From the Guidelines
Azathioprine can be used in non-specific interstitial pneumonia (NSIP) with renal impairment, but dose adjustment is necessary based on creatinine clearance. For patients with reduced renal function, the initial dose should be at the lower end of the normal range (1-2 mg/kg/day) with close monitoring of complete blood counts and liver function tests. When creatinine clearance falls below 50 ml/min, consider reducing the dose by 25%; for clearance below 30 ml/min, reduce by 50%. Patients with severe renal impairment (clearance <10 ml/min) may require doses as low as 25% of standard. Monitor for myelosuppression more frequently in these patients, typically every 1-2 weeks initially, then monthly once stable. Azathioprine works in NSIP by suppressing T-cell function and reducing inflammation in lung tissue, potentially stabilizing or improving lung function. However, its efficacy must be balanced against increased risk of adverse effects in renal impairment, including bone marrow suppression and opportunistic infections. Consider TPMT testing before initiation to identify patients at higher risk for toxicity, as noted in studies such as 1.
Some key points to consider when using azathioprine in NSIP with renal impairment include:
- Dose adjustment based on creatinine clearance to minimize the risk of adverse effects
- Close monitoring of complete blood counts and liver function tests
- Consideration of TPMT testing to identify patients at higher risk for toxicity
- Potential benefits of azathioprine in reducing inflammation and stabilizing lung function, as supported by guidelines such as those from the American College of Rheumatology 1
- Importance of balancing the efficacy of azathioprine against the potential risks of adverse effects in patients with renal impairment, as discussed in studies such as 1.
Overall, the use of azathioprine in NSIP with renal impairment requires careful consideration of the potential benefits and risks, as well as close monitoring and dose adjustment to minimize the risk of adverse effects.
From the FDA Drug Label
Use in Renal Dysfunction: Relatively oliguric patients, especially those with tubular necrosis in the immediate postcadaveric transplant period, may have delayed clearance of AZASAN or its metabolites, may be particularly sensitive to this drug, and are usually given lower doses.
The dose of azathioprine should be reduced in patients with renal dysfunction, especially those who are relatively oliguric.
- Key consideration: Patients with renal dysfunction may have delayed clearance of azathioprine or its metabolites and may be particularly sensitive to the drug.
- Dosing recommendation: Lower doses are usually given to patients with renal dysfunction. However, the label does not provide a specific creatinine clearance limit for azathioprine use in ILD NSIP patients 2.
From the Research
Azathioprine in ILD NSIP
- Azathioprine is an immunosuppressive medication that may be used in the treatment of idiopathic non-specific interstitial pneumonia (NSIP) 3, 4, 5.
Creatinine Clearance Limit
- There is no specific information in the provided studies regarding the use of azathioprine in ILD NSIP with creatinine clearance limit 3, 6, 4, 7, 5.
Treatment of ILD NSIP
- Treatment of idiopathic NSIP is generally instituted in the form of immunosuppression, although the optimal approach to management is still uncertain 3, 4, 5.
- Patients with fibrotic, progressive, and immunosuppressive treatment-refractory NSIP may require alternative treatment strategies such as lung transplantation 6, 4, 5.
Disease Characteristics
- NSIP is an interstitial lung disease that may be idiopathic or secondary to connective tissue disease, toxins, or numerous other causes 3, 7.
- Idiopathic NSIP is a rare diagnosis and requires exclusion of these other possible causes 3.
- Patients typically present in mid-adulthood with dyspnoea, cough, and often constitutional symptoms including fever and fatigue 3, 5.