doxorubicin hydrochloride, liposomal

doxorubicin hydrochloride, liposomal

Caelyx (CA) (UK), Doxil, Myocet (UK)

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.

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