Doxorubicin (Liposomal)

• Doxil
• Lipodox 50
• Lipodox [DSC]

Severe hypersensitivity (including anaphylaxis) to doxorubicin liposomal, conventional doxorubicin, or any component of the formulation

Canadian labeling: Additional contraindications (not in the US labeling): Breast-feeding

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Concerns related to adverse effects:

• Bone marrow suppression: Neutropenia, anemia, and thrombocytopenia may occur. Monitor blood counts. Treatment delay, dosage modification, or discontinuation may be required. Hematologic toxicity may occur at a higher frequency and severity with combination chemotherapy.

• Infusion reactions: [US Boxed Warning]: Acute infusion-related reactions consisting of, but not limited to, flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and/or hypotension occurred in 11% of patients with solid tumors treated with doxorubicin (liposomal). Serious, life-threatening and fatal infusion reactions have been reported. Infusion reactions have also included chest pain, pruritus, rash, cyanosis, syncope, tachycardia, bronchospasm, asthma, and apnea. Most reactions occurred during the first infusion. Some reactions have resulted in dose interruption. Medication and equipment to manage infusion reactions should be immediately available during infusion. Initiate infusion at a rate of 1 mg/minute, with the rate increased (to complete infusion over 60 minutes) as tolerated. If an infusion reaction occurs, temporarily interrupt infusion until resolved and resume at a reduced rate. Discontinue for serious or life-threatening infusion reactions.

• Myocardial toxicity: [US Boxed Warning]: Doxorubicin liposomal may cause myocardial damage (including congestive heart failure) as the total cumulative dose of doxorubicin approaches 550 mg/m2. In a clinical study of 250 patients with advanced cancer who were treated with doxorubicin liposomal, the risk of cardiotoxicity was 11% when the cumulative anthracycline dose was between 450 to 550 mg/m2. Prior use of other anthracyclines or anthracenediones should be included in calculations of total cumulative dosage. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation. Myocardial damage may manifest as acute left ventricular failure; cardiotoxicity is defined as a >20% decrease in resting left ventricular ejection fraction (LVEF) from baseline (if LVEF remained in the normal range) or a >10% decrease from baseline (where LVEF was less than the institutional lower limit of normal). Some patients developed signs/symptoms of heart failure without documented evidence of cardiotoxicity. The risk of cardiomyopathy with doxorubicin is generally proportional to the cumulative exposure, although the relationship between cumulative doxorubicin liposomal dose and the risk of cardiotoxicity is not known. Anthracycline-induced cardiotoxicity may be delayed (after discontinuation of anthracycline treatment). Assess left ventricular function with echocardiogram or MUGA prior to and during treatment to detect acute changes; monitor after treatment to detect delayed cardiotoxicity. Use in patients with a history of cardiovascular disease only if potential benefits outweigh cardiovascular risk.

• Palmar-plantar erythrodysesthesia (hand-foot syndrome): Hand-foot syndrome has been reported in patients receiving doxorubicin liposomal. It is usually seen after 2 to 3 treatment cycles, although may also occur earlier. Dosage modification may be required; in severe or debilitating cases, treatment discontinuation may be required.

• Secondary malignancy: Cases of secondary oral cancers (primarily squamous cell carcinoma) have been reported with long-term (>1 year) doxorubicin liposomal exposure; these secondary oral malignancies have occurred during treatment and up to 6 years after treatment. The development of oral ulceration or discomfort should be monitored and further evaluated in patients with past or present use of doxorubicin liposomal. Tissue distribution of the liposomal doxorubicin compared to free doxorubicin may play a role in the development of oral secondary malignancies associated with long-term use.

Disease-related concerns:

• Hepatic impairment: Pharmacokinetics in patients with hepatic impairment have not been adequately studied. Doxorubicin is predominantly eliminated hepatically; reduce doxorubicin liposomal dose in patients with serum bilirubin ≥1.2 mg/dL.

Special populations:

• Splenectomized patients: Use in splenectomized patients with AIDS-related Kaposi sarcoma has not been studied and is not recommended (Canadian labeling [Caelyx] 2016).

Concurrent drug therapy issues:

• Drug-drug interactions: 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.

Dosage form specific issues:

• Liposomal vs conventional formulation dosing: Liposomal formulations of doxorubicin should NOT be substituted for conventional doxorubicin hydrochloride on a mg-per-mg basis.

Doxorubicin liposomal is a cancer medication.

Doxorubicin liposomal may increase the risk of heart or liver problems. Before you receive doxorubicin liposomal, tell your doctor if you have heart or liver disease.

Doxorubicin liposomal can lower blood cells that help your body fight infections and help your blood to clot. You may get an infection or bleed more easily. Call your doctor if you have unusual bruising or bleeding, or signs of infection (fever, chills, body aches).

Some side effects may occur during the injection. Tell your caregiver right away if you feel dizzy, nauseated, light-headed, sweaty, or have a headache, chest tightness, back pain, trouble breathing, or swelling in your face.

Doxorubicin liposomal is injected into a vein through an IV. A healthcare provider will give you this injection.

Tell your caregivers if you feel any burning, pain, or swelling around the IV needle when doxorubicin liposomal is injected.

If this medicine accidentally gets on your skin, wash it thoroughly with soap and warm water.

Doxorubicin liposomal can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Call your doctor for instructions if you miss an appointment for your doxorubicin liposomal injection.

 No formal drug interaction studies have been conducted with doxorubicin hydrochloride liposome injection.

Acute overdosage with doxorubicin hydrochloride causes increased risk of severe mucositis, leukopenia, and thrombocytopenia.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Mutagenicity or carcinogenicity studies have not been conducted with doxorubicin hydrochloride liposome injection, however doxorubicin was shown to be mutagenic in the in vitro Ames assay, and clastogenic in multiple in vitro assays (CHO cell, V79 hamster cell, human lymphoblast, and SCE assays) and the in vivo mouse micronucleus assay. The possible adverse effects on fertility in animals have not been adequately evaluated. Doxorubicin hydrochloride liposome injection resulted in mild to moderate ovarian and testicular atrophy in mice after administration of a single dose of 36 mg/kg (about 2 times the 50 mg/m2 human dose on a mg/m2 basis). Decreased testicular weights and hypospermia were observed in rats after repeat doses ≥ 0.25 mg/kg/day (about 0.03 times the 50 mg/m2 human dose on a mg/m2 basis), and diffuse degeneration of the seminiferous tubules and a marked decrease in spermatogenesis were observed in dogs after repeat doses of 1 mg/kg/day (about 0.4 times the 50 mg/m2 human dose on a mg/m2 basis).