EPIRUBICIN HYDROCHLORIDE
Clinical safety rating: avoid
Contraindicated (not allowed)
Intercalates between DNA base pairs, inhibits topoisomerase II, generates free radicals, and induces DNA cleavage, thereby inhibiting DNA replication and transcription.
| Metabolism | Primarily hepatic metabolism via glucuronidation (UGT2B7) and reduction by carbonyl reductases to epirubicinol; also metabolized by aldose reductase and aldehyde reductase; elimination via biliary and renal routes. |
| Excretion | Primarily hepatic metabolism and biliary excretion (approximately 40-50% of the dose as unchanged drug and metabolites in bile); renal excretion accounts for about 9-15% of the administered dose, mostly as metabolites. |
| Half-life | Terminal elimination half-life approximately 30-40 hours (mean 33 hours); in patients with hepatic impairment, half-life may be prolonged, requiring dose reduction. |
| Protein binding | Approximately 75-85% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 1000-1400 L/m² (equivalent to 20-30 L/kg), indicating extensive tissue distribution and binding to intracellular components. |
| Bioavailability | Not available for oral route due to extensive first-pass metabolism; administered only intravenously. |
| Onset of Action | Intravenous administration: clinical effects (e.g., antitumor activity) typically observed within 1-2 weeks; peak plasma concentrations achieved immediately after IV bolus. |
| Duration of Action | Duration of antitumor effect is variable, associated with multiple cycles; myelosuppression and other toxicities may persist for 2-3 weeks after administration. |
60-90 mg/m2 IV bolus or infusion over 3-5 minutes on day 1 of a 21-day cycle, or 12-25 mg/m2 IV daily for 3 consecutive days every 21 days.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl <30 mL/min), consider a 50% dose reduction. |
| Liver impairment | For Child-Pugh class A: no adjustment. For Child-Pugh class B: reduce dose by 50%. For Child-Pugh class C: contraindicated or avoid use. |
| Pediatric use | 75-90 mg/m2 IV every 21 days, or 30 mg/m2 IV on days 1-3 every 21 days. Dosing based on body surface area; reduce in low weight patients. |
| Geriatric use | Use standard dosing with close monitoring for myelosuppression and cardiotoxicity. Consider starting at lower end of dose range (60 mg/m2) in frail elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.
| Breastfeeding | Epirubicin is excreted in human breast milk; M/P ratio not specified. Potential for serious adverse reactions in nursing infants (immunosuppression, neutropenia, cardiotoxicity). Breastfeeding is contraindicated during treatment and for at least 1 month after last dose. |
| Teratogenic Risk | Epirubicin is embryotoxic and teratogenic in animal studies. Human data are limited. It is contraindicated in pregnancy, particularly during the first trimester due to high risk of fetal malformations (similar to other anthracyclines). Second and third trimester exposure may increase risk of fetal growth restriction, preterm birth, and neonatal myelosuppression. Avoid use in pregnancy unless no safer alternative. |
■ FDA Black Box Warning
Cardiotoxicity including cardiomyopathy and congestive heart failure, especially at cumulative doses >900 mg/m²; secondary acute myeloid leukemia or myelodysplastic syndrome; extravasation leading to tissue necrosis; myelosuppression; hepatic impairment requiring dose reduction; reduced left ventricular ejection fraction.
| Common Effects | other cancers |
| Serious Effects |
Hypersensitivity to epirubicin or any component, severe hepatic impairment (Child-Pugh C), severe myocardial insufficiency (NYHA class III/IV), recent myocardial infarction, uncontrolled arrhythmias, severe renal impairment (CrCl <30 mL/min), and baseline neutrophil count <1500 cells/mm³.
| Precautions | Cardiotoxicity (monitor LVEF), myelosuppression (monitor blood counts), extravasation (administer via IV only), secondary malignancies (especially AML/MDS), hepatic impairment (dose adjustment), renal impairment, severe mucositis, and thrombosis. |
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| Fetal Monitoring | Monitor maternal CBC with differential, liver function tests, renal function, ECG, and echocardiogram (left ventricular ejection fraction). During pregnancy, monitor fetal growth and amniotic fluid volume via ultrasound. Assess for signs of fetal distress. Monitor neonate for myelosuppression and infection. |
| Fertility Effects | Epirubicin is gonadotoxic. May cause amenorrhea, premature ovarian failure in females, and oligospermia or azoospermia in males. Fertility preservation strategies should be considered prior to treatment. |