Doxorubicin

Severe myelosuppression resulting in serious infection, septic shock, transfusion requirements, hospitalization, and death may occur. Myelosuppression may be dose-limiting and primarily manifests as leukopenia and neutropenia; anemia and thrombocytopenia may also occur. The nadir typically occurs 10 to 14 days after administration with cell count recovery by day 21. Monitor blood counts at baseline and regularly during therapy.

Myocardial damage, including acute left ventricular failure can occur with doxorubicin. The risk of cardiomyopathy is proportional to the cumulative exposure with incidences from 1% to 20% for cumulative doses from 300 mg/m2 to 500 mg/m2 when doxorubicin is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess left ventricular ejection fraction (LVEF) before and regularly during and after doxorubicin treatment. Assess LVEF by MUGA or echocardiogram; use the same assessment method at all time points; increase the frequency of assessments as the cumulative dose exceeds 300 mg/m2. Discontinue doxorubicin in patients who develop signs/symptoms of cardiomyopathy during treatment. Delayed cardiotoxicity may occur late in treatment or within months to years after completion of therapy, and is typically manifested by decreased LVEF and/or signs/symptoms of heart failure. The total cumulative doxorubicin dose should take into account prior treatment with other anthracyclines or anthracenediones. The risk for delayed cardiotoxicity is estimated to range from 1% to 2% at cumulative lifetime doses of 300 mg/m2 to 6% to 20% at cumulative lifetime doses of 500 mg/m2 administered every 3 weeks. The risk of cardiomyopathy is increased in patients who have received radiotherapy to the mediastinum or concomitant therapy with other known cardiotoxic agents such as cyclophosphamide and trastuzumab. Pericarditis and myocarditis ha

Vesicant; extravasation may result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate infusion and apply ice to the affected area. For IV administration only; do not administer by intramuscular (IM) or subcutaneous routes. Ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.

In men, doxorubicin may damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities; may also result in oligospermia, azoospermia, and permanent loss of fertility (sperm counts have been reported to return to normal levels in some men, occurring several years after the end of therapy). In females of reproductive potential, doxorubicin may cause infertility and result in amenorrhea; premature menopause can occur.

Doxorubicin is associated with a moderate or high emetic potential (depending on dose or regimen); antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016).

[US Boxed Warnings]: Secondary acute myelogenous leukemia (AML) and myelodysplastic syndromes (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin. AML and MDS typically occur within 1 to 3 years of treatment; risk factors for development of secondary AML or MDS include treatment with anthracyclines in combination with DNA-damaging antineoplastics (eg, alkylating agents) and/or radiation therapy, heavily pretreated patients, and escalated anthracycline doses.

May cause tumor lysis syndrome and hyperuricemia (in patients with rapidly growing tumors). Urinary alkalinization and prophylaxis with an antihyperuricemic agent may be necessary. Monitor electrolytes, renal function, and hydration status. Disease-related concerns:

Dose reduction is recommended in patients with bilirubin levels of 1.2 to 5 mg/dL; toxicities may be increased in patients with hepatic impairment. Use is contraindicated in patients with severe impairment (Child-Pugh class C or bilirubin >5 mg/dL). Monitor hepatic function tests (ALT, AST, alkaline phosphatase, and bilirubin) at baseline and during treatment. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Children are at increased risk for developing delayed cardiotoxicity; long-term periodic cardiac function monitoring is recommended. Doxorubicin may contribute to prepubertal growth failure in children; may also contribute to gonadal impairment (usually temporary). Radiation recall pneumonitis has been reported in children receiving concomitant dactinomycin and doxorubicin.

Use with caution in patients who have received radiation therapy; radiation recall may occur. May increase radiation-induced toxicity to the myocardium, mucosa, skin, and liver. Dosage form specific issues:

Use caution when selecting product for preparation and dispensing; indications, dosages and adverse event profiles differ between conventional doxorubicin hydrochloride solution and doxorubicin liposomal. Both formulations are the same concentration. As a result, serious errors have occurred. Other warnings/precautions:

Administration of live vaccines to immunosuppressed patients may be hazardous.