Bleomycin A2

Summary

Bleomycin A2 is the predominant active component (~60–70%) of the clinically used bleomycin sulfate mixture. It is a glycopeptide-derived antineoplastic agent used primarily for squamous cell carcinomas, Hodgkin's and non-Hodgkin's lymphomas, and testicular germ cell tumors. Its notable toxicity profile includes pulmonary fibrosis, which limits cumulative dosing.

Mechanism of Action

Bleomycin A2 intercalates into DNA and, in the presence of Fe(II) and oxygen, generates free radicals that cause single- and double-strand DNA breaks, leading to cell death. It also inhibits DNA ligase and has minimal inhibitory effects on RNA and protein synthesis.

Routes of Administration

Goals & Uses

• Testicular germ cell tumor treatmentOncologyHigh
• Hodgkin's lymphoma treatmentOncologyHigh
• Squamous cell carcinoma treatmentOncologyHigh
• Malignant pleural effusion sclerotherapyPalliative OncologyModerate
• Non-Hodgkin's lymphoma treatmentOncologyModerate

Contraindications

• Significant pre-existing pulmonary diseasePulmonaryHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Hypersensitivity to bleomycinAllergy/immunologyHigh
• Severe renal impairment (CrCl <25 mL/min)RenalHigh
• Prior severe pulmonary toxicity from bleomycinPulmonaryHigh

Adverse Effects

• Pulmonary fibrosis / pneumonitisPulmonaryUncommon
• Mucocutaneous toxicity (skin thickening, hyperpigmentation, rash)DermatologicCommon
• Fever and chillsConstitutionalCommon
• Nausea and vomitingGastrointestinalCommon
• Raynaud's phenomenonVascularUncommon
• Anaphylactoid reactionsImmunologicUncommon

Drug Interactions

• Live vaccinesHigh
• Supplemental oxygen (high FiO2)High
• CisplatinHigh
• Vinca alkaloids (vincristine, vinblastine)Moderate
• Granulocyte colony-stimulating factors (G-CSF)Moderate

Population Constraints

• SmokersLifestyleRelative
• Elderly patients (≥70 years)AgeRelative
• Pediatric patientsAgeRelative
• Patients requiring general anesthesiaProceduralRelative
• Patients with renal impairmentOrgan ImpairmentRelative

Regulatory Status

• European UnionApprovedApproved: Squamous cell carcinoma, Hodgkin's and non-Hodgkin's lymphoma, Testicular germ cell tumors, Malignant pleural effusionAvailable through national authorizations in EU member states; indicated as bleomycin sulfate mixture.
• United StatesApprovedApproved: Squamous cell carcinoma (head, neck, skin, esophagus, genitourinary tract), Hodgkin's lymphoma, Non-Hodgkin's lymphoma, Testicular carcinoma, Malignant pleural effusion (sclerotherapy)Approved as bleomycin sulfate (mixture of A2 and B2); marketed under Blenoxane and generics. FDA-approved since 1973.
• United KingdomApprovedApproved: Squamous cell carcinoma, Hodgkin's lymphoma, Testicular tumors, Malignant pleural effusionLicensed in the UK as bleomycin sulfate; MHRA-regulated. Available as generic formulation.

Approved as part of the bleomycin sulfate mixture by the FDA. The mixture contains bleomycin A2 and B2 as primary components. Individual fractions are not separately approved but are covered under the bleomycin sulfate NDA. Cumulative dose limits (typically ≤400 units lifetime) are recommended to reduce pulmonary toxicity risk.

Evidence & Sources

No sources recorded yet.