their health care professional, Care One and more (refer to the Firm Press Release for full these patients can be considered for treatment under an list of affected brand names and products). IND or expanded access registry program. (10/31/13) The recall is being initiated because of the remote potential that a small number of packages might contain an oral Specialty Medicine Compounding Pharmacy: dosing syringe without dose markings. Using an oral Specialty Medicine Compounding Pharmacy is voluntarily syringe without dose markings can result in inaccurate recalling all lots of certain unexpired human and veterinary dosing, especially in infants who could mistakenly get too sterile products to the consumer level due to particulate high a dose. matter found in vials of a compounded dextrose injection This over the counter product is indicated for the relief of product dispensed to a local hospital. Further testing and fever and minor aches and pains and can be used in analysis of the medication is being conducted. If there is infants, children and adults. These recalled products are microbial contamination in products intended to be sterile, sold by distributors nationwide and distributed through patients are at risk for serious, potentially life-threatening retail stores. infections. If the oral dosing device contained in the package has dose The recalled products were distributed to hospitals and markings (for 1.25 mL, 2.5 mL, 3.75 mL, and 5 mL), no consumers located only within Michigan from July 1, 2013, action is required, and the consumer can continue to use through October 19, 2013. No products were distributed the product consistent with the label instructions. If the out of state. Refer to the Firm Press Release for a detailed package contains an oral dosing device that does not have list of affected products. dose markings, the consumer should not use the product Customers that have product which is being recalled should and should call Perrigo’s Consumer Affairs Department, stop using it and contact the pharmacy to arrange for toll free, 1-800-719-9260. Consumers should contact their return of unused product. Customers with questions physician or healthcare provider if they have any questions, regarding this recall may contact the pharmacy at 248-446- or if they or their children experience any problem that 2643, Monday through Friday, between 8:00 a.m. and 5:00 could possibly be related to this drug product. (11/2/13) p.m. EDT. Consumers should contact their physician or health care provider if they have experienced any problems For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 6 that may be related to taking or using these products. Approved Drugs (10/21/13) Please access www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm for in-depth drug approval information. Albuterol Sulfate Inhalation Solution: Ten lots of 0.083% albuterol sulfate inhalation solution are being re- called by Nephron Pharmaceuticals due to outcomes of its FDA Approves Tretten: The FDA today approved internal monitoring processes. At the time of production, Tretten, Coagulation Factor XIII A-Subunit all lots affected passed all qualifications. However, the (Recombinant), the first recombinant product for use in product is still being recalled as a precautionary measure to the routine prevention of bleeding in adults and children comply with the U.S. Food and Drug Administration’s who have a rare clotting disorder, known as congenital aseptic processing guidelines. Factor XIII A-subunit deficiency. Affected Lots: A3A33A, A3A33B, A3A34A, A3A35A, Congenital Factor XIII deficiency is an extremely rare A3A36A, A3A37A, A3A38A, A3A40A, A3A41A, and genetic disorder. Patients with this deficiency do not make A3A42A (10/16/13) enough Factor XIII, a protein that circulates in the blood and is important for normal clotting. Factor XIII is Cefepime Injection and Dextrose Injection—Visible composed of two subunits, A and B. Factor XIII deficiency Particulate Matter: B. Braun Medical Inc. is voluntarily is usually caused by a deficiency of the A-subunit. recalling one lot of 1g Cefepime for Injection USP and Tretten is a recombinant analogue of the human Factor Dextrose Injection USP (Lot H3A744, catalog 3193-11) to XIII A-subunit that is produced in yeast cells and then the consumer level. The 1g Cefepime for Injection USP and further purified. It is a sterile freeze-dried-powder to be Dextrose Injection USP lot has been found to contain reconstituted with diluent and injected intravenously. visible organic particulate matter in a reserve sample unit. Tretten received orphan-drug designation for this use by Visible particulate matter, including metals, and organic the FDA because it is intended for treatment of a rare material such as cotton fibers or hair, may illicit disease or condition. inflammatory responses, both chronic and acute, and may Tretten is made by Novo Nordisk A/S, Denmark, and is be life threatening (e.g. systemic inflammatory response distributed by Novo Nordisk, Inc., USA. (12/23/13) syndrome (SIRS and / or anaphylaxis). If a right to left cardiac shunt is present, the particulate may lead to arterial FDA Approves Anoro Ellipta: The FDA today ap- emboli and result in stroke, myocardial infarction, proved Anoro Ellipta (umeclidinium and vilanterol inhala- respiratory failure, and loss of renal and hepatic function or tion powder) for the once-daily, long-term maintenance tissue necrosis. Other adverse effects associated with treatment of airflow obstruction in patients with chronic intravenous injection of particulate matter include foreign obstructive pulmonary disease (COPD). body granulomata, particularly in the lungs, and local COPD is a serious lung disease that makes breathing diffi- irritation of blood vessels. B.Braun has not received any cult and worsens over time. Symptoms can include chest reports of adverse events related to this lot to date. tightness, chronic cough, and excessive phlegm. Cigarette The product is used as a cephalosporin antibacterial smoking is the leading cause of COPD. According to the indicated in the treatment of infections caused by National Heart, Lung, and Blood Institute, COPD is the susceptible strains of designated microorganisms. The third leading cause of death in the United States. product is packaged in a Duplex single dose intravenous, Anoro Ellipta is a combination of umeclidinium, an inhaled plastic container with 24 units per case. The affected lot anticholinergic that affects the muscles around the large H3A744, which expires January 2015, was distributed airways and stops the muscles from tightening, and nationwide to licensed distributors, hospitals and vilanterol, a long-acting beta2-adrenergic agonist (LABA) pharmacies, and distributed to customers between the that improves breathing by relaxing the muscles of the air- dates of February 4, 2013 and March 1, 2013. ways to allow more air to flow into and out of the lungs. Patients reporting any problems that may be related to the The drug carries a boxed warning that LABAs increase the use of this product should be advised to contact a physician risk of asthma-related death. The safety and efficacy of and report all issues to B.Braun at 1-800-854-6851. Anoro Ellipta in patients with asthma have not been estab- B.Braun is notifying its distributors and customers by lished, and it is not approved for the treatment of asthma. written, return receipt letters and is arranging for return of Anoro Ellipta should not be used as a rescue therapy to all recalled product. Distributors and customers that have treat sudden breathing problems (acute bronchospasm). inventory of the 1g Cefepime for Injection USP and The FDA approved Anoro Ellipta with a patient medication Dextrose Injection USP of lot H3A744 should discontinue guide that includes instructions for use and information use immediately and contact B.Braun’s Customer Support about the potential risks of taking the drug. Department at 1-800-227-2862, Monday through Friday, 8 Anoro Ellipta is manufactured by GlaxoSmithKline, Re- a.m. to 7 p.m. EST for instructions for returning the search Triangle Park, N.C. (12/18/13) affected product and to arrange for replacement product. (10/15/13) FDA Approval of Sovaldi: The FDA approved Sovaldi (sofosbuvir) to treat chronic hepatitis C virus (HCV) infection. Sovaldi is the first drug that has demonstrated safety and efficacy to treat certain types of HCV infection without the need for co-administration of interferon. For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 7 Hepatitis C is a viral disease that causes inflammation of as a component of a combination antiviral treatment the liver that can lead to diminished liver function or liver regimen. In clinical studies, Olysio was evaluated in failure. Most people infected with HCV have no symptoms combination with peginterferon-alfa and ribavirin, two of the disease until liver damage becomes apparent, which drugs also used to treat hepatitis C virus infection. Olysio is may take several years. Some people with chronic HCV intended for adults with compensated liver disease (a infection develop scarring and poor liver function diseased liver that is still functioning), including cirrhosis, (cirrhosis) over many years, which can lead to who have not received treatment for their infection complications such as bleeding, jaundice (yellowish eyes or (treatment naïve) or for whom previous treatment has not skin), fluid accumulation in the abdomen, infections or been effective (treatment experienced). liver cancer. According to the Centers for Disease Control The most common side effects reported in clinical study and Prevention, about 3.2 million Americans are infected participants treated with Olysio in combination with with HCV. peginterferon-alfa and ribavirin were rash (including Sovaldi is a nucleotide analog inhibitor that blocks a photosensitivity), itching (pruritis), and nausea. Serious specific protein needed by the hepatitis C virus to replicate. photosensitivity reactions resulting in hospitalization were Sovaldi is to be used as a component of a combination reported. Patients will be advised to limit sun exposure and antiviral treatment regimen for chronic HCV infection. to use sun protective measures during treatment with There are several different types of HCV infection. Olysio in combination with peginterferon alfa and Depending on the type of HCV infection a patient has, the ribavirin. Olysio should not be used alone to treat chronic treatment regimen could include Sovaldi and ribavirin or hepatitis C infection. Sovaldi, ribavirin and peginterferon-alfa. Ribavirin and Olysio is marketed by Janssen Pharmaceuticals, based in peginterferon-alfa are two drugs also used to treat HCV Raritan, N.J. Victrelis is marketed by Whitehouse Station, infection. N.J.-based Merck, and Incivek is marketed by Cambridge, Sovaldi is the third drug with breakthrough therapy Mass.-based Vertex Pharmaceuticals. (11/22/13) designation to receive FDA approval. Sovaldi is marketed by Gilead, based in Foster City, Calif. Crizotinib: The FDA granted regular approval for Olysio is marketed by Raritan, N.J.-based Janssen crizotinib (Xalkori, Pfizer, Inc.) capsules for the treatment Pharmaceuticals. (12/6/13) of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase Avian Influenza Vaccination Approval: The FDA (ALK)-positive as detected by an FDA-approved test. today approved the first adjuvanted vaccine for the preven- Today’s approval was based on demonstration of superior tion of H5N1 influenza, commonly known as avian or bird progression-free survival (PFS) and overall response rate flu. The vaccine, Influenza A (H5N1) Virus Monovalent (ORR) for crizotinib-treated patients compared to chemo- Vaccine, Adjuvanted, is for use in people 18 years of age therapy in patients with ALK-positive NSCLC with disease and older who are at increased risk of exposure to the progression after platinum-based doublet chemotherapy. H5N1 influenza virus. An open-label, active-controlled, multinational, random- The H5N1 avian influenza vaccine is not intended for ized trial enrolled 347 patients with ALK-positive, meta- commercial availability. The U.S. Department of Health static NSCLC. Patients were required to have progressed and Human Services has purchased the vaccine from the following platinum-based chemotherapy and to have ALK manufacturer, ID Biomedical Corporation of Quebec, Que- expression in tumor specimens detected by fluorescence in bec City, Canada (a subsidiary of GlaxoSmithKline situ hybridization on central laboratory testing. Patients Biologicals), for inclusion within the National Stockpile for were randomized to receive either crizotinib 250 mg orally distribution by public health officials if needed. (11/22/13) twice daily (n=173) or chemotherapy (n=174). Patients randomized to chemotherapy received pemetrexed (58%) FDA Approves New Treatment for Hepatitis C or docetaxel (42%) if they had received prior pemetrexed. Virus: The FDA today approved Olysio (simeprevir), a Approximately 64% of patients on the chemotherapy arm new therapy to treat chronic hepatitis C virus infection. subsequently received crizotinib. Hepatitis C is a viral disease that causes inflammation of The trial demonstrated significantly prolonged progres- the liver that can lead to diminished liver function or liver sion-free survival (PFS) for crizotinib treatment compared failure. Most people infected with the hepatitis C virus have to chemotherapy [HR=0.49, (95% CI: 0.37, 0.64), no symptoms of the disease until liver damage becomes p<0.0001]. Median PFS was 7.7 and 3.0 months on the apparent, which may take several years. Most of these crizotinib and chemotherapy arms, respectively. The ORR people then go on to develop chronic hepatitis C. Some will was significantly higher for the crizotinib arm (65% vs. also develop scarring and poor liver function (cirrhosis) 20%) with median response durations of 7.4 and 5.6 over many years, which can lead to complications such as months in the crizotinib and chemotherapy arms, respec- bleeding, jaundice (yellowish eyes or skin), fluid tively. No difference in overall survival was noted between accumulation in the abdomen, infections or liver cancer. the two arms [HR= 1.02 (95% CI: 0.68, 1.54)] in a planned According to the Centers for Disease Control and interim analysis. Prevention, about 3.2 million Americans are infected with Common adverse reactions in clinical trials with crizotinib, the hepatitis C virus. occurring at an incidence of 25% or higher, included visual Olysio is a protease inhibitor that blocks a specific protein disorders, nausea, diarrhea, vomiting, constipation, edema, needed by the hepatitis C virus to replicate. It is to be used elevated transaminases, and fatigue. For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 8 Crizotinib was previously granted accelerated approval in FDA Approves Aptiom to Treat Seizures in Adults: August, 2011 based on durable, objective response rates The FDA today approved Aptiom (eslicarbazepine acetate) (ORR) of 50% and 61% in two single-arm, open-label stud- as an add-on medication to treat seizures associated with ies. epilepsy. The recommended dose and schedule for crizotinib is 250 Epilepsy is a brain disorder caused by abnormal or exces- mg orally, twice daily, with or without food. (11/20/13) sive activity in the brain’s nerve cells. Approximately 200,000 new cases of seizures and epilepsy occur in the Luzu Cream Approval: Luzu 1% cream, generic name United States each year. luliconazole, has been approved by the FDA to topically Aptiom is approved for the treatment of partial seizures, treat patients who are 18 years of age an older with the most common type of seizure seen in people with epi- interdigital tinea pedis, tinea cruris, or tinea corporis. Luzu lepsy. Seizures can cause a wide range of symptoms, in- cream is manufactured by Valeant Pharmaceuticals. cluding repetitive limb movements, unusual behavior and (11/19/13) generalized convulsions with loss of consciousness. Sei- zures can have serious consequences, including injury and FDA Approves Imbruvica: The FDA today approved death. Imbruvica (ibrutinib) to treat patients with mantle cell “Some patients with epilepsy do not achieve satisfactory lymphoma (MCL), a rare and aggressive type of blood seizure control from existing treatments,” said Eric cancer. Bastings, M.D., acting director of the Division of Neurology MCL is a rare form of non-Hodgkin lymphoma and Products in the FDA’s Center for Drug Evaluation and Re- represents about 6 percent of all non-Hodgkin lymphoma search. “It is important we continue to make new treatment cases in the United States. By the time MCL is diagnosed, it options available to patients.” usually has already spread to the lymph nodes, bone Three clinical studies in which participants with partial marrow and other organs. epilepsy were randomly assigned to receive Aptiom or pla- Imbruvica is intended for patients with MCL who have cebo demonstrated that Aptiom is effective in reducing the received at least one prior therapy. It works by inhibiting frequency of seizures. the enzyme needed by the cancer to multiply and spread. The most common side effects reported by patients receiv- Imbruvica is the third drug approved to treat MCL. Velcade ing Aptiom in clinical trials included dizziness, drowsiness, (2006) and Revlimid (2013) are also approved to treat the nausea, headache, double-vision, vomiting, fatigue and loss disease. of coordination. These and other side effects and recom- Imbruvica is the second drug with breakthrough therapy mendations for monitoring are described in the drug label. designation to receive FDA approval. The Food and Drug Like other antiepileptic drugs, Aptiom may cause suicidal Administration Safety and Innovation Act, passed in July thoughts or actions in a very small number of people. Pa- 2012, gave the FDA the ability to designate a drug a tients should contact their health care professionals right breakthrough therapy at the request of the sponsor if away if they have thoughts about suicide or dying, new or preliminary clinical evidence indicates the drug may offer a worsened anxiety or depression, or other unusual changes substantial improvement over available therapies for in behavior or mood. patients with serious or life-threatening diseases. Aptiom is being approved with a Medication Guide that The FDA is approving Imbruvica under the agency's provides patients with important information about the accelerated approval program, which allows the FDA to medication that can help patients avoid serious adverse approve a drug to treat a serious disease based on clinical events. The guide will be distributed each time a patient data showing that the drug has an effect on a surrogate fills their prescription. (11/8/13) endpoint that is reasonably likely to predict a clinical benefit to patients. This program provides earlier patient Juvederm Voluma XC Approval by the FDA: access to promising new drugs while the company conducts Juvederm Voluma XC (hyaluronic acid with lidocaine) was confirmatory clinical trials. The FDA also granted approved by the FDA to treat loss of volume in the cheek Imbruvica priority review and orphan-product designation area. Juvederm Voluma XC is available as an injectable gel. because the drug demonstrated the potential to be a (11/8/13) significant improvement in safety or effectiveness in the treatment of a serious condition and is intended to treat a NovoLog FlexTouch and Levemir FlexTouch rare disease, respectively. Approval: NovoLog (insulin aspart) Flextouch and The most common side effects reported in participants Levemir (insulin detemir) FlexTouch were approved by the receiving Imbruvica are low levels of platelets in the blood FDA for improving glycemic control in children and adults (thrombocytopenia), diarrhea, a decrease in infection- who have diabetes mellitus. These products are prefilled fighting white blood cells (neutropenia), anemia, fatigue, insulin syringes but come with a new dosing mechanism. musculoskeletal pain, swelling (edema), upper respiratory The FlexTouch products are push-button devices that have infection, nausea, bruising, shortness of breath (dyspnea), a low-dose force button that ensures the dose will not be constipation, rash, abdominal pain, vomiting, and extended. NovoLog FlexTouch and Levemir FlexTouch are decreased appetite. Other clinically significant side effects manufactured by Novo Nordisk and should be available in include bleeding, infections, kidney problems and the the U.S. within the next year. Currently, the FlexTouch development of other types of cancers. (11/13/13) products are available in Canada and some European countries. (11/5/13) For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 9 Zohydro ER, a Schedule II controlled substance under the FDA Approval of Gazyva: The FDA today approved Controlled Substances Act, is the first FDA-approved Gazyva (obinutuzumab) for use in combination with single-entity (not combined with an analgesic such as chlorambucil to treat patients with previously untreated acetaminophen) and extended-release hydrocodone chronic lymphocytic leukemia (CLL). product. CLL is a blood and bone marrow disease that usually gets Zohydro ER is in the class of extended-release/long-acting worse slowly. According to the National Cancer Institute, (ER/LA) opioid analgesics. Due to the risks of addiction, 15,680 Americans will be diagnosed and 4,580 will die abuse, and misuse with opioids, even at recommended from the disease this year. doses, and because of the greater risks of overdose and Gazyva works by helping certain cells in the immune death with ER/LA opioid formulations, Zohydro ER should system attack cancer cells. Gazyva is intended to be used be reserved for use in patients for whom alternative with chlorambucil, another drug used to treat patients with treatment options are ineffective, not tolerated, or would CLL. be otherwise inadequate to provide sufficient management Gazyva is the first drug with breakthrough therapy of pain. Zohydro ER is not approved for as-needed pain designation to receive FDA approval. This designation was relief. requested by the sponsor and granted soon after the The approved labeling for Zohydro ER conforms to biologic license application to support marketing approval updated labeling requirements for all ER/LA opioid was submitted to the FDA. The FDA can designate a drug a analgesics announced by the FDA on Sept. 10, 2013. breakthrough therapy at the request of the sponsor if The new class labeling and stronger warnings will more preliminary clinical evidence indicates the drug may offer a clearly describe the risks and safety concerns associated substantial improvement over available therapies for with ER/LA opioid analgesics, along with the appropriate patients with serious or life-threatening diseases. use of these medications. These warnings are expected to The FDA also granted Gazyva priority review because the improve the safety of all such medicines by encouraging drug demonstrated the potential to be a significant more appropriate prescribing, patient monitoring, and improvement in safety or effectiveness in the treatment of a patient counseling practices. Zohydro ER is the first opioid serious condition. And the FDA granted Gazyva orphan to be labeled in this manner. product designation because it is intended to treat a rare The FDA is requiring postmarketing studies of Zohydro ER disease. to assess the known serious risks of misuse, abuse, The most common side effects observed in participants increased sensitivity to pain (hyperalgesia), addiction, receiving Gazyva in combination with chlorambucil were overdose, and death associated with long term use beyond infusion-related reactions, a decrease in infection-fighting 12 weeks. These studies will also be required for other white blood cells (neutropenia), a low level of platelets in ER/LA opioid analgesics. the blood (thrombocytopenia), low red blood cells The safety of Zohydro ER is based on clinical studies of (anemia), pain in the muscles and bones (musculoskeletal more than 1,100 people living with chronic pain. The pain), and fever (pyrexia). efficacy of Zohydro ER is based on a clinical study that Gazyva is being approved with a boxed warning regarding enrolled over 500 patients with chronic low back pain and Hepatitis B virus reactivation and a rare disorder that showed significant improvement in chronic pain compared damages the material that covers and protects nerves in the to placebo. white matter of the brain (progressive multifocal Zohydro ER will be part of the ER/LA Opioid Analgesics leukoencephalopathy). These are known risks with other Risk Evaluation and Mitigation Strategy (REMS). The most monoclonal antibodies in this class and rare cases were common side effects of Zohydro ER are constipation, identified in participants on other trials of Gazyva. Patients nausea, drowsiness (somnolence), fatigue, headache, should be advised of these risks and assessed for Hepatitis dizziness, dry mouth, vomiting and itching (pruritus). B virus and reactivation risk. (11/1/13) (10/25/13)

Ecoza Approval by FDA: Ecoza, generic name New Formulation Approved for Actemra: Actemra, econazole nitrate, was approved by the FDA for to treat manufactured by Genentech, has been approved by the patients who are 12 years of age or older and who have FDA as a subcutaneous formulation. Actemra interdigital tinea pedis caused by trichophyton (subcutaneous formulation) is indicated to treat adult rubrum, trichophyton mentagrophytes, patients suffering from moderate to severe active and epidermophyton floccosum. Ecoza is manufactured by rheumatoid arthritis who have not obtained relief after AmDerma and is available as a 1% topical foam. trying at least one disease-modifying antirheumatic (10/29/13) medication, such as methotrexate. This drug is the only one approved for subcutaneous and intravenous use in FDA Approves Extended-Release, Single-Entity rheumatoid arthritis that is in the class of humanized Hydrocodone Product: The FDA today approved interleukin-6 receptor antagonist monoclonal antibodies. Zohydro ER (hydrocodone bitartrate extended-release (10/21/13) capsules) for the management of pain severe enough to require daily, around-the-clock, long-term treatment and Zorvolex (diclofenac) Approved by the FDA: The for which alternative treatment options are inadequate. FDA approved Zorvolex, diclofenac, a nonsteroidal anti- inflammatory drug (NSAID) for adult patients experiencing For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 10 mild to moderate acute pain. Zorvolex, manufactured by Adempas (riociguat) Approval by FDA: The FDA Iroko Pharmaceuticals, is available as oral capsules that are approved Adempas tablets, manufactured by Bayer, to treat 20% lower in dosage strength than of other available adults who have persistent or recurrent chronic thrombo- diclofenac medications. This diclofenac formulation embolic pulmonary hypertension (CTEPH). The FDA also contains a boxed warning alerting patients of the increased approved this medication to treat adult patients with pul- risk in serious cardiovascular and gastrointestinal events. monary arterial hypertension (PAH). Adempas exemplifies Due to this warning, Zorvolex is dispensed with a a new class of drugs by stimulating soluble guanylate medication guide. (10/21/13) cyclase. This medication’s label also provides a boxed warning in regard to embryo-fetal toxicity in women who FDA Approves Opsumit to Treat Pulmonary Arte- are pregnant and will be dispensed with a medication rial Hypertension: The FDA today approved Opsumit guide. (10/9/13) (macitentan), a new drug to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive and Duavee Approval by FDA: The FDA approved Duavee debilitating disease that can lead to death or the need for tablets, generic name conjugated estrogens and lung transplantation. bazedoxifene, to treat the menopausal symptom of PAH is high blood pressure that occurs in the arteries that moderate to severe hot flashes. The FDA also approved connect the heart to the lungs. It causes the right side of Duavee for the prevention of osteoporosis in the heart to work harder than normal, which can lead to postmenopausal women who still have a uterus. This limitations on exercise ability and shortness of breath. medication is expected to be available in the first quarter of Opsumit belongs to a class of drugs called endothelin re- 2014 and is the first approved estrogen and estrogen ceptor blockers, which act to relax the pulmonary arteries, agonist/antagonist combination. (10/7/13) decreasing blood pressure in the lungs. Opsumit’s safety and effectiveness were established in a FDA Approval of Brintellix: The FDA today approved long-term clinical trial where 742 participants were ran- Brintellix (vortioxetine) to treat adults with major domly assigned to take Opsumit or placebo. The average depressive disorder. treatment duration was about two years. In the study, Major depressive disorder (MDD), commonly referred to as Opsumit was effective in delaying disease progression, a depression, is a mental disorder characterized by mood finding that included a decline in exercise ability, worsen- changes and other symptoms that interfere with a person's ing symptoms of PAH or need for additional PAH medica- ability to work, sleep, study, eat and enjoy once-pleasurable tion. activities. Episodes of depression often recur throughout a Similar to other members of its drug class, Opsumit carries person's lifetime, although some may experience a single a Boxed Warning alerting patients and health care profes- occurrence. sionals that the drug should not be used in pregnant wom- Other signs and symptoms of MDD include loss of interest en because it can harm the developing fetus. Female pa- in usual activities, significant change in weight or appetite, tients can receive the drug only through the Opsumit Risk insomnia or excessive sleeping (hypersomnia), Evaluation and Mitigation Strategy (REMS) Program. This restlessness/pacing (psychomotor agitation), increased restricted-distribution program requires prescribers to be fatigue, feelings of guilt or worthlessness, slowed thinking certified by enrolling in the program; all female patients to or impaired concentration, and suicide attempts or be enrolled in the program and comply with applicable thoughts of suicide. Not all people with MDD experience pregnancy testing and contraception requirements before the same symptoms. initiating treatment; and pharmacies to be certified and to Six clinical studies in which adults with MDD were dispense Opsumit only to patients who are authorized to randomly assigned to receive Brintellix or placebo receive it. demonstrated that Brintellix is effective in treating Common side effects observed in those treated with depression. An additional study showed Brintellix Opsumit include low red blood cell count (anemia), com- decreased the likelihood of participants becoming mon cold-like symptoms (nasopharyngitis), sore throat, depressed again after treatment of their MDD episode. bronchitis, headache, flu and urinary tract infection. These studies were conducted in the United States and Opsumit is marketed by San Francisco-based Actelion other countries. Pharmaceuticals US, Inc. (10/18/13) The most common side effects reported by participants taking Brintellix in clinical trials included nausea, Novoeight Approval by the FDA: Novoeight injection constipation and vomiting. (antihemophilic factor [recombinant]) has been approved Brintellix will be available in 5 mg, 10 mg, 15 mg and 20 mg by the FDA for control and prevention of bleeding in chil- tablets. dren and adults with hemophilia A. It has also been ap- Brintellix and other antidepressant drugs have a Boxed proved for the indications of perioperative management Warning and a Medication Guide alerting patients and and routine prophylactic therapy in the prevention or re- healthcare professionals that antidepressants can increase duction of bleeding episode frequency. Novoeight is ex- the risk of suicidal thoughts and behavior in children, pected to launch in April 2015 with Mixpro, a prefilled de- adolescents and young adults ages 18 to 24 during initial vice, and is manufactured by Novo Nordisk. (10/18/13) treatment. Studies show adults older than 24 years of age do not appear to have an increased risk of suicidal thoughts and behavior, while adults ages 65 and older appear to For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 11 have a reduced risk. Patients starting antidepressant brand Tobi, tobramycin inhalation solution should be therapy should be closely monitored for worsening of their launched in November 2013. (10/14/13) depression and the emergence of suicidal thoughts and behavior. Generic Zymaxid Approved by the FDA: The FDA Brintellix is co-marketed by Takeda Pharmaceuticals and has approved gatifloxacin 0.5% ophthalmic solution, brand Lundbeck, both based in Deerfield, Ill. (9/30/13) name Zymaxid, to treat bacterial conjunctivitis caused by several aerobic gram-positive bacteria including Staphylo- coccus aureus and by aerobic gram-negative bacteria New Generics Haemophilus influenza. (10/7/13)

Generic Zemplar Approved by FDA: The FDA ap- Generic Cymbalta Approved: The FDA approved the proved generic Zemplar capsules (generic name first generic versions of Cymbalta (duloxetine delayed- paricalcitol) for the use in patients with chronic kidney dis- release capsules), a prescription medicine used to treat de- ease in stages 3 or 4 to prevent and treat secondary hy- pression and other conditions. perparathyroidism. Paricalcitol is an active form of vitamin Aurobindo Pharma Ltd., Dr. Reddy’s Laboratories Ltd., D also used for the prevention and treatment of hyperpara- Lupin Ltd., Sun Pharma Global FZE, Teva Pharmaceuticals thyroidism for patients in stage 5 of chronic kidney disease USA, and Torrent Pharmaceuticals Ltd. have received FDA who are also on hemodialysis or peritoneal dialysis. approval to market duloxetine in various strengths. (10/3/13) Duloxetine and other antidepressant drugs have a boxed warning describing the increased risk of suicidal thinking and behavior during treatment in children, adolescents, New Indications and young adults ages 18 to 24. The warning also says data does not show this increased risk in those older than 24 years and that patients ages 65 and older who take antide- Complera Indication Expanded: Complera pressants have a decreased risk of suicidal thinking and (emtricitabine/rilpivirine/tenofovir disoproxil fumarate), behavior. manufactured by Gilead, has had its indication expanded The warning says depression and other serious psychiatric by the FDA. This drug is now also approved to replace ex- disorders themselves are the most important causes of sui- isting treatment regimens in adult patients who have HIV-1 cide and that close monitoring of patients starting these infection and are virologically suppressed. These patients medications is necessary. Duloxetine must be dispensed must also have HIV-1 RNA less than 50 copies/mL on a with a patient medication guide that describes important stable treatment regimen at the start of their current thera- information about the drug’s uses and risks. py. Complera was previously approved by the FDA for the Common adverse reactions reported by people taking treatment of HIV-1 infection in treatment-naïve adult pa- Cymbalta include nausea, dry mouth, drowsiness, fatigue, tients with HIV-1 RNA 100,000 copies/mL or less at the decreased appetite, increased sweating, and dizziness. start of their regimen. This medication is supplied as oral Generic prescription drugs approved by the FDA have the tablets. (12/16/13) same high quality and strength as brand-name drugs. Generic prescription drug manufacturing and pack- FDA Approves Nexavar to Treat Type of Thyroid aging sites must pass the same quality standards as those Cancer: The FDA today expanded the approved uses of of brand-name drugs. (12/11/13) Nexavar (sorafenib) to treat late-stage (metastatic) differentiated thyroid cancer. Approval of Fosrenol Generic by the FDA: Thyroid cancer is a cancerous growth of the thyroid gland, Lanthanum carbonate, the generic of Fosrenol, was which is located in the neck. Differentiated thyroid cancer approved by the FDA for the reduction of serum phosphate is the most common type of thyroid cancer. The National in end-stage renal disease patients. Lanthanum carbonate Cancer Institute estimates that 60,220 Americans will be is manufactured by Prasco and is available as 500, 750, and diagnosed with thyroid cancer and 1,850 will die from the 1,000mg chewable oral tablets. The brand Fosrenol is disease in 2013. manufactured by Shire and has contracted with Prasco in a Nexavar works by inhibiting multiple proteins in cancer supply agreement to allow the generic to be considered an cells, limiting cancer cell growth and division. The drug’s authorized generic. This means that Shire will manufacture new use is intended for patients with locally recurrent or the drug but it will be marketed by Prasco’s private label metastatic, progressive, differentiated thyroid cancer that and sold at generic prices. (10/31/13) no longer responds to radioactive iodine treatment. The most common side effects in patients treated with Generic Tobi (tobramycin) Approval by FDA: The Nexavar were diarrhea, fatigue, infection, hair loss FDA approved the generic version of Tobi (tobramycin in- (alopecia), hand-foot skin reaction, rash, weight loss, halation solution) manufactured by Teva Pharmaceutical decreased appetite, nausea, gastrointestinal and abdominal Industries. Tobi and its generic equivalent are indicated for pains, and high blood pressure (hypertension). Thyroid patients who have cystic fibrosis with Pseudomonas stimulating hormone, a potential promoter of thyroid aeruginosa. Due to an agreement Teva Pharmaceutical cancer, is more likely to become elevated while on Industries has made with Novartis, the manufacturer of the

For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 12 treatment with Nexavar, requiring adjustment of thyroid hormone replacement therapy. Revised Labeling/ The FDA approved Nexavar to treat advanced kidney Prescribing Information cancer in 2005. In 2007, the agency expanded the drug’s label to treat liver cancer that cannot be surgically removed. Rosiglitazone Products—Removal of Some Dis- Nexavar is co-marketed by Bayer HealthCare pensing Restrictions: The FDA has determined that Pharmaceuticals Inc., based in Wayne, N.J., and Onyx recent data for rosiglitazone-containing drugs, such as Pharmaceuticals based in South San Francisco, California. Avandia, Avandamet, Avandaryl, and generics, do not show (11/22/13) an increased risk of heart attack compared to the standard type 2 diabetes medicines metformin and sulfonylurea. As Sabril (vigabatrin) Indication Expanded: Sabril, a result, FDA is requiring removal of the prescribing and manufactured by Lundbeck, was approved by the FDA to dispensing restrictions for rosiglitazone medicines that treat refractory complex partial seizures as add-on therapy were put in place in 2010. This decision is based on FDA in children who are 10 years of age or older. This review of data from a large, long-term clinical trial and is medication should be used in those patients who have had supported by a comprehensive, outside, expert re- inadequate response to multiple other treatment regimens evaluation of the data conducted by the Duke Clinical Re- and when the potential benefit outweighs the risk of vision search Institute (DCRI). loss. Previously, Sabril was approved as monotherapy in Previous data from a large, combined analysis of mostly infant and child patients, aged 1 month to two years, with short-term, randomized clinical trials of rosiglitazone had infantile spasms. Sabril was also indicated to treat adult suggested an elevated risk of heart attack, so FDA required patients as add-on therapy for refractory complex partial a Risk Evaluation and Mitigation Strategy (REMS), called seizures who have had inadequate response to numerous the Rosiglitazone REMS program. The Rosiglitazone REMS alternative treatments and when the benefit outweighed program restricted the use of rosiglitazone medicines to the risk of vision loss. This drug is available through the help ensure that their benefits outweighed the risks. Risk Evaluation and Mitigation Strategy (REMS) program Although some scientific uncertainty about the cardiovas- only and when dispensed, is accompanied by a patient cular safety of rosiglitazone medicines still remains, in light medication guide. (10/29/13) of the new re-evaluation of the Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in FDA Expands Exelon Patch Indication: Exelon Diabetes (RECORD) trial, FDAs concern is substantially patches (rivastigmine patches) were approved by the FDA reduced and the rosiglitazone REMS program require- to treat patients who have Alzheimer’s disease with severe ments will be modified. FDA is also requiring revisions to dementia. This medication was previously approved to the rosiglitazone prescribing information and the patient treat patients who suffer from mild to moderate dementia Medication Guide to include this new information. related to Alzheimer’s disease or Parkinson’s disease. Rosiglitazone is a treatment option that can improve blood (10/28/13) sugar control in some patients with type 2 diabetes. Patients with type 2 diabetes should continue to work New Indication for Cimzia: Cimzia, manufactured by closely with their health care professionals to determine UCB Pharma, has been approved by the U.S. Food and treatment options that are most appropriate. Health care Drug Administration (FDA) to treat active ankylosing professionals, pharmacies, and patients will no longer be spondylitis in adult patients. Previously, Cimzia was required to enroll in the rosiglitazone REMS program to be indicated to treat active psoriatic arthritis, moderate to able to prescribe, dispense, or receive rosiglitazone medi- severe active rheumatoid arthritis, and Crohn’s disease. cines. As part of the REMS, sponsors will ensure that When dispensed, Cimzia is accompanied with a medication health care professionals who are likely to prescribe rosig- guide due to a boxed warning relating to the risk of serious litazone medicines are provided training based on the cur- infections and malignancy. (10/18/13) rent state of knowledge concerning the cardiovascular risk of rosiglitazone medicines. Manufacturers will also send Hecoria Capsules Receive Expanded Indication: Dear Healthcare Provider and Dear Professional Society The FDA has expanded the indication for Hecoria capsules, letters to educate prescribers about the new information. manufactured by Novartis, to include organ rejection (11/25/13) prophylaxis in patients who are receiving heart transplants. Previously, Hecoria was approved as prophylaxis therapy OTC Anti-Septic Products Labeling Changes: The in patients receiving liver or kidney transplants. (9/30/13) FDA is requesting label and packaging changes to enhance the safe use of certain over-the-counter (OTC) topical Indication for Cimzia Expanded: The FDA has antiseptic products. This request is the result of our updated the indication of Cimzia, manufactured by UCB ongoing evaluation of infrequent but continuing reports of Pharmaceuticals, to treat active psoriatic arthritis in adult infections resulting from antiseptic products labeled for patients. In addition to this new indication, Cimzia is preoperative or preinjection skin preparation. When used already approved to treat moderate to severe Crohn’s properly, topical antiseptics are safe and effective products disease as well as moderate to severe rheumatoid arthritis to reduce the number of bacteria on patients’ skin prior to in adult patients. (9/30/13) surgery or injections. However, most often, contamination For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 13 of topical antiseptics occurs when organisms are decrease the frequency of seizures, or epilepsy, and for introduced into the product by users. Therefore, health whom the benefits of treatment outweigh the risks. care professionals and patients should follow all label These risks were previously described in a Drug Safety directions to decrease the chances of infection. Communication in April 2013. To further reduce the risk of infection with improper FDA recommends that patients have eye exams by an oph- topical antiseptic use and the possibility of these products thalmic professional before starting Potiga and every six becoming contaminated with bacteria during use, we are months during treatment. These exams should include vis- requesting that manufacturers package antiseptics ual acuity and dilated fundus photography, with additional indicated for preoperative or pre-injection skin preparation vision testing as necessary. Patients whose vision cannot be in single-use containers. The antiseptics in these single- monitored should generally not take Potiga. It is not known use containers should be applied only one time to one which individual patients are at risk for retinal abnormali- patient. We also recommend that health care professionals ties to develop, how long it takes for any sign of abnormali- and patients do not dilute antiseptic products after opening ty to be detected, their rate of progression, or their reversi- them. Applicators and any unused solution should be bility after stopping Potiga. discarded after the single application. If retinal pigmentary abnormalities or vision changes are In order to provide users with important information about detected, Potiga should be stopped unless no other suitable contamination that may occur during the manufacturing seizure treatment options are available and the benefits of process, we are also asking manufacturers to voluntarily treatment outweigh the potential risk of vision loss. In ad- revise the product labels for topical antiseptics to indicate dition, health care professionals should stop Potiga treat- whether the drug is manufactured as a sterile or nonsterile ment in patients who do not show substantial clinical bene- product. We believe this will assist health care fit after adequate dose titration. Seizures, which are due to professionals in making informed decisions about using unusual electrical activity in the brain, are serious, and pa- these products. Topical antiseptics are not required to be tients should not stop taking the drug without first discuss- manufactured as sterile and so may become contaminated ing their treatment with their health care professionals. with bacteria during manufacturing. Labeling stating a Also included in the updated label are warnings regarding product is sterile means it was treated with a process the risk for discoloration of the skin, nail, mucous mem- during manufacturing to eliminate all potential brane, and white-of-the-eye (see April 2013 Drug Safety microorganisms. Communication). The updated Potiga drug label states that All topical antiseptic products should always be used if a patient develops skin discoloration, an alternate medi- according to the directions on the label. Health care cation should be considered. These recommendations have professionals should consider these topical antiseptics as a been added to the Warnings and Precautions section of the possible source of infection when trying to determine the drug label and to the patient Medication Guide, which cause of postoperative or post-injection infections. In past should be included with every Potiga prescription filled. years, outbreaks associated with the use of contaminated FDA is working on modifying the current Risk Evaluation topical antiseptics have led to some product recalls (see and Mitigation Strategy (REMS) for Potiga to address the Data Summary). Reported outcomes ranged from localized risk of retinal pigmentary abnormalities, potential vision infections at injection sites to more widespread infections loss, and skin discoloration. (10/31/13) resulting in death. (11/13/13)

Labeling Changes for Incivek Approved: Incivek, Miscellaneous generic name telepravir, has been approved for labeling changes by the FDA regarding dosage amounts. Previously, Incivek was recommended to be taken as 750mg every 8 Aciphex Sprinkle Availability: Aciphex Sprinkle hours and is now recommended to be taken twice daily at (rabeprazole sodium), approved by the FDA back on March 1,125mg per dose, every 10 to 14 hours. Incivek is indicated 26, 2013, is being launched by Elsai Pharmaceuticals no to treat adult patients, in combination with peginterferon later than November 8, 2013. Aciphex Sprinkle delayed- alfa and ribavirin, with chronic hepatitis C who also have release capsules are available as 5mg and 10mg and are compensated liver disease. It is only indicated for those approved to treat gastroesophageal reflux disease (GERD) patients who are treatment-naïve or who previously have for up to 12 weeks in children aged 1 to 11 years. (11/8/13) been treated with interferon-based regimens. (11/1/13) FDA Approves Over-the-counter Nasacort Potiga (ezogabine) Labeling Changes: The FDA has Allergy 24HR to Treat Hay Fever and Nasal approved changes to the drug label of the anti-seizure drug Allergies: The FDA today approved Nasacort Allergy Potiga (ezogabine), underscoring risks of abnormalities to 24HR (triamcinolone acetonide), a nasal spray for the the retina in the eye, potential vision loss, and skin discol- nonprescription or over-the-counter (OTC) treatment of oration, all of which may become permanent. The revised nasal allergy symptoms (nasal congestion, runny nose, label includes a new boxed warning, the most serious type sneezing, and itchy nose). Nasacort Allergy 24HR is of warning FDA gives, because of the risk of abnormalities labeled for use in children 2 years of age and older, to the retina, a part of the eye that is needed for vision. We adolescents, and adults. advise that Potiga use be limited to patients who have not Nasacort Allergy 24HR belongs to a class of drugs known responded adequately to several alternative therapies to as glucocorticoids. It is the first drug in this class to be For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 14 made available OTC for treatment of the symptoms of nasal allergies. Nasacort Allergy 24HR is a nasal spray and is indicated for use once daily. There are different dosing instructions for adults and children 12 years of age and older, children 6 to under 12 years of age, and children 2 to under 6 years of age. Nasacort Allergy 24HR should not be used in children under age 2. Additional information included in the labeling informs consumers that when using this product, the growth rate of some children might be slightly slower. The labeling also states that if a child needs to use the spray for longer than two months a year, the parent should talk to the child’s doctor. Nasacort Allergy 24HR was initially approved as a prescription-only product (called Nasacort AQ) in the U.S. in 1996 for use in adults and adolescents 12 years of age or older. In 1997 it was approved for children 6 through 11 years of age and older, and in 2008 it was approved for children 2 through 5 years of age. Nasacort is marketed by Sanofi-Aventis U.S. Inc. based in Bridgewater, N.J. (10/11/13)

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FUTURE DRUG RELEASES LISTED ON NEXT PAGE.

For informational purposes only, consult a physician for any drug changes. “FDA” stands for the United States Food and Drug Administration. Even with FDA approval, drug availability depends on each manufacturer. 15

GENERIC DRUGS PIPELINE

† indicates the medication has been approved but may or may not be available

* indicates the medication is anticipated to be filed with the FDA at the listed date Estimated Generic Name Brand Name Brand Manufacturer Indication(s) / Use Approval/ Market Date nedocromil ophthalmic Alocril Allergan Allergies approved† rosiglitazone Avandia GlaxoSmithKline Type 2 diabetes approved† sodium phosphate monobasic monohy- drate & sodium phos- Visicol Salix Pharmaceuticals Colon cleansing prior to colonoscopy approved† phate dibasic anhy- drous fluocinonide Vanos Medicis Plaque-type psoriasis DEC 2013 estradiol Vivelle-Dot Novartis Symptoms of menopause DEC 2013 transdermal patch capecitabine Xeloda Roche Breast cancer, colorectal cancer DEC 2013 flunisolide Aerospan Acton Asthma 2013 mesalamine Asacol Warner Chilcott Ulcerative colitis, proctitis 2013 imiglucerase injection Cerezyme Genzyme Gaucher disease 2013 alendronate/ Fosamax Plus D Merck Osteoporosis 2013 cholecalciferol tolterodine extended- Detrol LA Pfizer Overactive bladder JAN 2014 release (ER) ethinyl estradiol/ Loestrin 24 Fe Warner Chilcott Birth control pill JAN 2014 norethindrone telmisartan Micardis Boehringer Ingelheim High blood pressure JAN 2014 telmisartan/ Micardis HCT Boehringer Ingelheim High blood pressure JAN 2014 hydrochlorothiazide sirolimus tablet Rapamune Wyeth Organ rejection prevention JAN 2014 doxercalciferol Hectorol Sanofi-Aventis Hyperparathyroidism FEB 2014 moxifloxacin Avelox Bayer Antibiotic MAR 2014 raloxifene Evista Lilly Osteoporosis, breast cancer risk reduction MAR 2014 sirolimus oral solution Rapamune Wyeth Organ rejection prevention MAR 2014 sevelamer Renvela Genzyme Chronic kidney disease MAR 2014 carbonate tablet ezetimibe/simvastatin Vytorin Merck Cholesterol MAR 2014 prednisolone Orapred ODT Shionogi Pharma Asthma, atopic dermatitis, allergic rhinitis APR 2014 diclofenac sodium vis- Nuvo Research, Pennsaid Osteoarthritis of the knees APR 2014 cous solution Mallinckrodt nelfinavir mesylate Viracept ViiV Healthcare Antiretroviral APR 2014 eszopiclone Lunesta Sepracor Insomnia MAY 2014 esomeprazole Nexium AstraZeneca GERD, ulcers MAY 2014 cyclosporine Restasis Allergan Chronic dry eye MAY 2014 argatroban 100mg/mL Acova Pfizer Thrombosis JUN 2014 risedronate Actonel Procter & Gamble Osteoporosis JUN 2014 tazarotene Tazorac Gel Allergan Acne vulgaris, plaque psoriasis JUN 2014 mometasone furoate Nasonex Schering Allergies JUL 2014 bimatoprost Lumigan Allergan Glaucoma, ocular hypertension AUG 2014 sevelamer hydrochlo- Renagel Genzyme Chronic kidney disease SEP 2014 ride sevelamer carbonate Renvela Genzyme Chronic kidney disease SEP 2014 suspension amlodipine/valsartan Exforge Novartis High blood pressure OCT 2014 amlodipine/valsartan/ Exforge HCT Novartis High blood pressure OCT 2014 hydrochlorothiazide travoprost Travatan Z Travatan Z Glaucoma, ocular hypertension DEC 2014 memantine tablet Namenda Forest Alzheimer’s disease JAN 2015 ritonavir Norvir Abbott Antiviral JAN 2015 trandolapril/ Tarka Abbott High blood pressure FEB 2015 verapamil efavirenz Sustiva Bristol-Myers Squibb Antiviral MAR 2015 colesevelam tablet Welchol Daiichi Sankyo Cholesterol MAR 2015

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omega-3-acid Lovaza GlaxoSmithKline Cholesterol 1Q2015 ethyl esters aripiprazole Abilify Otsuka Psychiatric conditions APR 2015 Chemo-associated nausea & vomiting; pre- aprepitant Emend Merck APR 2015 vention of post-op nausea & vomiting oxybutynin Oxytrol Watson Overactive bladder APR 2015 linezolid tablet Zyvox Pfizer Bacterial infections MAY 2015 epinephrine Epipen Mylan Anaphylactic reactions JUN 2015 gemifloxacin tablet Factive Cornerstone Antibiotic JUN 2015 aspirin/dipyridamole Aggrenox Boehringer Ingelheim Stroke prevention JUL 2015 imatinib Gleevec Novartis Cancer JUL 2015 testosterone Androgel 1% Solvay Hormone replacement AUG 2015 glatiramer acetate Copaxone Teva Multiple sclerosis SEP 2015 guanfacine ER tablets Intuniv Actavis ADHD SEP 2015 fenofibrate Fenoglide Santarus Cholesterol OCT 2015 dutasteride Avodart GlaxoSmithKline Benign prostatic hyperplasia NOV 2015 almotriptan Axert Ortho-McNeil-Janssen Migraine NOV 2015 frovatriptan succinate Frova Endo Pharmaceuticals Migraine NOV 2015 dutasteride/tamsulosin Jalyn GlaxoSmithKline Benign prostatic hypertrophy NOV 2015 bosentan Tracleer Actelion Pulmonay arterial hypertension NOV 2015 celecoxib Celebrex Pfizer Osteoarthritis, pain DEC 2015 norgestimate/ Ortho Tri-Cyclen Ortho Mcneil Janssen Birth control pill DEC 2015 ethinyl estradiol Lo olopatadine Pataday Alcon Allergic conjunctivitis DEC 2015 olopatadine Patanol Alcon Allergic conjunctivitis DEC 2015 metformin hydrochlo- Glumetza Santarus Type 2 diabetes mellitus FEB 2016 ride ER abacavir/lamivudine Epzicom GlaxoSmithKline Antiviral MAR 2016 lamivudine/abacavir/ Trizivir ViiV Healthcare HIV-1 infection MAR 2016 zidovudine armodafinil Nuvigil Teva Sleep disorders JUN 2016 rosuvastatin Crestor AstraZeneca Cholesterol JUL 2016 clindamycin phos- Ziana Medicis Acne JUL 2016 phate/tretinoin darifenacin Enablex Novartis Overactive bladder AUG 2016 olmesartan Benicar Daiichi Sankyo High blood pressure OCT 2016 olmesartan/ hydro- Benicar HCT Daiichi Sankyo High blood pressure OCT 2016 chlorothiazide bexarotene Targretin Eisai Cutaneous T-cell lymphoma OCT 2016 quetiapine ER tablet Seroquel XR AstraZeneca Antipsychotic NOV 2016 lopinavir/ritonavir Kaletra Abbott Antiviral DEC 2016 cinacalcet tablet Sensipar Amgen Hyperparathyroidism, hypercalcemia DEC 2016 ezetimibe Zetia Merck Cholesterol DEC 2016 atomoxetine Strattera Lilly ADHD MAY 2017 atazanavir Reyataz Bristol-Myers Squibb Antiretroviral JUL 2017 caspofungin acetate Cancidas Merck Fungal infections SEP 2017 tadalafil Adcirca Synthon Pulmonary arterial hypertension NOV 2017 tenofovir Viread Gilead Antiviral JAN 2018 fentanyl buccal tablet Fentora Cephalon Breakthrough cancer pain OCT 2018 vardenafil Levitra Teva Erectile dysfunction OCT 2018 Diabetic peripheral neuropathy, postherpetic pregabalin Lyrica Pfizer DEC 2018 neuralgia, seizure, fibromyalgia lovastatin/niacin Advicor Abbott Cholesterol uncertain dolasetron Anzemet Sanofi Aventis Nausea/vomiting uncertain efavirenz/ emtricitabine/ Atripla Gilead Antiviral uncertain tenofovir metformin/ Avandamet GlaxoSmithKline Type 2 diabetes uncertain rosiglitazone rosiglitazone/ Avandaryl GlaxoSmithKline Type 2 diabetes uncertain glimepiride mycophenolate injec- CellCept Roche Palo Kidney, heart, or liver transplant uncertain tion valsartan Diovan Novartis High blood pressure uncertain hydromorphone hy- Exalgo Mallinckrodt Moderate to severe pain uncertain drochloride rivastigmine solution Exelon Novartis Alzheimer’s disease/Parkinson’s disease uncertain

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fluvastatin ER tablet Lescol XL Novartis Cholesterol uncertain trazodone ER tablet Oleptro Angelini Depression uncertain valganciclovir Valcyte Roche Cytomegalovirus uncertain BRAND DRUGS PIPELINE TBA = to be announced

† indicates the medication has been approved but may or may not be available

* indicates the medication is anticipated to be filed with the FDA at the listed date Estimated FDA Filing/ Drug Name Manufacturer Indication(s) / Use Approval/ Market Date Human Genome Abthrax (raxibacumab) Inhalation anthrax approved† Sciences Duavee (bazedoxifene/ Menopausal symptoms and prevention Ligand, Pfizer approved† conjugated estrogens of postmenopausal osteoporosis Stendra (avanafil) Vivus A PDE5 inhibitor for erectile dysfunction approved† A synthetic surfactant for prevention of respiratory Surfaxin (lucinactant) Discovery Labs approved† distress syndrome in premature infants 4Q2013 (fil- TBA (daclatasvir) Bristol Myers Squibb Hepatitis C virus infection ing*) TBA (canagliflozin/ Janssen Type 2 diabetes OCT–DEC 2013 metformin IR) Grazax, Alutard SQ NOV 2013 – (ALK grass pollen tablet, Merck, ALK-Abello Prevention of allergies caused by grass pollen allergen JAN 2014 phleum pretense) NOV 2013 – Syncria (albiglutide) GlaxoSmithKline Type 2 diabetes JAN 2014 Lulicon, Lulifin Topica, Vanda Topical treatment of Tinea Pedis; onychomycosis DEC 2013 (luliconazole) Sanofi Aventis, Zea- Lyxumia (lixisenatide) Type 2 diabetes DEC 2013 land AstraZeneca, Forxiga (dapagliflozin) Type 2 diabetes 2013 Bristol Myers Squibb Girosa (filbanserin) Sprout Hypoactive sexual desire disorder in premenopausal women 2013 Impavido (miltefosine) Paladin Treatment of leishmaniasis 2013 Hyponatremia associated with heart failure & syndrome of inap- Lixar (lixivaptan) Cornerstone 2013 propriate antidiuretic hormone Luveniq (voclosporin) Lux Biosciences Uveitis 2013 Decrease birthing time to vaginal delivery for women who have an Misopress (misoprostol) Ferring 2013 unfavorable cervix Solpura (liprotamase) Eli Lilly Exocrine pancreatic insufficiency 2013 Stedesa (eslicarbazepine) Sunovion Adjunct therapy for partial-onset seizures 2013 4Q2013 (fil- TBA (eliglustat tartrate) Genzyme Gaucher disease type 1 ing*) Actimid (pomalidomide) Celgene Myelofibrosis 2013 (filing*) AL-60371 Alcon Otitis externa and media with a tympanostomy tube 2013 (filing*) Elonva Merck Infertility 2013 (filing*) (corifollitropin alfa) Faridak (panobinostat) Novartis Multiple myeloma 2013 (filing*) Ideglira (insulin Novo Nordisk Type 2 diabetes 2013 (filing*) degludec/liraglutide) Kremezin (carbonaceous Mitsubishi Tanabe Chronic kidney disease 2013 (filing*) oral adsorbent) Lixiana (edoxaban) Daiichi Sankyo Stroke prevention in atrial fibrillation 2013 (filing*) Chelsea Therapeu- Northera (droxidopa) Neurogenic orthostatic hypotension 2013 (filing*) tics GW Pharmaceuticals Sativex (nabiximols) Cancer pain; spasticity in multiple sclerosis 2013 (filing*) Otsuka Solorel (macimorelin) Aeterna Zentaris Growth hormone deficiency, treatment of cachexia 2013 (filing*) TBA (bardoxolone me- Reata, Abbott Diabetic nephropathy, chronic kidney disease 2013 (filing*) thyl) TBA (dovitinib) Novartis Renal cell cancer 2013 (filing*) TBA (dulaglutide) Eli Lilly Type 2 diabetes 2013 (filing*) TBA (dutogliptin) Phenomix Type 2 diabetes 2013 (filing*) TBA (ecopipam) Psyadon Lesch Nyhan disease 2013 (filing*) TBA (edivoxetine) Eli Lilly Major depressive disorder, ADHD 2013 (filing*)

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Myeloproliferative disorders including polycythemia vera, TBA (fedratinib) Sanofi thrombocythemia, essential thrombocytosis, & myelofibrosis with 2013 (filing*) myeloid metaplasia TBA (linifanib) Abbott Hepatocellular carcinoma 2013 (filing*) TBA (rolapitant) OPKO, Tesaro Prevention of chemotherapy-induced nausea & vomiting 2013 (filing*) Newron, TBA (safinamide) Parkinson’s disease 2013 (filing*) Merck Serono TBA (secukinumab) Novartis Moderate to severe plaque psoriasis 2013 (filing*) TBA (taspoglutide) Ispen Type 2 diabetes 2013 (filing*) TBA (tavaborole) Anacor Oncyhomycosis 2013 (filing*) SIGA Technologies, TBA (tecovirimat) Smallpox infection 2013 (filing*) ViroPharma TBA (tedizolid phos- Trius Acute bacterial skin & skin structure infections 2013 (filing*) phate) TBA (umeclidinium) GlaxoSmithKline Chronic obstructive pulmonary disease (COPD), asthma 2013 (filing*) Accidental overexposure to fluorouracil (5-FU) due to dosing errors TBA (uridine triacetate) BTG, Wellstat 2013 (filing*) or impaired clearance of 5-FU from the body GlaxoSmithKline, TBA (vilanterol) COPD 2013 (filing*) theravance TBA (vorapaxar sulfate) Merck Cardiovascular event prevention in select patients 2013 (filing*) Vivageln/A Starpharma Bacterial vaginosis 2013 (filing*) Acute bacterial skin & skin structure infections caused by gram- Zeven (dalbavancin) Durata Therapeutics positive bacteria including MRSA (methicillin resistant Staphylo- 2013 (filing*) coccus aureus) Zydena (udenafil) Warner Chilcott Erectile dysfunction 2013 (filing*) 2013 – 2014 TBA (avatrombopag) Eisai Immune thrombocytopenic purpura (filing*) TBA 2013 – 2014 Eisai Endometrial cancer, thyroid cancer (lenvatinib mesylate) (filing*) 2013 – 2014 TBA (orteronel) Takeda Metastatic castrate-resistant prostate cancer (filing*) TBA (palonosetron/ 2013 – 2014 Helsinn, Eisai Chemotherapy-induced nausea & vomiting netupitant) (filing*) Grastek (Timothy grass pollen extract/phleum Merck; ALK-Abello Prevention of allergies caused by grass pollen allergen JAN 2014 pretense) Vanda, Bristol Myers Hetlioz (tasimelteon) Non-24-hour disorder in the totally blind JAN 2014 Squibb TBA (apremilast) Celgene Psoriatic arthritis MAR 2014 TBA (vedolizumab) Millenium, Takeda Moderate to severely active Crohn’s disease, and ulcerative colitis JUN 2014 Targiniq ER (oxyco- Purdue Management of chronic pain SEP 2014 done/naltrexone) Forest, Schizophrenia; acute treatment of manic or mixed episodes associ- TBA (cariprazine) 2014 Gedeon Richter ated with bipolar I disorder Esbriet (pirfenidone) InterMune Idiopathic pulmonary fibrosis 2014 TBA (asfotase alfa) Alexion Hypophosphotasia 1Q2014 (filing*) Boehringer TBA (empagliflozin) Type 2 diabetes 1Q2014 (filing*) Ingelheim, Eli Lilly TBA (apricitabine) 4Q2014 (fil- TBA (lasmiditan) CoLucid Treatment of migraine ing*) Arimenda Adamas, Forest Alzheimer’s dementia 2014 (filing*) (memantine/donepezil) Cinquil (reslizumab) UCB Eosinophilic asthma 2014 (filing*) FV-100 Inhibitex Varicella zoster virus infection, herpes zoster 2014 (filing*) Lupuzor (forigerimod) ImmuPharma Systemic Lupus erythematosus 2014 (filing*) Mitizax (allergy immuno- Rhinitis & asthma allergy symptoms caused by house Merck, ALK-Abello 2014 (filing*) therapy tablet) dust mite allergen MuDelta: JNJ-27018966 Furiex Diarrhea-predominant irritable bowel syndrome 2014 (filing*) Prevention & treatment of muscle wasting in patients with ad- Ostarine (enobosam) GTx 2014 (filing*) vanced non-small cell lung cancer TBA Novartis Heart failure 2014 (filing*) (AHU-377/valsartan) Regeneron, Sanofi TBA (alirocumab) Cholesterol 2014 (filing*) Aventis Helsinn Therapeu- TBA (anamorelin) Treatment of cachexia & anorexia in cancer patients 2014 (filing*) tics 19

TBA (auriclosene) NovaBay Adenoviral conjunctivitis 2014 (filing*) TBA (brexpiprazole) Otsuka, Lundbeck Schizophrenia, adjunctive therapy for major depressive disorder 2014 (filing*) TBA (cobimetinib) Genentech In combination with Zelboraf for metastatic melanoma 2014 (filing*) TBA (eluxadoline Furiex Diarrhea-predominant irritable bowel syndrome 2014 (filing*) dihydrochloride) TBA (erismodegib) Novartis Solid tumors 2014 (filing*) Boehringer TBA (faldaprevir) Hepatitis C virus infection 2014 (filling*) Ingelheim TBA (lebrikizumab) Genentech Asthma 2014 (filing*) Ardea Biosciences, TBA (lesinurad) Hyperuricemia, gout 2014 (filing*) AstraZeneca TBA Vertex Cystic fibrosis homozygous for F508del CFTR mutation 2014 (filing*) (lumacaftor/ivacaftor) TBA (mavoglurant) Novartis Fragile X syndrome 2014 (filing*) Amicus Therapeu- TBA (migalastat) tics, Glax- Fabry disease 2014 (filing*) oSmithKline Acute uncomplicated influenza as monotherapy or in combination TBA (nitazoxanide) Romark 2014 (filing*) with oseltamivir TBA (obeticholic acid) Intercept Primary biliary cirrhosis, hepatic fibrosis 2014 (filing*) TBA (odanacatib) Merck, Celera Osteoporosis 2014 (filing*) TBA (omarigliptin) Merck Type 2 diabetes 2014 (filing*) TBA (patiromer) Relypsa Hyperkalemia in patients with chronic kidney disease 2014 (filing*) TBA (pimavanserin) Acadia, Biovail Parkinson’s disease psychosis 2014 (filing*) TBA (pradigastat) Novartis Familial chylomicronemia syndrome 2014 (filing*) TBA (preladenant) Merck Parkinson’s disease 2014 (filing*) Dainippon Sumito- TBA (ranirestat) Diabetic peripheral neuropathy 2014 (filing*) mo Pharma, Eisai Sanofi Aventis, TBA (sarilumab) Rheumatoid arthritis, ankylosing spondylitis 2014 (filing*) Regeneron TBA (tildrakizumab) Merck Psoriasis 2014 (filing*) FSH-GEX, 2014 -2015 (fil- Glycotype Infertility GT-GP 2.4 GEX ing*) Eleison, Threshold 2014 -2015 (fil- TBA (glufosfamide) Pancreatic cancer Pharmaceuticals ing*) Visonac 2014 -2015 (fil- Photocure Topical treatment for acne (methyl aminoevulinate) ing*) Firdapse (amifampridine Catalyst Lambert-Eaton myasthenic syndrome 2015 (filing*) phosphate) Isis-ApoIIIRx, Isis Hypertriglyceridemia 2015 (filing*) Isis-304801 Rydapt (midostaurin) Novartis Acute myeloid leukemia, aggressive systemic mastocytosis 2015 (filing*) Stedicor (azimilide) Forest Ventricular arrhythmia 2015 (filing*) Cardiovascular disease risk reduction in TBA (aleglitazar) Takeda 2015 (filing*) high-risk patients with type 2 diabetes TBA (bevenopran) Eli Lilly Opioid-induced constipation 2015 (filing*) TBA (bitopertin) Roche Schizophrenia 2015 (filing*) TBA (brodalumab) Amgen, AstraZeneca Moderate to severe plaque psoriasis 2015 (filing*) TBA (buparlisib) Novartis Breast cancer 2015 (filing*) TBA (ozenoxacin) Ferrer Skin & skin structure infections 2015 (filing*) TBA (surotomycin) Cubist Clostridium difficile-associated diarrhea 2015 (filing*) Bone loss disorders, including postmenopausal 2015-2016 (fil- TBA (romosozumab) UCB, Amgen osteoporosis and bone fractures ing*) TBA (alisporivir) Novartis Hepatitis C virus infection 2016 (filing*) TBA (elagolix) Abbott, Neurocrine Endometriosis 2016 (filing*) Beriplex (human 4-factor Urgent reversal of vitamin K-antagonist (warfarin) therapy prothrombin complex CSL, Behring uncertain in patients with acute major bleeding concentrate) Linjeta (insulin, human) Biodel Type 1 or Type 2 diabetes uncertain Oralair (grass pollen al- Stallergenes, Sublingual tablet formulation of a freeze dried extract of uncertain lergen immunotherapy) Paladini grass pollen allergens for allergic rhinitis Pandemrix, Prepandrix H5N1 avian influenza for pre-pandemic use (Prepandrix) GlaxoSmithKline uncertain (H5N1 influenza vaccine) & pandemic use (Pandemrix) Striverdi Respimat Boehringer Asthma, COPD uncertain (olodaterol) Ingelheim TBA (cobicistat) Gilead HIV-1 infection uncertain TBA (efinaconazole) Kaken, Valeant Distal lateral subungal onychomycosis uncertain TBA (elvitegravir) Gilead HIV-1 infection in treatment-experienced adults uncertain 20

Diabetes and/or hypertriglyceridemia in those with TBA (metreleptin) Amylin uncertain rare forms of lipodystrophy TBA (naloxegol) AstraZeneca, Nektar Opioid-induced constipation uncertain TBA (suvorexant) Merck Insomnia uncertain Vyndaqel FoldRx, Pfizer Transthyretin familial amyloid polyneuropathy uncertain (tafamidis meglumine) BRAND DRUGS PIPELINE — New Formulations TBA = to be announced

† indicates the medication has been approved but may or may not be available

* indicates the medication is anticipated to be filed with the FDA at the listed date Estimated FDA Filing/ Drug Name Manufacturer Indication(s) / Use Approval/ Market Date Adasuve (loxapine) Alexza, Valeant Rapid treatment of agitation in schizophrenia & bipolar disorder approved† Sitavig (acyclovir lauriad) BioAlliance Herpes simplex virus-1 infections approved† Ximino (minocycline ER) Ranbaxy Moderate to severe acne approved† Neugranin (balugrastim) Teva Chemotherapy-induced neutropenia 4Q2013 Zecuity (sumatriptan NuPathe Migraine 4Q2013 transdermal) Anoro Ellipta GlaxoSmithKline, (umeclidinium bromide/ COPD DEC 2013 Theravance vilanterol) TBA Actavis New external form for prevention of pregnancy DEC 2013 (norethindrone acetate) adenovirus types 4 & 7 Teva Prevention of severe acute respiratory diseases 2013 (live oral vaccines) Clearazide Yaupon Therapeu- Early stage (stages I-IIA) mycosis fungoides 2013 (mechlorethamine) tics, Ceptaris Contrave (naltrexone/ Orexigen, Takeda Obesity 2013 bupropion ER) Milprosa (progesterone) Teva Luteal phase support for women undergoing in-vitro fertilization 2013 MoxDuo IR (mor- QRxPharma, Actavis New oral formulation for moderate to severe acute pain 2013 phine/oxycodone) Remoxy (oxycodone con- Pfizer, Pain Thera- Moderate to severe chronic pain 2013 trolled-release) peutics Durect Rytary (carbidopa/ levo- Impax Parkinson’s disease 2013 dopa ER) TBA (zucapsaicin/ Winston Osteoarthritis 2013 ciscapsaicin) Treatment of keratoconus & corneal ectasia Vibex (riboflavin) Avedro 2013 following refractive surgery Zoely (nomegesterol ace- Merck Prevention of pregnancy 2013 tate/17 beta-estradiol) Zohydro (hydrocodone Zogenix, Elan Moderate to severe chronic pain 2013 bitartrate ER) Lightlake Therapeu- 3Q2013 – 2014 TBA (naloxone) Binge eating disorder tics (filing*) Ventrus, SLA 4Q2013 (fil- Anoheal (diltiazem) Pain associated with anal fissure Pharma ing*) 4Q2013 (fil- TBA (ondansetron) RedHill BioPharma Prevention of nausea & vomiting in cancer patients ing*) TBA 4Q2013 (fil- (perindopril arginine/ Symplmed, XOMA Hypertension ing*) amlodipine besylate) Ameluz (5-aminolevulinic acid Biofrontera Actinic keratosis 2013 (filing*) nanocolloidal) Bromsite (bromfenac) InSite Vision Pain, swelling, & inflammation associated with ocular surgery 2013 (filing*) CompleoTRT (testos- Trimel Male hypogonadism 2013 (filing*) terone intranasal) Dexasite (dexame- InSite Vision Blepharitis 2013 (filing*) thasone) Duromist (sildenafil) NovaDel Erectile dysfunction 2013 (filing*) Watson, Gedeon Esmya (ulipristal acetate) Anemia associated with uterine leiomyomas 2013 (filing*) Richter Kalbitor (ecallantide) Dyax Concentrated formulation for hereditary angioedema 2013 (filing*) 21

Lecette (desogestrel/ Teva Prevention of pregnancy 2013 (filing*) ethinyl estradiol) Mycova (terbinafine) ApriCus Onychomycosis 2013 (filing*) Natpara (recombinant human NPS, Takeda Hypoparathyroidism 2013 (filing*) parathyroid hormone) Octreolin Chiasma, Roche Acromegaly 2013 (filing*) (ocreotide acetate) Posidur (bupivacaine SR) Durect, Hospira Postoperative pain 2013 (filing*) Relistor (methylnaltrexone bro- Salix Opioid-induced constipation in chronic pain 2013 (filing*) mide) TBA (dapagliflozin/ AstraZeneca, Bristol Type 2 diabetes 2013 (filing*) metformin) Myers Squibb TBA (dexamethasone) EyeGate Dry eye, uveitis 2013 (filing*) TBA (dexamethasone) Icon Bioscience Treatment of inflammation associated with cataract surgery 2013 (filing*) TBA KemPharm, Mono- ADHD 2013 (filing*) (dextroamphetamine) Sol Rx TBA (ethinyl estradi- Agile Therapeutics Prevention of pregnancy 2013 (filing*) ol/levonorgestrel) TBA (etodolac/lidocaine) IL Pharma, Kowa Pain & inflammation 2013 (filing*) TBA (ferric iron complex) Shield Therapeutics Iron deficiency anemia associated with inflammatory bowel disease 2013 (filing*) TBA (ferric trimaltol) Vitra Iron deficiency anemia associated with inflammatory bowel disease 2013 (filing*) Eli Lilly, Boehringer TBA (insulin glargine) Type 1 & 2 diabetes 2013 (filing*) Ingelheim TBA (ketoprofen/ Irrigation solution formulation for the treatment of pain & im- amitriptyline/ Omeros 2013 (filing*) provement of joint function associated with arthroscopy oxymetazoline) TBA Shionogi, Sciele Premature ejaculation 2013 (filing*) (lidocaine/prilocaine) TBA (oxycodone) Phosphagenics Moderate to severe pain 2013 (filing*) TBA Santarus Infectious diarrhea 2013 (filing*) (rifamycin SV MMX) Improved tablet formulation for kidney transplant rejection pre- TBA (tacrolimus) Veloxis 2013 (filing*) vention Tredaptive Merck Cholesterol 2013 (filing*) (niacin ER/laropiprant) Zerenex (ferric citrate) Keryx, Panacor Hyperphosphatemia in end-stage renal disease 2013 (filing*) Copaxone Teva Relapsing remitting multiple sclerosis JAN 2014 (glatiramer acetate) Prophylaxis of invasive Aspergillus & Candida infections in those Noxafil (posaconazole) Merck FEB 2014 who are severely immunocompromised Genvir (filbanserin) Flamel Technologies Herpes simplex virus infection APR 2014 Epanova Omthera, (eicosapentaenoic acid/ High triglycerides MAY 2014 AstraZenca docosahexaenoic acid) Plegridy (peginterferon Biogen Idec Relapsing remitting multiple sclerosis MAY 2014 beta-1a) Bunavail (buprenor- phine/naltrexone [high BioDelivery Opioid dependence JUN 2014 dose, buccal]) Alisade (fluticasone GlaxoSmithKline Asthma OCT 2014 furoate) Seebri Breezhaler (glycopyrronium bromide Vectura, Novartis COPD 1Q2014 (filing*) long-acting) TBA (aclidinium bro- Forest, Almirall COPD 1Q2014 (filing*) mide/formoterol) TBA Forest Hypertension 1Q2014 (filing*) (nebivolol/valsartan) TBA (omeprazole imme- Secondary prevention of cardio- and cerebro-vascular events, re- diate-release/ JAN 2014 (fil- Pozen duce the risk of gastric ulcers in patients at risk of aspirin induced aspirin delayed-release ing*) gastric ulcers [DR]) Neuropathic pain associated with chemotherapy-induced peripher- Amiket (keta- EpiCept al neuropathy in patients previously treated with taxane-based 2014 (filing*) mine/amitriptyline) chemotherapy

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Androxal Repros Secondary hypogonadism 2014 (filing*) (enclomiphene citrate) Gram-negative lung infections caused by pseudomonas aeruginosa Arikace Insmed, Transave in patients with cystic fibrosis & bronchiectasis, non-tuberculous 2014 (filing*) (amikacin liposomal) mycobacteria lung infections Bema LA BioDelivery, Endo Moderate to severe chronic pain 2014 (filing*) (buprenorphine buccal) Impracor (ketoprofen) Imprimis Acute pain 2014 (filing*) TBA Eli Lilly, Boehringer Type 1 and type 2 diabetes 2014 (filing*) (basal insulin analog) Ingelheim TBA (carvedilol CR) RedHill Biopharma Hypertension, heart failure 2014 (filing*) TBA (daclizumab) Biogen Idec, AbbVie Relapsing remitting multiple sclerosis 2014 (filing*) TBA (glycopyrronium Novartis Moderate to severe COPD 2014 (filing*) bromide/indacaterol) Eli Lilly, Boehringer TBA (insulin peglispro) Type 1 and type 2 diabetes 2014 (filing*) Ingelheim TBA (olopatadine) Alcon, Novartis Ocular allergy 2014 (filing*) TBA (pediatric hexavalent Merck Hepatitis B virus infection 2014 (filing*) combination vaccine) RedHill BioPharma, TBA (rizatriptan) Acute migraine 2014 (filing*) IntelGenX TBA Merck Type 2 diabetes, atherosclerosis 2014 (filing*) (sitagliptin/atorvastatin) TBA Gilead Hepatitis C virus infection 2014 (filing*) (sofosbuvir/ledipasvir) TBA (sumatriptan in- OptiNose, Avanir Acute treatment of migraine 2014 (filing*) tranasal) Toctino (alitretinoin) Basilea, Stiefel Atopic dermatitis (eczema) 2014 (filing*) Vycavert (hydrocodone/ Acura Moderate to severe pain 2014 (filing*) acetaminophen) Phenylase (phenylalanine BioMarin Phenylketonuria 2015 (filing*) hydroxylase) Secondary hyperparathyroidism associated with vitamin D insuffi- Replidea (calcifediol) Cytochroma 2015 (filing*) ciency in patients with chronic kidney disease TBA (exenatide sus- Intarcia Therapeu- Type 2 diabetes 2015 (filing*) tained-release [SR]) tics TBA (glycopyrronium Pearl Therapeutics, bromide/ COPD 2015 (filing*) AstraZeneca formoterol fumarate) TBA Taiho Pharmaceuti- Metastatic colorectal cancer 2015 (filing*) (trifluridine/tipiracil) cal Ryzodeg (insulin Novo Nordisk Type 1 & type 2 diabetes 2016 degludec/insulin aspart) Tresiba Novo Nordisk Type 1 & type 2 diabetes 2016 (insulin degludec) Afrezza (insulin human [rDNA origin] inhalation MannKind Type 1 & Type 2 diabetes uncertain powder) Alprox-TD, Vitaros Warner Chilcott Erectile dysfunction uncertain (alprostadil) Asacard Flamel, NewHaven Secondary prevention of cardiovascular disease uncertain (acetylsalicylic acid) Aveed (testosterone Endo Male hypogonadism uncertain undecanoate) Bronchitol (mannitol) Pharmaxis Cystic fibrosis uncertain Civanex Winston Osteoarthritis of the knee uncertain (civamide/zucapsaicin) Duodopa Abbott Parkinson’s disease uncertain (carbidopa/levodopa) Dyloject Javelin, Hospira Management of acute moderate to severe pain in adults uncertain (cyclodextrin/diclofenac) Heplisav (hepatitis B Prevention of hepatitis B virus infection in healthy Dynavax uncertain virus vaccine) adults 18-70 years of age Iluvien (fluocinolone Alimera, pSivida Diabetic macular edema uncertain acetonide ER) Levadex Map, Nektar, Aller- Migraine uncertain (dihydroergotamine) gan

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Optaflu Novartis Influenza virus infection prevention in patients >/= 18 years of age uncertain (influenza virus vaccine) Ostora (calcitonin/ re- Tarsa Therapeutics, Osteoporosis uncertain combinant salmon) Unigene Probuphine (buprenor- Titan Opioid dependence in adults uncertain phine SR) Sefelsa (gabapentin CR) Depomed, Abbott Moderate to severe vasomotor symptoms due to menopause uncertain TBA Neos Therapeutics ADHD uncertain (amphetamine polistirex) TBA (carbinoxamine) Tris Allergies uncertain TBA (cysteamine DR/ Raptor Nephropathic cystinosis uncertain mercaptamine DR) TBA (granisetron SR) AP Pharma Chemotherapy-induced nausea & vomiting uncertain TBA (sufentanil nanotab) AcelRx Post-operative pain uncertain Twirla (ethinyl estradi- Agile Therapeutics Prevention of pregnancy uncertain ol/levonorgestrel)

References:

1. Pharmacist’s Letter, New Drugs Approved† by the FDA in 2012, Therapeutic Research Center, 1995-2012, last accessed 12/6/12, http://pharmacistsletter.therapeuticresearch.com/pl/NewDrugs.aspx?cs=&s=PL&pt=20 2. Pharmacist’s Letter, Anticipated Availability of First-Time Generics, Therapeutic Research Center, 3120 W. March Lane, PO Box 8190, Stockton, CA 95208, Copyright © 1995-2012, All rights reserved, last accessed 12/6/12, http://pharmacistsletter.therapeuticresearch.com/pl/ArticleDD.aspx?nidchk=1&cs=&s=PL&dd=251011&pb=&pt=2&fpt=55&m enu=ftg 3. HealthTrans,Generic Pipeline Report, SXC company, 2012, last accessed 11/6/12, http://www.healthtrans.com/Clinical/Clinical_v2/Clinical%20Documents/2012-01-Drug%20Pipeline%20Report.pdf 4. Rx Outlook: Generic Pipeline 2012-2014, SXC Drug Information Services, 2012 SXC Health Solutions, Inc. Volume 6, Issue 1, 1st Quarter 2012 5. Rx Outlook: Generic Pipeline October 2012-2015, SXC Drug Information Services, 2012 SXC Health Solutions, Inc. Volume 6, Issue 4, 4st Quarter 2012 6. Rx Outlook: Generic Pipeline December 2013-December 2016, SXC Drug Information Services, 2013 SXC Health Solutions, Inc. Volume 7, Issue 12, 4st Quarter 2013 7. Rx Outlook: Non-specialty pipeline – remainder of 2012-2014, SXC Drug Information Services, 2012 SXC Health Solutions, Inc. Volume 6, Issue 5, 4st Quarter 2012 8. Rx Outlook: Non-specialty pipeline – 2013-2016, Catamaran Inc. Drug Intelligence Services, 2013 Catamaran Inc. Volume 7, Is- sue 5, 2nd Quarter 2013 9. Rx Outlook: Non-specialty pipeline – 2013-2016, Catamaran Inc. Drug Intelligence Services, 2013 Catamaran Inc. Volume 7, Is- sue 9, 3rd Quarter 2013 10. Rx Outlook: Non-specialty pipeline – Q4 2013 to 2017, Catamaran Inc. Drug Intelligence Services, 2013 Catamaran Inc. Volume 7, Issue 13, 4th Quarter 2013 11. Rx Outlook: Specialty pipeline – 2013-2016, Catamaran Inc. Drug Intelligence Services, 2013 Catamaran Inc. Volume 7, Issue 10, 3rd Quarter 2013 12. Rx Outlook: Specialty pipeline – Q4 2013-2017, Catamaran Inc. Drug Intelligence Services, 2013 Catamaran Inc. Volume 7, Is- sue 13, 4th Quarter 2013 13. Rx Outlook: Generic Pipeline April 2013 to April 2016, Catamaran Inc. Drug Intelligence Services, 2013 Catamaran Inc. Volume 7, Issue 4, 2nd Quarter 2013 14. Rx Outlook: Generic Pipeline July 2013 to July 2016, Catamaran Inc. Drug Intelligence Services, 2013 Catamaran Inc. Volume 7, Issue 8, 3rd Quarter 2013 15. RxHighlights, SXC Health Solutions, Inc. Volume 5, Issue 7, 8 and 9, August 2012 16. RxHighlights, SXC Health Solutions, Inc. Volume 5, Issue 10, September 2012 17. RxHighlights, Catamaran, Volume 5, Issue 11, October 2012 18. RxHighlights, Catamaran, Volume 6, Issue 10, September 2013 19. RxHighlights, Catamaran, Volume 6, Issue 11, October 2013 20. RxHighlights, Catamaran, Volume 6, Issue 12, November 2013 21. Express Scripts, Medco, Estimated Dates of Possible First-time Generics/Rx-to-OTC Market Entry, June 2012

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