Usage
Epirubicin is prescribed for the treatment of various cancers, including:
- Breast cancer (adjuvant therapy after surgery for patients with axillary node involvement)
- Gastric cancer
- Ovarian cancer
- Small cell lung cancer
- Non-Hodgkin’s lymphoma
- Advanced/metastatic soft tissue sarcoma
- Superficial bladder cancer (including prophylaxis of recurrence after transurethral resection)
Pharmacological Classification: Antineoplastic agent, Anthracycline, Topoisomerase II inhibitor
Mechanism of Action: Epirubicin intercalates into DNA, inhibiting topoisomerase II and preventing DNA replication and repair, ultimately leading to cell death. It also generates free radicals, further contributing to its cytotoxic effect.
Alternate Names
- International Nonproprietary Name (INN): Epirubicin
- Brand Names: Pharmorubicin, Ellence
How It Works
Pharmacodynamics: Epirubicin exerts its antineoplastic effect by multiple mechanisms, including DNA intercalation, topoisomerase II inhibition and free radical generation, leading to cell cycle arrest and apoptosis (programmed cell death).
Pharmacokinetics:
- Absorption: Administered intravenously or intravesically; not given orally due to poor absorption.
- Metabolism: Metabolized in the liver to epirubicinol (active metabolite) and other inactive metabolites.
- Elimination: Primarily eliminated via biliary excretion (in feces); some renal excretion. Elimination is impaired in patients with hepatic dysfunction.
Mode of Action: Epirubicin intercalates between DNA base pairs, disrupting DNA synthesis and function. It inhibits the enzyme topoisomerase II, preventing the re-ligation of DNA strands, leading to DNA damage and cell death. Additionally, epirubicin generates free radicals, which cause oxidative stress and further damage cancer cells.
Elimination Pathways: Hepatobiliary excretion is the primary route, with a smaller fraction excreted renally.
Dosage
Standard Dosage
Adults:
- Adjuvant therapy for breast cancer: 100-120 mg/m² IV, administered every 3-4 weeks, either as a single dose on Day 1 or divided equally on Days 1 and 8. Dosage may be reduced when used in combination with other chemotherapeutic agents.
Children:
Safety and efficacy in pediatric patients have not been established. Children are potentially at greater risk for cardiotoxicity.
Special Cases:
- Elderly Patients: Caution advised; lower starting doses may be considered, particularly in women over 70 due to decreased clearance.
- Patients with Renal Impairment: Dose adjustment may be necessary in patients with severe renal impairment (serum creatinine > 5 mg/dL).
- Patients with Hepatic Dysfunction: Dose reduction necessary; contraindicated in severe hepatic impairment (Child-Pugh Class C or serum bilirubin > 5 mg/dL). Dosage should be based on serum bilirubin and AST/ALT levels.
- Patients with Comorbid Conditions: Pre-existing cardiac disease increases the risk of cardiotoxicity. Patients with mediastinal radiotherapy are also at increased risk.
Clinical Use Cases
Epirubicin’s dosage in specific clinical settings, such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations, is generally adjusted based on the underlying cancer being treated, and considerations mentioned above (standard adult dose, special cases, and combination therapies). Therefore, there is no separate dosage regimen specifically for these clinical settings.
Dosage Adjustments
Dose adjustments are made based on hematologic toxicity (neutropenia, thrombocytopenia), non-hematologic toxicity, hepatic and renal function, and concomitant medications.
Side Effects
Common Side Effects
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Nausea and vomiting
- Stomatitis/mucositis
- Alopecia
- Fatigue
- Red-colored urine (transient)
- Gastrointestinal disturbances (diarrhea, abdominal pain)
Rare but Serious Side Effects
- Cardiotoxicity (congestive heart failure, arrhythmias)
- Secondary malignancies (e.g., acute myeloid leukemia)
- Severe hypersensitivity reactions
- Extravasation injury (tissue necrosis)
Long-Term Effects
- Cardiomyopathy
- Increased risk of secondary malignancies
Adverse Drug Reactions (ADR)
- Anaphylaxis
- Severe myelosuppression
- Cardiotoxicity
- Extravasation with severe tissue damage
Contraindications
- Hypersensitivity to epirubicin, other anthracyclines, or anthracenediones
- Severe myelosuppression
- Severe hepatic impairment
- Severe myocardial insufficiency
- Recent myocardial infarction
- Severe arrhythmias
- Prior treatment with maximum cumulative doses of anthracyclines or anthracenediones
- Pregnancy and breastfeeding
Drug Interactions
- CYP450 Interactions: Epirubicin is metabolized by CYP450 enzymes, so inhibitors (e.g., cimetidine) can increase epirubicin levels and toxicity. Inducers can decrease efficacy.
- Other Drug Interactions: Trastuzumab, other anthracyclines (doxorubicin), and cardiotoxic drugs can increase the risk of cardiotoxicity.
- Other Interactions: Vaccinations (live attenuated) are contraindicated due to risk of infection in immunocompromised patients.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated in pregnancy (may cause fetal harm).
- Breastfeeding: Contraindicated during breastfeeding.
Drug Profile Summary
- Mechanism of Action: DNA intercalation, topoisomerase II inhibition, free radical generation.
- Side Effects: Myelosuppression, nausea/vomiting, stomatitis, alopecia, cardiotoxicity.
- Contraindications: Severe myelosuppression, hepatic impairment, cardiac dysfunction, prior anthracycline use, pregnancy, breastfeeding.
- Drug Interactions: CYP450 inhibitors/inducers, trastuzumab, other cardiotoxic drugs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 100-120 mg/m² IV every 3-4 weeks for breast cancer (adjuvant). Dose adjustments based on toxicity, organ function, and concomitant medications.
- Monitoring Parameters: Complete blood count (CBC), liver function tests (LFTs), renal function tests, cardiac function (ECG, LVEF).
Popular Combinations
Epirubicin is often used in combination regimens, particularly for breast cancer. Common combinations include:
- FEC (5-fluorouracil, epirubicin, cyclophosphamide)
- CEF (cyclophosphamide, epirubicin, 5-fluorouracil)
Precautions
- General Precautions: Monitor for myelosuppression, cardiotoxicity, and extravasation. Pre-screen for cardiac, hepatic, and renal function.
- Specific Populations: Contraindicated in pregnancy and breastfeeding. Caution in elderly patients and those with renal or hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Epirubicin?
A: For adjuvant treatment of breast cancer, the recommended starting dose is 100-120 mg/m² IV every 3-4 weeks.
Q2: What are the common side effects of Epirubicin?
A: Common side effects include myelosuppression (low blood counts), nausea/vomiting, mucositis (mouth sores), alopecia (hair loss), fatigue, and red-tinged urine.
Q3: What are the serious side effects of Epirubicin?
A: Serious side effects can include cardiotoxicity (heart damage), secondary cancers (like leukemia), and severe allergic reactions. Extravasation (drug leaking out of the vein) can cause severe tissue damage.
Q4: How is Epirubicin administered?
A: Epirubicin is administered intravenously (IV) through a vein. It is given as a slow push injection or infusion. For bladder cancer it can also be administered intravesically (into the bladder).
Q5: Can Epirubicin be given during pregnancy or breastfeeding?
A: No, Epirubicin is contraindicated during pregnancy and breastfeeding as it can cause harm to the fetus or infant.
Q6: What are the key drug interactions with Epirubicin?
A: Epirubicin interacts with drugs that can affect heart function (like trastuzumab or other anthracyclines), as well as drugs that affect liver enzymes (like cimetidine). These interactions can increase the risk of side effects or reduce the effectiveness of the drug.
Q7: How is Epirubicin cleared from the body?
A: Epirubicin is primarily cleared by the liver and excreted in the bile and feces. A smaller amount is cleared by the kidneys and excreted in urine.
Q8: What monitoring is required during treatment with Epirubicin?
A: Close monitoring of blood counts (CBC), liver function tests (LFTs), and heart function (ECG, echocardiogram or MUGA scan) is required during treatment with Epirubicin.
Q9: What is the maximum lifetime cumulative dose of Epirubicin?
A: The recommended lifetime cumulative dose of Epirubicin is generally 900-1000 mg/m², but this may be lower in patients with pre-existing cardiac risk factors.
