DOXORUBICIN HYDROCHLORIDE (LIPOSOMAL)
Clinical safety rating: avoid
Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.
Topoisomerase II inhibitor; intercalates DNA, inhibits DNA and RNA synthesis, and generates free radicals; liposomal formulation enhances accumulation in tumor tissue.
| Metabolism | Hepatic metabolism via aldo-keto reductases (e.g., AKR1A1, AKR1C3) and carbonyl reductases to doxorubicinol; also undergoes deglycosylation; biliary excretion. |
| Excretion | Predominantly biliary/fecal; <5% renal excretion as unchanged drug and metabolites. |
| Half-life | Terminal half-life ranges from 30 to 60 hours (mean ~45 h), with a prolonged distribution phase. Encapsulation in liposomes extends circulation time compared to conventional doxorubicin. |
| Protein binding | Approximately 70% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd is small, approximately 0.05 L/kg (about 3–4 L in adults), limited largely to plasma volume due to liposomal encapsulation. |
| Bioavailability | Bioavailability is 100% via intravenous administration; no oral formulation available. |
| Onset of Action | Clinical effect onset is variable, typically within 1–3 weeks after first dose due to cumulative drug exposure. |
| Duration of Action | Duration of action (antitumor effect) persists for the remainder of the treatment cycle, with repeated dosing every 2–4 weeks. |
| Molecular Weight | 579.98 |
Liposomal doxorubicin 20 mg/m2 IV over 60 minutes every 3 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). |
| Liver impairment | Child-Pugh A: Reduce dose by 50% to 10 mg/m2 every 3 weeks. Child-Pugh B: Reduce dose by 75% to 5 mg/m2 every 3 weeks. Child-Pugh C: Contraindicated. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment, but monitor for increased toxicity (cardiac, myelosuppression). Start at lower end of dosing range (e.g., 20 mg/m2) and titrate based on tolerance. |
| 1st trimester | Contraindicated due to risk of teratogenicity, including cardiovascular and neural tube defects. |
| 2nd trimester | Avoid unless no alternative; potential for fetal growth restriction and preterm birth. |
| 3rd trimester | Avoid near term due to risk of neonatal myelosuppression and cardiotoxicity. |
Clinical note
Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.
| FDA category | Contraindicated |
| Placental transfer | Doxorubicin crosses the placenta; liposomal formulation may reduce transfer but still significant. |
| Breastfeeding |
■ FDA Black Box Warning
Cardiotoxicity (may lead to heart failure); extravasation (tissue necrosis); myelosuppression (severe, with liposomal formulation).
| Common Effects | Myelosuppression |
| Serious Effects |
Hypersensitivity to doxorubicin or any componentSevere hepatic impairmentCardiac compromise (e.g., prior anthracycline therapy exceeding cumulative dose)Severe myelosuppression
| Precautions | Cardiotoxicity: cumulative dose limit (400-450 mg/m2 for liposomal); myelosuppression; hand-foot syndrome (palmar-plantar erythrodysesthesia); infusion-related reactions; hepatic impairment; secondary malignancies. |
| Food/Dietary | Grapefruit and grapefruit juice may increase doxorubicin exposure and should be avoided due to CYP3A4 inhibition. St. John's wort may reduce efficacy via CYP3A4 induction. Avoid alcohol due to hepatotoxic potential. |
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| Doxorubicin is excreted into breast milk in low concentrations; potential for infant toxicity. American Academy of Pediatrics recommends discontinuing breastfeeding during therapy. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | Pregnancy Category D. First trimester: High risk of teratogenicity; cardiac defects, CNS anomalies, and other malformations reported. Second and third trimesters: Fetal toxicity including myelosuppression, cardiotoxicity, and growth restriction; risk of preterm labor and low birth weight. Avoid use unless maternal benefit outweighs fetal risk. |
| Fetal Monitoring | Monitor maternal CBC with differential, LVEF via echocardiogram or MUGA scan, renal and liver function tests. Fetal monitoring includes serial ultrasound for growth, anatomy, and amniotic fluid volume; consider fetal echocardiography if cardiotoxicity suspected. |
| Fertility Effects | Doxorubicin is gonadotoxic; causes ovarian failure and premature menopause in women. In men, oligospermia or azoospermia; potentially irreversible. Fertility preservation counseling recommended before treatment. |
| Clinical Pearls | Liposomal doxorubicin demonstrates reduced cardiotoxicity compared to conventional doxorubicin due to altered biodistribution. Premedicate with dexamethasone and antihistamines to prevent infusion reactions. Monitor for palmar-plantar erythrodysesthesia (hand-foot syndrome), especially after multiple cycles. Cumulative lifetime dose limits (conventional plus liposomal) should not exceed 550 mg/m² (450 mg/m² with prior mediastinal radiation). Do not use inline filters smaller than 15 microns. Administer over 90 minutes; do not bolus. Consider dexrazoxane for cardioprotection if cumulative dose exceeds 300 mg/m². |
| Patient Advice | This drug may cause a red-orange discoloration of urine for 1-2 days after infusion; this is harmless. · Report any new or worsening shortness of breath, swelling of ankles, or rapid weight gain to your doctor. · Contact your doctor immediately if you develop painful redness, swelling, or peeling of hands or feet. · Avoid prolonged sun exposure and use sunscreen, as radiation recall reactions can occur. · Use effective contraception during treatment and for at least 6 months after the last dose. · Do not receive live vaccines during therapy. |