There have been no studies in pregnant women. If Bleomycin is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant during therapy with Bleomycin.
Precautions
General
Patients with creatinine clearance values of less than 50 mL/min should be treated with caution and their renal function should be carefully monitored during the administration of Bleomycin. Lower doses of Bleomycin may be required in these patients than those with normal renal function (see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION).
Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of Bleomycin in humans is unknown. A study in F344-type male rats demonstrated an increased incidence of nodular hyperplasia after induced lung carcinogenesis by nitrosamines, followed by treatment with Bleomycin. In another study where the drug was administered to rats by subcutaneous injection at 0.35 mg/kg weekly (3.82 units/m2 weekly or about 30% at the recommended human dose), necropsy findings included dose-related injection site fibrosarcomas as well as various renal tumors. Bleomycin has been shown to be mutagenic both in vitro and in vivo. The effects of Bleomycin on fertility have not been studied.
Pregnancy
Pregnancy Category D
(see WARNINGS section).
Nursing Mothers
It is not known whether the drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that nursing be discontinued by women receiving Bleomycin therapy.
Pediatric Use
Safety and effectiveness of Bleomycin in pediatric patients have not been established.
Geriatric Use
In clinical trials, pulmonary toxicity was more common in patients older than 70 years than in younger patients (see BOXED WARNING, WARNINGS, and ADVERSE REACTIONS, Pulmonary). Other reported clinical experience has not identified other differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Bleomycin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Adverse Reactions
Pulmonary
The most serious side effects are pulmonary adverse reactions, occurring in approximately 10% of treated patients. The most frequent presentation is pneumonitis occasionally progressing to pulmonary fibrosis. Approximately 1% of patients treated have died of pulmonary fibrosis. Pulmonary toxicity is both dose and age related, being more common in patients over 70 years of age and in those receiving over 400 units total dose. This toxicity, however, is unpredictable and has been seen in young patients receiving low doses.
Some published reports have suggested that the risk of pulmonary toxicity may be increased when Bleomycin is used in combination with G-CSF (filgrastim) or other cytokines. However, randomized clinical studies completed to date have not demonstrated an increased risk of pulmonary complications in patients treated with Bleomycin and G-CSF.
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