Ciclosporin Bezafibrate

The use of bezafibrate with ciclosporin has resulted in significantly increased serum creatinine and reductions, no change, or increased serum ciclosporin levels. The use of fenofibrate has also been associated with reduced renal function and possibly reduced serum ciclosporin levels. Two studies found no pharmacokinetic interaction between ciclosporin and gemfibrozil while a third found gemfibrozil caused a significant reduction in ciclosporin levels. 

A kidney transplant patient had a rise in his previously stable ciclosporin blood levels from a range of 150 to 200 nanograms/mL to about 340 nanograms/mL over a 6-week period after bezafibrate 200 mg twice daily was given. The rise was aeeompanied by increases in blood urea nitrogen and creatinine levels. Renal biopsy found evidence of possible ciclosporin toxicity, and rejection. The patient recovered when the bezafibrate was stopped. ... 

Two other transplant patients (one kidney and the other heart) had a reversible deterioration in renal function when they were given bezafibrate. This was severe in one, and the other had the effect on two occasions. Neither had any changes in ciclosporin blood levels. Two other similar cases have been reported, one of whom was subsequently given gemfibrozil without problems. ... 

Another study over 3 months in 40 heart transplant patients taking ciclosporin found that bezafibrate was associated with a rise in serum creatinine levels, although none of the patients had to be withdrawn from the study because of this. The ciclosporin level tended to be lower (198 nanograms/mL at baseline, compared with 144 nanograms/mL after 3 months). ... 

Neither the incidence nor the reasons for these reactions are known, but because the outcome is uncertain and potentially serious, keep a close check on the effects of adding bezafibrate to ciclosporin in any patient. The manufacturers of bezafibrate suggest close monitoring of renal function. ... 

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