MedWatch - December 2006 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- December 2006

The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, or PATIENT PACKAGE INSERT/MEDICATION GUIDE sections. Deletions or editorial revisions made to these sections are not included in this summary.

Summary View

Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Activella (estradiol/norethindrone acetate) Tablets Prescribing Information Patient Package Insert	BOXED WARNING Cardiovascular and Other Risks WARNINGS Cardiovascular Disorders Stroke Coronary Heart Disease Venous Thromboembolism Malignant Neoplasms Breast Cancer Dementia PRECAUTIONS Drug Test Interactions Carcinogenesis, Mutagenesis, Impairment of Fertility Initial Paragraph Geriatric Use ADVERSE REACTIONS Table 8 PATIENT PACKAGE INSERT	See highlighted prescribing information for labeling revisions.

Diskets Dispersible Tablets (methadone hydrochloride tablets, USP) For Oral Use Only (following dispersion in a liquid) Prescribing Information	BOXED WARNING (new) CONTRAINDICATIONS WARNINGS Respiratory Depression Cardiac Conduction Effects Incomplete Cross-tolerance between Methadone and other Opioids Misuse, Abuse, and Diversion of Opioids Interactions with other CNS Depressants Interactions with Alcohol and Drugs of Abuse Head Injury and Increased Intracranial Pressure Acute Abdominal Conditions PRECAUTIONS Initial Section Drug Interactions Initial Section Opioid Antagonists, Mixed Agonist/Antagonists, and Partial Agonists Anti-retroviral Agents Cytochrome P450 Inducers St. John's Wort, Phenobarbital, Carbamazepine Cytochrome P450 Inhibitors Potentially Arrhythmogenic Agents Interactions with Alcohol or Drugs of Abuse Physical Dependence Information for Patients Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Labor and Delivery Nursing Mothers Pediatric Use Geriatric Use Renal Impairment Hepatic Impairment Gender ADVERSE REACTIONS Initial Administration Other Adverse Reactions Body as a Whole Cardiovascular Digestive Metabolic and Nutritional Nervous Respiratory Special Senses Urogenital	See highlighted prescribing information for extensive labeling revisions.

Trasylol (aprotinin injection) Prescribing Information See MedWatch Safety Alert posted 12/15/2006.	BOXED WARNING (new) CONTRAINDICATIONS WARNINGS Anaphylactic or Anaphylactoid Reactions Re-exposure to Aprotinin Renal Dysfunction PRECAUTIONS General Initial (Test) Dose Renal Dysfunction ADVERSE REACTIONS Myocardial Infarction Table: Incidence of Myocardial Infarctions by Treatment Group Population..... Laboratory Findings Serum Creatinine Serum Transaminases	BOXED WARNING Trasylol administration may cause fatal anaphylactic or anaphylactoid reactions. Fatal reactions have occurred with an initial (test) dose as well as with any of the components of the dose regimen. Fatal reactions have also occurred in situations where the initial (test) dose was tolerated. The risk for anaphylactic or anaphylactoid reactions is increased among patients with prior aprotinin exposure and a history of any prior aprotinin exposure must be sought prior to Trasylol administration. The risk for a fatal reaction appears to be greater upon re-exposure within 12 months of the most recent prior aprotinin exposure..... CONTRAINDICATIONS Administration of Trasylol to patients with a known or suspected previous aprotinin exposure during the last 12 months is contraindicated. For patients with known or suspected history of exposure to aprotinin greater than 12 months previously, see WARNINGS. Aprotinin may also be a component of some fibrin sealant products and the use of these products should be included in the patient history. WARNINGS See highlighted WARNINGS section of prescribing information for revisions.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Crixivan (indinavir sulfate) Capsules Prescribing Information Patient Package Insert	CONTRAINDICATIONS Table 7: Drug Interactions with Crixivan: Contraindicated Drugs Alprazolam PRECAUTIONS Drug Interactions Table 8: Drugs That Should Not Be Coadministered with Crixivan Alprazolam PATIENT PACKAGE INSERT Medicines You Should Not Take With Crixivan Xanax (alprazolam)	CONTRAINDICATIONS Inhibition of CYP3A4 by Crixivan can result in elevated plasma concentrations of the following drugs, potentially causing serious or life-threatening reaction: Alprazolam (added to Sedative/Hypnotics Drug Class.)

Vfend I.V. (voriconazole) for Injection Vfend (voriconazole) Tablets Vfend (voriconazole) for Oral Suspension Prescribing Information Patient Package Insert	CONTRAINDICATIONS PRECAUTIONS Drug Interactions Table 9: Effect of Other Drugs on Voriconazole Pharmacokinetics Efavirenz Table 10: Effect of Voriconazole on Pharmacokinetics of Other Drugs Efavirenz PATIENT PACKAGE INSERT Who should not take Vfend?	CONTRAINDICATIONS Coadministration of standard doses of Vfend with efavirenz is contraindicated because efavirenz significantly decreases voriconazole plasma concentrations while Vfend also significantly increases efavirenz plasma concentrations. Concomitant use of adjusted doses of voriconazole and efavirenz may be administered.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Colazal (balsalazide disodium) Capsules Prescribing Information Patient Counseling Information Read about new Physician's Labeling Format	HIGHLIGHTS SECTION: WARNINGS & PRECAUTIONS Exacerbations of Ulcerative Colitis FULL PRESCRIBING INFORMATION: WARNINGS & PRECAUTIONS Section 5.1: Exacerbations of Ulcerative Colitis ADVERSE REACTIONS Section 6.1: Clinical Studies Experience Pediatric Ulcerative Colitis Table 2 USE IN SPECIFIC POPULATIONS Section 8.4: Pediatric Use PATIENT COUNSELING INFORMATION (new)	HIGHLIGHT SECTION: WARNINGS & PRECAUTIONS: Exacerbations of Ulcerative Colitis Exacerbation of the symptoms of ulcerative colitis was reported in both adult and pediatric patients. Observe patients closely for worsening of these symptoms while on treatment. FULL PRESCRIBING INFORMATION: WARNINGS & PRECAUTIONS: Exacerbations of Ulcerative Colitis In the adult clinical trials, 3 out of 259 patients reported exacerbation of the symptoms of ulcerative colitis. In the pediatric clinical trials, 4 out of 68 patients reported exacerbation of the symptoms of ulcerative colitis.

Emtriva (emtricitabine) Capsules and Oral Solution Prescribing Information Patient Package Insert	WARNINGS Other PRECAUTIONS Pediatric Use ADVERSE REACTIONS Adult Patients Studies 301A and 303 – Treatment-Emergent Adverse Events Studies 301A and 303 – Laboratory Abnormalities Study 934 - Treatment Emergent Adverse Events Table 10 Study 934 – Laboratory Abnormalities Table 11 PATIENT PACKAGE INSERT What is Emtriva? Who should not take Emtriva?	WARNINGS: Other Emtriva is a component of Truvada (a fixed-dose combination of emtricitabine and tenofovir disoproxil fumarate) and Atripla (a fixed-dose combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate). Emtriva should not be coadministered with Truvada or Atripla. Due to similarities between emtricitabine and lamivudine, Emtriva should not be coadministered with other drugs containing lamivudine, including Combivir, Epivir, Epivir-HBV, Epzicom, or Trizivir.

Ibuprofen Capsules, 200 mg (over the counter) Prescribing Information See MedWatch Safety Alert posted 09/08/2006.	WARNINGS As a doctor or pharmacist before use if you are.....	WARNINGS Ask a doctor or pharmacist before use if you are [bulleted] taking aspirin for heart attack or stroke, because ibuprofen may decrease this benefit of aspirin.

Pexeva (paroxetine mesylate) Tablets Prescribing Information See MedWatch Safety Alert posted 7/19/2006.	WARNINGS Clinical Worsening and Suicide Risk Serotonin Syndrome Usage in Pregnancy Teratogenic Effects Animal Findings Nonteratogenic Effects PRECAUTIONS General Discontinuation of Treatment with Paroxetine Tinnitus Information for Patients Drug Interactions Pimozide Serotonergic Drugs Triptans Drugs Metabolized by Cytochrome CYP2D6 Fosamprenavir/Ritonavir Pregnancy Pregnancy Category D ADVERSE REACTIONS Associated with Discontinuation of Treatment Table: [GAD Column Added] Commonly Observed Adverse Events Generalized Anxiety Disorder Generalized Anxiety Disorder Table 3 In a fixed-dose study comparing placebo and 20 and 40 mg of paroxetine..... Male and Female Sexual Dysfunction with SSRIs Table 5 Hallucinations Other Events Observed During the Premarketing Evaluation of Paroxetine	WARNINGS: Clinical Worsening and Suicide Risk In addition, patients with a history of suicidal behavior or thoughts, those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at an increased risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. WARNINGS: Serotonin Syndrome The development of a potentially life-threatening serotonin syndrome may occur in association with treatment with paroxetine, particularly with concomitant use of serotonergic drugs (including triptans) and with drugs which may have impaired metabolism of serotonin (including MAOIs)..... WARNINGS: Usage in Pregnancy See highlighted WARNINGS section of prescribing information for revisions.

Suprane (desflurane, USP) Volatile Liquid for Inhalation Prescribing Information	WARNINGS Respiratory Adverse Reactions in Pediatric Patients PRECAUTIONS Pediatric Use ADVERSE REACTIONS Initial Section Table: Frequency of Events Occurring in Greater Than 1% of Clinical Trial Patients Frequency of Events Occurring in Less Than 1% of Patients (in Reports Deemed "Probably Causally Related") Frequency of Events Occurring in Less Than 1% of Clinical Trial Patients (in Reports Deemed "Causal Relationship Unknown")	WARNINGS: Respiratory Adverse Reactions in Pediatric Patients Suprane is not recommended for induction of general anesthesia via mask in children due to a high incidence of moderate to severe respiratory adverse reactions seen in clinical studies. Suprane is not approved for maintenance of anesthesia in non-intubated children due to an increased incidence of respiratory adverse reactions, including coughing, laryngospasm and secretions.

Twinject Auto-Injector (epinephrine injection, USP 1:1000) Prescribing Information Patient Package Insert	WARNINGS PATIENT PACKAGE INSERT	WARNINGS Epinephrine is light sensitive and should be stored in the carrying-case provided. Store at room temperature (20º - 25ºC/68º - 77ºF) with excursions permitted to 15º - 30ºC (59º - 86ºF). Do not refrigerate; protect from freezing. Patients should periodically check the solution in Twinject for any discoloration and/or precipitates. If the solution is discolored or contains a precipitate, the patient should replace their Twinject.

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Brand (Generic) Name	Sections Modified
Byetta (exenatide) Injection Prescribing Information Patient Package Insert	PRECAUTIONS General Hypoglycemia Most episodes of hypoglycemia were mild to moderate in intensity..... Table 3 Drug Interactions Warfarin ADVERSE REACTIONS Use with Metformin and/or a Sulfonylurea Use with a Thiazolidinedione Spontaneous Data General INR Increased with concomitant warfarin use.... Immunogenicity PATIENT PACKAGE INSERT What is Byetta?

Celebrex (celecoxib) Capsules Prescribing Information	PRECAUTIONS Systemic Onset Juvenile Rheumatoid Arthritis Animal Toxicity Pediatric Use ADVERSE REACTIONS Adverse Events from Juvenile Rheumatoid Arthritis Study Table 4

Clarinex (desloratadine) Tablets, Syrup, and RediTabs Tablets Prescribing Information	PRECAUTIONS Carcinogenesis, Mutagenesis, and Impairment of Fertility In a 2-year dietary study in mice, males and females given up to 16 mg/kg/day and 32 mg/kg/day of desloratadine, respectively, did not show significant increases in the incidence of any tumors..... ADVERSE REACTIONS Observed During Clinical Practice Palpitations Psychomotor Hyperactivity Seizures Very Rarely Hepatitis

Dostinex (cabergoline) Tablets Prescribing Information	PRECAUTIONS Fibrosis/Valvulopathy Information for Patients A patient should notify her physician if she develops dyspnea or cough. ADVERSE REACTIONS Post-marketing Surveillance Data Valvulopathy and Fibrosis

Equetro (carbamazepine) Extended-Release Capsules Prescribing Information	PRECAUTIONS Drug Interactions Agents with Decreased Levels in the Presence of Carbamazepine due to Induction of Cytochrome P450 Enzymes Trazodone

Fuzeon (enfuvirtide) for Injection Prescribing Information Patient Package Insert	PRECAUTIONS Administration with Biojector 2000 Information for Patients Patients and caregivers should be instructed on the preferred anatomical sites..... ADVERSE REACTIONS Local Injection Site Reactions Biojector 2000 Needle-Free Device PATIENT PACKAGE INSERT How should I use Fuzeon? .....Do not inject Fuzeon into the following areas..... What are the possible side effects of Fuzeon? Injection using Biojector 2000

Inderal (propranolol hydrochloride) Tablets Prescribing Information	PRECAUTIONS Pregnancy: Pregnancy Category C Intrauterine growth retardation, small placentas, and congenital anomalies have been reported in neonates whose mothers received propranolol during pregnancy.....

Inderide (propranolol hydrochloride and hydrochlorothiazide) Tablets Prescribing Information	PRECAUTIONS Pregnancy: Pregnancy Category C Propranolol Hydrochloride (Inderal) Intrauterine growth retardation, small placentas, and congenital anomalies have been reported in human neonates whose mothers received propranolol during pregnancy.....

Kaletra (lopinavir/ritonavir) Capsules and Oral Solution Prescribing Information Patient Package Insert	PRECAUTIONS Drug Interactions Other Drugs Drug interaction studies reveal no clinically significant interaction between Kaletra and desipramine (CYP2D6 probe), pravastatin, stavudine, lamivudine, omeprazole or ranitidine. PATIENT PACKAGE INSERT Can I Take Kaletra With Other Medications? Kaletra can be taken with acid reducing agents (such as omeprazole and ranitidine) with no dose adjustment.

Kaletra (lopinavir/ritonavir) Tablets and Oral Solution Prescribing Information Patient Package Insert	PRECAUTIONS Drug Interaction Other Drugs Drug interaction studies reveal no clinically significant interaction between Kaletra and desipramine (CYP2D6 probe), pravastatin, stavudine, lamivudine, omeprazole or ranitidine. PATIENT PACKAGE INSERT Can I take Kaletra with other medications? Kaletra can be taken with acid reducing agents (such as omeprazole and ranitidine) with no dose adjustment.

Kineret (anakinra) Prescribing Information	PRECAUTIONS Pediatric Use

Singulair (montelukast sodium) Tablets, Chewable Tablets, and Oral Granules Prescribing Information	PRECAUTIONS Pregnancy Teratogenic Effects During worldwide marketing experience, congenital limb defects have been rarely reported in the offspring of women being treated with Singulair during pregnancy.....

Velcade (bortezomib) for Injection Prescribing Information Patient Package Insert	PRECAUTIONS Peripheral Neuropathy Hypotension Cardiac Disorders Laboratory Tests Geriatric Use ADVERSE REACTIONS The Phase 2 Open-Label Extension Study in Relapsed Multiple Myeloma Integrated Summary of Safety (Multiple Myeloma and Mantle Cell Lymphoma) Serious Adverse Events (SAEs) and Events Leading to Discontinuation in the Integrated Summary of Safety Most Commonly Reported Adverse Events in Integrated Summary of Safety Table 8 Description of Selected Adverse Events from the Phase 2 and 3 Multiple Myeloma and Phase 2 Mantle Cell Lymphoma Studies Gastrointestinal Events Thrombocytopenia Peripheral Neuropathy Hypotension Neutropenia Asthenic Conditions (Fatigue, Malaise, Weakness) Pyrexia Reactivation of Herpes Virus Infection Additional Adverse Events from Clinical Studies and Post-marketing Eye Disorders Blurred Vision Skin and Subcutaneous Tissue Disorders Rash (which may be pruritic) PATIENT PACKAGE INSERT Herpes Zoster (Shingles) Heart Failure and Lung Disease

Viracept (nelfinavir mesylate) Tablets and Oral Powder Prescribing Information Patient Package Insert	PRECAUTIONS Drug Interactions Table 9 Omeprazole decreases the plasma concentrations of Nelfinavir. Concomitant use of proton pump inhibitors and Viracept may lead to a loss of virologic response and development of resistance. PATIENT PACKAGE INSERT Medicines You Should Not Take With Viracept. Prilosec (omeprazole) (for stomach acid reduction)

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Brand (Generic) Name	Sections Modified
Evoxac (cevimeline hydrochloride) Capsules Prescribing Information	ADVERSE REACTIONS Post-marketing Adverse Events Liver and Biliary System Disorders Cholecystitis

Fosamax (alendronate sodium) Tablets and Oral Solution Prescribing Information Patient Package Insert	ADVERSE REACTIONS Post-marketing Adverse Experiences Body as a Whole Asthenia Rarely, Peripheral Edema Musculoskeletal Joint Swelling Nervous System Dizziness Vertigo PATIENT PACKAGE INSERT (see highlighted PPI for revisions)

Fosamax Plus D (alendronate sodium/cholecalciferol) Tablets Prescribing Information Patient Package Insert	ADVERSE REACTIONS Post-marketing Experience Body as a Whole Asthenia Rarely, Peripheral Edema Musculoskeletal Joint Swelling Nervous System Dizziness Vertigo PATIENT PACKAGE INSERT (see highlighted PPI for revisions)

Gliadel Wafer (polifeprosan 20 with carmustine implant) Prescribing Information	ADVERSE REACTIONS Surgery for Recurrent Disease Post-marketing experience includes spontaneous reports of cyst formation after Gliadel wafer implantation. These occurred at varying time intervals post-implantation.....

Santura (trospium chloride) Tablets Prescribing Information	ADVERSE REACTIONS Post-Marketing Surveillance General Rash

Spiriva HandiHaler (tiotropium bromide inhalation powder) for Oral Inhalation Only Prescribing Information Patient Package Insert	ADVERSE REACTIONS The following adverse reactions have been identified during worldwide post-approval use of Spiriva..... Dizziness Dysphasia Hoarseness Intestinal Obstruction including Ileus Paralytic Intraocular Pressure Increased Oral Candidiasis Tachycardia Throat Irritation PATIENT PACKAGE INSERT What should you know about Spiriva and the HandiHaler? How do you take your dose of Spiriva using the HandiHaler? Removing the Spiriva capsule from the blister..... Opening the HandiHaler device and inserting the Spiriva capsule..... Taking your dose of Spiriva.....

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Brand (Generic) Name	Sections Modified
Depakote Sprinkle Capsules (divalproex sodium coated particles in capsules) Patient Package Insert	PATIENT PACKAGE INSERT Administration Guide (new - see page 2)

Hyzaar (losartan potassium-hydrochlorothiazide tablets) Patient Package Insert	PATIENT PACKAGE INSERT (new)

PegIntron (peginterferon alfa-2b) Powder for Injection Medication Guide	MEDICATION GUIDE (new)

PegIntron (peginterferon alfa-2b) Redipen Single Dose Delivery System Medication Guide	MEDICATION GUIDE (new)

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