Cytobin-50

Epirubicin HCl

Neoplastic conditions including breast, ovarian, gastric, lung & colorectal carcinomas, malignant lymphomas, leukaemias & multiple myeloma. Treatment of superficial bladder cancer, carcinoma-in-situ prophylaxis of recurrences after transurethral resection, superficial bladder cancer & advanced metastatic soft tissue sarcoma.

IV Adult 60-90 mg/m² as single agent inj over 3-5 min & should be repeated at 21-day intervals. Small cell lung cancer (previously untreated) 120 mg/m² day 1, every 3 wk. NSCLC (squamous, large cell, & adenocarcinoma previously untreated) 135 mg/m² day 1 or 45 mg/m² days 1, 2, 3, every 3 wk. Early breast cancer w/ +ve lymph nodes 100 mg/m² (as single dose on day 1) to 120 mg/m² (in 2 divided doses on days 1 & 8) every 3-4 wk, in combination w/ IV cyclophosphamide & 5-fluorouracil & oral tamoxifen are recommended. High dose treatment IV bolus over 3-5 min or as infusion of up to 30 min duration. Impaired bone marrow function Lower doses (60-75 mg/m² for conventional treatment & 105-120 mg/m² for high dose schedules). Total dose per cycle may be divided over 2-3 successive days. Impaired liver function 1.4-3 mg/100 mL serum bilirubin 50% dose reduction. >3 mg/100 mL serum bilirubin 75% dose reduction. Severe renal impairment (serum creatinine >5 mg/dL) Lower starting dose should be considered. Intravesical Therapy 8 x wkly instillations of 50 mg/50 mL (diluted w/ saline or distilled sterile water). Local toxicity (chemical cystitis) Dose reduction to 30 mg/50 mL is advised. Carcinoma-in-situ Depending on individual tolerability, dose may be increased up to 80 mg/50 mL. Prophylaxis 4 wkly administration of 50 mg/50 mL, followed by 11 x mthly instillations at the same dosage.

Hypersensitivity to epirubicin HCl, other anthracyclines or anthracenediones. Lactation. IV Patients w/ marked or persistent myelosuppression induced by previous treatment w/ either other anti-neoplastic agents or RT; severe hepatic impairment; severe myocardial insufficiency; recent MI; severe arrhythmias; previous treatments w/ max cumulative doses of epirubicin &/or other anthracyclines eg, doxorubicin or daunorubicin & anthracenediones; previous history of cardiac impairment (including 4th degree muscular heart failure, acute heart attack & previous heart attack which led to 3rd & 4th degree muscular heart failure, acute inflammatory heart diseases, severe arrhythmia, myocardiopathy, recent MI) patients w/ acute systemic infections; unstable angina pectoris; myocardiopathy. Intravesical UTI; bladder inflammation; haematuria; invasive tumours penetrating the bladder; catheterisation problems; large vol of residual urine; contracted bladder.

Myelosuppression. Not active when given orally & should not be injected IM or intrathecally. Patients should recover from acute toxicities (eg, stomatitis, neutropenia, thrombocytopenia, generalised infections) of prior cytotoxic treatment. Cardiotoxicity. Risk of irreversible CHF. Cardiac function should be assessed before undergoing treatment. Cardiomyopathy. Risk factors for cardiac toxicity include active or dormant CV disease, prior or concomitant RT to the mediastinal/pericardial area, previous therapy w/ other anthracyclines or anthracenediones, concomitant use of other drugs w/ the ability to suppress cardiac contractility or cardiotoxic drugs (eg, trastuzumab) w/ an increased risk in the elderly. Haematologic toxicity. RBC, WBC, neutrophil & platelet counts should be carefully monitored both before & during each cycle of therapy. Secondary leukaemia, w/ or w/o preleukaemic phase. Mucosal inflammation/stomatitis. May impart red colour to the urine for 1 or 2 days after administration. Phlebosclerosis. Discontinue if signs or symptoms of extravasation occur during IV administration. Thrombophlebitis & thromboembolic phenomena, including pulmonary embolism. Tumour lysis syndrome. Vaccination w/ live vaccine should be avoided; killed or inactivated vaccines may be administered however, the response may be diminished. Intravesical route may produce symptoms of chemical cystitis (eg, dysuria, polyuria, nocturia, stranguria, haematuria, bladder discomfort, necrosis of the bladder wall) & bladder constriction. Special attention is required for catheterization problems (eg, urethral obstruction due to massive intravesical tumours). IA route can lead to widespread necrosis of perfused tissue. Before starting & during treatment, liver function should be evaluated. Severe hepatic impairment. Dosage adjustment is necessary in patients w/ serum creatinine >5 mg/mL. Genotoxicity; men & women treated w/ epirubicin should adopt appropriate contraceptives. Pregnancy & lactation. Childn.

Infection, conjunctivitis; myelosuppression; keratitis; hot flashes, phlebitis; mucositis, stomatitis, vomiting, diarrhoea, nausea which can result in loss of appetite & abdominal pain; alopecia, skin toxicity; chromaturia; amenorrhoea; malaise, pyrexia; changes in transaminase levels; chemical cystitis, sometimes haemorrhagic (observed following intravesical administration). Bacterial cystitis; loss of appetite, dehydration; ventricular tachycardia, AV block, bundle-branch block, bradycardia, CHF (dyspnoea; oedema, hepatomegaly, ascites, pulmonary oedema, pleural effusions, extrasystoles); haemorrhage, flushing; oesophagitis, GI pain/erosion/haemorrhage/ulcer, abdominal pain, oral mucosa erosion, oral pain, mucosal burning sensation; rash, pruritus, nail hyperpigmentation, skin disorders, skin hyperpigmentation, local tissue toxicity; dysuria, haematuria, pollakisuria; chills, infusion site erythema; asymptomatic decrease in LVEF.

Additive toxicity may occur especially w/ bone marrow/hematologic & GI effects w/ other cytotoxic drugs. Monitoring of cardiac function throughout treatment in combination chemotherapy w/ other potentially cardiotoxic drugs & concomitant use of other cardioactive compd (eg, Ca channel blockers). Increased risk of cardiotoxicity in patients receiving anthracyclines after stopping treatment w/ other cardiotoxic agents, especially those w/ long t_1/2 eg, trastuzumab. Cimetidine should be discontinued during treatment w/ epirubicin. Increased plasma conc of unchanged epirubicin & its metabolites w/ paclitaxel. Co-administration of paclitaxel or docetaxel (may be used if staggered administration). Alter pharmacokinetics & possibly increase bone marrow depressant effects w/ Dexverapamil. May have influence on the RBCs partitioning of epirubicin w/ quinine. Reduction in both terminal elimination t_1/2 & total clearance w/ interferon α2b. Possibility of a marked disturbance of haematopoiesis w/ a (pre-) treatment w/ medications which influence bone marrow (ie, cytostatic agents, sulphonamide, chloramphenicol, diphenylhydantoin, amidopyrine-derivate, antiretroviral agents). Decreased AUC w/ prior administration of higher doses (900 mg/m² & 1,200 mg/m²) of dexrazoxane. Increased myelosuppression in patients receiving combination therapy of anthracycline & dexrazoxane. Risk of cardiotoxicity may increase in patients who have received concomitant cardiotoxic agents (eg, 5-fluorouracil, cyclophosphamide, cisplatin, taxanes), or concomitant (or prior) RT to the mediastinal area.

Cytotoxic Chemotherapy

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

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