Mycophenolate Allopurinol

Azathioprine, mycophenolate mofetil, and enteric-coated MPA are not metabolized through the CYP isozyme system therefore, they do not experience the same DDI profiles as cyclosporine, tacrolimus, and sirolimus. Azathioprine s major DDIs involve allopurinol, angiotensin-converting enzyme (ACE) inhibitors, aminosalicylates (e.g., mesalamine and sulfasalazine), and warfarin.11 The interaction with allopurinol is seen frequently and has clinical significance. Allopurinol inhibits xanthine oxidase, the enzyme responsible for metabolizing azathioprine. Combination of azathioprine and allopurinol has resulted in severe toxicities, particularly myelosuppression. It is recommended that concomitant therapy with azathioprine and allopurinol be avoided, but if combination therapy is necessary, the azathioprine doses must be reduced to one-third or one-fourth of the current dose. Use of azathioprine with the ACE inhibitors or aminosalicylates also can result in enhanced myelosuppression.11 Some case reports exist demonstrating that warfarin s therapeutic effects may be decreased by azathioprine.43-45... 

Combined administration of azathioprine and allopurinol may result in severe pancytopenia. The dose of Azathioprine should be reduced by two-thirds when given with allopurinol. Azathioprine rarely causes liver dysfunction, frequently manifested by an isolated rise in ALT and bilirubin. With the introduction of mycophenolate mofetil, azathioprine may be relegated to a second-line anti metabolite for the prevention of graft rejection. 

Clinically important, potentially hazardous interactions with allopurinol, chlorambucil, cyclophosphamide, cyclosporine, hemophilus B vaccine, imidapril, mycophenolate, olsalazine, vaccines, warfarin... 

No clinically relevant interactions have been seen between mycophenolate mofetil and allopurinol. 

No special precautions would therefore seem necessary if allopurinol is used with mycophenolate, although the authors of both studies suggest that long-term randomised studies are needed to confirm safety. 

Jacobs F, Mam zer-Bruneel MF, Skhiri H, Thervet E, Legendre Ch, Kreis H. Safety of the mycophenolate mofetil-allopurinol combination in kidney transplant recipients with gout. Transplantation (1997) 64,1087-8. 

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