Bleomycin Sulfate

Approved Indications

• Hodgkin’s Lymphoma: Part of combination chemotherapy (e.g., ABVD regimen).
• Non-Hodgkin’s Lymphoma: Used in selected protocols.
• Testicular Cancer: Especially effective in germ cell tumors as part of BEP regimen.
• Squamous Cell Carcinomas of:
• Head and neck region
• Cervix
• Penis
• Vulva
• Skin
• Malignant Pleural Effusion: For pleurodesis to reduce recurrent effusion.

Off-label (Clinically Accepted) Uses

• Cutaneous warts and genital warts (intralesional injection)
• Kaposi’s Sarcoma
• Chylothorax and pericardial effusion sclerotherapy

Adults

• Cancer Chemotherapy (IV/IM/Subcutaneous):
  Usual dose: 10–20 units/m² once or twice weekly.
  Maximum cumulative dose: 400 units due to pulmonary toxicity risk.
• Malignant Pleural Effusion (Intrapleural):
  60 units diluted in 100 mL normal saline instilled via chest tube.

Pediatrics

• Hodgkin’s lymphoma (off-label):
  5–10 units/m² per dose, typically every 1–2 weeks as per protocol.

Elderly

• Dose adjustment may be required based on renal function and increased susceptibility to pulmonary toxicity.

Renal Impairment

• Dose reduction required. Monitor renal function and adjust accordingly.

Hepatic Impairment

• No specific guidelines; use with caution.

Administration Routes: IV, IM, Subcutaneous, Intrapleural, Intralesional.
Frequency & Duration: Varies by indication; often used in cycles every 2–3 weeks.

Bleomycin Sulfate binds to DNA and induces single- and double-strand breaks through the generation of free radicals, primarily mediated by the presence of iron and oxygen. The DNA cleavage results in the inhibition of DNA synthesis and cell cycle arrest, particularly at the G2 and M phases, leading to apoptosis. Bleomycin exhibits cytotoxic effects on rapidly dividing cells, especially malignant cells.

• Absorption: Poor oral absorption; administered parenterally.
• Distribution: Widely distributed; low penetration into CNS.
• Protein Binding: ~1%.
• Metabolism: Inactivated by bleomycin hydrolase; enzyme levels are low in the lungs and skin.
• Half-life: Approximately 2–4 hours in patients with normal renal function.
• Excretion: Primarily renal (urine), unchanged.

• Pregnancy: Category D (positive evidence of fetal risk); use only if potential benefit justifies risk.
• Lactation: Unknown if excreted in human milk. Avoid breastfeeding or discontinue the drug due to potential for serious adverse effects in infants.
• Caution: Recommended in both pregnancy and breastfeeding due to lack of human safety data and risk of toxicity.

• Primary Class: Antineoplastic Agent
• Subclass: Cytotoxic Antibiotic (Glycopeptide antibiotic from Streptomyces verticillus)

• Known hypersensitivity to Bleomycin or any component of the formulation
• Pulmonary fibrosis or severe lung disease
• Concurrent use of high concentrations of oxygen (e.g., in surgery)
• Pregnancy (unless benefits outweigh risks)
• Severe renal impairment without ability to monitor drug levels

• Pulmonary Toxicity: Dose-limiting toxicity; monitor for dry cough, dyspnea, or infiltrates on imaging. Risk increases with age, renal impairment, or cumulative dose >400 units.
• Anaphylaxis/Idiosyncratic Reactions: Particularly in lymphoma patients; test dose may be used.
• Renal Impairment: Risk of toxicity increases; monitor renal function and adjust dose accordingly.
• Mucocutaneous Toxicity: Rash, hyperpigmentation, stomatitis, and nail changes can occur.
• Fever/Chills: Common; may require symptomatic management.
• Monitoring: Regular pulmonary function tests, renal function tests, complete blood count (CBC), and chest imaging.

Common

• Pulmonary: Cough, dyspnea, pulmonary infiltrates, pneumonitis
• Skin: Hyperpigmentation, erythema, rash, desquamation, ulcers
• Gastrointestinal: Anorexia, stomatitis, nausea
• Systemic: Fever, chills

Serious

• Pulmonary Fibrosis (may be fatal)
• Anaphylaxis or hypotensive shock
• Renal toxicity
• Myelosuppression (less than other antineoplastics)
• Vascular thrombosis (rare)

Rare

• Cardiac toxicity
• Alopecia
• Skin ulceration at injection site

• High inspired oxygen concentration: Enhances risk of pulmonary toxicity.
• Cisplatin: May enhance nephrotoxicity and reduce bleomycin clearance.
• Filgrastim (G-CSF): Increases risk of pulmonary complications.
• Live vaccines: Avoid due to immunosuppression.

Enzyme Systems: Not significantly metabolized by CYP450; primarily inactivated by bleomycin hydrolase.

• NCCN & ESMO Guidelines: Continue to support use of bleomycin in Hodgkin’s lymphoma and testicular cancer, but emphasize pulmonary monitoring and limiting cumulative doses.
• FDA Safety Alerts: No recent black box updates, but recommendations highlight pulmonary monitoring and avoidance in patients requiring high oxygen support.
• Global Trends: Shift towards bleomycin-sparing regimens (e.g., AVD instead of ABVD in Hodgkin’s lymphoma) in certain patient populations.

• Storage Temperature: 2°C to 8°C (refrigerated)
• Protection: Store in original container; protect from light
• Reconstitution: Use sterile water for injection; use immediately or store reconstituted solution at 2°C to 8°C for up to 24 hours
• Handling Precautions: Cytotoxic—use protective equipment during preparation and disposal. Avoid contact with skin and mucous membranes.