BLEOMYCIN SULFATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BLEOMYCIN SULFATE (BLEOMYCIN SULFATE).
Bleomycin acts by chelating metal ions (primarily iron) and producing reactive oxygen species that cause single- and double-strand DNA breaks, leading to inhibition of DNA, RNA, and protein synthesis.
| Metabolism | Primarily inactivated by the enzyme bleomycin hydrolase, a cysteine protease found in many tissues except the lungs and skin. Renal excretion accounts for 60-70% of clearance. |
| Excretion | Renal: 60-70% unchanged; impaired renal function necessitates dose adjustment. |
| Half-life | 2-4 hours; prolonged in renal impairment up to 20+ hours. |
| Protein binding | 1-2% bound; primarily to albumin. |
| Volume of Distribution | 0.2-0.4 L/kg; limited tissue distribution, low CNS penetration. |
| Bioavailability | IM: 50-70%; topical: minimal systemic absorption. |
| Onset of Action | IM/IV: within hours; intralesional/pleural: variable, 1-2 weeks for sclerotherapy. |
| Duration of Action | Antineoplastic effect persists for weeks; pleural sclerotherapy effect lasts 2-4 weeks. |
10-20 units/m2 IV, IM, or SC once weekly or twice weekly; cumulative lifetime dose should not exceed 400 units. For Hodgkin lymphoma, 10 units/m2 IV on days 1 and 15 of a 28-day cycle.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 10-50 mL/min: reduce dose by 25-50%; CrCl <10 mL/min: reduce dose by 50-75%; consider alternative agent if CrCl <10 mL/min. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or reduce dose by 75% and monitor closely. |
| Pediatric use | For Hodgkin lymphoma: 10 units/m2 IV on days 1 and 15 of a 28-day cycle; for testicular cancer: 30 units/m2 IV weekly for 12 weeks. Maximum cumulative dose 400 units. |
| Geriatric use | No specific dose adjustment beyond renal function; initiate at lower end of dosing range (e.g., 10 units/m2) due to decreased renal function and increased risk of pulmonary toxicity; monitor pulmonary function closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BLEOMYCIN SULFATE (BLEOMYCIN SULFATE).
| Breastfeeding | Excretion into human milk unknown; M/P ratio not established. Due to potential for serious adverse reactions (e.g., pulmonary toxicity) in nursing infants, discontinue breastfeeding or drug. |
| Teratogenic Risk | Pregnancy Category D. First trimester: Avoid due to teratogenic potential (case reports of skeletal anomalies, growth retardation). Second and third trimesters: Use only if clearly needed; risk of fetal harm (pulmonary fibrosis, growth restriction). |
| Fetal Monitoring |
■ FDA Black Box Warning
Pulmonary fibrosis, including fatal outcomes, occurs in up to 10% of patients. Risk factors include age >70, cumulative doses >400 units, concomitant thoracic radiation, and lung disease. Monitor for pulmonary toxicity with chest imaging and pulmonary function tests.
| Serious Effects |
["Hypersensitivity to bleomycin sulfate or any component of the formulation","Significant pre-existing pulmonary disease (e.g., severe restrictive or obstructive lung disease)"]
| Precautions | ["Pulmonary toxicity (pneumonitis, fibrosis): monitor symptoms, chest X-ray, and pulmonary function tests (DLCO).","Renal impairment: reduce dose; monitor renal function.","Hematologic toxicity: myelosuppression (leukopenia, thrombocytopenia, anemia).","Hypersensitivity reactions: may present as fever, chills, anaphylaxis; test dose recommended for lymphoma patients.","Dermatologic toxicity: hyperpigmentation, nail changes, erythema, blistering."] |
| Food/Dietary | No major food interactions. However, avoid concurrent intake of foods that may cause respiratory irritation. Maintain adequate hydration. No specific restrictions. |
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| Maternal: Pulmonary function tests (DLCO, FVC) every 1-2 weeks; renal function; complete blood counts; chest imaging for pneumonitis. Fetal: Serial ultrasound for growth and anatomy; non-stress test if used near term. |
| Fertility Effects | Associated with gonadal toxicity; may cause azoospermia in males and ovarian failure in females; reversible in some cases; use fertility preservation strategies if appropriate. |
| Clinical Pearls | Bleomycin is associated with dose-dependent pulmonary toxicity; cumulative doses >400 U increase risk. Monitor for pneumonitis; consider holding if acute decline in DLCO or new infiltrates. Administer test dose (1-2 U) in lymphoma patients to avoid anaphylaxis. Can cause hyperpigmentation and flagellate erythema. Use with caution in renal impairment (CrCl <35 mL/min) as clearance is reduced. Concomitant oxygen therapy during surgery may precipitate pulmonary fibrosis. |
| Patient Advice | Report any new cough, shortness of breath, or fever, as these may indicate lung inflammation. · Avoid excessive sun exposure; use sunscreen to prevent skin discoloration. · Nausea and vomiting may occur; take antiemetics as prescribed. · Bleomycin can cause hair loss, but it is usually reversible. · Skin changes, including dark streaks and nail changes, are common and not dangerous. · Do not smoke; it increases the risk of lung toxicity. |