Schedule H

Intravenous, Intramuscular, Subcutaneous, Intrapleural

• Injection: 15 units (lyophilised powder for reconstitution)

• Injection: 30 units (lyophilised powder for reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hodgkin Lymphoma (ABVD or Similar Regimens) — Adults

Parameter Recommendation

Starting dose 10 units/m² IV or IM on Days 1 and 15 of 28-day cycle

Titration Not applicable

Usual maintenance dose 10 units/m² per dose as per protocol

Maximum dose 20 units/m² per cycle; cumulative lifetime dose ≤400 units

Clinical Notes:

• Administer test dose (1–2 units IM/IV) before first full dose due to anaphylactoid reaction risk

• Part of ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine)

• Pulmonary function assessment mandatory before and during treatment

1. Testicular Germ Cell Tumours (BEP Regimen) — Adults

Parameter Recommendation

Starting dose 30 units IV on Days 1, 8, and 15 of each 21-day cycle

Titration Not applicable

Usual maintenance dose 30 units IV weekly as per BEP protocol

Maximum dose 30 units per dose; cumulative lifetime dose 360–400 units

Duration: Up to 3–4 cycles (typically 9–12 weekly doses)

Clinical Notes:

• Given with cisplatin and etoposide

• Monitor pulmonary function closely — DLCO before each cycle

• Cumulative dose must be strictly tracked

1. Squamous Cell Carcinoma (Head and Neck, Cervix, Oesophagus) — Adults

Parameter Recommendation

Starting dose 10–15 units/m² IV or IM once or twice weekly

Titration Not applicable

Usual maintenance dose 10–15 units/m² per dose

Maximum dose 15 units/m² per dose; cumulative lifetime dose ≤400 units

Duration: Response-guided; typically 4–8 weeks

Clinical Notes:

• May be used as single agent or in combination with radiotherapy for radiosensitisation

• Monitor for mucositis and pulmonary toxicity

1. Non-Hodgkin Lymphoma (CHOP-Bleo or Similar Regimens) — Adults

Parameter Recommendation

Starting dose 10–15 units/m² IV once weekly

Titration Not applicable

Usual maintenance dose 10–15 units/m² weekly

Maximum dose Cumulative lifetime dose ≤400 units

Clinical Notes:

• Used as part of combination chemotherapy regimens

• Less commonly used compared to other NHL protocols

1. Malignant Pleural Effusion (Intrapleural Sclerotherapy) — Adults

Parameter Recommendation

Starting dose 60 units diluted in 50–100 mL normal saline instilled intrapleurally

Titration Not applicable

Usual maintenance dose Single dose usually sufficient

Maximum dose 60 units per procedure; may repeat once if inadequate response

Procedure:

• Drain pleural effusion completely before instillation

• Clamp chest tube and retain drug for 4 hours with position changes

• Unclamp and allow drainage

Clinical Notes:

• Effective sclerosing agent for malignant effusions

• Fever common post-procedure — premedicate with paracetamol

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Kaposi's Sarcoma (AIDS-related) 10–15 units/m² IV every 1–2 weeks Response-guided OFF-LABEL • Specialist only • Part of ABV regimen (with vincristine, doxorubicin) • International case series

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Hodgkin Lymphoma (Paediatric Modified ABVD/OEPA-COPDAC)

≥5 years 5–10 units/m² IV Days 1 and 15 of each cycle (or as per protocol)

Parameter Recommendation

Starting dose 5–10 units/m² IV per protocol

Titration Not applicable

Usual maintenance dose As per specific protocol

Maximum dose 10 units/m² per dose; cumulative ≤200–300 units/m²

Clinical Notes:

• Paediatric oncologist supervision mandatory

• Pulmonary function tests before treatment and after cumulative dose reaches 100 units/m²

1. Germ Cell Tumours (Paediatric BEP/PEB Protocols)

Parameter Recommendation

Starting dose 10–15 units/m² IV weekly

Titration Not applicable

Usual maintenance dose 15 units/m² IV weekly × 6–9 doses

Maximum dose 15 units/m² per dose; cumulative limit applies

Duration: 6–9 weeks as part of combination chemotherapy

Safety Monitoring:

• Pulmonary function tests (DLCO, spirometry) before and during therapy

• Baseline chest X-ray; repeat if respiratory symptoms develop

• Complete blood count before each dose

• Avoid supplemental oxygen >30% FiO₂ during/after treatment

Secondary Indications — Paediatric (Off-label)

Not recommended for any non-oncologic use in children

Age Restrictions:

• Not recommended in children <5 years except under specialist paediatric oncology protocols

• Pulmonary toxicity risk increases significantly in younger children — extreme caution required

Notes:

• Bleomycin is not significantly removed by haemodialysis

• Monitor pulmonary function more closely in renal impairment — drug accumulation increases toxicity risk

• Known hypersensitivity to bleomycin or any component

• Severe pulmonary disease or significantly impaired pulmonary function (DLCO <35% predicted)

• History of bleomycin-induced pulmonary toxicity or pneumonitis

• Severe renal impairment (CrCl <15 mL/min) without capacity for close monitoring

• Elderly patients (age >70 years) — significantly increased pulmonary toxicity risk

• Renal impairment — drug accumulation leads to enhanced toxicity

• Prior or concurrent thoracic radiotherapy — synergistic pulmonary damage

• Cumulative dose approaching lifetime limit — pulmonary fibrosis risk escalates >200 units

• Concurrent or recent oxygen therapy — avoid FiO₂ >30% during and for months after bleomycin

• Smokers — increased pulmonary toxicity risk

• Pre-existing pulmonary disease

• Patients receiving concurrent nephrotoxic agents (e.g., cisplatin)

Parameter Information

Risk Category Contraindicated — Category D (teratogenic and fetotoxic in animal studies)

Overall Safety Avoid during pregnancy; documented fetal harm

Preferred Alternatives Defer treatment until after delivery if clinically feasible; alternative regimens without bleomycin if available

When May Be Used Only for life-threatening malignancy where no alternatives exist — oncologist + obstetrician joint decision

Monitoring Fetal growth surveillance; maternal pulmonary function; detailed anomaly scan

Parameter Information

Compatibility Not compatible with breastfeeding

Expected Milk Levels Unknown — presumed risk due to cytotoxicity

Preferred Alternatives Discontinue breastfeeding during treatment; do not express and store milk

Decision Breastfeeding must be stopped if treatment is essential

Infant Monitoring Not applicable — avoid exposure entirely

Parameter Recommendation

Starting dose Lower end of dose range (e.g., 10 units/m² maximum)

Titration Not applicable

Special considerations Significantly increased pulmonary toxicity risk in patients >70 years

Extra monitoring Baseline and serial pulmonary function tests (DLCO) every 2 cycles; renal function assessment

Risk factors Reduced renal reserve leads to drug accumulation; lower cumulative dose threshold (≤200–250 units recommended)

Interacting Drug Effect & Mechanism Management

High-flow Oxygen (>30% FiO₂) Dramatically increases risk of fatal pulmonary toxicity — oxygen free radical damage Avoid FiO₂ >30% during and for months post-bleomycin; communicate with anaesthesia team prior to any surgery

Filgrastim / Pegfilgrastim (G-CSF) May increase pulmonary toxicity risk Avoid concurrent use if possible; if essential, monitor pulmonary function closely

Cisplatin Decreases bleomycin clearance; enhanced pulmonary and renal toxicity Monitor renal function; adjust bleomycin dose for renal impairment

Cyclophosphamide Increased risk of pulmonary fibrosis Monitor pulmonary function closely

Brentuximab vedotin Increased pulmonary toxicity risk when combined Avoid combination

Interacting Drug Effect Management

Digoxin Reduced digoxin absorption and serum levels Monitor digoxin levels; adjust dose if needed

Phenytoin May reduce bleomycin efficacy; phenytoin levels may decrease Monitor phenytoin levels; assess treatment response

Live vaccines Risk of disseminated infection due to immunosuppression Avoid live vaccines during and for 3–6 months after treatment

Other nephrotoxic drugs Additive renal impairment affecting bleomycin clearance Monitor renal function; adjust bleomycin dose accordingly

• Fever and chills (occurs in 25–50% of patients; usually within hours of dose)

• Cutaneous reactions: hyperpigmentation, erythema, skin thickening

• Mucositis and stomatitis

• Nausea and vomiting (usually mild)

• Alopecia (less common than other cytotoxics)

• Raynaud's phenomenon

• Nail changes

• Injection site reactions

Adverse Effect Clinical Action

Pulmonary fibrosis / Interstitial pneumonitis Immediate discontinuation; supportive care; corticosteroids may be considered; potentially fatal

Anaphylactoid reaction (especially first dose) Immediate discontinuation; resuscitation measures; do not rechallenge

Severe idiosyncratic reaction (hypotension, fever, cardiorespiratory collapse) Immediate discontinuation; intensive supportive care

Flagellate dermatitis (linear hyperpigmentation) Usually self-limiting but characteristic — not dangerous

Severe mucositis Supportive care; dose modification for subsequent cycles

Note: Test dose (1–2 units IM or IV) recommended before first full dose to assess hypersensitivity risk

Before each dose Assess for respiratory symptoms (cough, dyspnoea); repeat pulmonary function if symptoms develop

Every 2–3 cycles Repeat DLCO — discontinue if DLCO decreases by >30% from baseline

Cumulative dose tracking Mandatory documentation; increased monitoring after cumulative dose exceeds 200 units

Long-term (post-treatment) Pulmonary function assessment for ≥6 months after treatment completion if cumulative dose >200 units

• Bleocel (Celon Labs)

• Bleocin (Zydus Cadila)

• Bleo (Biochem)

• Bleomycin (Khandelwal / Neon)

• Oncobleo (United Biotech)

FDCs: Not applicable

Note: Not included in NLEM 2022; significant price variation between government procurement and private retail. Available in government cancer centres.

• Always administer test dose (1–2 units IM or IV) before first full dose — anaphylactoid reactions can be fatal

• Pulmonary toxicity is the dose-limiting toxicity — track cumulative dose meticulously; limit to <400 units lifetime (ideally <250 units in elderly)

• Oxygen is dangerous post-bleomycin — inform anaesthetists and surgical teams to avoid FiO₂ >30% for at least 6 months post-treatment; even years later, perioperative oxygen can trigger acute lung injury

• Flagellate dermatitis (linear hyperpigmented streaks) is characteristic and diagnostic — not clinically dangerous but cosmetically distressing

• Fever post-infusion is common — not necessarily infection; premedicate with paracetamol and observe

• Renal function directly affects toxicity — always calculate eGFR and adjust dose before each administration

Bleomycin; antineoplastic; cytotoxic antibiotic; Hodgkin lymphoma; ABVD; BEP regimen; testicular cancer; germ cell tumour; pulmonary fibrosis; cumulative dose limit; pleurodesis; oxygen toxicity; oncology

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• AIIMS Oncology Treatment Protocols

• API Textbook of Medicine, 11th Edition

• ICMR Guidelines on Childhood Cancer Management

• Harrison's Principles of Internal Medicine, 21st Edition

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO Model List of Essential Medicines

• Published RCTs on ABVD and BEP regimens (supportive)