February 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
Abilify Aripiprazole Otsuka Pharmaceutical Co. Ltd.	Adds class warning concerning metabolic changes associated with atypical antipsychotics, including hyperglycemia/diabetes mellitus, dyslipidemia and body weight gain, noting that while all drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile	2/22/2012 (21-436/034) (21-866/020) (21-713/025) (21-729/018)
Adderall Shire Development LLC Amphetamine aspartate/ amphetamine sulfate/ dextroamphetamine saccharate/ dextroamphetamine sulfate	Adds irritability, tics, aggression, anger, logorrhea and dermatillomania to Central Nervous System adverse reactions; creates new Eye Disorders subheading listing blurred vision and mydriasis; creates new Skin subheading listing alopecia	2/7/2012 (21-303/023)
Amturnide Aliskiren/amlodipine/ hydrochlorothiazide Novartis Pharmaceuticals Corp.	Clarifies and strengthens language concerning the threat of fetal injury and death from drugs that act directly on the renin-angiotensin system in boxed warning and elsewhere in labeling; arranges warning information under a new Fetal Toxicity section subtitled Pregnancy Category D; revises several sections of labeling to clarify safety information mainly regarding hydrochlorothiazide	2/2/2012 (200-045/010) (200-045/006)
Angeliq Drospirenone/estradiol Bayer HealthCare Pharmaceuticals Inc.	Expands labeling with a low-dose formulation for women with an intact uterus for the treatment of moderate to severe vasomotor symptoms due to menopause	2/29/2012 (21-355/003)
Aptivus Tipranavir Boehringer Ingelheim Pharmaceuticals Inc.	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (21-814/013) (22-292/006)
Avalide Irbesartan/ hydrochlorothiazide Sanofi-Aventis/Bristol-Myers Squibb Co.	Revises several sections of labeling to clarify safety information mainly regarding hydrochlorothiazide	2/9/2012 (20-758/060)
Benicar Olmesartan Daiichi Sankyo Inc.	Revises indication for treatment of hypertension to 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 wide variety of classes, including the class to which Benicar principally belongs, but that there are no controlled trials demonstrating risk reduction with Benicar, although at least one pharmacologically similar drug has demonstrated such benefits; adds information on pediatric use noting Benicar has not been shown to be effective for hypertension in children <6 years of age and that children <1 year of age must not receive Benicar because drugs that act directly on the renin-angiotensin aldosterone system can have effects on development of immature kidneys	2/15/2012 (21-286/021)
Beyaz Drospirenone/ethinyl estradiol/levomefolate Bayer HealthCare Pharmaceuticals Inc.	Adds new information regarding the risk of venous thromboembolic events in women using combined oral contraceptives to Warnings, specifically concerning the temporal trend in the increased risk relative to starting a COC or restarting the same or a different COC following temporary discontinuation, based on data from a large, prospective cohort safety study of various COCs	2/13/2012 (22-532/001)
Cardiogen-82 Rubidium chloride RB-82 Bracco Diagnostics Inc.	Adds a boxed warning that describes the risk for unintended strontium-82 (Sr-82) and strontium-85 (Sr-85) radiation exposure and methods to minimize the risk	2/8/2012 (19-414/014)
Crestor Rosuvastatin AstraZeneca Pharmaceuticals LP	Applies new class labeling for HMG-CoA reductase inhibitors that replaces instruction that liver enzymes should be monitored before and during treatment with a recommendation that liver function be tested before starting therapy and as clinically indicated thereafter; notes under postmarketing experience that there have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use and that these issues have been reported for all statins and are generally nonserious and reversible upon discontinuation	2/28/2012 (21-366/024)
Crixivan Indinavir Merck Sharp & Dohme Corp.	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (20-685/075)
Diovan Valsartan Novartis Pharmaceuticals Corp.	Adds safety information on pediatric use, noting Diovan is not recommended for patients under 6 years of age and that no data are available in pediatric patients undergoing dialysis	2/28/2012 (21-283/035)
Diovan HCT Valsartan/ hydrochlorothiazide Novartis Pharmaceuticals Corp.	Revises several sections of labeling to clarify safety information mainly regarding hydrochlorothiazide	2/16/2012 (20-818/051)
EES, PCE & Ery-Ped Erythromycin Arbor Pharmaceuticals Inc.	Adds warning that erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia; cases of torsades de pointes have been spontaneously reported, and fatalities have been reported	2/2/2012 (50-207/071) (50-611/035)
Elestrin Estradiol gel Azur Pharma International II Ltd/Beckloff Assoc. Inc.	Adds a new warning that exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema	2/24/2012 (21-813/003)
Eryc Erythromycin Warner Chilcott	Adds warning that erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia; cases of torsades de pointes have been spontaneously reported, and fatalities have been reported	2/14/2012 (50-536/022)
Erythrocin Erythromycin Hospira Inc.	Adds warning that erythromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia; cases of torsades de pointes have been spontaneously reported, and fatalities have been reported	2/2/2012 (50-609/033)
Exforge HCT Amlodipine/valsartan/ hydrochlorothiazide Novartis Pharmaceuticals Corp.	Revises several sections of labeling to clarify safety information mainly regarding hydrochlorothiazide	2/16/2012 (22-314/009)
Famvir Famciclovir Novartis Pharmaceuticals Corp.	Adds information to the Pediatric Use section from a pediatric study in patients aged 12 years to <18 years of age with recurrent herpes labialis, including addition of angioedema to skin and subcutaneous tissue adverse reactions and information regarding use in patients with severe hepatic impairment	2/9/2012 (20-363/038 & 040)
Hepsera Adefovir Gilead Sciences Inc.	Adds osteomalacia that manifests as bone pain and that may contribute to fractures to postmarketing experience	2/29/2012 (21-355/018)
Invirase Saquinavir Hoffmann-La Roche Inc./Genentech Inc.	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (20-628/038) (21-785/015)
Kaletra Lopinavir/ritonavir Abbott Laboratories	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (21-226/035) (21-251/042) (21-906/035)
Lescol Fluvastatin Novartis Pharmaceuticals Corp.	Applies new class labeling for HMG-CoA reductase inhibitors that replaces instruction that liver enzymes should be monitored before and during treatment with a recommendation that liver function be tested before starting therapy and as clinically indicated thereafter; notes under postmarketing experience that there have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use and that these issues have been reported for all statins and are generally nonserious and reversible upon discontinuation; warns that increases in HbA1c and fasting serum glucose levels have been reported with statins, including Lescol	2/28/2012 (20-261/046) (21-192/019)
Letairis Ambrisentan Gilead Sciences Inc.	Strengthens language throughout labeling regarding pregnancy contraindication and the restricted access program based on the REMS assessment; updates Clinical Studies section to add that open-label follow-up on 383 patients from two pivotal studies generated estimates of survival at 1, 2 and 3 years of 93%, 85% and 79%, respectively, noting these uncontrolled observations do not allow comparison with a group not given Letairis and cannot be used to determine the long-term effect of the therapy on mortality	2/15/2012 (22-081/014)
Lexiva Fosamprenavir ViiV Healthcare Co./GlaxoSmithKline	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (21-548/029) (22-116/013)
Lipitor Atorvastatin Pfizer Inc./Pfizer Ireland Pharmaceuticals	Applies new class labeling for HMG-CoA reductase inhibitors that replaces instruction that liver enzymes should be monitored before and during treatment with a recommendation that liver function be tested before starting therapy and as clinically indicated thereafter; notes under postmarketing experience that there have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use and that these issues have been reported for all statins and are generally nonserious and reversible upon discontinuation; warns that increases in HbA1c and fasting serum glucose levels have been reported with statins, including Lipitor	2/28/2012 (20-702/060)
Livalo Pitavastatin Kowa Pharmaceuticals America Inc./Kowa Co. Ltd.	Applies new class labeling for HMG-CoA reductase inhibitors that replaces instruction that liver enzymes should be monitored before and during treatment with a recommendation that liver function be tested before starting therapy and as clinically indicated thereafter; notes under postmarketing experience that there have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use and that these issues have been reported for all statins and are generally nonserious and reversible upon discontinuation; warns that increases in HbA1c and fasting serum glucose levels have been reported with statins, including Livalo	2/28/2012 (22-363/008 & 009)
Lotensin HCT Benazepril/ hydrochlorothiazide Novartis Pharmaceuticals Corp.	Revises several sections of labeling to clarify safety information mainly regarding hydrochlorothiazide	2/16/2012 (20-033/043)
Mevacor Lovastatin Merck Sharp & Dohme Corp.	Applies new class labeling for HMG-CoA reductase inhibitors that replaces instruction that liver enzymes should be monitored before and during treatment with a recommendation that liver function be tested before starting therapy and as clinically indicated thereafter; notes under postmarketing experience that there have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use and that these issues have been reported for all statins and are generally nonserious and reversible upon discontinuation; warns that increases in HbA1c and fasting serum glucose levels have been reported with statins, including Mevacor; adds new contraindications and dose limitations when Mevacor is taken with certain medicines that can increase the risk for muscle injury (myopathy/rhabdomyolysis)	2/28/2012 (19-643/085)
Natazia Estradiol & Estradiol/dienogest Bayer HealthCare Pharmaceuticals Inc.	Adds warning regarding the risk of venous thromboembolic events in women using combined oral contraceptives, specifically concerning the temporal trend in the increased risk relative to starting a COC or restarting the same or a different COC following temporary discontinuation, based on data from a large, prospective cohort safety study of various COCs	2/13/2012 (22-252/001)
Norvir Ritonavir Abbott Laboratories	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (20-659/056) (22-417/007)
Ozurdex Dexamethasone intravitreal implant Allergan Inc.	Adds a warning that patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber	2/24/2012 (22-315/005)
Phendimetrazine Sandoz Inc.	Revises labeling to add pregnancy to contradictions and change the pregnancy category from “C” to “X”; notes that because pediatric obesity is a chronic condition requiring long-term treatment, use of phendimetrazine, which is approved for short-term therapy, is not recommended for patients <17 years of age; adds primary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevated blood pressure and ischemic events to cardiovascular adverse events section	2/10/2012 (18-074/034)
Pravachol Pravastatin Bristol-Myers Squibb Co.	Applies new class labeling for HMG-CoA reductase inhibitors that replaces instruction that liver enzymes should be monitored before and during treatment with a recommendation that liver function be tested before starting therapy and as clinically indicated thereafter; notes under postmarketing experience that there have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use and that these issues have been reported for all statins and are generally nonserious and reversible upon discontinuation	2/28/2012 (19-898/062)
Precose Acarbose Bayer HealthCare Pharmaceuticals	Adds pneumatosis cystoides intestinalis to postmarket adverse events, noting there have been rare reports associated with the use of alpha-glucosidase inhibitors, including Precose	2/29/2012 (20-482/025)
Premarin Conjugated estrogens Wyeth Pharmaceuticals Inc./Pfizer Inc.	Adds warnings for anaphylactic reaction and angioedema and hereditary angioedema; notes that exogenous estrogens may exacerbate symptoms of angioedema in women with hereditary angioedema	2/14/2012 (20-216/073, 074 & 075)
Prempro & Premphase Conjugated estrogens/ medroxyprogesterone Wyeth Pharmaceuticals Inc./Pfizer Inc.	Adds two new warnings for anaphylactic reaction and angioedema and hereditary angioedema; adds ischemic colitis and growth potentiation of benign meningioma to postmarketing experience	2/2/2012 (20-527/051, 054 & 056)
Prezista Darunavir Janssen Products LP	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	2/17/2012 (21-976/022) (202-895/001)
Reyataz Atazanavir Bristol-Myers Squibb Co.	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (21-567/027)
Safyral Drospirenone/ethinyl estradiol/levomefolate Bayer HealthCare Pharmaceuticals Inc.	Updates warnings with new information regarding the risk of venous thromboembolic events in women using combined oral contraceptives, specifically concerning the temporal trend in the increased risk relative to starting a COC or restarting the same or a different COC following temporary discontinuation, based on data from a large, prospective cohort safety study of various COCs	2/13/2012 (22-574/001)
Simcor Niacin/simvastatin Abbott Laboratories	Applies new class labeling for HMG-CoA reductase inhibitors that replaces instruction that liver enzymes should be monitored before and during treatment with a recommendation that liver function be tested before starting therapy and as clinically indicated thereafter; notes under postmarketing experience that there have been rare reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use and that these issues have been reported for all statins and are generally nonserious and reversible upon discontinuation; warns that increases in HbA1c and fasting serum glucose levels have been reported with statins, including simvastatin	2/28/2012 (22-078/013)
Tekturna & Tekturna HCT Aliskiren & aliskiren/ hydrochlorothiazide Novartis Pharmaceuticals Corp.	Clarifies and strengthens language concerning the threat of fetal injury and death from drugs that act directly on the renin-angiotensin system in boxed warning and elsewhere in labeling; arranges warning information under a new Fetal Toxicity section subtitled Pregnancy Category D	2/2/2012 (21-985/022) (22-107/019)
Tekturna HCT Aliskiren & aliskiren/ hydrochlorothiazide Novartis Pharmaceuticals Corp.	Revises several sections of labeling to clarify safety information mainly regarding hydrochlorothiazide	2/14/2012 (22-107/016)
Thalomid Thalidomide Celgene Corp.	Updates labeling with results of trial THAL-MM-033, one of two accelerated approval commitments, which compared thalidomide plus dexamethasone to dexamethasone alone in treatment-naïve patients with multiple myeloma	2/3/2012 (207-85/040)
Valturna Aliskiren/valsartan Novartis Pharmaceuticals Corp.	Clarifies and strengthens language concerning the threat of fetal injury and death from drugs that act directly on the renin-angiotensin system in boxed warning and elsewhere in labeling; arranges warning information under a new Fetal Toxicity section subtitled Pregnancy Category D	2/2/2012 (22-217/017)
Vaseretic Enalapril/ hydrochlorothiazide Valeant International (Barbados) SRL	Clarifies and strengthens language concerning the threat of fetal injury and death from drugs that act directly on the renin-angiotensin system in boxed warning and elsewhere in labeling; arranges warning information under a new Fetal Toxicity section subtitled Pregnancy Category D	2/17/2012 (19-221/042)
Vasotec Enalapril Valeant International (Barbados) SRL	Clarifies and strengthens language concerning the threat of fetal injury and death from drugs that act directly on the renin-angiotensin system in boxed warning and elsewhere in labeling; arranges warning information under a new Fetal Toxicity section subtitled Pregnancy Category D	2/17/2012 (18-998/076)
Vexol Rimexolone ophthalmic suspension Alcon Laboratories Inc./Alcon Research Ltd.	Adds precaution against using the same bottle for both eyes when used in association with surgery	2/22/2012 (20-474/021)
Viracept Nelfinavir Pfizer Inc.	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 class labeling based on recent studies demonstrating decreased transmission of HIV when HIV-infected patients or their uninfected partners take antiretroviral medication	2/17/2012 (20-778/037) (20-779/058) (21-503/020)
Xalkori Crizotinib Pfizer Inc.	Adds a warning that drug-induced hepatotoxicity with fatal outcome occurred during treatment in <1% of patients in clinical trials	2/17/2012 (202-570/003)
Yasmin Drospirenone/ethinyl estradiol Bayer HealthCare Pharmaceuticals Inc.	Updates warning with new information regarding the risk of venous thromboembolic events in women using combined oral contraceptives, specifically concerning the temporal trend in the increased risk relative to starting a COC or restarting the same or a different COC following temporary discontinuation, based on data from a large, prospective cohort safety study of various COCs	2/13/2012 (21-098/019)
Zyvox Linezolid Pharmacia and Upjohn Co. Inc., a subsidiary of Pfizer Inc.	Adds warning on hypoglycemia, noting postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus, though a causal relationship has not been established, and that some MAO inhibitors have been associated with hypoglycemic episodes	2/13/2012 (21-130/028) (21-131/024) (21-132/027)
Biologic
Avonex Interferon beta-1a Biogen Idec Inc.	Provides for an Avonex Pen single-use pre-filled autoinjector and an Avostartgrip titration kit, a three-pack of dose limiting devices to be used with Avonex pre-filled syringes	2/27/2012 (103628/5189 & 5191)
Orencia Abatacept Bristol-Myers Squibb Co.	Revises warnings to note that serious infections, including sepsis and pneumonia, have been reported, some of them fatal, and that many of them occurred in patients on concomitant immunosuppressive therapy	2/17/2012 (125118/138)
Xiaflex Collagenase clostridium histolyticum Auxilium Pharmaceuticals Inc.	Removes MedGuide as a requirement of the REMS, while retaining the MedGuide as part of labeling; modifies REMS to consist of an updated communication plan and a timetable for submission of assessments of the REMS	2/24/2012 (125338/0040)