Bleomycin

Indications

Bleomycin is used for: Lymphoma, Squamous cell or Testicular tumours, Malignant effusions

Adult Dose

Squamous Cell Carcinoma, Testicular Carcinoma 0.25-0.5 unit/kg (10 to 20 unit/m²) IV/IM/SC q1-2Weeks Hodgkin's Disease, Non-Hodgkin's Lymphoma Administer test dose of 1-2 units of bleomycin before first 1-2 doses; monitor vital signs q15min; wait 1 hour minimum before administering remainder of dose; if no acute reaction observe, may administer regular dosage schedule 0.25 to 0.5 unit/kg (10 to 20 unit/m²) IV/IM/SC q1-2Weeks; reduce to maintenance dose of 1 unit qDay or 5 unit qWeek IV/IM after 50% response Hepatic Impairment: Dose adjustment not necessary

Child Dose

Not recommended

Renal Dose

Renal Impairment CrCl >50 mL/min: Dose adjustment not necessary CrCl 40-50 mL/min: 70% of normal dose CrCl 30-40 mL/min: 60% of normal dose CrCl 20-30 mL/min: 55% normal dose CrCl 10-20 mL/min: 45% normal dose CrCl 5-10 mL/min: 40% normal dose

Administration

IV/IM Preparation IV: reconstitute 15 U vial in 5 mL & 30 U vial in 10 mL NS to yield 3 U/mL solution IM/SC: reconstitute 15 U vial in 1-5 mL & 30 U vial in 2-10 mL NS/SWI/BWI Do not use dextrose-containing diluents Although may be stable for longer periods, preferably use within 24 hr of reconstitution In lymphoma patients, give first 2 doses at 1-2 units to test for anaphylactoid reaction Limit lifetime dose to <400 units because of risk of pulmonary fibrosis Low ADRs w/intrapleural administration

Contra Indications

Hypersensitivity. Severe pulmonary disease; pregnancy and lactation.

Precautions

Pulmonary infection, preexisting pulmonary function impairment, renal impairment. Patients who received radiotherapy, particularly to the thorax. Regular chest x-rays should be done. Elderly. Discontinue treatment if chest x-rays show infiltrates or breathlessness occurs. Lactation: It is not known whether the drug is excreted in milk. Because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued by women receiving bleomycin therapy.

Pregnancy-Lactation

Pregnancy Category: D Lactation: It is not known whether the drug is excreted in milk. Because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued by women receiving bleomycin therapy.

Interactions

Increased incidence and severity of lung toxicity w/ previous or concurrent radiotherapy to the chest. Combination w/ vinca alkaloids may result to a syndrome corresponding to morbus Raynaud, ischaemia which can lead to necrosis of peripheral parts of the body (fingers, toes, nose tip). May reduce the absorption of phenytoin. Increased risk of agranulocytosis w/ clozapine. Potentially Fatal: Increased pulmonary toxicity w/ oxygen, cisplatin or brentuximab.

Adverse Effects

Side effects of Bleomycin : >10% Mucocutaneous toxicity including rash, erythema, hyperpigmentation, urticaria (>50%), Febrile reactions, acute (25-50%), Mucositis (30%), Stomatitis (30%), Interstitial pneumonitis (10%), Pulmonary fibrosis (10%), Anorexia, Weight loss, Rales, Tachypnea 1-10% Alopecia (1-10%), Fatal pulmonary fibrosis (1%), Confusion, Shivering, Anphylactoid rxns, Onycholysis, Pruritus, Skin thickening, Skleroderma <1% Nausea, Malaise, Myocardial infarction, Hypotension, Cerebral vascular accident, Raynaud's phenomenon, Fatal pulmonary fibrosis, Hepatotoxicity, Renal toxicity, Necrolysis, Hyperpigmentation Potentially Fatal: Pulmonary toxicity, interstitial pneumonitis, fibrosis, cardiorespiratory collapse in patients with lymphoma.

Mechanism of Action

Bleomycin causes breakage of single- and double- stranded DNA by binding to DNA and inhibiting DNA synthesis. To a lesser extent, it also inhibits RNA and protein synthesis. It causes very little bone marrow suppression.