DRUG NAME: Epirubicin
SYNONYM(S): 4’-epidoxorubicin,1 IMI-28,1 NSC-2569421 COMMON TRADE NAME(S): PHARMORUBICIN®,2 ELLENCE®3 CLASSIFICATION: anthracycline antineoplastic antibiotic4 MECHANISM OF ACTION: 2 The mechanism of action of epirubicin appears to be related to its ability to bind to nucleic acids. It forms a complex 4 with DNA by intercalation between base pairs, resulting in inhibition of DNA and RNA synthesis. Intercalation also 3,4 triggers DNA cleavage by topoisomerase II, resulting in cytocidal activity. Binding to cell membranes and plasma 2 proteins may also be involved. Epirubicin also generates cytotoxic free radicals.3,4 Epirubicin is the 4’-epimer of 4 DOXOrubicin; i.e., there is a different spatial orientation of the hydroxyl group at the 4’ carbon of the sugar moiety. This difference may account for faster elimination and reduced toxicity.2
Distribution rapidly and widely distributed into tissues3; may concentrate in red blood cells, whole blood 3 concentrations are approximately twice those of plasma cross blood brain barrier? no 3 volume of distribution 21-27 L/kg plasma protein binding3 77% extensive hepatic metabolism; also metabolized by other organs and cells, including red blood cells3 active metabolite(s) epirubicinol (13-OH epirubicin)3; cytotoxic activity onetenth that of epirubicin; plasma levels consistently lower than epirubicin inactive metabolite(s) glucuronides of epirubicin and epirubicinol; DOXOrubicin; aglycones of doxorubicinol, 73 deoxydoxorubicin, and 7-deoxydoxorubicinol predominantly hepatobiliary; rapid elimination of parent compound from plasma urine 9-10% within 48 h2; 20-27% within 4 days3 feces 40% of dose recovered in bile within 72 h terminal half life3 33 h 3 65-83 L/h clearance 3 no differences observed clearance may be decreased in elderly women3 3
Adapted from standard reference unless specified otherwise.
BC Cancer Agency Cancer Drug Manual© Developed: February 2006 Revised: 01 March 2006, 1 March 2012
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Primary uses: * Breast cancer * Gastric cancer * Lung cancer, non-small cell * Lung cancer, small cell * Lymphoma, Hodgkin’s * Lymphoma, non-Hodgkin’s * Ovarian cancer *Health Canada approved indication
Other uses: Bladder cancer5,6 7 Pediatric, soft tissue sarcoma Soft tissue sarcoma8-10
Contraindicated in patients with the following conditions3: • • • • • • • • • • hypersensitivity to epirubicin or any component of the product hypersensitivity to other anthracyclines (e.g., DAUNOrubicin, DOXOrubicin) hypersensitivity to anthracenediones (e.g., mitoXANTRONE, mitomycin) severe hepatic impairment severe myocardial insufficiency recent myocardial infarction severe arrhythmias history of severe cardiac disease previous therapy with high cumulative doses of anthracyclines (e.g., DOXOrubicin, DAUNOrubicin, epirubicin, IDArubicin) previous therapy with high cumulative doses of some anthracenediones (e.g., mitoXANTRONE)
Cardiac toxicity is a risk of epirubicin therapy that may be manifested by early (acute) or late (delayed) effects.4 Cardiac function should be assessed at baseline and continue during treatment; refer to Side Effects section for more information. Risk factors for developing epirubicin-induced cardiotoxicity include3: • • • • high cumulative dose, previous therapy with other anthracyclines or anthracenediones prior or concomitant radiotherapy to the mediastinal/pericardial area pre-existing heart disease concomitant use of drugs that can suppress cardiac contraction
Carcinogenicity: Epirubicin has been associated with an increased risk of secondary leukemia in human trials.3 Mutagenicity: Epirubicin is mutagenic and clastogenic in animals, and may induce chromosomal damage in human 3 spermatozoa. 3 Fertility: Dose-related infertility has been observed in mammals of both sexes. Epirubicin...
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