doxorubicin hydrochloride, liposomal
doxorubicin hydrochloride, liposomal
Pharmacologic class: Anthracycline
Therapeutic class: Antibiotic antineoplastic
Pregnancy risk category D
FDA Box Warning
• Drug may cause cardiotoxicity. Myocardial damage may lead to heart failure and may occur as total cumulative dose (which includes previous use of other anthracyclines or anthracenediones) approaches 550 mg/m2. Toxicity may occur at lower cumulative doses in patients who have had previous mediastinal irradiation or are receiving concurrent cyclophosphamides.
• Acute infusion-related reactions occur in up to 10% of patients. They usually resolve over several hours to 1 day after infusion ends; in some patients, they resolve with slower infusion rate. Serious and sometimes life-threatening allergic or anaphylactoid-like infusion reactions may occur. Keep emergency equipment and drugs to treat reaction available for immediate use.
• Drug may cause severe myelosuppression.
• Reduce dosage in hepatic impairment.
• Accidental substitution of liposomal form for doxorubicin hydrochloride may cause severe adverse effects. Don't substitute on mg-per-mg basis.
Unclear. Thought to inhibit DNA and RNA synthesis by forming complex with DNA. Also exerts immunosuppressive activity. Liposomal encapsulation increases uptake by tumors, prolongs drug action, and may decrease toxicity. Cell-cycle-S-phase specific.
Liposomal dispersion for injection: 2 mg/ml in 10-ml vial, 2 mg/ml in 25-ml vials
Indications and dosages
➣ AIDS-related Kaposi's sarcoma
Adults: 20 mg/m2 I.V. once q 3 weeks
➣ Metastatic ovarian carcinoma
Adults: Initially, 50 mg/m2 I.V. at a rate of 1 mg/minute q 4 weeks for at least four courses. If no adverse reactions occur, increase infusion rate to complete the infusion over 1 hour.
• Hepatic impairment
• Hypersensitivity to drug
• Malignant melanoma
• CNS metastases
• Bone marrow depression
• Cardiac disease
Use cautiously in:
• hepatic impairment, brain tumor, renal carcinoma, myelosuppression
• elderly patients
• females of childbearing age
• pregnant patients
• Follow facility policy for handling and preparing antineoplastics.
• Dilute dose (up to 90 mg) in 250 ml of dextrose 5% in water. Don't use any other diluent.
☞ Don't dilute solution with bacteriostatic diluent. Don't mix with other drugs.
• Don't use in-line filter.
• Administer slowly by I.V. infusion at initial rate of 1 mg/minute. If no infusion reaction occurs, increase rate to complete infusion over 1 hour. Don't give as I.V. bolus.
☞ Avoid rapid infusion, which may increase the risk of infusion-related reactions (back pain, chest tightness, flushing).
☞ If extravasation occurs, stop infusion immediately, apply ice, and notify prescriber.
• Don't give I.M. or subcutaneously.
• Know that drug is a translucent red dispersion, not a clear solution.
CNS: drowsiness, dizziness, asthenia, fatigue, malaise, paresthesia, headache, depression, insomnia, anxiety, emotional lability
CV: chest pain, hypotension, tachycardia, peripheral edema, cardiomyopathy, heart failure, arrhythmias, pericardial effusion
GI: nausea, vomiting, diarrhea, constipation, abdominal pain, enlarged abdomen, dyspepsia, moniliasis, stomatitis, glossitis, oral candidiasis, esophagitis, dysphagia
GU: albuminuria, red urine
Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia, bone marrow depression
Metabolic: hypocalcemia, hyperglycemia
Musculoskeletal: myalgia, back pain, hand-foot syndrome
Respiratory: dyspnea, increased cough, pneumonia
Skin: rash, dry skin, pruritus, skin discoloration, alopecia, diaphoresis, exfoliative dermatitis, palmar-plantar erythrodysesthesia
Other: altered taste, fever, chills, infection, herpes zoster, injection site reactions, allergic reactions including anaphylaxis, acute infusion reaction
Drug-drug. Antineoplastics: additive bone marrow depression
Cyclophosphamide: increased risk of hemorrhagic cystitis
Cyclosporine: profound and prolonged hematologic toxicity, increased risk of coma and seizures, increased cardiotoxicity
Dactinomycin (in children): increased risk of pneumonitis
Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions
Paclitaxel (if administered first): reduced doxorubicin clearance, increased incidence and severity of neutropenia and stomatitis
Phenobarbital: increased clearance and decreased effects of doxorubicin
Phenytoin: decreased phenytoin blood level
Progesterone: increased risk and severity of neutropenia and thrombocytopenia
Streptozocin: prolonged doxorubicin half-life
Verapamil: increased doxorubicin blood level
Drug-diagnostic tests. Alkaline phosphatase, bilirubin, glucose, prothrombin time, serum and urine uric acid: increased levels
Calcium, hemoglobin, neutrophils, platelets, white blood cells: decreased levels
☞ Observe patient closely for anaphylaxis and bleeding problems.
☞ Stay alert for acute life-threatening arrhythmias, which may occur during or within a few hours after administration.
☞ Assess for cardiomyopathy and subsequent heart failure with chronic overdose (more common in children).
☞ Monitor closely for acute infusion reaction.
• Assess for and report liver engorgement and yellowing of skin or eyes.
• Check CBC, coagulation tests, hepatic profile, and bilirubin, glucose, calcium and uric acid levels.
• Watch for nausea and vomiting. Give antiemetics, as needed and prescribed.
• Assess for constipation and give fluids and stool softeners, as needed and prescribed.
☞ Instruct patient to immediately report shortness of breath; tingling or burning, redness, flaking, bothersome swelling, small blisters, or small sores on palms of hands or soles of feet; rash, chest pain, or palpitations.
• Advise patient to avoid people with colds, flu, or other contagious illnesses.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.