Epirubicin

Intravenous
Acute leukaemia
Adult: As a single agent: 60-90 mg/m² as a single dose every 3 weeks. May give doses of up to 120 mg/m² every 3 weeks if needed. Max total cumulative dose: 900-1,000 mg/m². All doses are given via IV bolus inj over 3-5 minutes or via IV infusion of up to 30 minutes; administer into a free-flowing infusion of NaCl 0.9% solution or dextrose 5% in water solution. Dosing interruption or dose reduction may be required according to individual safety or tolerability. Treatment protocols may vary among countries or individual products (refer to country- or product-specific guidelines).
Renal impairment: Severe: Initiate at the lower end of the dosing range.
Hepatic impairment: Serum bilirubin 1.2-3 mg/dL: Decrease initial dose by 50%. Serum bilirubin >3 mg/dL: Decrease initial dose by 75%. Severe: Contraindicated.
Incompatibility: Incompatible with any solution of an alkaline pH (if prolonged contact); heparin, fluorouracil.

Intravenous
Ovarian cancer
Adult: As a single agent: 60-90 mg/m² as a single dose every 3 weeks. May give doses of up to 120 mg/m² every 3 weeks if needed. Max total cumulative dose: 900-1,000 mg/m². All doses are given via IV bolus inj over 3-5 minutes or via IV infusion of up to 30 minutes; administer into a free-flowing infusion of NaCl 0.9% solution or dextrose 5% in water solution. Dosing interruption or dose reduction may be required according to individual safety or tolerability. Treatment protocols may vary among countries or individual products (refer to country- or product-specific guidelines).
Renal impairment: Severe: Initiate at the lower end of the dosing range.
Hepatic impairment: Serum bilirubin 1.2-3 mg/dL: Decrease initial dose by 50%. Serum bilirubin >3 mg/dL: Decrease initial dose by 75%. Severe: Contraindicated.
Incompatibility: Incompatible with any solution of an alkaline pH (if prolonged contact); heparin, fluorouracil.

Intravenous
Small cell lung cancer
Adult: As a single agent: 60-90 mg/m² as a single dose every 3 weeks. May give doses of up to 120 mg/m² every 3 weeks if needed. Max total cumulative dose: 900-1,000 mg/m². All doses are given via IV bolus inj over 3-5 minutes or via IV infusion of up to 30 minutes; administer into a free-flowing infusion of NaCl 0.9% solution or dextrose 5% in water solution. Dosing interruption or dose reduction may be required according to individual safety or tolerability. Treatment protocols may vary among countries or individual products (refer to country- or product-specific guidelines).
Renal impairment: Severe: Initiate at the lower end of the dosing range.
Hepatic impairment: Serum bilirubin 1.2-3 mg/dL: Decrease initial dose by 50%. Serum bilirubin >3 mg/dL: Decrease initial dose by 75%. Severe: Contraindicated.
Incompatibility: Incompatible with any solution of an alkaline pH (if prolonged contact); heparin, fluorouracil.

Intravenous
Lymphoma
Adult: As a single agent: 60-90 mg/m² as a single dose every 3 weeks. May give doses of up to 120 mg/m² every 3 weeks if needed. Max total cumulative dose: 900-1,000 mg/m². All doses are given via IV bolus inj over 3-5 minutes or via IV infusion of up to 30 minutes; administer into a free-flowing infusion of NaCl 0.9% solution or dextrose 5% in water solution. Dosing interruption or dose reduction may be required according to individual safety or tolerability. Treatment protocols may vary among countries or individual products (refer to country- or product-specific guidelines).
Renal impairment: Severe: Initiate at the lower end of the dosing range.
Hepatic impairment: Serum bilirubin 1.2-3 mg/dL: Decrease initial dose by 50%. Serum bilirubin >3 mg/dL: Decrease initial dose by 75%. Severe: Contraindicated.
Incompatibility: Incompatible with any solution of an alkaline pH (if prolonged contact); heparin, fluorouracil.

Intravenous
Multiple myeloma
Adult: As a single agent: 60-90 mg/m² as a single dose every 3 weeks. May give doses of up to 120 mg/m² every 3 weeks if needed. Max total cumulative dose: 900-1,000 mg/m². All doses are given via IV bolus inj over 3-5 minutes or via IV infusion of up to 30 minutes; administer into a free-flowing infusion of NaCl 0.9% solution or dextrose 5% in water solution. Dosing interruption or dose reduction may be required according to individual safety or tolerability. Treatment protocols may vary among countries or individual products (refer to country- or product-specific guidelines).
Renal impairment: Severe: Initiate at the lower end of the dosing range.
Hepatic impairment: Serum bilirubin 1.2-3 mg/dL: Decrease initial dose by 50%. Serum bilirubin >3 mg/dL: Decrease initial dose by 75%. Severe: Contraindicated.
Incompatibility: Incompatible with any solution of an alkaline pH (if prolonged contact); heparin, fluorouracil.

Intravenous
Breast cancer
Adult: As an adjuvant therapy component in patients with evidence of axillary node tumour involvement following resection of primary breast cancer: Usual dose: 100-120 mg/m² given in repeated 3- to 4-week cycles; total dose for each cycle may be given as a single dose on Day 1 or as 2 equally divided doses on Days 1 and 8 of each cycle. All doses are given via IV bolus inj over 3-5 minutes or via IV infusion of up to 30 minutes; administer into a free-flowing infusion of NaCl 0.9% solution or dextrose 5% in water solution. Dosing interruption or dose reduction may be required according to individual safety or tolerability. Treatment protocols may vary among countries or individual products (refer to country- or product-specific guidelines).
Renal impairment: Severe: Initiate at the lower end of the dosing range.
Hepatic impairment: Serum bilirubin 1.2-3 mg/dL: Decrease initial dose by 50%. Serum bilirubin >3 mg/dL: Decrease initial dose by 75%. Severe: Contraindicated.
Incompatibility: Incompatible with any solution of an alkaline pH (if prolonged contact); heparin, fluorouracil.

Intravesical
Bladder cancer
Adult: Treatment of superficial bladder cancer: 50 mg (25 mL of 2 mg/mL epirubicin inj) in 25 mL of sterile water for inj or NaCl 0.9% solution to make 50 mL of bladder instillation solution, instilled weekly for 8 weeks; in case of local toxicity (chemical cystitis), instil 30 mg (15 mL of 2 mg/mL epirubicin inj) in 35 mL of sterile water for inj or NaCl 0.9% solution to make 50 mL of bladder instillation solution. For carcinoma in situ: May instil up to 80 mg (40 mL of 2 mg/mL epirubicin inj) in 10 mL of sterile water for inj or NaCl 0.9% solution to make 50 mL of bladder instillation solution. For prophylaxis of recurrence following transurethral resection: 50 mg (25 mL of 2 mg/mL epirubicin inj) in 25 mL of sterile water for inj or NaCl 0.9% solution to make 50 mL of bladder instillation solution, instilled weekly for 4 weeks; followed by 50 mg (25 mL of 2 mg/mL epirubicin inj) in 25 mL of sterile water for inj or NaCl 0.9% solution to make 50 mL of bladder instillation solution, in
Incompatibility: Incompatible with any solution of an alkaline pH (if prolonged contact); heparin, fluorouracil.

IV: Severe persistent myelosuppression, severe stomatitis associated by previous drug treatment or radiotherapy; acute systemic infections, recent MI, severe cardiac failure, severe arrhythmias, cardiomyopathy, unstable angina pectoris. Severe hepatic impairment. Prior treatment with Max cumulative doses of epirubicin and/or other anthracyclines and anthracenediones. Intravesical: Invasive tumours that penetrated the bladder wall, bladder inflammation; UTI, catherisation problems, haematuria. Lactation.

Patient with active, dormant or history of CV disease; previous or concurrent radiotherapy to the mediastinal or pericardial area; rapid tumour proliferation. Avoid concurrent vaccination with live vaccines. Mild to moderate hepatic impairment. Pregnancy. Monitoring Parameters Confirm pregnancy status before treatment initiation in females of reproductive potential. Monitor CBC with differential and platelet count, LFTs (ALT, AST, total bilirubin), serum creatinine, cardiac function (LVEF using ECG or multi-gated radionuclide angiography [MUGA]) before and periodically during treatment; serum electrolytes (e.g. Ca, K, phosphate), and uric acid. Assess for signs of extravasation or infusion-related reactions; signs and symptoms of tumour lysis syndrome and secondary malignancies.

Significant: Cardiomyopathy (including acute left ventricular failure), secondary malignancy (e.g. acute myeloid leukaemia, myelodysplastic syndrome), extravasation (may lead to severe local tissue injury and necrosis), tumour lysis syndrome resulting to hyperuricaemia, radiation recall (in patients who received prior radiation therapy). Blood and lymphatic system disorders: Anaemia, leucopenia, granulocytopenia, neutropenia, thrombocytopenia, febrile neutropenia. Cardiac disorders: Bradycardia, ventricular tachycardia, arrhythmias, atrioventricular and bundle branch block, congestive heart failure. Eye disorders: Keratitis, infective conjunctivitis. Gastrointestinal disorders: Nausea, vomiting, diarrhoea stomatitis, mucositis, oesophagitis, gastrointestinal pain, haemorrhage, erosion and ulcer. General disorders and administration site conditions: Fever, chills, lethargy, infusion site erythema, anaphylaxis. Investigations: Abnormal transaminase values. Metabolism and nutrition disorders: Decrease in appetite, dehydration, hyperuricaemia. Nervous system disorders: Dizziness. Renal and urinary disorders: Red colouration of urine for 1-2 days. Intravesical: increased frequency of urination, chemical and haemorrhagic cystitis, dysuria, haematuria, strangury, bladder constriction. Reproductive system and breast disorders: Amenorrhoea. Rarely, azoospermia. Skin and subcutaneous tissue disorders: Pruritus, rash, skin and nail hyperpigmentation, alopecia. Vascular disorders: Hot flushes, phlebitis.
Potentially Fatal: Severe myelosuppression (resulting in serious infection, septic shock), thromboembolic events (e.g. thrombophlebitis, pulmonary embolism).

Symptoms: Severe myelosuppression, toxic gastrointestinal reactions, acute cardiac dysfunction. Management: Symptomatic and supportive treatment.

Increased risk of cardiotoxicity with other antineoplastic agents (e.g. trastuzumab, cyclophosphamide, cisplatin, taxanes) and other cardioactive compounds (e.g. calcium channel blockers). Additive cardiotoxic effect with propranolol. Increased occurrence of bone marrow depression when co-administered with dexrazoxane. Increased serum concentration with cimetidine. Increased systemic exposure with paclitaxel (when given immediately after epirubicin). Increased bone marrow depression with dexverapamil. Increased myocardial toxicity with concurrent mediastinal radiotherapy. May disrupt haematopoiesis when co-administered with drugs that can affect bone marrow function (e.g. chloramphenicol, sulphonamide, antiretroviral agents). May decrease clearance and terminal elimination half-life of epirubicin when co-administered with interferon α-2b.

Epirubicin an anthracycline antineoplastic, is a semisynthetic derivative of daunorubicin. It is believed to be involved in the inhibition of DNA and RNA synthesis through steric obstruction after intercalating between DNA base pairs. This intercalation triggers DNA cleavage by topoisomerase II, thereby causing cytocidal activity. Additionally, it prevents DNA helicase activity and generates cytotoxic free radicals.
Distribution: Rapidly and extensively distributed into body tissues. Plasma protein binding: Approx 77%, mainly to albumin.
Metabolism: Extensively metabolised in the liver into epirubicinol (13-hydroxyepirubicin) and glucuronides of epirubicin and epirubicinol.
Excretion: Via faeces (34-35%); urine (20-27%). Terminal elimination half-life: Approx 30-40 hours.

Intravenous: Powder for inj: Store below 30°C. Solution for inj: Store between 2-8°C. Protect from light. Do not freeze. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal. Intravesical: Powder for inj: Store below 30°C. Solution for inj: Store between 2-8°C. Protect from light. Do not freeze. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.

Cytotoxic Chemotherapy

L01DB03 - epirubicin ; Belongs to the class of cytotoxic antibiotics, anthracyclines and related substances. Used in the treatment of cancer.