MedWatch - April 2005 Safety-Related Drug Labeling Changes

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Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) -- April 2005

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

Novantrone (mitoxantrone for injection concentrate)

(click product name to read prescribing information)

For additional details, see MedWatch 05/24/2005 Safety Alert

BOXED WARNING

Cardiotoxicity
Secondary Leukemia (AML)

WARNINGS

Cardiac Effects
- Multiple Sclerosis

BOXED WARNING - CARDIOTOXICITY

Use of Novantrone has been associated with cardiotoxicity. Cardiotoxicity can occur at any time during Novantrone therapy, and the risk increases with cumulative dose. Congestive heart failure (CHF), potentially fatal, may occur either during therapy with Novantrone or months to years after termination of therapy. All patients should be carefully assessed for cardiac signs and symptoms by history and physical examination prior to start of Novantrone therapy. ..... (See prescribing information)

BOXED WARNING - SECONDARY LEUKEMIA (AML)

Secondary acute myelogenous leukemia (AML) has been reported in multiple sclerosis and cancer patients treated with mitoxantrone. In a cohort of mitoxantrone treated MS patients followed for varying periods of time, an elevated leukemia risk of 0.25% (2/802) has been observed. Postmarketing cases of secondary AML have also been reported. .....(See prescribing information)

CARDIAC EFFECTS WARNINGS

LVEF should be evaluated by echocardiogram or MUGA prior to administration of the initial dose of Novantrone. Multiple sclerosis patients with a baseline LVEF of <50% should not be treated with Novantrone. Subsequent LVEF evaluations are recommended if signs or symptoms of congestive heart failure develop, and prior to all doses administered to multiple sclerosis patients. NOVANTRONE should not be administered to multiple sclerosis patients with an LVEF of <50%, with a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of >1 40 mg/m².

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
Mevacor (lovastatin) Tablets (click product name to read prescribing information)	WARNINGS Liver Dysfunction	It is recommended that liver function tests be performed prior to initiation of therapy in patients with a history of liver disease, or when otherwise clinically indicated. It is recommended that liver function tests be performed in all patients prior to use of 40 mg or more daily and thereafter when clinically indicated.

Nitro-Dur (nitroglycerin) Transdermal Infusion System (click product name to read prescribing information)	WARNINGS	Amplification of the vasodilatory effects of the Nitro-Dur patch by phosphodiesterase inhibitors, e.g., sildenafil can result in severe hypotension.

Plavix (clopidogrel bisulfate tablets) (click product name to read prescribing information)	WARNINGS Thrombotic Thrombocytopenic Purpura (TTP) PRECAUTIONS General ADVERSE REACTIONS Post-Marketing Experience Skin and Subcutaneous Tissue Disorders Stevens-Johnson Syndrome Lichen Planus Vascular Disorders Hypotension Gastrointestinal Disorders Pancreatitis Musculoskeletal, Connective Tissue and Bone Disorders Myalgia	TTP is a serious condition and requires urgent referral to a hematologist for prompt treatment.

Prevpac (lansoprazole/amoxicillin/clarithromycin tablets) (click product name to read prescribing information)	WARNINGS Amoxicillin Amoxicillin and/or Clarithromycin PRECAUTIONS Amoxicillin Drug Interactions Probenicid Macrolides Drug/Laboratory Test Interactions Nursing Mothers ADVERSE REACTIONS Amoxicillin Gastrointestinal Hemorrhagic/pseudomembranous Colitis Hypersensitivity Reactions Serum Sickness Like Reactions, Exfoliative Dermatitis, Acute Generalized Exanthematous Pustulosis, Hypersensitivity Vasculitis Liver Hepatic Dysfunction Cholestatic Jaundice Hepatic Cholestasis Acute Cytolytic Hepatitis Renal Crystalluria Hemic and Lymphatic Systems Hemolytic Anemia Miscellaneous Tooth Discoloration	After the diagnosis of pseudomembranous colitis has been established, appropriate therapeutic measures should be initiated. Mild cased of pseudomembranous colitis usually respond to drug discontinuation of the drug alone.

Sustiva (efavirenz) Capsules and Tablets (click product name to read prescribing information) For additional details, see MedWatch 06/10/2005 Safety Alert	WARNINGS Reproductive Risk Potential Category D Antiretroviral Pregnancy Registry PRECAUTIONS Information for Patients Pregnancy ADVERSE REACTIONS Postmarketing Experience Skin and Appendages Photoallergic Dermatitis PATIENT PACKAGE INSERT	Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. Pregnancy should be avoided in women receiving Sustiva. .....(See Prescribing Information) There are no adequate and well-controlled studies in pregnant women. Sustiva should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus, such as in pregnant women without other therapeutic options. As of July 2004, the Antiretroviral Pregnancy Registry has received prospective reports of 237 pregnancies exposed to efavirenz-containing regimens, nearly all of which were first-trimester exposures (232 pregnancies). Birth defects occurred in 5 of 188 live births (first trimester exposure) and 0 of 13 live births (second/third trimester exposure). None of these prospectively reported defects were neural tube defects. However, there have been four retrospective reports of findings consistent with neural tube defects, including meningomyelocele. All mothers were exposed to efavirenz-containing regimens in the first trimester. Although a causal relationship of these events to the use of Sustiva has not been established, similar defects have been observed in preclinical studies of efavirenz.

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Brand (Generic) Name	Sections Modified
Adalat CC (nifedipine) Extended Release Tablets (click product name to read prescribing information)	PRECAUTIONS Drug Interactions

BenzaClin (clindamycin 1% - benzoyl peroxide 5% gel) Topical Gel (click product name to read prescribing information)	PRECAUTIONS Information for Patients Carcinogenesis, Mutagenesis, Impairment of Fertility

Dovonex (calcipotriene cream) Cream (click product name to read prescribing information)	PRECAUTIONS Carcinogens, Mutagenesis, Impairment of Fertility

Dovonex (calcipotriene ointment) (click product name to read prescribing information)	PRECAUTIONS Carcinogens, Mutagenesis, Impairment of Fertility

Dovonex (calcipotriene solution) Scalp Solution (click product name to read prescribing information)	PRECAUTIONS Carcinogens, Mutagenesis, Impairment of Fertility

Gemzar (gemcitabine HCl) for Injection (click product name to read prescribing information)	PRECAUTIONS Pediatric Patients

Hyzaar (losartan potassium-hydrochlorothiazide tablets) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use ADVERSE REACTIONS Post-Marketing Experience Hemic Thrombocytopenia has been reported rarely with losartan Metabolic and Nutrition Hyperkalemia, hyponatremia have been reported with losartan Musculoskeletal Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin ll receptor blockers

Kaletra (lopinavir/ritonavir) Capsules and Oral Solution (click product name to read prescribing information)	PRECAUTIONS Table 10 ADVERSE REACTIONS Adults Treatment-Emergent Adverse Events Table 11 Laboratory Abnormalities Table 13

Trental (pentoxifylline) Tablets (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

Zantac (ranitidine hydrochloride) Tablets and Syrup Zantac (ranitidine hydrochloride effervescent) EFFERdose Tablets (click product name to read prescribing information)	PRECAUTIONS Information for Patients

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Brand (Generic) Name	Sections Modified
Coreg (carvedilol) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS COMET Trial

Cozaar (losartan potassium tablets) (click product name to read prescribing information)	ADVERSE REACTIONS Post-Marketing Experience Hemic Thrombocytopenia (reported rarely) Metabolic and Nutrition Hyperkalemia Hyponatremia Musculoskeletal Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin ll receptor blockers

Entocort EC (budesonide) Capsules (click product name to read prescribing information)	ADVERSE REACTIONS

Natrecor (nesiritide) for Injection (click product name to read prescribing information) For additional details, see MedWatch 05/19/2005 Safety Alert	ADVERSE REACTIONS Effect on Mortality

Rifater (rifampin, isoniazid and pyrazinamide) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Adverse Reactions Reported for Individual Components Rifampin Hematologic Agranulocytosis Pyrazinamide Other Angioedema

Toprol-XL (metoprolol succinate) Extended Release Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Post-Marketing Experience Skin Urticaria

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