No

Antineoplastic Agent, Antibiotic

Treatment of squamous cell carcinomas, melanomas, sarcomas, testicular carcinoma, Hodgkin's lymphoma, and non-Hodgkin's lymphoma; may also be used as a sclerosing agent for malignant pleural effusion

D

Hypersensitivity to bleomycin sulfate or any component, severe pulmonary disease

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal of antineoplastic agents be considered. Occurrence of pulmonary fibrosis is higher in elderly patients and in those receiving >400 units total and in smokers and patients with prior radiation therapy. A severe idiosyncratic reaction consisting of hypotension, mental confusion, fever, chills and wheezing (similar to anaphylaxis) has been reported in 1% of lymphoma patients treated with bleomycin. Since these reactions usually occur after the first or second dose, careful monitoring is essential after these doses. Check lungs prior to each treatment for fine rales (1st sign). Follow manufacturer recommendations for administering 0₂ during surgery to patients who have received bleomycin.

>10%:

Cardiovascular: Raynaud's phenomenon

Central nervous system: Mild febrile reaction, fever, chills, patients may become febrile after intracavitary administration

Dermatologic: Pruritic erythema

Integument: ~50% of patients will develop erythema, induration, and hyperkeratosis and peeling of the skin; hyperpigmentation, alopecia, nailbed changes may occur; this appears to be dose-related and is reversible after cessation of therapy

Irritant chemotherapy

Gastrointestinal: Mucocutaneous toxicity, stomatitis, nausea, vomiting, anorexia

Emetic potential: Moderately low (10% to 30%)

Local: Phlebitis, pain at tumor site

1% to 10%:

Dermatologic: Alopecia

Gastrointestinal: Weight loss

Respiratory: Toxicities (usually pneumonitis) occur in 10% of treated patients; 1% of patients progress to pulmonary fibrosis and death

Miscellaneous: Idiosyncratic: Similar to anaphylaxis and occurs in 1% of lymphoma patients; may include hypotension, confusion, fever, chills, and wheezing. May be immediate or delayed for several hours; symptomatic treatment includes volume expansion, pressor agents, antihistamines, and steroids

<1%: Myocardial infarction, cerebrovascular accident, skin thickening,scleroderma-like skin changes, hepatotoxicity, renal toxicity; respiratory effects are dose-related when total dose is >400 units or with single doses >30 units; pathogenesis is poorly understood, but may be related to damage of pulmonary, vascular, or connective tissue; manifested as an acute or chronic interstitial pneumonitis with interstitial fibrosis, hypoxia, and death; symptoms include cough, dyspnea, and bilateral pulmonary infiltrates noted on CXR; it is controversial whether steroids improve symptoms of bleomycin pulmonary toxicity; tachypnea, rales

Myelosuppressive:

WBC: Rare

Platelets: Rare

Onset (days): 7

Nadir (days): 14

Recovery (days): 21

Symptoms of overdose include chills, fever, pulmonary fibrosis, hyperpigmentation

Decreased effect:

Digitalis glycosides: May decrease plasma levels and renal excretion of digoxin

Phenytoin: Results in decreased phenytoin levels, possibly due to decreased oral absorption

Increased toxicity: Cisplatin: Results in delayed bleomycin elimination due to decrease in creatinine clearance secondary to cisplatin

Refrigerate intact vials of powder; intact vials are stable for up to one month at 45°C

Reconstitute powder with 1-5 mL SWI or NS which is stable at room temperature for 28 days or in refrigerator for 14 days; may use bacteriostatic agent if prolonged storage is necessary

Incompatible with amino acid solutions, aminophylline, ascorbic acid, cefazolin, cisplatin, cytarabine, furosemide, diazepam, hydrocortisone sodium succinate, methotrexate, mitomycin, nafcillin, penicillin G

Compatible with amikacin, cyclophosphamide, dexamethasone, diphenhydramine, doxorubicin, fluorouracil, gentamicin, heparin, hydrocortisone mesna, phenytoin, sodium phosphate, streptomycin, tobramycin, vinblastine, vincristine

Standard I.V. dilution: Dose/50-1000 mL NS or D₅W

Stable for 96 hours at room temperature and 14 days under refrigeration

Inhibits synthesis of DNA; binds to DNA leading to single- and double-strand breaks; isolated from Streptomyces verticillus

Absorption: I.M. and intrapleural administration produces serum concentrations of 30% of I.V. administration; intraperitoneal and S.C. routes produce serum concentrations equal to those of I.V.

Distribution: V_d: 22 L/m²; highest concentrations seen in skin, kidney, lung, heart tissues; low concentrations seen in testes and GI tract; does not cross blood-brain barrier

Protein binding: 1%

Metabolism: By several tissue types, including the liver, GI tract, skin, lungs, kidney, and serum

Half-life (biphasic): Dependent upon renal function:

Normal renal function:

Initial: 1.3 hours

Terminal: 9 hours

End-stage renal disease:

Initial: 2 hours

Terminal: 30 hours

Time to peak serum concentration: I.M.: Within 30 minutes

Elimination: 50% to 70% of dose excreted in urine as active drug; not removed by hemodialysis

Refer to individual protocols; 1 unit = 1 mg

Children and Adults:

Test dose for lymphoma patients: I.M., I.V., S.C.: Because of the possibility of an anaphylactoid reaction, less than or equal to 2 units of bleomycin for the first 2 doses; monitor vital signs every 15 minutes; wait a minimum of 1 hour before administering remainder of dose; if no acute reaction occurs, then the regular dosage schedule may be followed

Single-agent therapy:

I.M./I.V./S.C.: Squamous cell carcinoma, lymphoma, testicular carcinoma: 0.25-0.5 units/kg (10-20 units/m²) 1-2 times/week

CIV: 15 units/m² over 24 hours daily for 4 days

Combination-agent therapy:

I.M./I.V.: 3-4 units/m²

I.V.: ABVD: 10 units/m² on days 1 and 15

Maximum cumulative lifetime dose: 400 units

Dosing adjustment in renal impairment:

Cl_cr 10-50 mL/minute: Administer 75% of normal dose

Cl_cr <10 mL/minute: Administer 50% of normal dose

Hemodialysis: None

CAPD effects: None

CAVH effects: None

Adults: Intracavitary injection for malignant pleural effusion: 60 international units (range of 15-120 units; dose generally does not exceed 1 unit/kg) in 50-100 mL SWI

Pulmonary function tests (total lung volume, forced vital capacity, carbon monoxide diffusion), renal function, chest x-ray, temperature initially, CBC with differential and platelet count

None reported

May rarely produce myelosuppression; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

You may experience loss of appetite, nausea, vomiting, mouth sores; small frequent meals, frequent mouth care with soft swab, frequent mouth rinses, sucking lozenges, or chewing gum may help. If unresolved notify prescriber. You may experience fever or chills (will usually resolve); redness, peeling, or increased color of skin, or loss of hair (reversible after cessation of therapy). Report any change in respiratory status; difficulty breathing; wheezing; air hunger; increased secretions; difficulty expectorating secretions; confusion; unresolved fever or chills; sores in mouth; vaginal itching, burning, or discharge; sudden onset of dizziness; or acute headache. Breast-feeding precautions: Breast-feeding is not recommended.

Patients should be closely monitored for signs of pulmonary toxicity; check body weight at regular intervals

Powder for injection, as sulfate: 15 units, 30 units

Alberts DS, Chen HS, Liu R, et al, "Bleomycin Pharmacokinetics in Man. I. Intravenous Administration," Cancer Chemother Pharmacol, 1978, 1(3):177-81.

Berg SL, Grisell DL, Delaney TF, et al, "Principles of Treatment of Pediatric Solid Tumors," Pediatr Clin North Am, 1991, 38(2):249-67.

D'Arcy PF, "Reactions and Interactions in Handling Anticancer Drugs," Drug Intell Clin Pharm, 1983, 17(7-8):532-8.

Goldmer P, Carlon GC, Cvitkovic E, et al, "Factors Influencing Postoperative Morbidity and Mortality in Patients Treated With Bleomycin," Br Med J, 1978, 1:1664.

Haisa T, Ueki K, and Yoshida S, "Toxic Effects of Bleomycin on the Hypothalamus Following Its Administration Into a Cystic Craniopharyngioma," Br J Neurosurg, 1994, 8(6):747-50.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement, "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Lamantia KR, Glick JH, and Marshall BE, "Supplemental Oxygen Does Not Cause Respiratory Failure in Bleomycin-Treated Surgical Patients," Anesthesiology, 1984, 60:65.

Lamey PJ and Lewis MAO, "Oral Medicine in Practice: White Patches," Br Dent J, 1990, 168(4):147-52.

Lazo JS and Sebti SM, "Bleomycin," Cancer Chemother Biol Response Modif, 1994, 15:44-50.

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Mir LM, Tounekti O, and Orlowski S, "Bleomycin: Revival of an Old Drug," Gen Pharmacol, 1996, 27(5):745-8.

Zanetti CL, "Scuba Diving and Bleomycin Therapy," JAMA, 1990, 264(22):2869.