Is it safe to take prednisone and Imuran (azathioprine) at the same time of day in terms of liver function?

Taking Prednisone and Azathioprine (Imuran) Together: Liver Safety Considerations

It is safe to take prednisone and azathioprine (Imuran) at the same time of day, as there is no evidence of increased hepatotoxicity when these medications are taken simultaneously. 1

Standard Treatment Regimens

• The recommended treatment regimen for autoimmune hepatitis includes prednisolone (prednisone) initially at 30 mg/day (reducing to 10 mg/day over 4 weeks) plus azathioprine 1 mg/kg/day, with both medications typically administered together 1
• This combination therapy is considered the preferred treatment approach due to lower occurrence of corticosteroid-related side effects compared to higher-dose prednisone regimens alone (10% versus 44%) 1
• Guidelines specifically recommend the concurrent use of these medications without any timing separation requirements 1

Liver-Related Considerations

• Hepatotoxicity from azathioprine occurs in less than 1% of patients with autoimmune conditions and is generally reversible after interruption of the medication 2
• Monitoring of liver function is recommended regardless of medication timing:
  • Regular liver function tests should be performed to detect any potential hepatotoxicity 1
  • Periodic measurement of serum transaminases, alkaline phosphatase, and bilirubin is indicated for early detection of hepatotoxicity 2

Important Precautions

• TPMT (thiopurine methyltransferase) measurement should be considered before starting azathioprine to exclude homozygote TPMT deficiency, especially in patients with pre-existing leucopenia 1, 2
• Patients with low or absent TPMT activity are at increased risk for severe myelosuppression from azathioprine 2
• If taking azathioprine with allopurinol or febuxostat (xanthine oxidase inhibitors), dose reduction of azathioprine is necessary as these medications can increase azathioprine toxicity 2

Monitoring Recommendations

• Complete blood counts should be performed:
  • Weekly during the first month
  • Twice monthly for the second and third months
  • Monthly thereafter or more frequently if dosage changes are necessary 2
• Liver function tests should be monitored regularly to detect any potential hepatotoxicity 1, 2
• Bone mineral density should be assessed at 1-2 year intervals while on steroids, with calcium and vitamin D supplementation recommended 1

Special Considerations

• In patients with impaired liver function, the metabolism of prednisone may be affected, leading to increased exposure to the biologically active unbound prednisolone 3
• However, this does not necessitate taking the medications at different times of day, but rather may require dose adjustments based on clinical response and monitoring 3

The combination of prednisone and azathioprine remains a cornerstone of treatment for autoimmune hepatitis and other autoimmune conditions, with established safety and efficacy when administered together 1.