MedWatch - March 2003 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 2003

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

XELODA (capecitabine) Tablets

(click product name to read prescribing information)

CONTRAINDICATIONS

PRECAUTIONS

PATIENT PACKAGE INSERT

XELODA is contraindicated in patients with known hypersensitivity to capecitabine or to any of its components. XELODA is contraindicated in patients who have a known hypersensitivity to 5-fluorouracil. XELODA is contraindicated in patients with known dihydropyrimidine
dehydrogenase (DPD) deficiency. XELODA is also contraindicated in patients with severe renal
impairment (creatinine clearance below 30 mL/min [Cockroft and Gault]) (see CLINICAL
PHARMACOLOGY: Special Populations).

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
8-MOP (methoxsalen) Capsules (click product name to read prescribing information)	BOXED WARNING WARNINGS General	Methoxsalen with UV radiation should be used only by physicians who have special competence in the diagnosis and treatment of psoriasis and vitiligo and who have special training and experience in photochemotherapy. Psoralen and ultraviolet radiation therapy should be under constant supervision of such a physician. For the treatment of patients with psoriasis, photochemotherapy should be restricted to patients with severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, and only when the diagnosis is certain. Because of the possibilities of ocular damage, aging of the skin, and skin cancer (including melanoma), the patient should be fully informed by the physician of the risks inherent in this therapy. When methoxsalen is used in combination with photopheresis, refer to the UVAR* System Operator's Manual for specific warnings, cautions, indications, and instructions related to photopheresis.

COSMEGAN (dactinomycin) for Injection (click product name to read prescribing information)	BOXED WARNING	COSMEGEN (Dactinomycin for injection) should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents. This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. Due to the toxic properties of dactinomycin (e.g., corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently. Dactinomycin is extremely corrosive to soft tissue. If extravasation occurs during intravenous use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms.

MUSTARGEN (mechlorethamine HCl) for Injection (click product name to read prescribing information)	BOXED WARNING	MUSTARGEN (Mechlorethamine HCl) should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents. This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. Due to the toxic properties of mechlorethamine (e.g., corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently. Extravasation of the drug into subcutaneous tissues results in a painful inflammation. The area usually becomes indurated and sloughing may occur. If leakage of drug is obvious, prompt infiltration of the area with sterile isotonic sodium thiosulfate (1/6 molar) and application of an ice compress for 6 to 12 hours may minimize the local reaction. For a 1/6 molar solution of sodium thiosulfate, use 4.14 g of sodium thiosulfate per 100 mL of Sterile Water for Injection or 2.64 g of anhydrous sodium thiosulfate per 100 mL or dilute 4 mL of Sodium Thiosulfate Injection (10%) with 6 mL of Sterile Wate for Injection.

OXSORALEN-ULTRA (methosalen) Capsules (click product name to read prescribing information)	BOXED WARNING WARNINGS General PRECAUTIONS Geriatric Use	Methoxsalen with UV radiation should be used only by physicians who have special competence in the diagnosis and treatment of psoriasis and who have special training and experience in photochemotherapy. The use of Psoralen and ultraviolent radiation therapy should be under constant supervision of such a physician. For the treatment of patients with psoriasis, photochemotherapy should be restricted to patients with severe, recalcitrant, disabling psoriasis which is not adequately responsive to other forms of therapy, and only when the diagnosis is certain. Because of the possibilities of ocular damage, aging of the skin, and skin cancer (including melanoma), the patient should be fully informed by the physician of the risks inherent in this therapy.

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Brand (Generic) Name	Sections Modified	Summary of Changes to Contraindications and Warnings
CUPRIC CHLORIDE Injection Please contact Abbott Laboratories at 1-800-633-9110 for prescribing information.	WARNINGS	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 phosphate 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 5 mcg/kg/day accumulate aluminum at levels associated with central nervous system and bone toxicity. Tissue loading may occur at even lower rates of administration.

DRIXORAL Cold & Flu Extended Release DRIXORAL Allergy Sinus Extended Release (acetaminophen, dexbrompheniramine maleate, and pseudoephedrine sulfate extended release tablet) Please contact Schering-Plough Healthcare Products at 1-908-298-4000 for prescribing information.	WARNINGS	Overdose Warning: Taking more than the recommended dose may cause liver damage. In case of overdose, get medical help or contact a Poison Control Center right away. Quick medical attention is critical for adults as well as children even if you do not notice any signs or symptoms.

ETHYOL (amifostine) for Injection (click product name to read prescribing information)	WARNINGS Hypersensitivity PRECAUTIONS ADVERSE REACTIONS Geriatric	Hypersensitivity: Allergic manifestations including anaphylaxis and severe cutaneous reactions have been associated rarely with ETHYOL administration. Serious cutaneous hypersensitivity reactions have included erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, toxoderma and exfoliative dermatitis, which have been reported more frequently when ETHYOL is used as a radioprotectant (see ADVERSE REACTIONS). Some of these reactions have been fatal or have required hospitalization and/or discontinuance of therapy. Patients should be carefully monitored prior to, during and after ETHYOL administration (see PRECAUTIONS).

LEVULAN Kerastick (aminolevulinic acid HCl) for Topical Solution (click product name to read prescribing information)	WARNINGS	The Levulan Kerastick for Topical Solution contains alcohol and is intended for topical use only. Do not apply to the eyes or the mucous membranes. Excessive irritation may be experienced if this product is applied under occlusion.

MAXIPIME (cefepime hydrochloride) for Injection (click product name to read prescribing information)	WARNINGS PRECAUTIONS Geriatric Use ADVERSE REACTIONS Postmarketing Experience	During postmarketing surveillance, serious adverse events have been reported including life-threatening or fatal occurrences of the following: encephalopathy (disturbance of consciousness including confusion, hallucinations, stupor, and coma), myoclonus, and seizures. (See ADVERSE REACTIONS: Postmarketing Experience). Most cases occurred in patients with renal impairment who received doses of cefepime that exceeded the recommended dosage schedules. However, some cases of encephalopathy occurred in patients receiving a dosage adjustment for their renal function. In the majority of cases, symptoms of neurotoxicity were reversible and resolved after discontinuation of cefepime and/or after hemodialysis.

RAPAMUNE (sirolimus) Oral Solution and Tablets (click product name to read prescribing information)	WARNINGS Liver Transplantation Lung Transplantation - Bronchial Dehiscence	Liver Transplantation - Excess Mortality, Graft Loss, and Hepatic Artery Thrombosis (HAT): The use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant recipients. Many of these patients had evidence of infection at or near the time of death. In this and another study in de novo liver transplant recipients, the use of sirolimus in combination with cyclosporine or tacrolimus was associated with an increase in HAT; most cases of HAT occurred within 30 days post-transplantation and most led to graft loss or death. Lung Transplantation - Bronchial Anastomotic Dehiscence: Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when sirolimus has been used as part of an immunosuppressive regimen. The safety and efficacy of Rapamune (sirolimus) as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended.

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Brand (Generic) Name	Sections Modified
BLENOXANE (bleomycin sulfate) for Injection (click product name to read prescribing information)	PRECAUTIONS Geriatric

CARDIZEM (diltiazem hydrochloride) Tablets CARDIZEM SR (diltiazem hydrochloride) Capsules CARDIZEM CD (diltiazem hydrochloride) Capsules (click product name to read prescribing information)	PRECAUTIONS Drug Interactions Benzodiazepines Buspirone Lovastatin Quinidine Rifampin Geriatric Use ADVERSE REACTIONS

CECLOR (cefaclor) Pulvules and Oral Suspension Please contact Eli Lilly & Company at 1-800-545-5979 for prescribing information.	PRECAUTIONS Geriatric Use

CEFOTAN (cefotetan disodium) for Injection CEFOTAN (cefotetan injection) in Galaxy Plastic Container (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

DILANTIN-125 (phenytoin) Oral Suspension Please contact Pfizer Pharmaceuticals at 1-800-879-3477 for prescribing information.	PRECAUTIONS General Section removed regarding adverse events associated with the combination use of phenytoin, cranial radiation, and reduction of corticosteroids.

HYCAMTIN (topotecan hydrochloride) for Injection (click product name to read prescribing information)	PRECAUTIONS Drug Interactions

LOTRISONE (clotrimazole and betamethasone dipropionate) Cream and Lotion (click product name to read prescribing information)	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects: Pregnancy Category C

NASONEX (mometasone furoate monohydrate) Nasal Spray (click product name to read prescribing information)	PRECAUTIONS Pregnancy Teratogenic Effects: Pregnancy Category C

PRIMAXIN IV (imipenem and cilastatin) for Injection PRIMAXIN IM (imipenem and cilastatin) Injectable Suspension Please contact Merck & Company, Inc. at 1-866-448-7590 for prescribing information.	PRECAUTIONS Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy Teratogenic Effects: Pregnancy Category C The labels have been revised to reflect the comparison between dose levels used in animal teratology and reproduction tests to those doses used in humans on the basis of body surface area (mg/m²) rather than body weight (mg/kg).

TAXOL (paclitaxel) Injection (click product name to read prescribing information)	PRECAUTIONS Hepatic ADVERSE REACTIONS

TEMODAR (temozolomide) Capsules (click product name to read prescribing information)	PRECAUTIONS Pediatric Use

TERAZOL 7 (terconazole) Vaginal Cream TERAZOL 3 (terconazole) Vaginal Cream and Vaginal Suppositories (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

TESLAC (testolactone tablets) (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

TIMOLIDE (timolol maleate-hydrochlorothiazide) Tablets (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

TRANXENE T and SD (clorazepate dipotassium) Tablets (click product name to read prescribing information)	PRECAUTIONS Geriatric Use

VFEND (voriconazole) Tablets VFEND (voriconazole) IV for Injection (click product name to read prescribing information)	PRECAUTIONS General Laboratory Tests ADVERSE REACTIONS Less Common Adverse Events

VIDEX (didanosine) Chewable/Dispersible Buffered Tablets VIDEX (didanosine) Buffered Powder for Oral Solution VIDEX (didanosine) Pediatric Powder for Oral Solution VIDEX (didanosine) Delayed-Release Capsules Enteric Coated (click product name to read prescribing information)	PRECAUTIONS Drug Interactions

WESTCORT (hydrocortisone valerate cream) (click product name to read prescribing information)	PRECAUTIONS General Information for Patients Carcinogenesis, Mutagenesis, Impairment of Fertility Pregnancy: Teratogenic Effects, Pregnancy Category C Pediatric Use ADVERSE REACTIONS

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Brand (Generic) Name	Sections Modified
FOSAMAX (alendronate sodium) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS Post-Marketing Experience Special Senses

Gris-PEG (griseofulvin ultramicrosize) Tablets (click product name to read prescribing information)	ADVERSE REACTIONS

KALETRA (lopinavir/ritonavir) Capsules and Oral Solution (click product name to read prescribing information)	ADVERSE REACTIONS

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