DOXIL (LIPOSOMAL)
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DOXIL (LIPOSOMAL) (DOXIL (LIPOSOMAL)).
Doxorubicin intercalates between DNA base pairs, inhibits topoisomerase II, and generates free radicals, leading to DNA damage and cell death. Liposomal encapsulation prolongs circulation time and alters biodistribution.
| Metabolism | Primarily hepatically metabolized by aldo-keto reductases to doxorubicinol (active metabolite); also metabolized by cytochrome P450 (minor) and glycosidases. |
| Excretion | Primarily hepatic metabolism and biliary excretion; urinary excretion accounts for <10% of the administered dose as unchanged drug. |
| Half-life | Terminal half-life is approximately 30–40 hours, prolonging drug exposure and allowing every-4-week dosing. |
| Protein binding | Approximately 90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd approximately 2.8 L/m² (not directly L/kg; low Vd indicates predominant plasma compartment retention). |
| Bioavailability | Only intravenous administration; oral bioavailability is negligible. |
| Onset of Action | Onset of antineoplastic effect typically observed after 2–4 weeks of treatment. |
| Duration of Action | Duration of action extends over the dosing interval (4 weeks) due to prolonged circulation of liposomal formulation. |
Doxorubicin HCl liposome injection 20 mg/m2 intravenously over 1 hour every 4 weeks.
| Dosage form | INJECTABLE, LIPOSOMAL |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended, but monitor for increased toxicity (e.g., cardiotoxicity, myelosuppression) due to age-related organ function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DOXIL (LIPOSOMAL) (DOXIL (LIPOSOMAL)).
| Breastfeeding | Doxorubicin is excreted in human milk. The milk-to-plasma (M/P) ratio for doxorubicin is approximately 0.5 to 2.0 based on limited data. Because of the potential for serious adverse reactions in nursing infants from doxorubicin (e.g., myelosuppression, cardiotoxicity), discontinue breastfeeding during and for at least 3 months after the last dose of DOXIL. |
| Teratogenic Risk | Doxorubicin hydrochloride liposome injection (DOXIL) is classified as Pregnancy Category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans. Potential benefits may warrant use of the drug in pregnant women despite potential risks. First trimester: High risk of teratogenicity including major malformations (e.g., cardiovascular, neural tube defects). Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and neonatal myelosuppression. Use only if clearly needed and no safer alternative. |
■ FDA Black Box Warning
Cardiotoxicity: risk of myocardial damage, including acute left ventricular failure. Myelosuppression: severe, dose-limiting. Hepatic impairment: requires dose reduction. Infusion reactions: may be severe or life-threatening. Must be administered by physician experienced in cancer chemotherapy.
| Serious Effects |
Absolute: history of hypersensitivity to doxorubicin or other anthracyclines. Relative: severe hepatic impairment, severe myelosuppression, pre-existing cardiomyopathy, prior treatment with maximum cumulative doses of anthracyclines (e.g., doxorubicin >550 mg/m², liposomal doxorubicin >900 mg/m²).
| Precautions | Cardiotoxicity (cumulative dose-dependent, monitor LVEF), myelosuppression (neutropenia, thrombocytopenia), infusion reactions (premedicate), hand-foot syndrome (palmar-plantar erythrodysesthesia), secondary malignancies, extravasation necrosis, hepatic impairment (dose adjustment), immunosuppression, embryo-fetal toxicity. |
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| Fetal Monitoring | Monitor complete blood counts (CBC) with differential, cardiac function (LVEF via echocardiogram or MUGA scan), liver function tests (LFTs), renal function (serum creatinine, BUN), and urine output. During pregnancy, monitor fetal growth and amniotic fluid volume via ultrasound. Assess for signs of fetal distress (e.g., non-stress test, biophysical profile) if maternal complications arise. |
| Fertility Effects | Doxorubicin causes gonadal suppression and may lead to irreversible infertility in both males and females. In women, it can cause premature ovarian failure with amenorrhea and elevated FSH levels. In men, it may cause oligospermia or azoospermia. The risk is dose-dependent and more pronounced in older reproductive age groups. Effects may persist after treatment. |