Epirubin

Approved Indications:

• Breast Cancer:
• Early-stage, locally advanced, or metastatic breast cancer as monotherapy or in combination regimens.
• Gastric Cancer:
• Advanced or metastatic gastric adenocarcinoma, usually in combination chemotherapy protocols.
• Ovarian Cancer:
• Advanced ovarian carcinoma, often in combination with platinum-based therapy.
• Bladder Cancer:
• Intravesical therapy for superficial transitional cell carcinoma to reduce recurrence risk.

Off-Label / Clinically Accepted Uses:

• Soft Tissue Sarcomas: In selected cases as part of combination chemotherapy.
• Lung Cancer: Small-cell or non-small-cell lung carcinoma in combination therapy.
• Other Solid Tumors: As part of investigational or combination protocols, per oncologist discretion.

Adults – Intravenous Administration:

• Breast Cancer: 60–120 mg/m² IV every 21 days (single-agent); dose may vary with combination regimens.
• Gastric Cancer: 50–60 mg/m² IV every 21 days in combination therapy.
• Ovarian Cancer: 50–75 mg/m² IV every 21 days in combination regimens.
• Bladder Cancer (Intravesical): 50 mg weekly for 6–8 weeks; retention time 1–2 hours.

Pediatric Use: Safety and efficacy not well established; use only in specialized centers.

Elderly: Dose adjustment may be required based on cardiac function and renal/hepatic status.

Renal/Hepatic Impairment:

• Hepatic impairment: Dose reduction recommended for elevated bilirubin or transaminases.
• Renal impairment: Usually tolerated, monitor closely; adjust combination therapy doses as needed.

Administration Notes:

• Administer via slow IV push or infusion.
• Use central venous access for high-dose therapy to minimize extravasation risk.
• Avoid intrathecal administration; fatal neurotoxicity may occur.

Epirubicin is an anthracycline antibiotic that exerts its anticancer effects primarily through DNA intercalation and inhibition of topoisomerase II. By intercalating between DNA base pairs, epirubicin prevents DNA replication and transcription, resulting in cell cycle arrest and apoptosis. Additionally, it generates reactive oxygen species (ROS), contributing to oxidative damage of cellular components. Its dual action—DNA intercalation and topoisomerase II inhibition—targets rapidly dividing malignant cells, producing cytotoxic effects in solid tumors and hematologic malignancies.

• Absorption: Administered intravenously; complete bioavailability.
• Distribution: Widely distributed; binds extensively to plasma proteins; large volume of distribution (~21–35 L/m²).
• Metabolism: Hepatic metabolism via reduction, hydrolysis, and conjugation; active metabolite is epirubicinol.
• Elimination: Primarily biliary excretion; 11%–15% renal excretion.
• Half-Life: Biphasic elimination; initial 4–10 hours, terminal 30–40 hours.
• Onset of Action: Cytotoxic effects occur rapidly after cellular uptake.

• Pregnancy: FDA Category D – Positive evidence of fetal risk; use only if potential benefit outweighs risks.
• Lactation: Excreted in breast milk; breastfeeding contraindicated during therapy.
• Caution: Avoid conception during treatment; contraception recommended for both sexes.

• Primary Class: Antineoplastic Agent
• Subclass: Anthracycline; Cytotoxic Antibiotic

• Known hypersensitivity to epirubicin or other anthracyclines.
• Severe myocardial insufficiency or recent myocardial infarction.
• Baseline severe leukopenia, thrombocytopenia, or neutropenia.
• Active, severe infections.
• Pregnancy (unless benefit outweighs risk).

• Cardiotoxicity: Risk of congestive heart failure, especially with cumulative doses >900 mg/m². Monitor LVEF via echocardiography or MUGA scan.
• Myelosuppression: Dose-dependent neutropenia, anemia, thrombocytopenia; monitor CBC frequently.
• Hepatic Impairment: Increased toxicity; dose adjustment required.
• Extravasation Risk: Can cause severe tissue necrosis; use central line if possible.
• Secondary Malignancy: Rare therapy-related leukemia reported.
• Radiation Recall: May induce inflammation at previously irradiated sites.

Hematologic:

• Neutropenia, leukopenia, anemia, thrombocytopenia

Gastrointestinal:

• Nausea, vomiting, mucositis, diarrhea, anorexia

Cardiac:

• Dose-dependent cardiomyopathy, arrhythmias

Dermatologic:

• Alopecia, skin hyperpigmentation at injection site, rash

Other:

• Fatigue, fever, hepatotoxicity, transient red urine

Serious / Rare:

• Severe myelosuppression, cardiac failure, anaphylaxis, secondary leukemia

Timing / Dose Dependence:

• Myelosuppression typically occurs 7–14 days post-infusion; nadir monitored accordingly.
• Cardiotoxicity cumulative-dose dependent.

• Other Myelosuppressive Agents: Additive risk of neutropenia or thrombocytopenia.
• Cardiotoxic Drugs (e.g., trastuzumab, anthracyclines): Increased risk of heart failure.
• CYP3A4 and CYP2D6 Substrates: Minor interactions; monitor liver function.
• Radiation Therapy: May exacerbate local tissue reactions (radiation recall).
• Live Vaccines: Avoid during therapy due to immunosuppression.

• Approved Regimens: Confirmed as first-line in breast cancer combination therapy (with cyclophosphamide or 5-FU).
• Cardiotoxicity Monitoring: Latest guidelines emphasize baseline and periodic LVEF monitoring.
• Hepatic Dose Adjustment: Reinforced guidance for dose reduction with elevated bilirubin.
• Combination Therapy: Optimized sequencing with platinum-based chemotherapy in gastric and ovarian cancer.

• Temperature: 2°C–8°C (refrigerated)
• Light & Humidity: Protect from light; store in original container.
• Handling: Avoid direct contact; use gloves when handling; preparation in a biological safety cabinet recommended.
• Reconstitution: Dilute in 0.9% NaCl or 5% dextrose prior to infusion; use immediately or within 24 hours if refrigerated.
• Do Not Freeze