Epirubicin Hydrochloride Injection is indicated as part of adjuvant chemotherapy for patients with breast cancer who have evidence of axillary lymph node involvement after surgical removal of the primary tumor. It is used to help reduce the risk of cancer recurrence following surgery.

Epirubicin Hydrochloride is an anthracycline anticancer agent with cytotoxic activity. It interferes with DNA and RNA synthesis by inserting itself between DNA base pairs, a process known as intercalation. This action disrupts the structure of DNA and leads to DNA damage through the activation of topoisomerase II, resulting in DNA strand breaks. Epirubicin also inhibits DNA helicase activity and promotes the formation of cytotoxic free radicals, which further damage cancer cells and contribute to its anticancer effects.

Distribution: After intravenous administration, Epirubicin is rapidly and widely distributed throughout body tissues. Approximately 77% of the drug binds to plasma proteins, mainly albumin, and this binding is not significantly influenced by drug concentration.

Metabolism: Epirubicin is rapidly and extensively metabolized in the liver, and additional metabolism may occur in other tissues and cells, including red blood cells.

Excretion: Epirubicin and its metabolites are primarily eliminated through bile, while a smaller amount is excreted in urine. The terminal elimination half-life ranges from about 30 to 40 hours.

When possible, to reduce the risk of developing cardiotoxicity in patients receiving Epirubicin after stopping treatment with other cardiotoxic agents, especially those with long half-lives such as Trastuzumab, Epirubicin-based therapy should be delayed until the other agents have cleared from the circulation. Epirubicin Injection should be administered by intravenous infusion. Epirubicin is given in repeated 3-to 4-week cycles. The total dose of Epirubicin may be given on day 1 of each cycle or divided equally and given on days 1 and 8 of each cycle.

The recommended dose of Epirubicin is 100 to 120 mg/m². The following regimens are recommended:

CEF-120:

• Cyclophosphamide: 75 mg/m² PO D 1-14
• Epirubicin: 60 mg/m² IV D 1, 8
• 5-Fluorouracil: 500 mg/m² IV D 1, 8
• Repeated every 28 days for 6 cycles

FEC-100:

• 5-Fluorouracil: 500 mg/m²
• Epirubicin: 100 mg/m²
• Cyclophosphamide: 500 mg/m²

All drugs were administered intravenously on day 1 and repeated every 21 days for 6 cycles. Patients administered the 120-mg/m² regimen of Epirubicin should receive prophylactic antibiotic therapy. Or, as directed by the registered physician.

Cardioactive Drugs: Using Epirubicin Hydrochloride together with other medications that affect the heart, such as calcium channel blockers, may increase the risk of heart failure. Patients receiving this combination should have their cardiac function closely monitored throughout treatment.

Cimetidine: The use of cimetidine may increase the blood concentration of epirubicin. Therefore, cimetidine should be discontinued during Epirubicin therapy.

Other Cytotoxic Medicines: When Epirubicin is combined with other anticancer drugs, the toxic effects may become additive, particularly bone marrow suppression and gastrointestinal side effects.

Paclitaxel: Administration of Epirubicin immediately before or after paclitaxel may increase systemic exposure to epirubicin and its metabolites.

Docetaxel: Using Epirubicin before or after docetaxel does not significantly affect epirubicin levels, but it may increase the levels of some epirubicin metabolites.

Radiation Therapy: If Epirubicin is given after radiation therapy, it may cause a radiation recall reaction, leading to inflammation at the previously irradiated site.

Liver Function: Since Epirubicin is mainly metabolized by the liver, any therapy that alters liver function may affect the drug’s metabolism, effectiveness, or toxicity.

Epirubicin Hydrochloride should not be used in patients who have hypersensitivity to epirubicin, other anthracycline drugs, anthracenediones, or any component of the formulation.

The most commonly reported adverse effects include myelosuppression, cardiotoxicity, alopecia, hyperpyrexia, lethargy, amenorrhea, nausea, vomiting, diarrhea, fever, rash, anorexia, and a harmless reddish discoloration of urine lasting for 1–2 days.

Pregnancy Category D. There are no adequate and well-controlled studies of Epirubicin in pregnant women. The drug should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. It is not known whether Epirubicin passes into human breast milk. Because of the possibility of serious adverse reactions in nursing infants, a decision should be made either to discontinue breastfeeding or to stop the medication, depending on the importance of treatment to the mother.

Storing the injectable solution under refrigerated conditions may lead to the formation of a gel. This gelled preparation will revert to a slightly viscous, free-flowing solution after being kept at controlled room temperature (15°–25°C) for approximately 2 to 4 hours. Parenteral products should be visually inspected for particulate matter and discoloration before administration, whenever possible. Appropriate procedures for the safe handling and disposal of anticancer agents must be followed when preparing and administering Epirubicin.

Epirubicin Injection should only be administered under the supervision of physicians experienced in cytotoxic chemotherapy. Before initiating therapy, patients should recover from acute toxicities (such as stomatitis, neutropenia, thrombocytopenia, and generalized infections) caused by prior cytotoxic treatment. Initial therapy should also be preceded by a thorough baseline evaluation, including blood counts, serum bilirubin, AST, creatinine levels, and cardiac function assessed by left ventricular ejection fraction (LVEF). Patients should be closely monitored during treatment for complications related to myelosuppression. Supportive care may be required in cases of severe neutropenia or serious infections. Monitoring for cardiotoxicity is essential, particularly with increasing cumulative doses of Epirubicin.

Epirubicin dose modifications for hematologic and non-hematologic toxicities within a treatment cycle are determined based on nadir platelet counts <50,000/mm³, absolute neutrophil counts (ANC) <250/mm³, occurrence of neutropenic fever, or Grade 3/4 non-hematologic toxicities. In subsequent cycles, the Day 1 dose of Epirubicin should be reduced to 75% of the dose administered in the current cycle. Chemotherapy on Day 1 should be delayed in future cycles until platelet counts reach ≥100,000/mm³, ANC ≥1500/mm³, and non-hematologic toxicities have improved to ≤Grade 1.

Bone Marrow Dysfunction: A reduced starting dose (75–90 mg/m²) should be considered in heavily pretreated patients, those with existing bone marrow suppression, or in cases of neoplastic bone marrow infiltration. For patients receiving divided dosing of Epirubicin (Day 1 and Day 8), the Day 8 dose should be 75% of the Day 1 dose if platelet counts are 75,000–100,000/mm³ and ANC is 1000–1499/mm³. If Day 8 platelet counts are <75,000/mm³, ANC <1000/mm³, or if Grade 3/4 non-hematologic toxicity occurs, the Day 8 dose should be omitted.

Hepatic Impairment: Specific recommendations for Epirubicin use in patients with hepatic impairment are limited, as such patients were not included in adjuvant trials. In patients with elevated serum AST or total bilirubin levels, the following dose adjustments are advised:
Bilirubin 1.2 to 3 mg/dL or AST 2 to 4 times the upper limit of normal: administer ½ of the recommended starting dose.
Bilirubin >3 mg/dL or AST >4 times the upper limit of normal: administer ¼ of the recommended starting dose.

Renal Impairment: Due to limited data, no definitive dosing recommendations can be provided for patients with renal impairment; however, dose reduction should be considered in patients with severe renal dysfunction (serum creatinine >5 mg/dL).

Pediatric Use: The safety and efficacy of Epirubicin in pediatric patients have not been established. Pediatric patients may have a higher risk of anthracycline-induced acute cardiotoxicity and chronic congestive heart failure (CHF). The pharmacokinetics of Epirubicin in pediatric patients have not been studied.

Geriatric Use: Although lower initial doses were not used in clinical trials involving elderly female patients, careful monitoring for toxicity is recommended when administering Epirubicin to patients aged ≥70 years.

Cytotoxic Chemotherapy

Store Epirubicin Hydrochloride Injection in a refrigerator at 2°C–8°C. Do not freeze. Protect from light and keep out of the reach of children.