MedWatch - March 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) -- March 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
Lupron (leuprolide acetate) Injection (click product name to read prescribing information)	CONTRAINDICATIONS PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility ADVERSE REACTIONS Postmarketing PATIENT PACKAGE INSERT	Hypersensitivity to GnRH, GnRH agonist analogs or any of the excipients in Lupron Injection. Reports of anaphylactic reactions to synthetic GnRH (Factrel) or GnRH agonist analogs have been reported in the medical literature. Lupron is contraindicated in women who are or may become pregnant while receiving the drug. Lupron may cause fetal harm when administered to a pregnant woman. Major fetal abnormalities were observed in rabbits but not in rats after administration of leuprolide acetate throughout gestation. There was increased fetal mortality and decreased fetal weights in rats and rabbits. The effects on fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug. Therefore, the possibility exists that spontaneous abortion may occur if the drug is administered during pregnancy. If this drug is administered during pregnancy or if the patient becomes pregnant while taking any formulation of Lupron, the patient should be apprised of the potential hazard to the fetus.

Myambutol (ethambutol hydrochloride) Tablets (click product name to read prescribing information)	CONTRAINDICATIONS PRECAUTIONS Drug Interactions Nursing Mothers Pediatric Use ADVERSE REACTIONS Hypersensitivity Anaphylactic/Anaphylactoid Reactions Neutropenia Pulmonary Infiltrates with or without Eosinophilia Hypersensitivity Syndrome	Myambutol is contraindicated in patients who are known to be hypersensitive to this drug. It is also contraindicated in patients with known optic neuritis unless clinical judgment determines that it may be used. Myambutol is contraindicated in patients who are unable to appreciate and report visual side effects or changes in vision (e.g., young children, unconscious patients).
Vancocin Hydrochloride (vancomycin injection, USP) (click product name to read prescribing information)	CONTRAINDICATIONS SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients	Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Accolate (zafirlukast) Tablets (click product name to read prescribing information)	WARNINGS Hepatotoxicity PRECAUTIONS Information for Patients	Cases of life-threatening hepatic failure have been reported in patients treated with Accolate. Patients should be advised to be alert for signs and symptoms of liver dysfunction (eg, right upper quadrant abdominal pain, nausea, fatigue, lethargy, pruritus, jaundice, flu-like symptoms, and anorexia) and to contact their physician immediately if they occur.

Cipro (ciprofloxacin hydrochloride) Tablets and Oral Suspension (click product name to read prescribing information)	WARNINGS SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients Drug Interactions ADVERSE REACTIONS Body as a Whole Cardiovascular Central Nervous System Gastrointestinal Hemic/Lymphatic Skin/Hypersensitivity Special Senses Postmarketing Adverse Events	After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone. In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against C. difficile colitis. Drugs that inhibit peristalsis should be avoided. Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability have been reported with ciprofloxacin and other quinolones. Post-marketing surveillance reports indicate that the risk may be increased in patients receiving concomitant corticosteroids, especially in the elderly. Ciprofloxacin should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon.

Flonase (fluticasone propionate) Nasal Spray (click product name to read prescribing information)	WARNINGS PRECAUTIONS Drug Interactions Ritonavir PATIENT PACKAGE INSERT	A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Flovent (fluticasone propionate) Inhalation Aerosol (click product name to read prescribing information)	WARNINGS PRECAUTIONS Drug Interactions Ritonavir PATIENT PACKAGE INSERT	A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Flovent Rotadisk (fluticasone propionate inhalation powder) (click product name to read prescribing information)	WARNINGS PRECAUTIONS Drug Interactions Ritonavir PATIENT PACKAGE INSERT	A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations. During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing syndrome and adrenal suppression. Therefore, coadministration of fluticasone propionate and ritonavir is not recommended unless the potential benefit to the patient outweighs the risk of systemic corticosteroid side effects.

Glucophage (metformin HCl tablets) Glucophage XR (metformin HCl extended-release tablets) (click product name to read prescribing information)	WARNINGS Lactic Acidosis	In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis.

Prinivil (lisinopril) Tablets (click product name to read prescribing information)	WARNINGS Head and Neck Angioedema Intestinal Angioedema ADVERSE REACTIONS Angioedema	Angioedema heading revised to read "Head and Neck Angioedema". Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Prinzide (lisinopril-hydrochlorothiazide) Tablets (click product name to read prescribing information)	WARNINGS Head and Neck Angioedema Intestinal Angioedema ADVERSE REACTIONS Angioedema	Angioedema heading revised to read "Head and Neck Angioedema". Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.

Reyataz (atazanavir sulfate) Capsules (click product name to read prescribing information)	WARNINGS Drug Interactions PRECAUTIONS Information for Patients Drug Interactions Table 9 PATIENT PACKAGE INSERT	Particular caution should be used when prescribing PDE5 inhibitors for erectile dysfunction (eg, sildenafil, tadalafil, or vardenafil) for patients receiving protease inhibitors, including Reyataz. Coadministration of a protease inhibitor with a PDE5 inhibitor is expected to substantially increase the PDE5 inhibitor concentration and may result in an increase in PDE5 inhibitor-associated adverse events, including hypotension, visual changes, and priapism.

Suprax (cefixime) Tablets Suprax (cefixime) Oral Suspension Please contact Wyeth at 1-800-934-5556 for prescribing information.	WARNINGS PRECAUTIONS Drug Interactions Warfarin & Anticoagulants ADVERSE REACTIONS Hypersensitivity Reactions Anaphylactic/Anaphylactoid Reactions Angioedema Facial Edema Hepatic Hepatitis Jaundice Renal Acute Renal Failure Central Nervous System Seizures Hemic and Lymphatic Systems Neutropenia Abnormal Laboratory Tests Hyperbilirubinemia Other Toxic Epidermal Necrolysis	Anaphylactic/anaphylactoid reactions (including shock and fatalities) have been reported with the use of cefixime.

TrophAmine (amino acid injections) (click product name to read prescribing information)	WARNINGS PRECAUTIONS Laboratory Tests Drug Interactions Pregnancy - Teratogenic Effects Nursing Mothers Pediatric Use Geriatric Use	Frequent clinical evaluation and laboratory determinations are necessary for proper monitoring of parenteral nutrition. This product contains aluminum that may be toxic. Aluminum may reach toxic levels with prolonged parenteral administration if kidney function is impaired. Premature neonates are particularly at risk because their kidneys are immature, and they require large amounts of calcium and phosphorous solutions, which contain aluminum. Research indicates that patients with impaired kidney function, including premature neonates, who receive parenteral levels of aluminum at greater than 4 to 5mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

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Brand (Generic) Name	Sections Modified
Aldara (imiquimod) Cream (click product name to read prescribing information)	PRECAUTIONS General Information for Patients General Information Patients Being Treated for Actinic Keratosis (AK) Carcinogenesis, Mutagenesis, and Impairment of Fertility Pregnancy Category C ADVERSE REACTIONS Actinic Keratosis

Avelox (moxifloxacin hydrochloride) Tablets Avelox I.V. (moxifloxacin hydrochloride in sodium chloride 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

Ceclor (cefaclor pulvules) Ceclor (cefaclor for oral suspension) Please contact Eli Lilly and Company at 1-800-545-5979 for prescribing information.	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients ADVERSE REACTIONS Other Effects Moniliasis

Cortisporin (neomycin and polymyxin B sulfates, bacitracin zinc, and hydrocortisone ophthalmic ointment, USP) Ophthalmic Ointment Sterile (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Cozaar (losartan potassium tablets) (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Pediatric Use ADVERSE REACTIONS Pediatric Patients

Desyrel (trazodone hydrochloride) Tablets Please contact Bristol-Myers Squibb at 212-546-4000 for prescribing information.	PRECAUTIONS Drug Interactions Norvir (ritonavir)

E.E.S. (erythromycin ethylsuccinate) (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

Effexor (venlafaxine hydrochloride) Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions CNS-Active Drugs ADVERSE REACTIONS Postmarketing Reports Dyskinesia Rhabdomyolysis

Effexor XR (venlafaxine hydrochloride) Extended-Release Capsules (click product name to read prescribing information)	PRECAUTIONS Drug Interactions CNS-Active Drugs ADVERSE REACTIONS Postmarketing Reports Dyskinesia Rhabdomyolysis

EryPed (erythromycin ethylsuccinate, 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

Eskalith (lithium carbonate) Capsules Eskalith CR (lithium carbonate) Controlled-Release Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions

Flagyl 375 (metronidazole 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

Flagyl (metronidazole 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

Flagyl ER (metronidazole extended release 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

Floxin (ofloxacin 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

Glucovance (glyburide and metformin HCl tablets) (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

Levaquin (levofloxacin) Tablets and Injection Levaquin (levofloxacin in 5% dextrose) 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

Lopid (gemfibrozil tablets, USP) (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Repaglinide

Lotensin (benazepril HCl) Tablets (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Pediatric Patients

Macrodantin (nitrofurantoin macrocrystals) Capsules Please contact Procter & Gamble Pharmaceuticals, Inc at 1-800-836-0658 for prescribing information.	SYSTEMIC ANTIBACTERIAL DRUG PRODUCTS STATEMENT to reduce the development of drug-resistant bacteria. PRECAUTIONS General Information for Patients

Maxaquin (lomefloxacin hydrochloride 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

Nasacort AQ (triamcinolone acetonide) Nasal Spray (click product name to read prescribing information)	PRECAUTIONS Carcinogenicity, Mutagenesis, and Impairment of Fertility Pregnancy

NovoLog (insulin aspart [rDNA origin] injection) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Oxacillin Injection, USP (click product name to read prescribing information)	PRECAUTIONS Carcinogenicity, Mutagenesis, and Impairment of Fertility Pregnancy: Teratogenic Effects

PCE (erythromycin particles in tablets) Dispertab 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

Periostat (doxycycline hyclate tablets) (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility

Prometrium (progesterone, USP) Capsules (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Protonix I.V. (pantoprazole sodium) for Injection (click product name to read prescribing information)	PRECAUTIONS Nursing Mothers

Romazicon (flumazenil) Injection (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Information for Patients ADVERSE REACTIONS Serious Adverse Reactions Additional Adverse Reactions Reported During Postmarketing Experience

3% Sorbitol Urologic Irrigation Solution (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Spectracef (cefditoren pivoxil) 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 ADVERSE EVENTS Postmarketing Experience Pneumonia Interstitial Eosinophilic Pneumonia Acute Acute Renal Failure Arthralgia Thrombocytopenia

Tofranil-PM (imipramine pamoate) Capsules Please contact Mallinckrodt Pharmaceuticals at 1-888-744-1414 for prescribing information.	PRECAUTIONS Geriatric Use

Ultiva (remifentanil hydrochloride) for Injection (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE EVENTS Pediatrics Table 9

Vancocin (vancomycin hydrochloride) Pulvules Please contact Eli Lilly and Company at 1-800-545-5979 for prescribing information.	PRECAUTIONS Geriatric Use

Vibramycin Monohydrate (doxycycline monohydrate) for Oral Suspension Vibramycin Hyclate (doxycycline hyclate) Capsules Vibramycin Calcium (doxycycline calcium) Oral Suspension Syrup Vibra-Tabs (doxycycline hyclate) Film Coated 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

Viracept (nelfinavir mesylate) Tablets and Oral Powder (click product name to read prescribing information)	PRECAUTIONS Pediatric Use ADVERSE REACTIONS Pediatric Population

Zestril (lisinopril) Tablets (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Zithromax (azithromycin) Capsules, Tablets, and for 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

Zyprexa (olanzapine tablets) Zyprexa Zydis (olanzapine orally disintegrating tablets) Zyprexa IntraMuscular (olanzapine for injection) (click product name to read prescribing information)	PRECAUTIONS General Intramuscular Olanzapine for Injection Drug Interactions Lorazepam ADVERSE REACTIONS Intramuscular Olanzapine for Injection

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Brand (Generic) Name	Sections Modified
Arava (leflunomide) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Pediatric Patients

Aredia (pamidronate disodium for injection) for Intravenous Infusion (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience Osteonecrosis (primarily of the jaw)

Cancidas (caspofungin acetate) for Injection (click product name to read prescribing information)	ADVERSE REACTIONS General

GlucaGen (glucagon [rDNA origin] for injection) (click product name to read prescribing information)	ADVERSE REACTIONS

Micardis (telmisartan) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience

Protonix (pantoprazole sodium) Delayed-Release Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Reports Elevated CPK

Rocephin (ceftriaxone sodium) for Injection (click product name to read prescribing information)	ADVERSE REACTIONS Allergic Pneumonitis Seizures

Thalomid (thalidomide) Capsules (click product name to read prescribing information)	ADVERSE REACTIONS Other Adverse Events Observed in Postmarketing Use Digestive System Intestinal Perforation Metabolic and Endocrine Tumor Lysis Syndrome

Thyrogen (thyrotropin alfa for injection) (click product name to read prescribing information)	ADVERSE REACTIONS Respiratory Distress Papillary Carcinoma

Vioxx (rofecoxib tablets and oral suspension) (click product name to read prescribing information)	ADVERSE REACTIONS Migraine with or without aura

Zometa (zoledronic acid) Injection (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience

Zyrtec (cetirizine hydrochloride) Tablets and Syrup (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience Aggressive Reaction Convulsions

Zyrtec-D 12 Hour (cetirizine hydrochloride 5mg and pseudoephedrine hydrochloride 120mg) Extended Release Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Postmarketing Experience Aggressive Reaction Convulsions

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