Doxorubicin is usually administered by intravenous injection. Intravesical and intra-arterial routes may be used as indicated.
Intravenous (IV) Administration: The total doxorubicin dose per cycle may differ according to its use within a specific treatment regimen (e.g., given as a single agent or in combination with other cytotoxic drugs) and according to the indication.
Doxorubicin should be administered into the tubing of a freely flowing intravenous infusion (0.9% sodium chloride or 5% glucose solution) for not less than 3 minutes and not more than 10 minutes to minimize the risk of thrombosis or perivenous extravasation. A direct push injection is not recommended due to the risk of extravasation, which may occur even in the presence of adequate blood return upon needle aspiration (see Precautions).
Standard starting dose regimens: As a single agent, the recommended standard starting dose of doxorubicin per cycle in adults is 60-90 mg/m2 of body surface area. The total starting dose per cycle may be given as a single dose or divided over 3 successive days or given on days 1 and 8. Under conditions of normal recovery from drug-induced toxicity (particularly bone marrow depression and stomatitis), each treatment cycle could be repeated every 3 to 4 weeks. Administration of doxorubicin in a weekly regimen of 10-20 mg/m2 has also been shown to be effective. If doxorubicin is used in combination with other cytotoxic drugs with potentially overlapping toxicities, the recommended dose per cycle is in the 30-60 mg/m2 range.
Adjuvant therapy: In a large randomized study conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-15 of patients with early breast cancer involving axillary lymph nodes, (see Adverse Reactions and Pharmacology: Pharmacodynamics: Clinical Studies under Actions) the combination dosage regimen of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) was administered intravenously on day 1 of each 21-day treatment cycle. Four cycles of treatment were administered.
Dose modifications: Hepatic Dysfunction: Dose reductions are recommended in patients with the following serum chemistry values: Bilirubin 1.2 to 3 mg/dL: ½ of recommended starting dose; Bilirubin > 3 mg/dL: ¼ of recommended starting dose.
Doxorubicin should not be administered to patients with severe hepatic impairment (see Contraindications).
Other Special Populations: Lower starting doses or longer intervals between cycles may need to be considered for heavily pre-treated patients, children, elderly patients, obese patients, or patients with neoplastic bone marrow infiltration (see Precautions).
Intravesical Administration: Doxorubicin administered intravesically can be used for the treatment of superficial bladder tumors or as prophylaxis to reduce recurrence after transurethral resection. Intravesical administration is not suitable for the treatment of invasive tumors that have penetrated the muscular layer of the bladder wall. Instillations of 30-50 mg in 25-50 mL of saline solution are recommended. In the case of local toxicity (chemical cystitis), the dose should be instilled in 50-100 mL of saline solution. Patients may continue to receive instillations in weekly to monthly intervals (see Precautions).
Doxorubicin should be instilled using a catheter and retained intravesically for 1 to 2 hours. During instillation, the patient should be rotated to ensure that the vesical mucosa of the pelvis receives the most extensive contact with the solution. To avoid undue dilution with urine, the patient should be instructed not to drink any fluid in the 12 hours prior to instillation. The patient should be instructed to void at the end of the instillation.
Intra-arterial Administration: Doxorubicin has been also used by the intra-arterial route in an attempt to produce intense local activity with reduced systemic toxicity in patients with hepatocellular carcinoma. Since this technique is potentially hazardous and can lead to widespread necrosis of the perfused tissue, intra-arterial administration should only be attempted by those physicians fully trained with this technique. Patients may receive an infusion into the main hepatic artery in doses of 30 to 150 mg/m² at intervals of 3 weeks to 3 months, with higher doses reserved for administration with concurrent extracorporeal drug elimination. Lower doses are suitable for administration of doxorubicin with iodized oil (see Precautions).