Bleomycin


Generic Medicine Info
Indications and Dosage
Intracavitary
Malignant effusions
Adult: 60,000 IU in 100 mL NaCl 0.9% instilled into the affected serous cavity, may be repeated up to a lifetime cumulative dose of 360,000 IU, as necessary.
Elderly: Total dose: 60-69 years 200,000-300,000 IU (30,000-60,000 IU weekly); 70-79 years 150,000-200,000 IU (30,000 IU weekly); ≥80 years 100,000 IU (15,000 IU weekly).

Intramuscular
Lymphoma
Adult: 15,000 IU once or twice weekly, up to a total dose of 225,000 IU. Max lifetime cumulative dose: 360,000 IU.
Elderly: Total dose: 60-69 years 200,000-300,000 IU (30,000-60,000 IU weekly); 70-79 years 150,000-200,000 IU (30,000 IU weekly); ≥80 years 100,000 IU (15,000 IU weekly).

Parenteral
Squamous cell or testicular tumours
Adult: 15,000 IU 3 times weekly or 30,000 IU twice weekly via IM/IV inj, repeated at intervals of 3-4 weeks up to a lifetime cumulative dose of 360,000 IU. Dose is adjusted according to tolerance. Alternatively, may be given via IV infusion at a rate of 15,000 IU/24 hours for up to 10 days or 30,000 units/24 hours for up to 5 days.
Elderly: Total dose: 60-69 years 200,000-300,000 IU (30,000-60,000 IU weekly); 70-79 years 150,000-200,000 IU (30,000 IU weekly); ≥80 years 100,000 IU (15,000 IU weekly).
Renal Impairment
CrCl 20-40 mcg/mL: Admin 50% of normal dose.
Reconstitution
IM/SC: Add 1-5 mL or 2-10 mL of sterile water for inj, NaCl 0.9% inj, or bacteriostatic water for inj to the vial labelled as containing 15 IU or 30 IU of bleomycin, respectively, to provide a soln containing 3-15 IU/mL. IV: Add 5 mL or 10 mL of NaCl 0.9% into the vial labelled as containing 15 IU or 30 IU of bleomycin, respectively, to provide a soln containing ≤3 IU/mL. Admin slowly over a 10-min period. Intrapleural: Dissolve 60 IU of bleomycin in 50-100 mL NaCl 0.9% inj.
Incompatibility
Incompatible w/ soln of essential amino acids, riboflavin, dexamethasone or furosemide; carbenicillin, cefazolin or cefalotin Na, nafcillin Na, benzylpenicillin Na, methotrexate, mitomycin, hydrocortisone Na succinate, aminophylline, ascorbic acid or terbutaline.
Contraindications
Acute pulmonary infection or greatly reduced lung function. Concomitant brentuximab, cisplatin or oxygen. Lactation.
Special Precautions
Patient w/ severe heart disease. Renal impairment. Elderly. Pregnancy.
Adverse Reactions
Rash, erythema, pruritus, vesiculation, hyperkeratosis, nail changes, alopecia, hyperpigmentation, striae, stomatitis, fever, acute anaphylactoid reactions w/ hyperpyrexia and cardioresp collapse, depression of bone marrow, local reactions and thrombophlebitis (site of inj).
Potentially Fatal: Pulmonary toxicity, severe idiosyncratic reactions consisting of hypotension, mental confusion, fever, chills and wheezing; renal toxicity, hepatotoxicity.
IM/Intra-arterial/Intrapleural/IV/Parenteral/SC: D
Monitoring Parameters
Closely monitor for signs of pulmonary toxicity; take chest radiographs every 1-2 wk. Perform sequential measurement of pulmonary diffusion capacity for carbon monoxide mthly during therapy. Carefully monitor fluid replacement, renal and liver function.
Overdosage
Symptoms: Hypotension, fever, rapid pulse and general symptoms of shock. Management: Symptomatic. In case of resp complications, treat w/ a corticosteroid and a broad-spectrum antibiotic.
Drug 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.
Action
Description:
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.
Pharmacokinetics:
Absorption: Poorly absorbed from the GI tract. Rapidly absorbed after parenteral, intraperitoneal or intrapleural use. Bioavailability: 100% (IM), 70% (SC), 45% (intraperitoneal/intrapleural). Time to peak plasma concentration: Approx 30 min (IM).
Distribution: Crosses the placenta. Volume of distribution: 22 L/m2. Plasma protein binding is low.
Metabolism: Undergoes enzymatic degradation by bleomycin hydrolase in plasma, liver and other organs.
Excretion: Via urine as active drug (50-70%). Half-life: IV bolus: 0.5 hr (initial), 4 hr (terminal); IV infusion: 1.3 hr (initial), 9 hr (terminal).
Chemical Structure

Chemical Structure Image
Bleomycin

Source: National Center for Biotechnology Information. PubChem Database. Bleomycin a2, CID=5360373, https://pubchem.ncbi.nlm.nih.gov/compound/Bleomycin-a2 (accessed on Jan. 21, 2020)

Storage
Store between 2-8°C. Protect from light.
MIMS Class
Cytotoxic Chemotherapy
References
Anon. Bleomycin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/06/2014.

Bleomycin Injection, Powder, Lyophilized, for Solution (Hospira Worldwide, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 13/06/2014.

Buckingham R (ed). Bleomycin sulfate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/06/2014.

McEvoy GK, Snow EK, Miller J et al (eds). Bleomycin sulfate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 13/06/2014.

New Boxed Warning and Contraindication for Adcetris (brentuximab vedotin). U.S. FDA. https://www.fda.gov/. Accessed 13/06/2014.

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