MedWatch - June 2004 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- June 2004

The detailed view includes drug products with safety labeling changes to the CONTRAINDICATIONS, BOXED WARNING, WARNINGS, PRECAUTIONS, or ADVERSE REACTIONS sections. The prescribing information may be accessed by clicking on the drug name.

Summary View

Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
CombiPatch (estradiol/norethindrone acetate transdermal system) (click product name to read prescribing information)	CONTRAINDICATIONS WARNINGS Cardiovascular Disorders Venous Thromboembolism (VTE) Malignant Neoplasms Breast Cancer PRECAUTIONS General Addition of a progestin when a woman has not had a hysterectomy Familial Hyperlipoproteinemia PATIENT PACKAGE INSERT	CONTRAINDICATIONS: Estrogens/progestins combined should not be used in women under any of the following conditions: Known, suspected, or history of cancer of the breast. Active deep vein thrombosis, pulmonary embolism or history of these conditions. Active or recent (e.g. within the past year) arterial thromboembolic disease (e.g., stroke, myocardial infarction)...see prescribing information. WARNINGS: Extensive revisions to WARNINGS section of labeling. Please see prescribing information.

Efudex (fluorouracil) Topical Cream (click product name to read prescribing information)	CONTRAINDICATIONS WARNINGS	CONTRAINDICATIONS: Efudex should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency. Rarely, life-threatening toxicities such as stomatitis, diarrhea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency. WARNINGS: Patients should discontinue therapy with Efudex if symptoms of DPD enzyme deficiency develop.

Percodan (oxycodone and aspirin tablets, USP) (click product name to read prescribing information)	CONTRAINDICATIONS Reye Syndrome Allergy Oxycodone WARNINGS Misuse, Abuse and Diversion of Opioids Respiration Depression Head Injury and Increased Intracranial Pressure Hypotensive Effect Alcohol Warning Coagulation Abnormalities GI Side Effects Peptic Ulcer Disease PRECAUTIONS General Pregnancy Renal Failure Hepatic Insufficiency Interactions with Other CNS Depressants Interactions with Mixed Agonist/Antagonist Opioid Analgesics Ambulatory Surgery and Postoperative Use Use in Pancreatic/Biliary Tract Disease Tolerance and Physical Dependence Information for Patients/Caregivers Drug/Drug Interactions with Oxycodone Drug/Drug Interactions with Aspirin Angiotensin Coverting Enzyme (ACE) Inhibitors Acetazolamide Anticoagulant Therapy Anticonvulsants Beta Blockers Diuretics Methotrexate Nonsteroidal Anti-Inflammatory Drugs Oral Hypoglycemic Agents Uricosuric Acid Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects Oxycodone Aspirin Labor and Delivery Nursing Mothers Hepatic Impairment Renal Impairment ADVERSE REACTIONS Body as a Whole Cardiovascular Central and Peripheral Nervous System Fluid and Electrolyte Gastrointestinal Hearing and Vestibular Hematologic Hypersensitivity Metabolic and Nutritional Musculoskeletal Reproductive Respiratory System Urogenital	CONTRAINDICATIONS: Reye Syndrome: Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye syndrome with concomitant use of aspirin in certain viral illnesses. Allergy: Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasm (asthma). Oxycodone is contraindicated in patients with known hypersensitivity to oxycodone. Oxycodone is contraindicated in any situation where opioids are contraindicated including patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone is contraindicated in the setting of suspected or known paralytic ileus. WARNINGS: Extensive revisions to WARNINGS section of labeling. Please see prescribing information.

Percodan-Demi (oxycodone and aspirin tablets, USP) (click product name to read prescribing information)	CONTRAINDICATIONS Reye Syndrome Allergy Oxycodone WARNINGS Misuse, Abuse and Diversion of Opioids Respiration Depression Head Injury and Increased Intracranial Pressure Hypotensive Effect Alcohol Warning Coagulation Abnormalities GI Side Effects Peptic Ulcer Disease PRECAUTIONS General Pregnancy Renal Failure Hepatic Insufficiency Interactions with Other CNS Depressants Interactions with Mixed Agonist/Antagonist Opioid Analgesics Ambulatory Surgery and Postoperative Use Use in Pancreatic/Biliary Tract Disease Tolerance and Physical Dependence Information for Patients/Caregivers Drug/Drug Interactions with Oxycodone Drug/Drug Interactions with Aspirin Angiotensin Coverting Enzyme (ACE) Inhibitors Acetazolamide Anticoagulant Therapy Anticonvulsants Beta Blockers Diuretics Methotrexate Nonsteroidal Anti-Inflammatory Drugs Oral Hypoglycemic Agents Uricosuric Acid Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects Oxycodone Aspirin Labor and Delivery Nursing Mothers Hepatic Impairment Renal Impairment ADVERSE REACTIONS Body as a Whole Cardiovascular Central and Peripheral Nervous System Fluid and Electrolyte Gastrointestinal Hearing and Vestibular Hematologic Hypersensitivity Metabolic and Nutritional Musculoskeletal Reproductive Respiratory System Urogenital	CONTRAINDICATIONS: Reye Syndrome: Aspirin should not be used in children or teenagers for viral infections, with or without fever, because of the risk of Reye syndrome with concomitant use of aspirin in certain viral illnesses. Allergy: Aspirin is contraindicated in patients with known allergy to nonsteroidal anti-inflammatory drug products and in patients with the syndrome of asthma, rhinitis, and nasal polyps. Aspirin may cause severe urticaria, angioedema, or bronchospasm (asthma). Oxycodone is contraindicated in patients with known hypersensitivity to oxycodone. Oxycodone is contraindicated in any situation where opioids are contraindicated including patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone is contraindicated in the setting of suspected or known paralytic ileus. WARNINGS: Extensive revisions to WARNINGS section of labeling. Please see prescribing information.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Axert (almotriptan malate) Tablets (click product name to read prescribing information)	WARNINGS Cardiac Events and Fatalities Associated with 5-HT₁ Agonists Postmarketing Experience with Axert PRECAUTIONS General ADVERSE REACTIONS Initial Paragraph Postmarketing Experience Cardiovascular	Serious adverse cardiac events, including acute myocardial infarction, have been reported within a few hours following administration of almotriptan. Axert can cause coronary vasospasm; at least one of these events occurred in a patient with no cardiac history and with documented absence of coronary artery disease. Because of the close proximity of the events to use of Axert, a causal relationship cannot be excluded. Serious cardiovascular events have been reported in association with the use of Axert. The uncontrolled nature of postmarketing surveillance, however, makes it impossible to definitively determine the proportion of the reported cases that were actually caused by almotriptan or to reliably assess causation in individual cases.
Humira (adalimumab) (click product name to read prescribing information)	WARNINGS Malignancies Hypersensitivity Reactions Anaphylaxis Hematologic Events PRECAUTIONS Patients with Heart Failure	Malignancies: During the controlled portions of Humira trials in patients with moderately to severely active rheumatoid arthritis, 2 lymphomas were observed among 1380 Humira-treated patients versus 0 among 690 control patients (mean duration of controlled treatment approximately 7 months). In the controlled and open-label portions of these clinical trials of Humira in rheumatoid arthritis patients, 10 lymphomas were observed in 2468 patients over 4870 patient-years of therapy. Hypersensitivity Reactions: In postmarketing experience, anaphylaxis has been reported rarely following Humira administration. In clinical trials of Humira, allergic reactions overall (e.g., allergic rash, anaphylactoid reaction, fixed drug reaction, non-specified drug reaction, urticaria) have been observed in approximately 1 % of patients. Hematologic Events: Rare reports of pancytopenia including aplastic anemia have been reported with TNFα-blocking agents. Adverse events of the hematologjc system, including medically significant cytopenia (e. g. thrombocytopenia, leukopenia) have been infrequently reported with Humira.

Inderal (propranolol hydrochloride) LA Capsules (click product name to read prescribing information)	WARNINGS Initial Paragraph Skin Reactions ADVERSE REACTIONS Allergic Skin	Initial Paragraph: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been associated with the administration of propranolol. Skin Reactions: Cutaneous reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, and urticaria, have been reported with use of propranolol.

Inderide (propranolol hydrochloride and hydrochlorothiazide) Tablets (click product name to read prescribing information)	WARNINGS Propranolol hydrochloride (Inderal) Skin Reactions ADVERSE REACTIONS Propranolol hydrochloride (Inderal) Allergic Ski	Initial Paragraph: Hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, have been associated with the administration of propranolol. Skin Reactions: Cutaneous reactions, including Stevens-Johnson Syndrome, toxic epidermal necrolysis, exfoliative dermatitis, erythema multiforme, and urticaria, have been reported with use of propranolol.

ProSom (estazolam tablets) (click product name to read prescribing information)	WARNINGS Estazolam Interaction with Drugs that Inhibit Metabolism via Cytochrome P450 3A (CYP3A) PRECAUTIONS Estazolam Interaction with Drugs that Inhibit Metabolism via Cytochrome P450 3A (CYP3A) Initial Paragraph Drug Interaction with Fluoxetin	Estazolam should be avoided in patients receiving ketoconazole and itraconazole, which are very potent inhibitors of CYP3A. With drugs inhibiting CYP3A to a lesser, but still significant degree, estazolam should be used only with caution and consideration of appropriate dosage reduction. The following are examples of drugs known to inhibit the metabolism of other related benzodiazepines, presumably through inhibition of CYP3A4: nefazodone, fluvoxamine, cimetidine, diltiazem, isoniazide, and some macrolide antibiotics. While no in vivo drug-drug interaction studies were conducted between estazolam and inducers of CYP3A4, compounds that are potent CYP3A inducers (such as carbamazepine, phenytoin, rifampin and barbiturates) would be expected to decrease estazolam concentrations.

Remeron (mirtazapine) Tablets Remeron SolTab (mirtazapine) Orally Disintegrating Tablets (click product name to read prescribing information)	WARNINGS Clinical Worsening and Suicide Risk PRECAUTIONS Information for Patients	Patients with major depressive disorder, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality), whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Although there has been a long-standing concern that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients, a causal role for antidepressants in inducing such behaviors has not been established. Nevertheless, patients being treated with antidepressants should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of drug therapy, or at the time of dose changes, either increases or decreases.

Riomet (metformin HCl oral solution) (click product name to read prescribing information)	WARNINGS Lactic Acidosis	The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis.

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Brand (Generic) Name	Sections Modified
Ancef (cefazolin) for Injection (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Camptosar Injection (irinotecan hydrochloride) (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

Cefazolin for Injection USP and Dextrose Injection USP (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Cefotan (cefotetan disodium for injection) (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Ceftin (cefuroxime axetil) for Oral Suspension Ceftin (cefuroxime axetil) Tablets (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

CefUROXime for Injection USP and Dextrose Injection USP (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Cefzil (cefprozil monohydrate) for Oral Suspension Cefzil (cefprozil monohydrate) Tablets (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients

Claforan (cefotaxime sodium, USP) Sterile Claforan (cefotaxime sodium) Injection Please contact Aventis Pharmaceuticals at 1-800-633-1610 for prescribing information.	PRECAUTIONS Geriatric Use

Dextrose in Sodium Chloride Injection, USP (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Ditropan XL (oxybutynin chloride) Extended Release Tablets (click product name to read prescribing information)	PRECAUTIONS Information for Patients ADVERSE REACTIONS Adverse Events with Ditropan XL

Epoetin (epoetin alfa) for Injection (click product name to read prescribing information)	PRECAUTIONS Seizures Thrombotic Events ADVERSE REACTIONS Cancer Patients on Chemotherapy

Flagyl I.V. RTU (metronidazole injection, USP) (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients

Florinef (fludrocortisone acetate tablets, USP) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Hiprex (methenamine hippurate USP) Tablets (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Imodium A-D (loperamide HCl) Liquid Imodium (loperamide HCl/simethicone) Caplets Imodium Advanced (loperamide HCl/simethicone) Chewable Tablets and Caplets Please contact McNeil Consumer and Specialty Pharmaceuticals at 1-800-962-5357 for prescribing information.	PRECAUTIONS Stop use and ask doctor if Other information

INOmax (nitric oxide) for Inhalation (click product name to read prescribing information)	PRECAUTIONS Drug Interactions POST-MARKETING EXPERIENCE

Keflex (cephalexin) Capsules (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients Drug Interactions Metformin

Lexxel (enalapril maleate/felodipine ER) Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Tacrolimus

Lidocaine Hydrochloride and 5% Dextrose Injection, USP Please contact B. Braun Medical, Inc. 1-800-854-6851 for prescribing information.	PRECAUTIONS General Laboratory Tests Drug Interactions Amiodarone Carcinogenesis, Mutagenesis, and Impairment of Fertility Nursing Mothers Pediatric Use Geriatric Use

Lincocin (lincomycin hydrochloride) Capsules Lincocin (lincomycin) Injection (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients

Maxipime (cefepime hydrochloride, USP) for Injection (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients

Mefoxin Injection (cefoxitin for injection) (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients Geriatric Use ADVERSE REACTIONS Allergic Reactions Urticaria Flushing

Merrem IV (meropenem for injection) (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients

Nesacaine (chloroprocaine HCl Injection, USP) Nesacaine-MPF (chloroprocaine HCl Injection, USP) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Nitro-Dur (nitroglycerin) Transdermal Infusion System Please contact Schering-Plough Corporation at 1-908-298-4000 for prescribing information.	PRECAUTIONS General Geriatric Use

Penicillin G Potassium Injection, USP (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients

Plendil (felodipine) Extended-Release Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Tacrolimus

Prograf (tacrolimus) Capsules and Injection (click product name to read prescribing information)	PRECAUTIONS Information for Patients Drugs That May Alter Tacrolimus Concentrations Drugs that May Increase Tacrolimus Blood Concentrations Table Drugs that May Decrease Tacrolimus Blood Concentrations Table Antimicrobials Caspofungin Other Drugs Sirolimus ADVERSE REACTIONS Less Frequently Reported Adverse Reactions Myocardial Hypertrophy Post-Marketing QT prolongation Torsades de Pointes

Potassium Chloride in 5% Dextrose and Sodium Chloride, USP in Plastic Container Please contact Baxter Healthcare Corporation at 1-800-422-9837 for prescribing information.	PRECAUTIONS Geriatric Use

Prevacid (lansoprazole) Delayed-Release Capsules Prevacid (lansoprazole) for Delayed- Release Oral Suspension Prevacid SoluTab (lansoprazole) Delayed-Release Orally Disintegrating Tablet (click product name to read prescribing information)	PRECAUTIONS Pediatric Use 12 to 17 years of age

Rebetol (ribavirin, USP) Capsules and Oral Solution (click product name to read prescribing information)	PRECAUTIONS Ribavirin Pregnancy Registry MEDICATION GUIDE

Rebetron Combination Therapy containing Rebetol (ribavirin, USP) Capsules and Intron A (interferon alfa-2b, recombinant) Injection (click product name to read prescribing information)	PRECAUTIONS Ribavirin Pregnancy Registry MEDICATION GUIDE

Thalitone (chlorthalidone tablets, USP) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Vantin (cefpodoxime proxetil) Tablets Vantin (cefpodoxime proxetil) Oral Suspension (click product name to read prescribing information)	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria PRECAUTIONS General Information for Patients

Viracept (nelfinavir mesylate) Tablets Viracept (nelfinavir mesylate) Oral Powder (click product name to read prescribing information)	PRECAUTIONS Carcinogenisis, Mutagenisis and Impairment of Fertility

Zerit (stavudine) Capsules Zerit (stavudine) Powder for Oral Solution (click product name to read prescribing information)	PRECAUTIONS Drug Interactions

Zerit XR Extended-Release (stavudine) Capsules (click product name to read prescribing information)	PRECAUTIONS Patient Information Drug Interactions

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Brand (Generic) Name	Sections Modified
Augmentin (amoxicillin/clavulanate potassium) Powder for Oral Suspension and Chewable Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Renal Crystalluria Miscellaneous Tooth Discoloration

Augmentin ES-600 (amoxicillin/clavulanate potassium) for Oral Suspension (click product name to read prescribing information)	ADVERSE REACTIONS Renal Crystalluria Miscellaneous Tooth Discoloration

Gleevec (imatinib mesylate) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Additional Data From Multiple Clinical Trials Cardiovascular Pericarditis Dermatologic Psoriasis Digestive Ileus/Intestinal Obstruction Pancreatitis General Disorders and Administration Site Conditions Tumor Necrosis Nervous System/Psychiatric Confusion Convulsions Special Senses: Glaucoma Vitreous Hemorrhage Vascular Disorders: Thrombosis/Embolism

Mylotarg (gemtuzumab ozogamicin) for Injection (click product name to read prescribing information)	ADVERSE REACTIONS Other Clinical Experience

Temodar (temozolomide) Capsules Please contact Schering-Plough at 1-908-298-4000 for prescribing information.	ADVERSE REACTIONS Adverse Reactions in Adults Rare cases of opportunistic infections including Pneumocystis carinii pneumonia (PCP) have also been reported.

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