Intercalates into DNA, which results in inhibition of DNA synthesis and function.
Inhibits topoisomerase II by forming a cleavable complex with topoisomerase II and DNA.
Formation of cytotoxic oxygen free radicals, which can cause single- and double-stranded DNA breaks.
Increased expression of the multidrug-resistant gene with enhanced drug efflux. This results in decreased intracellular drug accumulation.
Decreased expression of topoisomerase II.
Mutation in topoisomerase II, with decreased binding affinity to drug.
Increased expression of glutathione and glutathione-associated enzymes.
Rapid and extensive distribution to formed blood elements and to body tissues. Does not cross the blood-brain barrier. Extensively bound (about 80%) to plasma proteins. Peak plasma levels are achieved immediately.
Recommended dose is 100-120 mg/m2 IV every 3 weeks.
In heavily pretreated patients, consider starting at lower dose of 75-90 mg/m2 IV every 3 weeks.
Alternative schedule is 12-25 mg/m2 IV on a weekly basis.
Heparin—Epirubicin is incompatible with heparin as a precipitate will form.
5-FU, cyclophosphamide—Increased risk of myelosuppression when epirubicin is used in combination with 5-FU and cyclophosphamide.
Cimetidine—Cimetidine decreases the AUC of epirubicin by 50% and should be discontinued upon initiation of epirubicin therapy.
Use with caution in patients with abnormal liver function. Dose modification should be considered in patients with liver dysfunction.
Use with caution in patients with severe renal impairment. Dose should be reduced by at least 50% when serum creatinine >5 mg/dL.
Use with caution in elderly patients, as they are at increased risk for developing toxicity.
Careful monitoring of drug administration is necessary to avoid extravasation. If extravasation is suspected, stop infusion immediately, withdraw fluid, elevate arm, and apply ice to site. In severe cases, consult plastic surgeon.
Monitor cardiac function before (baseline) and periodically during therapy with either MUGA radionuclide scan or echocardiogram to assess LVEF. Risk of cardiac toxicity is higher in elderly patients >70 years of age, in patients with prior history of hypertension or pre-existing heart disease, in patients previously treated with anthracyclines, or in patients with prior radiation therapy to the chest. In patients with no prior history of anthracycline therapy, cumulative doses of 900 mg/m2 are associated with increased risk for cardiac toxicity.
Continuous infusion and weekly schedules are associated with decreased risk of cardiac toxicity. Dexrazoxane may be helpful in preventing epirubicin-mediated cardiac toxicity.
Monitor weekly CBC while on therapy.
Use with caution in patients previously treated with radiation therapy, as epirubicin may induce a radiation-recall reaction.
Patients may experience red-orange discoloration of urine for 24 hours after drug administration.
Pregnancy category D. Breastfeeding should be avoided.
Myelosuppression is dose-limiting toxicity with neutropenia more common than thrombocytopenia. Nadir typically occurs 8-14 days after treatment, with recovery of blood counts by day 21. Risk of myelosuppression greater in elderly patients and in those previously treated with chemotherapy and/or radiation therapy.
Mild nausea and vomiting. Occur less frequently than with doxorubicin.
Mucositis and diarrhea. Dose-dependent, common, and generally mild.
Cardiac toxicity. Cardiac effects are similar to but less severe than those of doxorubicin. Acute toxicity presents as rhythm or conduction disturbances, chest pain, and myopericarditis syndrome that typically occurs within the first 24-48 hours of drug administration. Transient and mostly asymptomatic, not dose-related.
Chronic form of cardiac toxicity presents as a dilated cardiomyopathy with congestive heart failure. Risk of congestive heart failure increases significantly with cumulative doses >900 mg/m2.
Alopecia occurs within 10 days of initiation of therapy and regrowth of hair upon termination of treatment. Less commonly observed than with doxorubicin and occurs in only 25%-50% of patients.
Potent vesicant. Extravasation can lead to tissue injury, inflammation, and chemical thrombophlebitis at the site of injection.
Skin rash, flushing, hyperpigmentation of skin and nails, and photosensitivity. Radiation-recall skin reaction can occur at previous sites of irradiation.
Red-orange discoloration of urine for 24 hours after drug administration.
