bleomycin sulfate
Blenoxane

Available forms
Available by prescription only
Injection: 15-unit, 30-unit vials

Indications and dosages
Dosages and indications may vary. Check literature for current protocol.
 Hodgkin’s disease, squamous cell carcinoma, malignant lymphoma, testicular carcinoma. Adults: 10 to 20 units/m² (0.25 to 0.5 units/kg) I.V., I.M., or S.C., one or two times weekly. After 50% response in regression of tumor size in Hodgkin’s disease, maintenance dosage of 1 unit daily or 5 units weekly.
 Malignant pleural effusion, to prevent recurrent pleural effusions or manage pneumothorax caused by AIDS and Pneumocystis carinii pneumonia ◇. Adults: 60 units in 50 to 100 ml of normal saline solution by intracavitary administration not to exceed 1 unit/kg.
≡ Dosage adjustment. For geriatric patients receiving intracavitary administration in the pleural space, don’t exceed 40 units/m².
 Tumors of the head and neck ◇. Adults: 10 to 20 units/m² daily by I.V. or regional arterial administration for 5 to 14 days.

Pharmacodynamics
Antineoplastic action: The exact mechanism of cytotoxicity is unknown. Drug’s action may be through scission of single- and double-stranded DNA and inhibition of DNA, RNA, and protein synthesis. Bleomycin also appears to inhibit cell progression out of the G2 phase.

Pharmacokinetics
Absorption: Poorly absorbed across the GI tract. I.M. administration results in lower serum levels than those occurring after equivalent I.V. doses.
Distribution: Distributed widely into total body water, mainly in the skin, lungs, kidneys, peritoneum, and lymphatic tissue.
Metabolism: Metabolic fate of drug is undetermined; however, extensive tissue inactivation occurs in the liver and kidneys and much less in the skin and lungs.
Excretion: Excreted primarily in urine. The terminal plasma elimination phase half-life is 2 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with renal or pulmonary impairment.

Interactions
Drug-drug. Digoxin, phenytoin: Decreases serum levels of these drugs. Monitor serum levels.

Adverse reactions
GI: stomatitis, anorexia, nausea, vomiting, diarrhea, fever.
Metabolic: increased blood and urine levels of uric acid, weight loss.
Respiratory: pulmonary fibrosis, PULMONARY TOXICITY such as PNEUMONITIS.
Skin: erythema, hyperpigmentation, acne, rash, reversible alopecia, striae, skin tenderness, pruritus.
Other: chills; severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills, and wheezing has occurred in about 1% of lymphoma patients.

Effects on lab test results
• May increase uric acid levels.

Overdose and treatment
Signs and symptoms of bleomycin overdose include pulmonary fibrosis, fever, chills, vesiculation, and hyperpigmentation.
 Treatment is usually supportive and includes antipyretics for fever.

Special considerations
• Pulmonary function tests may be useful in predicting fibrosis; they should be performed to establish a baseline and then monitored periodically.
• Use precautions in preparing and handling drug; wear gloves and wash hands after preparing and administering.
• Drug can be administered by intracavitary route (see manufacturer’s recommendation), intra-arterially, or via intratumoral injection. It can also be instilled into bladder for bladder tumors.
• Cumulative lifetime dose shouldn’t exceed 400 units.
• Response to bleomycin therapy may take 2 to 3 weeks.
• Administer a 1- to 2-unit test dose to lymphoma patients for the first two doses to assess hypersensitivity to bleomycin. If no reaction occurs, follow the dosing schedule. The test dose can be incorporated as part of the total dose for the regimen.
• Keep epinephrine, diphenhydramine, I.V. corticosteroids, and oxygen available in case of anaphylaxis.
• Premedication with aspirin, corticosteroids, and diphenhydramine may reduce drug fever and risk of anaphylaxis.
• For I.M. administration, reconstitute drug with 1 to 5 ml (15-unit vial) or 2 to 10 ml (30-unit vial) of normal saline solution, bacteriostatic water, or sterile water for injection. Don’t use D₅W or dextrose-containing diluents.
• For I.V. administration, dilute with at least 5 ml (15-unit vial) or 10 ml (30-unit vial) of diluent (don’t exceed 3 units/ml) and administer over 10 minutes as I.V. push injection.
• For intrapleural administration, dissolve 60 units of bleomycin in 50 to 100 ml of normal saline solution and administer via thoracostomy tube.
• Reduce dose in patients with renal or pulmonary impairment.
• Monitor chest X-rays and auscultate the lungs to check for pulmonary toxicity.
• Lung damage may occur at oxygen levels that are lower than normal. This is an important consideration for patients undergoing surgery.
• Drug concentrates in keratin of squamous epithelium. To prevent linear streaking, don’t use adhesive dressings on skin.
• Allergic reactions may be delayed, especially in patients with lymphoma.
• Investigational uses for the drug include treatment of AIDS-related Kaposi’s sarcoma, renal carcinomas, soft-tissue sarcomas, otorhinolaryngeal tumors, and mycosis fungoides.
• Bleomycin is stable for 24 hours at room temperature and 48 hours under refrigeration. Refrigerate unopened vials containing dry powder.
Pregnant patients
• Drug may cause fetal toxicity in pregnant women. Don’t give it to pregnant women.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. However, because of risk of serious adverse reactions, mutagenicity, and carcinogenicity in infants, breast-feeding isn’t recommended.
Geriatric patients
• Use cautiously in patients older than age 70 because they have an increased risk of pulmonary toxicity.

Patient education
• Explain that hair should grow back after treatment stops.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use