Doxorubicin

Doxorubicin Hydrochloride Injection is an anthracycline topoisomerase inhibitor indicated: • as a component of multi‑agent adjuvant chemotherapy for treatment of women with axillary lymph node involvement following resection of primary breast cancer. • for the treatment of: acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin lymphoma, Non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms' tumor, metastatic neuroblastoma, metastatic soft tissue sarcoma, metastatic bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, metastatic bronchogenic carcinoma

The cytotoxic effect of doxorubicin hydrochloride on malignant cells and its toxic effects on various organs are thought to be related to nucleotide base intercalation and cell membrane lipid binding activities of doxorubicin. Intercalation inhibits nucleotide replication and action of DNA and RNA polymerases. The interaction of doxorubicin with topoisomerase II to form DNA-cleavable complexes appears to be an important mechanism of doxorubicin hydrochloride cytocidal activity.

• Single agent: 60 to 75 mg/m 2 given intravenously every 21 days. • In combination: 40 to 75 mg/m 2 given intravenously every 21 to 28 days. • Discontinue Doxorubicin Hydrochloride Injection in patients who develop signs or symptoms of cardiomyopathy. • Reduce dose in patients with hepatic impairment

Doxorubicin Hydrochloride Injection are contraindicated in patients with: • Severe myocardial insufficiency • Recent (occurring within the past 4-6 weeks) myocardial infarction • Severe persistent drug-induced myelosuppression • Severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) • Severe hypersensitivity reaction to doxorubicin hydrochloride, including anaphylaxis • Severe myocardial insufficiency. • Recent myocardial infarction. • Severe persistent drug-induced myelosuppression. • Severe hepatic impairment. • Severe hypersensitivity to doxorubicin hydrochloride

Boxed warning (cardiomyopathy, secondary malignancies, extravasation and tissue necrosis, and severe myelosuppression •): Cardiomyopathy: Myocardial damage, including acute left ventricular failure, can occur with doxorubicin hydrochloride. • Radiation-Induced Toxicity: Can be increased by the administration of Doxorubicin Hydrochloride Injection. Radiation recall can occur in patients who receive Doxorubicin Hydrochloride Injection after prior radiation therapy. • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and on the use of effective contraception. Advise males with female partners of reproductive potential to use effective contraception. Advise males with pregnant partners to use condoms.

The following clinically significant adverse reactions are described elsewhere in the labeling. • Cardiomyopathy and Arrhythmias • Secondary Malignancies • Extravasation and Tissue Necrosis • Severe Myelosuppression • Tumor Lysis Syndrome • Radiation Sensitization and Radiation Recall The most common (>10%) adverse reactions are alopecia, nausea and vomiting.

• Avoid concomitant use of doxorubicin hydrochloride with inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp. • Do not administer doxorubicin hydrochloride in combination with trastuzumab due to increased risk of cardiac dysfunction

Store all vials at 2°C to 8°C (36°F to 46°F). Storage of Doxorubicin Hydrochloride Injection under refrigerated conditions can result in the formation of a gelled product. Place gelled product at room temperature [15ºC to 30ºC (59ºF to 86ºF)] for 2 to 4 hours to return the product to a slightly viscous, mobile solution. Protect from light.