Schedule H

Oral, Intravenous (IV)

• Tablet: 25 mg, 50 mg

• Injection: 100 mg/vial (lyophilized powder for reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Renal Transplant – Prevention of Graft Rejection

Parameter Details

Starting dose 3–5 mg/kg/day orally or IV (initiate on day of transplant)

Titration Reduce gradually to maintenance over several weeks

Usual maintenance dose 1–3 mg/kg/day orally once daily

Maximum dose 5 mg/kg/day

Clinical notes Typically combined with corticosteroids ± calcineurin inhibitors

1. Autoimmune Hepatitis

Parameter Details

Starting dose 1–2 mg/kg/day orally

Titration Increase by 0.5 mg/kg/day every 1–2 weeks based on LFTs and tolerability

Usual maintenance dose 1–2 mg/kg/day

Maximum dose 2.5 mg/kg/day

Clinical notes Assess TPMT activity and baseline LFTs before initiation; used as steroid-sparing agent

1. Inflammatory Bowel Disease (Crohn's Disease, Ulcerative Colitis – Maintenance)

Parameter Details

Starting dose 1–1.5 mg/kg/day orally

Titration Increase to 2–2.5 mg/kg/day over 2–4 weeks

Usual maintenance dose 2–2.5 mg/kg/day orally once daily

Maximum dose 2.5 mg/kg/day

Clinical notes Delayed onset of action (8–12 weeks); bridge with corticosteroids initially

1. Rheumatoid Arthritis (DMARD)

Parameter Details

Starting dose 1 mg/kg/day orally (single or divided dose)

Titration Increase by 0.5 mg/kg every 4 weeks based on response and blood counts

Usual maintenance dose 1–2.5 mg/kg/day orally

Maximum dose 3 mg/kg/day (under specialist supervision)

Clinical notes Usually second-line after methotrexate failure or intolerance

Secondary Indications – Adults Only (Off-label)

Indication Dose Duration Supervision Evidence Basis

Systemic Lupus Erythematosus (maintenance) – OFF-LABEL 1–2.5 mg/kg/day orally Long-term relapse prevention Specialist only AIIMS protocols, Indian rheumatology specialist practice

Pemphigus Vulgaris and Autoimmune Blistering Diseases – OFF-LABEL 1–3 mg/kg/day orally Taper based on clinical response Specialist only Indian dermatology specialist consensus

Myasthenia Gravis – OFF-LABEL Start 50 mg/day, increase to 2–3 mg/kg/day Long-term; latent onset 3–12 months Specialist only Indian neurology protocols; corticosteroid-sparing agent

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Renal Transplant (Prevention of Rejection)

Parameter Details

Age >1 year

Starting dose 2–2.5 mg/kg/day orally

Titration Adjust based on CBC and clinical response

Usual maintenance dose 1–3 mg/kg/day once daily

Maximum dose 3 mg/kg/day

Clinical notes TPMT enzyme testing advised before initiation (if feasible); monitor CBC, LFT every 1–2 weeks initially

1. Inflammatory Bowel Disease (Maintenance)

Parameter Details

Age >6 years (younger under specialist supervision)

Starting dose 1.5 mg/kg/day orally

Titration Increase based on leukocyte counts and tolerability

Usual maintenance dose 1.5–2.5 mg/kg/day as single daily dose

Maximum dose 2.5 mg/kg/day

Clinical notes Delayed onset (6–12 weeks); corticosteroid-sparing; monitor for GI intolerance and myelosuppression

Secondary Indications – Paediatric Doses (Off-label)

Indication Dose Duration Supervision Evidence Basis

Autoimmune Hepatitis – OFF-LABEL 1–2 mg/kg/day orally Long-term steroid-sparing Specialist only IAP hepatology guidelines

Lupus Nephritis – OFF-LABEL 1–2.5 mg/kg/day orally Long-term maintenance Specialist only Indian paediatric nephrology protocols

Age Restriction: Not recommended under 1 year of age except under specialist supervision.

Mild–Moderate impairment No specific dose adjustment required

Severe impairment (CrCl <30 mL/min) Initiate at lower end of dosing range; monitor closely for myelosuppression

Haemodialysis Not significantly dialysed; dosing unchanged post-dialysis

Peritoneal dialysis No specific adjustment; monitor blood counts

• Known hypersensitivity to azathioprine or 6-mercaptopurine

• Complete TPMT deficiency (risk of fatal myelotoxicity)

• Severe active bone marrow suppression

• Concurrent use with febuxostat (absolute contraindication)

• Pregnancy (unless clearly indicated for life-threatening conditions under specialist guidance)

• Partial TPMT deficiency (increased risk of myelosuppression – consider dose reduction)

• Chronic viral infections (risk of HBV, CMV reactivation)

• History of pancreatitis or severe gastrointestinal intolerance

• Prior or current malignancy (increased lymphoma risk with long-term use)

• Avoid administration of live vaccines during therapy

• Elderly patients with reduced marrow and renal reserve

Parameter Details

Risk category Use only if essential and clearly justified (teratogenic in animal studies; human data suggest fetal risk but may be acceptable in certain conditions)

When it may be used Transplant maintenance, severe autoimmune disease where no safer alternative exists; under specialist immunology/nephrology supervision

Preferred alternatives Mycophenolate is contraindicated; azathioprine may be preferred immunosuppressant in pregnancy if required

What to monitor Fetal growth (serial ultrasound), maternal CBC, LFTs

Parameter Details

Compatibility Generally compatible with breastfeeding

Drug levels in milk Low (small amounts excreted)

Preferred alternatives None clearly superior for transplant/autoimmune indications

What to monitor in infant CBC periodically, growth parameters, signs of infection

Parameter Recommendation

Starting dose Begin at lower end (0.5–1 mg/kg/day)

Titration Slower titration advised

Special risks Higher susceptibility to myelotoxicity and infections; reduced renal/marrow reserve

Monitoring More frequent CBC and renal function testing

Drug Interaction Management

Febuxostat Markedly increased azathioprine toxicity (impaired metabolism) Contraindicated – Do not co-administer

Allopurinol Inhibits xanthine oxidase → increased 6-MP levels → severe myelosuppression Reduce azathioprine dose to 25–33% of usual; monitor CBC closely

Ribavirin Antagonises azathioprine metabolism → severe bone marrow toxicity Avoid combination; if unavoidable, close haematological monitoring

Live vaccines (MMR, Varicella, BCG, OPV) Risk of disseminated infection due to immunosuppression Contraindicated during therapy

Warfarin Decreased anticoagulant effect (enhanced warfarin metabolism) Monitor INR; warfarin dose increase may be required

Drug Interaction Management

Cotrimoxazole Additive bone marrow suppression Monitor CBC regularly

Aminosalicylates (mesalamine, sulfasalazine) May inhibit TPMT activity → increased azathioprine toxicity Use lower azathioprine doses; monitor closely

Methotrexate Additive myelosuppression Avoid if possible; if used together, intensive haematological monitoring

Cyclosporine May alter azathioprine efficacy and toxicity profile Specialist titration required

ACE inhibitors Enhanced risk of leukopenia Monitor WBC counts

Inactivated vaccines Reduced immunological response Safe to administer but may require serological confirmation of immunity

• Nausea, vomiting

• Anorexia

• Skin rash

• Mild transaminase elevation

• Leukopenia (dose-related)

• Mild thrombocytopenia

• Fatigue, malaise

• Mild alopecia

Adverse Effect Clinical Significance

Severe myelosuppression (neutropenia, pancytopenia) May require discontinuation; often reversible

Acute pancreatitis More common in IBD patients; discontinue permanently

Hepatotoxicity (cholestatic jaundice) Discontinue; may require specialist evaluation

Hypersensitivity syndrome Fever, rash, vasculitis, hypotension; stop immediately

Lymphoproliferative disorders and malignancies Increased risk with chronic use, especially in transplant recipients; regular screening advised

Phase Parameters Frequency

Baseline CBC, LFTs, renal function, TPMT activity (if available), HBV/HCV serology Before initiation

First 3 months CBC with differential, LFTs Every 1–2 weeks

Long-term (>3 months) CBC, LFTs Every 1–2 months

Additional Skin examination for malignancy Annually in long-term users

• Azoran® (Ipca)

• Imuran® (GSK)

• Azamune® (Samarth)

• Azapure® (Intas)

• Transimune® (Glenmark)

Fixed-dose combinations are uncommon; mostly available as monotherapy.

Not currently listed under NLEM; prices vary by brand and retailer.

1. TPMT testing is crucial — Perform before initiation if accessible; prevents potentially fatal myelosuppression in deficient patients.

1. Febuxostat is absolutely contraindicated — Severe and sometimes fatal toxicity has been reported; use allopurinol with dose reduction if xanthine oxidase inhibition is essential.

1. Expect delayed benefit — Therapeutic effect in autoimmune conditions takes 6–12 weeks; bridge with corticosteroids initially.

1. Managing nausea — Dividing the daily dose or administering after meals can improve tolerability.

1. Leukopenia management — If WBC drops significantly, withhold drug; usually reversible upon discontinuation.

1. Pregnancy consideration — Among immunosuppressants, azathioprine is relatively preferred over mycophenolate in pregnant patients requiring immunosuppression; specialist input mandatory.

azathioprine; immunosuppressant; transplant; autoimmune-hepatitis; IBD; Crohn-disease; ulcerative-colitis; DMARD; corticosteroid-sparing; TPMT; pregnancy-caution; renal-safe

RxIndia v1.0 — 14 May 2025

• CDSCO approved product inserts

• Indian National Formulary (NFI)

• AIIMS Pharmacology Handbook

• API Textbook of Medicine

• ICMR IBD and Transplant Guidelines

• Indian Society of Nephrology Protocols

• Indian Dermatology Expert Consensus

• IAP Paediatric Guidelines

• WHO Essential Medicines List (supportive reference only)