November Supplemental Approvals

Chart lists efficacy supplements and labeling supplements selected by the editors of “Pharmaceutical Approvals Monthly.” This is not a comprehensive list of all supplemental approvals.

Product & Sponsor	Change	Date Approved (Application No.)
Drug
AndroGel Testosterone Abbott	Revises labeling and REMS to include new language for testosterone gels pertaining to the risk of secondary exposure to testosterone in children	11/30/2011 (21-015/032)
Agrylin Anagrelide Shire	Updates drug interactions with findings of major hemorrhagic events when co-administered with aspirin	11/22/2011 (18-060/019)
Alimta Pemetrexed Lilly	Revises warning regarding effects on patients with or without third space fluid, based on a study in 31 solid tumor patients with stable third space fluid that showed pemetrexed plasma concentrations were comparable to those in previous clinical trials in patients without third space fluid collections, making drainage of mild or moderate fluid accumulation before treatment “probably not necessary”	11/18/2011 (21-462/029)
Amturnide Aliskiren/amlodipine/ hydrochlorothiazide Novartis	Amends drug interactions to note that co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone, therefore the dose of simvastatin in patients on amlodipine should be limited to 20 mg daily	11/2/2011 (200-045/009)
Azor Amlodipine/olmesartan Daiichi Sankyo	Amends drug interactions to note that co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone, therefore the dose of simvastatin in patients on amlodipine should be limited to 20 mg daily	11/2/2011 (22-100/014)
Azor Amlodipine/olmesartan Daiichi Sankyo	Revises indication for treatment of hypertension to add information on the condition and note that the benefit of lowering blood pressure to reduce the risk of cardiovascular events has been seen in controlled trials of antihypertensive drugs from a variety of classes, however, there are no controlled trials demonstrating risk reduction with Azor, although at least one pharmacologically similar drug has demonstrated such benefit	11/14/2011 (22-100/013)
Calan Verapamil Pfizer	Adds a precaution that use of HMG-CoA reductase inhibitors that are CYP34A substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis	11/2/2011 (18-817//027) (18-925/008) (19-038/004)
Combivir Lamivudine/zidovudine ViiV	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (20-857/028)
Cordarone Amiodarone Pfizer	Adds a precaution that use of HMG-CoA reductase inhibitors that are CYP34A substrates in combination with amiodarone has been associated with reports of myopathy/rhabdomyolysis	11/14/2011 (18-972/044)
Covera-HS Verapamil Pfizer	Adds a precaution that use of HMG-CoA reductase inhibitors that are CYP34A substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis	11/2/2011 (20-552/007)
Cozaar Losartan Merck	Adds a precaution noting that dual blockade of the rennin-angiotensin-aldosterone system is associated with increased risk of hypotension, syncope, hyperkalemia and changes in renal function (including acute renal failure) and advising close monitoring of patients on Cozaar and ACE inhibitors	11/17/2011 (20-386/056)
Diflucan Fluconazole Pfizer	Removes references to Diflucan Capsules and Diflucan Syrup from labeling for tablets, I.V. and powder for oral suspension formulations because the capsule and syrup formulations are not approved	11/16/2011 (19-949/055) (19-950/059) (20-090/038)
Dilantin Phenytoin Pfizer	Includes additional warnings and precautions with respect to skin reactions, hypersensitivity and anticonvulsant hypersensitivity syndrome; upgrades boxed important note on cardiovascular risk associated with rapid infusion to a boxed warning; revises labeling to recommend that parenteral Dilantin be used only when oral phenytoin administration is not possible; adds warning about purple glove syndrome; updates information regarding CYP450-mediated metabolism	11/13/2011 (10-151/036)
Emtriva Emtricitabine Gilead	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (21-500/018 (21-896/015)
Epivir Lamivudine ViiV	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (20-564/031) (20-596/030)
Epzicom Abacavir/lamivudine ViiV	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (21-652/014)
Hyzaar Hydrochlorothiazide/ losartan Merck	Adds a precaution noting that dual blockade of the rennin-angiotensin-aldosterone system is associated with increased risk of hypotension, syncope, hyperkalemia and changes in renal function (including acute renal failure) and advising close monitoring of patients on Cozaar and ACE inhibitors	11/17/2011 (20-387/054)
Isentress Raltegravir Merck	Adds warning that severe, potentially life-threatening and fatal skin reactions have been reported, including cases of Stevens-Johnson syndrome and toxic epidermal necrolysis	11/2/2011 (22-145/020)
Klonopin Clonazepam Roche	Eliminates REMS requirement while retaining MedGuide	11/29/2011 (17-533/052 & 046) (20-813/008)
Kombiglyze XR Saxagliptin/metformin Bristol-Myers Squibb	Converts approved patient package insert to a MedGuide; updates Onglyza (saxagliptin) package insert with information regarding hypersensitivity reactions, including anaphylaxis and angioedema and acute pancreatitis	11/15/2011 (200-678/005)
Onglyza Saxagliptin Bristol-Myers Squibb	Adds reports of acute pancreatitis to warnings and precautions, noting it is unknown whether patients with a history of pancreatitis are at increased risk, and reports of serious hypersensitivity reactions, including anaphylaxis, angioedema and exfoliative skin conditions	11/15/2011 (22-350/007)
Prinivil Lisinopril Merck	Adds a precaution noting that dual blockade of the rennin-angiotensin-aldosterone system is associated with increased risk of hypotension, syncope, hyperkalemia and changes in renal function (including acute renal failure) and advising close monitoring of patients on Prinivil and ACE inhibitors	11/17/2011 (19-558/054)
Prinzide Hydrochlorothiazide/ lisinopril Merck	Adds a precaution noting that dual blockade of the rennin-angiotensin-aldosterone system is associated with increased risk of hypotension, syncope, hyperkalemia and changes in renal function (including acute renal failure) and advising close monitoring of patients on Prinivil and ACE inhibitors	11/17/2011 (19-778/046)
Prometrium Progesterone Unimed	Updates labeling with results from a postmarketing study; revises sections to reflect class labeling for combination estrogen plus progestin therapy	11/1/2011 (19-781/017) (20-843/011)
Retrovir Zidovudine ViiV	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (19-655/052) (19-910/039) (19-951/029) (20-518/022)
Seroquel Quetiapine AstraZeneca	Revises MedGuide to increase patient awareness of the risks associated with use, including mortality in elderly, hyperglycemia, hypercholesterolemia and weight gain; eliminates REMS requirement while retaining MedGuide	11/9/2011 (22-047/028) (20-639/055)
Tarka Trandolapril/verapamil Abbott	Strengthens precautions to state use of HMG-CoA reductase inhibitors that are CYP34A substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis and that co-administration of multiple doses of 10 mg verapamil with 80 mg simvastatin resulted in a 2.5-fold increase in exposure to simvastatin compared to simvastatin alone, therefore the dose of simvastatin in patients on verapamil should be limited to 10 mg daily, the dose of lovastatin should be limited to 40 mg and lower starting doses of other statins may be required, as verapamil may increase plasma concentration	11/14/2011 (20-591/019)
Tekamlo Aliskiren/amlodipine Novartis	Amends drug interactions to note that co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone, therefore the dose of simvastatin in patients on amlodipine should be limited to 20 mg daily	11/14/2011 (22-545/008)
Testim Testosterone Auxilium	Revises labeling and REMS to include new language for testosterone gels pertaining to the risk of secondary exposure to testosterone in children	11/22/2011 (21-454/014)
Tribenzor Amlodipine/ hydrochlorothiazide/ olmesartan Daiichi Sankyo	Amends drug interactions to note that co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone, therefore the dose of simvastatin in patients on amlodipine should be limited to 20 mg daily	11/1/2011 (200-175/007)
Trizivir Abacavir/lamivudine/ zidovudine ViiV	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (21-205/029)
Twynsta Amlodipine/telmisartan Boehringer Ingelheim	Amends drug interactions to note that co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone, therefore the dose of simvastatin in patients on amlodipine should be limited to 20 mg daily	11/14/2011 (22-401/010)
Velcade Bortezomib Millennium	Updates overall survival data based on 387 deaths (median follow-up of 60.1 months) to 56.4 months for the Velcade arm versus 43.1 months for background regimen alone	11/1/2011 (21-602/029 & 030)
Verelan Verapamil Alkermes	Adds precautions that use of HMG-CoA reductase inhibitors that are CYP34A substrates in combination with verapamil has been associated with reports of myopathy/rhabdomyolysis and that co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone, therefore the dose of simvastatin in patients on amlodipine should be limited to 20 mg daily	11/14/2011 (19-614/049) (20-943/028)
Vfend Voriconazole Pfizer	Updates postmarket experience to add a skeletal adverse events heading listing fluorosis and periostitis with long-term therapy	11/16/2011 (21-266/035) (21-267/040) (21-630/026)
Videx Didanosine Bristol-Myers Squibb	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (20-156/048) (21-183/025)
Vimovo Naproxen/esomeprazole AstraZeneca	Adds new safety information for the proton pump inhibitor class pertaining to the risk of hip, wrist and spine fractures with long-term use	11/18/2011 (22-511/001)
Viread Tenofovir Gilead	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (21-356/041)
Zerit Stavudine Bristol-Myers Squibb	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (20-412/038) (20-413/030)
Ziagen Abacavir ViiV	Adds new class safety information to warnings concerning the risk of immune reconstitution syndrome noting autoimmune disorders (such as Graves’ disease, polymyositis and Guillain-Barre syndrome) have been reported but that time to onset is more variable and can occur many months after initiation of treatment; adds classwide labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	11/18/2011 (20-977/023) (20-978/027)
Zortress Everolimus Novartis	Removes MedGuide from the REMS, while retaining the communication plan and timetable for submission of assessments; retains MedGuide as part of labeling	11/21/2011 (21-560/004)
Zyflo CR Zileuton Cornerstone	Adds section on pediatric patients stressing that due to the risk of hepatotoxicity it has not been tested in and is not appropriate for children less than 12 years of age	11/30/2011 (22-052/009)
Biologic
Erbitux Cetuximab Eli Lilly	Provides for use as first-line treatment of patients with recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU	11/7/2011 (125084/153)
Kepivance Palifermin Biovitrum	Limits use for patients undergoing autologous transplantation following a “chemotherapy-only” preparative regimen based on results of a post-approval study in multiple myeloma patients who received a high-dose melphalan conditioning regimen with palifermin that showed no significant differences between palifermin and placebo in the incidence of severe oral mucositis	11/18/2011 (125103/120)