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. |
| Molecular Weight | 543.52 |
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 | Avoid. Teratogenic risk; anthracyclines cause fetal malformations and spontaneous abortion. |
| 2nd trimester | Avoid. Risk of fetal cardiotoxicity and growth restriction. |
| 3rd trimester | Avoid. Risk of neonatal cardiotoxicity, myelosuppression, and premature labor. |
Clinical note
Other cardiotoxic drugs (eg trastuzumab) increase risk Can cause severe and irreversible cardiotoxicity and myelosuppression.
| Placental transfer | Crosses placenta; documented in human studies. |
| Breastfeeding | Contraindicated during breastfeeding. Excreted into human milk; may cause adverse effects in nursing infants, including cardiotoxicity and immunosuppression. |
| Lactation Rating |
■ 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 other anthracyclinesSevere hepatic impairmentSevere myocardial insufficiencyRecent myocardial infarctionSevere arrhythmiasPersistent myelosuppressionPrevious treatment with maximum cumulative doses of anthracyclines
| 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. |
| Food/Dietary |
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| L5 |
| 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. |
| 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. |
| Avoid grapefruit and grapefruit juice during treatment as they may affect drug metabolism. Maintain adequate hydration but avoid excessive intake of vitamin C-rich foods as they may increase risk of kidney stones. No other specific food restrictions; however, patients should avoid alcohol due to potential hepatotoxicity. |
| Clinical Pearls | Monitor left ventricular ejection fraction (LVEF) at baseline and periodically due to cumulative dose-related cardiotoxicity; lifetime cumulative dose should not exceed 900 mg/m². Avoid extravasation – administer through a secure IV line; if extravasation occurs, apply cold compresses and consider dexrazoxane. Pre-medicate for nausea and vomiting. Use with caution in hepatic impairment; dose reduce for bilirubin >1.2 mg/dL or AST >3x ULN. Urine may appear red for 1-2 days after administration. |
| Patient Advice | Urine may turn reddish for 1-2 days; this is harmless. · Report any signs of infection (fever, sore throat) or bleeding (easy bruising, nosebleeds). · Notify doctor if you experience shortness of breath, swelling, or rapid heartbeat. · Nausea and vomiting are common; take antiemetics as prescribed. · Avoid pregnancy during treatment; use effective contraception. · Limit sun exposure and use sunscreen; may cause photosensitivity. · Do not receive live vaccines during therapy. |