Azathioprine Dosing in Inflammatory Myopathy
The recommended dose of azathioprine for inflammatory myopathy is 2 mg/kg of ideal body weight per day, typically starting at 25-50 mg/day and gradually increasing to the target dose. 1
Dosing Protocol
Initial Dosing and Titration
- Start with 25-50 mg/day
- Increase by 25-50 mg weekly increments until reaching the target dose
- Target dose: 2 mg/kg of ideal body weight per day (not actual body weight)
- May be administered in divided doses to improve tolerance
Pre-Treatment Assessment
- Check thiopurine methyltransferase (TPMT) level before starting therapy
- Patients with TPMT deficiency are at high risk for severe myelosuppression
- Very low or absent TPMT activity is a contraindication to azathioprine use 1
- Baseline laboratory tests:
- Complete blood count
- Liver function tests
- Renal function tests
- Screening for hepatitis B and C
Monitoring and Safety
Laboratory Monitoring
- Weekly blood tests (CBC and liver function tests) until maintenance dose is achieved
- Once stable, reduce monitoring frequency to a minimum of once every 3 months 1
- More frequent monitoring for patients with:
- Higher doses
- Hepatic or renal impairment
- Low TPMT activity
Common Adverse Effects
- Gastrointestinal: nausea, loose stools
- Less common: fever, liver toxicity 1
- Serious: myelosuppression (leucopenia, thrombocytopenia) 2
Clinical Efficacy
Azathioprine serves as a steroid-sparing agent in inflammatory myopathy treatment. It is slow-acting and may take 3-6 months to reach full efficacy 1. While it has shown improvement in muscle strength, the evidence for superiority over other agents (methotrexate, mycophenolate mofetil) is limited.
Special Considerations
Drug Interactions
- Avoid concurrent use with allopurinol as this can cause significant myelosuppression 1
- Adjust dosing in patients with renal or hepatic impairment
Contraindications
- Very low or absent TPMT activity
- Pregnancy (except where benefit outweighs risk)
- Breastfeeding
- Known hypersensitivity to azathioprine
- Concurrent allopurinol treatment
- Active malignancy 1
Treatment Duration and Response Assessment
- If no improvement occurs within 3 months, consider withdrawing azathioprine 1
- For patients with incomplete response, consider:
- Increasing dose up to 2.5 mg/kg/day (doses >2.5 mg/kg/day are less likely to be efficacious and have higher risk of adverse effects) 3
- Alternative immunosuppressive agents like mycophenolate mofetil or methotrexate
Azathioprine is typically used in combination with corticosteroids, with the goal of eventually tapering and discontinuing the corticosteroid while maintaining disease control on azathioprine alone.