Adriamycin RDF doxorubicin hydrochloride for injection, USP FOR INTRAVENOUS USE ONLY WARNING

WARNING 1. Severe local tissue necrosis will occur if there is extravasation during administration (see DOSAGE AND ADMINISTRATION). Doxorubicin must not be given by the intramuscular or subcutaneous route. 2. Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The probability of developing impaired myocardial function based on a combined index of signs, symptoms and decline in left ventricular ejection fraction (LVEF) is estimated to be 1 to 2% at a total cumulative dose of 300 mg/m of doxorubicin, 3 to 5% at a dose of 400 mg/m, 5 to 8% at 450 mg/m and 6 to 20% at 500 mg/m.* The risk of developing CHF increases rapidly with increasing total cumulative doses of doxorubicin in excess of 450 mg/m. This toxicity may occur at lower cumulative doses in patients with prior mediastinal irradiation or on concurrent cyclophosphamide therapy or with pre-existing heart disease. Pediatric patients are at increased risk for developing delayed cardiotoxicity. 3. Dosage should be reduced in patients with impaired hepatic function. 4. Severe myelosuppression may occur. 5. Doxorubicin should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.