What it's for (Indications)
- Doxorubicin is indicated for the treatment of various cancers, including adjuvant breast cancer and other solid tumors, often used as a single agent or in combination with other chemotherapy drugs.
Dosage Information
| Type | Guideline |
|---|---|
| Standard | For single-agent therapy, the recommended dosage is 60 to 75 mg/m² administered intravenously every 21 days. In combination chemotherapy, the recommended dosage ranges from 40 to 75 mg/m² intravenously every 21 to 28 days. For adjuvant breast cancer, a recommended dosage is 60 mg/m² administered as an intravenous bolus on day 1 of each 21-day treatment cycle, in combination with cyclophosphamide, for a total of four cycles. Doxorubicin hydrochloride for injection should be discontinued in patients who develop signs or symptoms of cardiomyopathy. Dose reduction is necessary for patients with hepatic impairment. |
Safety & Warnings
Common Side Effects
- The most common adverse reactions (>10%) include alopecia, nausea, and vomiting.
- Other clinically significant adverse reactions can include cardiomyopathy and arrhythmias, secondary malignancies, extravasation and tissue necrosis, severe myelosuppression, tumor lysis syndrome, and radiation sensitization and recall.
Serious Warnings
- Black Box Warning: WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS, and SEVERE MYELOSUPPRESSION. Cardiomyopathy: Myocardial damage, including acute left ventricular failure, can occur with doxorubicin hydrochloride. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% to 20% for cumulative doses ranging from 300 mg/m² to 500 mg/m² when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with pre-existing cardiac disease, prior or concomitant mediastinal radiation, or concomitant use of other cardiotoxic agents. Secondary Malignancies: Doxorubicin hydrochloride can increase the risk of developing secondary malignancies, including acute myeloid leukemia and myelodysplastic syndrome. Extravasation and Tissue Necrosis: Extravasation of doxorubicin hydrochloride can cause severe local tissue necrosis, which may require surgical intervention. Severe Myelosuppression: Doxorubicin hydrochloride can cause severe myelosuppression, including leukopenia, neutropenia, anemia, and thrombocytopenia, leading to life-threatening infections and hemorrhage.
- Patients receiving doxorubicin are at risk for serious adverse events.
- These include cardiomyopathy (potentially leading to myocardial damage and acute left ventricular failure), secondary malignancies, extravasation with potential for tissue necrosis at the injection site, severe myelosuppression (which can be persistent), tumor lysis syndrome, and radiation sensitization or radiation recall phenomenon.
- Arrhythmias can also occur.
- The risk of cardiomyopathy is cumulative dose-dependent.
- Discontinuation of treatment is warranted if signs or symptoms of cardiomyopathy develop.
- Dose adjustments are required for patients with hepatic impairment.
How it Works (Mechanism of Action)
The cytotoxic effect of doxorubicin hydrochloride on malignant cells and its toxic effects on various organs are primarily related to nucleotide base intercalation into DNA and cell membrane lipid binding activities. This intercalation inhibits nucleotide replication and the action of DNA and RNA polymerases. Additionally, the interaction of doxorubicin with topoisomerase II to form DNA-cleavable complexes is considered an important mechanism of its cytocidal activity.