Pocket Drug Guide

Drug Nomenclature

Pharmacopoeias. In Europe and Japan.

European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Epirubicin Hydrochloride). A substance obtained by chemical transformation of a substance produced by certain strains of Streptomyces peucetius. An orange-red powder. Soluble in water and in methyl alcohol; slightly soluble in dehydrated alcohol; practically insoluble in acetone. A 0.5% solution in water has a pH of 4.0 to 5.5. Store at 2° to 8° in airtight containers. Protect from light.

Incompatibility. Licensed product information states that epirubicin hydrochloride is incompatible with heparin or fluorouracil, resulting in precipitation, and that it is hydrolysed in alkaline solutions.

Stability. Epirubicin was not subject to significant photodegra-dation at clinical concentrations, and special precautions to protect solutions from light during use do not appear to be necessary. However, photodegradation may be significant at lower concentrations (below 500 micrograms/mL).

Adverse Effects, Treatment, and Precautions

As for Doxorubicin. Cardiotoxicity and myelotoxicity may be less than with doxorubicin. Cardiotoxicity is more likely when the cumulative dose exceeds 0.9 to 1 g/m.

Effects on the heart. For further discussion of the cardiotoxicity of anthracyc lines, see under Adverse Effects of Doxorubicin.

Interactions

As for Doxorubicin.

Antineoplastics. Increased exposure to epirubicin, and a consequent increase in myelotoxicity, has been reported in patients given epirubicin immediately after paclitaxel, compared with patients who received epirubicin before paclitaxel. Similar interactions have been seen when paclitaxel was given before other anthracyclines. These and other studies have suggested that paclitaxel given in this way is associated with a reduced conversion of epirubicin to the less myelotoxic metabolite, epirubicinol, although the interaction is complex, and may involve both disposition and pharmacodynamics.

Cimetidine. Cimetidine increased the formation of the active metabolite of epirubicin in a study in 8 patients; there was also a substantial increase in systemic exposure to unchanged epirubicin. The mechanisms and potential clinical significance of the interaction were unclear.

Pharmacokinetics

After intravenous doses epirubicin is rapidly and extensively distributed into body tissues, and undergoes metabolism in the liver, with the formation of epirubicinol (13-hydroxyepirubicin) and appreciable amounts of glucuronide derivatives. Epirubicin is eliminated mainly in bile, with a terminal plasma elimination half-life of about 30 to 40 hours. About 10% of a dose is recovered in urine within 48 hours. Epirubicin does not cross the blood-brain barrier.

Uses and Administration

Epirubicin is an anthracycline antibiotic with antineoplastic actions similar to those of doxorubicin. It is used, alone or with other antineoplastics, in acute leukaemias, lymphomas, multiple myeloma, and in solid tumours including Wilms’ tumour, cancer of the bladder, breast, and stomach.

Epirubicin hydrochloride is given by intravenous injection of a solution in sodium chloride 0.9% or Water for Injections into a fast-running infusion of sodium chloride 0.9% or glucose 5% over 3 to 5 minutes, or by infusion over up to 30 minutes. It is given as a single agent in usual doses of 60 to 90 mg/m as a single dose every 3 weeks; this dose may be divided over 2 or 3 days if desired. A regimen of 12.5 to 25 mg/m once a week has also been tried in palliative care. High-dose regimens, of 120 mg/m or more every 3 weeks, or 45 mg/m for 3 consecutive days every 3 weeks have been used.

Doses may need to be reduced if epirubicin is given with other antineoplastics. Doses should also be reduced in patients with liver impairment (see below) and in those whose bone-marrow function is impaired by age or previous chemotherapy or radiotherapy.

A total cumulative dose of 0.9 to 1 g/m should not generally be exceeded, because of the risk of cardiotoxicity.

Epirubicin has also been given by intravesical instillation in the local treatment of bladder cancer. Instillation of 50 mg weekly as a 0.1% solution (in sodium chloride 0.9% or sterile water) for 8 weeks has been suggested, reduced to 30 mg in 50 mL weekly if chemical cystitis develops; for carcinoma in-situ, the dose may be increased, if tolerated, to 80 mg in 50 mL weekly. For the prophylaxis of recurrence in patients who have undergone transurethral resection, 50 mg weekly for 4 weeks, followed by 50 mg instilled once a month for 11 months is the suggested regimen. The solution should be retained in the bladder for 1 hour.

Blood counts should be made routinely during treatment with epirubicin (see also Bone-marrow Depression) and cardiac function should be carefully monitored. Liver function should be assessed before and if possible during therapy.

Administration in hepatic impairment. Doses of epirubicin should be halved in patients with moderate liver dysfunction (serum bilirubin concentrations of 12 to 30 micrograms/mL), while those with severe liver impairment (serum bilirubin greater than 30 micrograms/mL) should be given a quarter of the usual dose.

Amyloidosis. For reference to a regimen including epirubicin used to control disease in a patient with amyloidosis.

Proprietary Preparations

Argentina: Crisabon; Cuatroepi; Epidoxo; Epifil; Epikebir; EPR † Farmorubicin; Robanul; Rubifarm+;

Australia: Pharmorubicin;

Austria; Epi-Cell; Farmorubicin;

Belgium: Farmorubicine;

Brazil: Farmorubicina; Nuovodox; Rubina; Tecnomax;

Canada: Pharmorubicin;

Chile: Farmorrubicina;

Czech Republic: Farmorubicin;

Denmark: Farmorubicin;

Finland: Farmorubicin;

France: Farmorubicine;

Germany; Epi-Cell; Epi-NC; Farmorubicin; Riboepi;

Greece: Ciazil; Epirub; Farmorubicin; Megarubicin;

Hong Kong; Pharmorubicin;

Hungary: Farmorubicin;

Ireland: Pharmorubicin;

Israel: Farmorubicin;

Italy: Farmorubicina;

Japan: Farmorubicin;

Malaysia: Pharmorubicin;

Mexico: Binarin; Epilem; Farmorubicin;

The Netherlands: Farmorubicine;

Norway: Farmorubicin;

New Zealand: Pharmorubicin;

Philippines: Pharmorubicin;

Poland: Bioepicyna; Farmorubicin;

Portugal: Epicell; Farmorubicina;

Russia: Epilem; Farmorubicin;

South Africa: Farmorubicin;

Singapore: Pharmorubicin;

Spain: Farmorubicina;

Sweden: Farmorubicin;

Switzerland: Farmorubicin;

Thailand: Anthracin; E.RMycin; Epilem; Pharmorubicin;

Turkey: Farmorubicin;

United Kingdom (UK): Pharmorubicin;

United States of America (US and USA): Ellence;

Venezuela: Farmorubicin.

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