Trade Names:Doxil- Solution for injection equivalent to 2 mg/mL doxorubicin hydrochloride liposomal in single-use 10 or 30 mL vials
Binds DNA and inhibits nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations.
C max approximately 4.12 to 8.34 mcg/mL. AUC approximately 277 to 590 mcg/mL•h.
Vd approximately 2.72 to 2.83 L/m 2 (at steady-state).
Metabolized to doxorubicinol.
The t ½ is approximately 4.7 to 5.2 h (first phase) and approximately 52.3 to 55 h (second phase). Plasma Cl approximately 0.041 to 0.056 L/h/m 2 .
Treatment of ovarian cancer in patients whose disease has progressed or recurred after platinum-based chemotherapy; treatment of AIDS-related Kaposi sarcoma in patients whose disease has progressed on prior combination chemotherapy or who are intolerant to such therapy.
Hypersensitivity to doxorubicin or the components of this product; breast-feeding mothers.
IV 50 mg/m 2 /dose at an initial rate of 1 mg/ min. If no infusion events observed, can increase rate of drug to over 1 h. Repeat every 4 wk. Give minimum of 4 courses, continuing therapy until disease progression occurs. Consider pretreatment with or concomitant use of antiemetics.Kaposi SarcomaAdults
IV 20 mg/m 2 /dose at an initial rate of 1 mg/min. If no infusion adverse reactions observed, can increase rate of drug to over 1 h. Repeat every 3 wk, for as long as patient responds satisfactorily and tolerates treatment.Alternative Dose SchedulesAdults
IV Alternative dosing schedules are recommended for patients with palmar-plantar erythrodysesthesia, hematologic toxicity, or stomatitis.Dosage Adjustment for Hepatic Function Impairment
If serum bilirubin is 1.2 to 3 mg/dL, give 50% of adjusted dose from prior course. If serum bilirubin is more than 3 mg/dL, give 25% of adjusted dose from prior course.Lifetime Cumulative Doses Above Which Frequency of Cardiotoxicity IncreasesAdults
IV up to 500 mg/m 2 .Adults who have received mediastinal radiation or other cardiotoxic drugs
IV up to 400 mg/m 2 .Adults older than 70 yr of age with or without mediastinal radiation
IV up to 300 mg/m 2 .
Refrigerate vials (36° to 46°F). Avoid freezing. Prolonged freezing may adversely affect liposomal doxorubicin; short-term freezing (less than 1 mo) does not appear to have a deleterious effect. If not used immediately, store diluted solution in refrigerator for up to 24 h.
Doxorubicin may decrease oral absorption of digoxin tablets.
None well documented.
Cardiac arrest, chest pain, deep thrombophlebitis, hypotension, pallor, tachycardia, vasodilation (at least 1% to 5%).
Asthenia (40%); headache (11%); paresthesia (10%); dizziness (4%); agitation, anxiety, confusion, depression, emotional liability, hypertonia, insomnia, neuralgia, neuropathy, peripheral neuritis, somnolence, vertigo (at least 1% to 5%).
Hand-foot syndrome (51%); rash (28%); alopecia (19%); acne, pruritus, dry skin, exfoliative dermatitis, fungal dermatitis, furunculosis, herpes simplex, herpes zoster, itching, maculopapular rash, rash, skin discoloration, sweating, vesiculobullous rash (at least 1% to 5%).
Pharyngitis (16%); conjunctivitis, dry eyes, ear pain, retinitis, rhinitis, taste perversion (at least 1% to 5%).
Nausea (46%); stomatitis (41%); abdominal pain (34%); vomiting (33%); constipation (30%); diarrhea (21%); anorexia (20%); dyspepsia (12%); intestinal obstruction (11%); oral moniliasis (6%); ascites, dry mouth, dysphagia, enlarged abdomen, esophagitis, flatulence, gingivitis, ileus, mouth ulceration, rectal bleeding, anorexia, aphthous stomatitis, glossitis (at least 1% to 5%).
Albuminuria, cystitis, dysuria, hematuria, leucorrhea, pelvic pain, urinary frequency, urinary incontinence, UTI, urinary urgency, vaginal bleeding, vaginal moniliasis (at least 1% to 5%).
Thrombocytopenia (61%); anemia (58%); neutropenia (46%); hypochromic anemia (10%); hemolysis, ecchymosis, increased PT (at least 1% to 5%).
Hyperbilirubinemia (1% to 5%).
Increased alkaline phosphatase (8%).
Peripheral edema (11%); cachexia, dehydration, edema, hyperbilirubinemia, hypercalcemia, hypokalemia, hyponatremia, hyperglycemia, hypocalcemia, increased ALT, weight loss (at least 1% to 5%).
Back pain (12%); arthralgia, myalgia, pathological fracture (1% to 10%); back pain (1% to 5%).
Dyspnea (15%); increased cough (10%); apnea, epistaxis, pleural effusion, pneumonia, sinusitis (at least 1% to 5%).
Fever, pain (21%); mucous membrane disorder (14%); infection (12%); allergic reactions, chills (1% to 5%).
Doxorubicin may lead to cardiac toxicity. Myocardial damage leading to heart failure may be encountered as the total cumulative dose approaches 550 mg/m 2 . Include prior use of other anthracyclines or anthracenediones in calculations of total cumulative dose. Cardiac toxicity also may occur at lower cumulative doses (eg, 400 mg/m 2 ) in patients with prior mediastinal irradiation or who are receiving concurrent cyclophosphamide therapy.
Acute infusion-related reactions including serious and sometimes life-threatening or fatal allergic/anaphylactoid-like infusion reactions have been reported in up to 10% of patients. Flushing, shortness of breath, facial swelling, headache, chills, back pain, tightness in the chest or throat, and hypotension have occurred. In most cases, these reactions resolve over several hours to a day once the infusion is terminated. Slowing the infusion rate has resolved the reaction in some patients. Have medications and emergency equipment available for immediate use. Administer doxorubicin at an initial rate of 1 mg/min to minimize the risk of infusion reactions.
Severe myelosuppression may occur.
Liposomal doxorubicin cannot be substituted for doxorubicin hydrochloride on a mg/mg basis. Accidental substitution has resulted in severe adverse reactions.
Monitor cardiac function carefully (endomyocardial biopsy, echocardiography, or multigated radionuclide scans). Assess renal function before initiating therapy. Monitor WBC, CBC, differential, platelet counts, and Hgb/Hct frequently and at a minimum prior to each dose. Assess hepatic function before starting therapy.
Category D .
Undetermined. Discontinue breast-feeding prior to starting therapy.
Safety and efficacy not established.
Reduce dose in patient with hepatic function impairment.
Secondary acute myelogenous leukemia has been reported in patients treated with topoisomerase II inhibitors, including anthracyclines.
Use only when potential benefit outweighs risk.
Local irritation or phlebitis may occur. Refer to your institution-specific protocol.
Palmar-plantar skin eruptions can occur. Usually seen after 2 or 3 cycles of therapy but may occur earlier.
Recall of skin reaction because of prior radiotherapy has occurred.
Mucositis, leukopenia, and thrombocytopenia.
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