HDCN Article Review/Hyperlink

Segaert MF, De Soete C, Vandewiele I, Verbanck J

Drug-interaction-induced rhabdomyolysis

Nephrol Dial Transplant (Sep) 11:1846-1847 1996

Cyclosporine and simvastatin are both known to induce elevated CPK levels, and sometimes cause rhabdomyolysis when used in combination. Cyclosporin inhibits degradation of simvastatin, accentuating the risk of using these drugs together. In this paper, both drugs were used together without adverse effect for 3 years, but severe rhabdomyolysis developed after addition of itraconazole (for Alternaria fungus nose infection. Serum simvastatin levels were 22 and 26 ng/ml, of the lactone and acid form, respectively, ten times higher than in normal controls. To test the hypothesis that itraconazole could increase simvastating levels, a normal hypercholesterolemic volunteer was given simvastatin. Challenge with itraconazole caused a marked elevation of serum simvastatin levels.

Comment: The clinical message is, that itraconazole should not be used with either simvastatin or lovastatin, unless the dose of the latter is markedly reduced. (John T. Daugirdas, M.D., University of Illinois at Chicago)