Indications
Doxorubicin is an anthracycline topoisomerase II inhibitor indicated for:
- Ovarian cancer: After failure of platinum-based chemotherapy.
- AIDS-related Kaposi’s Sarcoma: After failure of prior systemic chemotherapy or intolerance to such therapy.
- Multiple Myeloma: In combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy.
Pharmacology
Doxorubicin is a cytotoxic anthracycline antibiotic. The cytotoxic action results from its binding to DNA and inhibition of nucleic acid synthesis. Doxorubicin has been shown to produce regression in a variety of disseminated malignancies.
Dosage And Administration
Administer Doxorubicin at an initial rate of 1 mg/min to minimize the risk of infusion reactions. If no infusion related reactions occur, increase rate of infusion to complete administration over 1 hour. Do not administer as bolus injection or undiluted solution.
- Ovarian cancer: 50 mg/m2 IV every 4 weeks
- AIDS-related Kaposi’s Sarcoma: 20 mg/m2 IV every 3 weeks
- Multiple Myeloma: 30 mg/m2 IV on day 4 following bortezomib
Interaction
Doxorubicin interacts with a number of other drugs e.g. antibiotics (aminoglycosides), steroids, aminophylline and propranolol.
Contraindications
Cardiac disease, neonates, pregnancy and lactation, prior irradiation to mediastinum. IM/SC admin. Severe myelosuppression due to previous treatment with antitumour agents or radiotherapy.
Side Effects
Leucopenia, thrombocytopenia, nausea, vomiting, diarrhoea. Rarely facial flushing, rash, alopecia. Blurred vision, headache, seizures, paraesthesia, confusion, malaise, lethargy, skin pigmentation.
Pregnancy And Lactation
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Precautions And Warnings
Elderly, children, hepatic impairment. Monitor blood counts and ECG.
Overdose Effects
Acute overdosage may increase the toxic effects of mucositis, leukopenia and thrombocytopenia. Treatment includes hospitalisation of the severely myelosuppressed patient, antimicrobials, platelet transfusions and symptomatic treatment of mucositis. Use of haemopoietic growth factor (G-CSF, GM-CSF) may be considered. Cumulative dosage increases risk of cardiomyopathy and resultant congestive heart failure which may be managed with digitalis preparations, diuretics, and after load reducers such as ACE inhibitors.
Therapeutic Class
Cytotoxic Chemotherapy
Use in special populations
Hepatic Impairment-
serum-bilirubin: 12-30 mcg/ml: Half the normal dose;
serum-bilirubin: >30 mcg/ml: Quarter of the usual dose.
Storage Conditions
Powder for injection: Store at 15-30°C.
Solution for injection & liposomal formulations: Refrigerate at 2-8°C. Do not freeze.