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.
Action
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.
Availability
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.
Dosage adjustment
• Hepatic impairment
Contraindications
• Hypersensitivity to drug
• Malignant melanoma
• CNS metastases
• Bone marrow depression
• Cardiac disease
• Breastfeeding
Precautions
Use cautiously in:
• hepatic impairment, brain tumor, renal carcinoma, myelosuppression
• elderly patients
• females of childbearing age
• pregnant patients
• children.
Administration
• 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.
Adverse reactions
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
Hepatic: jaundice
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
Interactions
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
Mercaptopurine: hepatitis
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
Patient monitoring
☞ 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.
Patient teaching
☞ 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.