Cardiac; Hepatic; Myelosuppression; Extravasation RiskExtravasation
- The use of doxorubicin liposome injection may lead to cardiac toxicity. Myocardial damage may lead to congestive heart failure and may be encountered as the total cumulative dose of doxorubicin HCl approaches 550 mg/m2.
- In a large clinical study in patients with advanced breast cancer, 250 patients received liposomal doxorubicin at a starting dose of 50 mg/m2 every 4 weeks. At all cumulative anthracycline doses between 450 to 500 mg/m2 or between 500 to 550 mg/m2, the risk of cardiac toxicity for patients treated with doxorubicin liposomal was 11%.
- Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. Cardiac toxicity may also occur at lower cumulative doses in patients with prior mediastinal irradiation or who are receiving concurrent cyclophosamide therapy.
Acute Infusion Reactions
- Acute infusion related reactions, including but not limited to flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension have occurred in up to 10% of patients treated with doxorubicin liposome. In most patients, these reactions resolved over the course of several hours to a day once the infusion is stopped. In some patients, the reaction has resolved with slowing the infusion rate.
- Serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have been reported.
- Medications to treat such reactions, as well as emergency equipment, should be available for immediate use.
- Liposomal doxorubicin should be administered at an initial rate of 1 mg/min to minimize risk of infusion reactions. (See warnings-Infusion reactions).
- Severe myelosuppression may occur
Dosage in Hepatic Impairment
- Dosage should be reduced in patients with impaired hepatic function.
Substitution of Products
- Doxil (liposomal) should not be substituted for doxorubicin HCl on a mg per mg basis. Accidental substitution has resulted in severe side effects.(See Dosage and Administration)
Cardiomyopathy and Infusion Related Reactions
- DOXIL can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy was 11% when the cumulative anthracycline dose was between 450 mg/m2 to550 mg/m2. Assess left ventricular cardiac function prior to initiation of DOXIL and during and after treatment.
- Serious, life-threatening, and fatal infusion-related reactions can occur. Acute infusion-related reactions occurred in 11% of patients with solid tumors. Withhold DOXIL for infusion-related reactions and resume at a reduced rate. Discontinue DOXIL for serious or life-threatening infusion-related reactions.
- Contraindications: DOXIL is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin hydrochloride.
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Irreversible myocardial toxicity leading to CHF(often unresponsive to cardiac support therapy)may occur at cumulative doses near 550 mg/m2.
- CHF may occur at lower cumulative doses in patient populations similar to conventional formulations(see above)
- Should be administered at an initial rate of 1 mg/min to minimize the risk of infusion reactions