Azathioprine Initial Dosing Protocol
The initial dose of azathioprine (Imuran) should be 50 mg daily for the first month of therapy, with dose increases considered after this period based on clinical response and laboratory monitoring. 1, 2
Initial Dosing Strategy
- Start azathioprine at 50 mg daily (approximately 1 mg/kg/day for most adults) to minimize early gastrointestinal side effects 1, 3
- Take medication with or shortly after food to reduce nausea 1
- Consider splitting the daily dose if gastrointestinal symptoms occur 1
- Maintain this initial dose for at least 4 weeks before considering dose increases 1, 2
Dose Escalation Protocol
- After the initial 4-week period, if no adverse effects are observed and clinical response is inadequate, increase the dose by 0.5 mg/kg/day (approximately 25 mg) 3, 4
- Continue dose increases at 4-week intervals until therapeutic response is achieved or maximum dose of 2.5 mg/kg/day is reached 3, 4
- Return to weekly blood monitoring (FBC and LFTs) for 4 weeks after each dose increase 1
- Doses above 2.5 mg/kg/day are associated with increased toxicity and limited additional benefit 4
Pre-Treatment Assessment
- Check thiopurine methyltransferase (TPMT) activity prior to initiating therapy 1, 2
- For normal TPMT activity: proceed with standard dosing protocol 1
- For intermediate (heterozygous) TPMT activity: reduce dose (1-1.5 mg/kg/day) 1, 3
- For absent (homozygous deficient) TPMT activity: azathioprine is contraindicated 1, 3
- Obtain baseline laboratory tests including complete blood count and liver function tests 1
Monitoring Protocol
- Monitor full blood count (FBC) and liver function tests (LFTs) weekly for the first 4 weeks of therapy 1
- Continue weekly monitoring until maintenance dose is achieved 1
- After stable maintenance dose is established, reduce monitoring frequency to a minimum of once every 3 months 1
- Instruct patients to report immediately any evidence of infection, unexpected bruising, bleeding, or jaundice 1
Common Pitfalls and Caveats
- Early nausea is common and often self-limiting; avoid premature discontinuation 1
- Isolated lymphopenia is common and may not require dose reduction unless levels fall below 0.5 × 10^9/L 1
- If no therapeutic response is observed within 3 months of starting azathioprine, consider withdrawing the medication 1
- Azathioprine has a slow onset of action with therapeutic response typically occurring after 6-8 weeks of treatment 1
- Patients with hepatic or renal impairment require more frequent monitoring and potentially lower doses 1
- Elderly patients should receive doses at the lower end of the recommended range 1
Special Considerations
- Avoid concomitant use with allopurinol, which inhibits xanthine oxidase and prolongs azathioprine action, potentially increasing toxicity 1
- Live vaccines are contraindicated during azathioprine therapy 1
- Patients who have not had chickenpox should seek immediate attention if exposed to varicella zoster virus 1
- Long-term treatment beyond 10 years and cumulative doses above 600g may increase malignancy risk 5