Epirubicin hydrochloride

UK SPC (Epirubicin hydrochloride 2 mg/ml solution for injection, https://www.medicines.org.uk/emc/product/6361/smpc). If signs of toxicity including severe neutropenia/neutropenic fever and thrombocytopenia occur (which could persist at day 21), dose modification or postponement of the subsequent dose may be required. HIGH DOSE SINGLE AGENT (lung cancer): previously untreated small cell lung cancer - 120 mg/m2 on day 1, every 3 weeks; for high-dose treatment epirubicin may be given as an IV bolus over 3-5 minutes or as an infusion of up to 30 minutes duration. BREAST CANCER: in adjuvant treatment of early breast cancer with positive lymph nodes, IV doses ranging from 100 mg/m2 (as a single dose on day 1) to 120 mg/m2 (in two divided doses on days 1 and 8) every 3-4 weeks, in combination with IV cyclophosphamide and 5-fluorouracil plus oral tamoxifen. LOWER DOSES (60-75 mg/m2 conventional; 105-120 mg/m2 high dose) are recommended for patients whose bone marrow function has been impaired by previous chemotherapy or radiotherapy, by age, or by neoplastic bone marrow infiltration; the total dose per cycle may be divided over 2-3 successive days. OTHER TUMOURS (mg/m2, monotherapy / combination therapy): advanced ovarian cancer 60-90 / 50-100; gastric cancer 60-90 / 50; small cell lung cancer 120 / 120. If used in combination with other cytotoxic products the dose should be reduced accordingly. INTRAVESICAL USE (superficial bladder cancer and carcinoma-in-situ; must NOT be given intravesically for invasive tumours that have penetrated the bladder wall): superficial bladder cancer - 8 weekly instillations of 50 mg/50 ml, diluted with 0.9% sodium chloride or water for injection, reduced to 30 mg/50 ml if local toxicity is observed; carcinoma-in-situ - up to 80 mg/50 ml depending on individual tolerability; prophylaxis after transurethral resection - 4 weekly administrations of 50 mg/50 ml followed by 11 monthly instillations at the same dose. Dilution for instillation: 30 mg = 15 ml of the 2 mg/ml injection + 35 ml diluent; 50 mg = 25 ml + 25 ml; 80 mg = 40 ml + 10 ml (total volume 50 ml in each case). The solution should be retained intravesically for 1-2 hours, the patient should not drink any fluids in the 12 hours before instillation, should be rotated occasionally during the instillation, and should void urine at the end of the instillation time. ADMINISTRATION CARE: check the needle is properly placed in the vein and take care to avoid extravasation - if extravasation occurs, stop administration immediately (paravenous injection can cause soft tissue necrosis). HEPATIC IMPAIRMENT (the hepatobiliary system is the major route of elimination): reduce the dose by 50% if serum bilirubin is 1.4-3 mg/100 ml; reduce by 75% if serum bilirubin is >3 mg/100 ml or SGOT is >4 times the upper normal limit. PAEDIATRIC: the safety and efficacy of epirubicin in children have not yet been established (UK SPC); US labelling adds that paediatric patients may be at greater risk for anthracycline-induced acute cardiotoxicity or late cardiovascular dysfunction and that paediatric pharmacokinetics have not been evaluated. Any under-18 use must be verified against a children's formulary and specialist paediatric oncology protocol.