OBJECT DRUGS

Antimetabolites:

• Azathioprine (Imuran, etc.)
• Mercaptopurine (Purinethol, etc.)

PRECIPITANT DRUGS

• Allopurinol (Zyloprim, etc.)
• Febuxostat (Uloric)

Comment:

Allopurinol and febuxostat inhibit the metabolism of mercaptopurine, which is also the active metabolite of azathioprine. This effect considerably increases antimetabolite effect and toxicity of both azathioprine and mercaptopurine. Generally, these combinations should be avoided, but they have sometimes been used intentionally with careful monitoring. For example, several studies in patients with inflammatory bowel disease suggest that low dose allopurinol (with lowered azathioprine dose and careful monitoring) may improve azathioprine efficacy without increasing toxicity. More study is needed.

Class 1: Avoid Combination

• Avoid: Patients taking azathioprine or mercaptopurine should generally not be administered allopurinol or febuxostat. If allopurinol or febuxostat must be used, consider selecting an alternative immunosuppressant.
• Circumvent/Minimize:If allopurinol is added to azathioprine or mercaptopurine therapy, it is generally recommended that the azathioprine or mercaptopurine dose be reduced to 25% to 33% of the original dose. Lower than normal doses of allopurinol have also been suggested.
• Monitor:If the combination is used, monitor for evidence of bone marrow suppression, and instruct the patient to contact their prescriber immediately if they experience evidence of pancytopenia such as fever, sore throat, easy bruising, or bleeding.