Epirubicin Hydrochloride

Indications

Epirubicin Hydrochloride is used for: Acute leukaemias; Lymphoma; Multiple myeloma, Breast cancer, Bladder carcinoma

Adult Dose

Adjuvant Breast Cancer Treatment Option 1 (Day 1 dose schedule) Day 1: Epirubicin 100 mg/m² IV, AND 5-fluorouracil 500 mg/m² IV, AND cyclophosphamide 500 mg/m² IV Repeat q21Days x 6 cycles Option 2 (Divided dose schedule) First dose divided equally between days 1 & 8: Epirubicin 60 mg/m² IV, AND 5-fluorouracil 500 mg/m² IV, AND Days 1-14: Cyclophosphamide 75 mg/m² PO Repeat q28Days x 6 cycles Intravenous Lymphoma; Multiple myeloma; Solid tumours; Acute leukaemias Adult: As a single agent: 60-90 mg/m2 every 3-4 wk. May divide dose over 2-3 days if desired. May admin as an inj over 3-5 minutes or as an infusion over up to 30 minutes. Max (total cumulative dose limit): 0.9-1 g/m2. For palliative care: 12.5-25 mg/m2 once wkly. Hepatic Impairment Billirubin < 1.2 mg/dL: Dose adjustment not necessary Bilirubin 1.2-3 mg/dL or AST 2-4 x ULN: 50% of recommended starting dose Bilirubin >3 mg/dL or AST > 4 x ULN: 25% of recommended starting dose (ie, decrease starting dose by 75%) Severe hepatic impairment: Not recommended

Child Dose

Safety & efficacy not established

Renal Dose

Renal Impairment SCr >5 mg/dL [>442 micromoles/L]: Decrease dose by 50%; test cardiac ejection fraction via MUGA before starting treatment

Administration

IV Administration Administer infuse into tubing of a freely flowing infusion (NS or D5W) over 3-5 min Avoid extravasation, associated with severe ulceration & soft tissue necrosis; flush with 5-10 mL of IV solution before & after drug administration

Contra Indications

Cardiac impairment, severe or recent MI; previous full cumulative doses of anthracyclines. Hypersensitivity; severe hepatic dysfunction. Not for intravesical use where invasive tumours have penetrated the bladder wall; urinary infections, bladder inflammation or catheterisation problems. Pregnancy, lactation.

Precautions

Previous extensive radiotherapy, bone infiltration by tumour, severe renal and hepatic dysfunction. May cause tumor lysis syndrome or radiation recall. Elderly women >70 yr. CV disease, hypertensive cardiomyopathy; monitor hematological and cardiac function regularly. Extravasation during IV admin may result in severe local tissue necrosis. Do not give via IM/SC routes as extravasation can lead to severe local necrosis. Lactation: not known if excreted in breast milk; do not nurse

Pregnancy-Lactation

Interactions

Paclitaxel and other anthracyclines. Cimetidine, heparin. Antineoplastic drugs, cardiotoxic drugs, radiation, hepatoactive drugs.

Adverse Effects

Side effects of Epirubicin Hydrochloride : >10% Alopecia (96%),Nausea and vomiting (92%),Leukopenia or neutropenia (80%),Amenorrhea (72%),Anemia (72%),Mucositis (59%),Thrombocytopenia (49%),Lethargy (46%),Hot flashes (39%),Diarrhea (25%),Conjunctivitis (15%) 1-10% Rash (9%),Fever (5%),Skin changes (5%),Anorexia (3%) <1% Acute lymphoid leukemia,Acute myelogenous leukemia,Atrioventricular block,Esophagitis,Hyperpigmentation,Myelodysplastic syndrome Frequency Not Defined Myocardial toxicity (including CHF),Severe myelosuppression,Risk of secondary AML

Mechanism of Action

Epirubicin, an anthracycline with cytotoxic properties. It inhibits DNA and RNA synthesis by steric obstruction after intercalating between DNA base pairs that triggers DNA cleavage by by topoisomerase II. It also inhibits DNA helicase and generates cytotoxic free radicals.