Drugs Potentiating Cyclosporin Nephrotoxicity

Michel Jadoul, University of Louvain Medical School, Department of Nephrology, Cliniques Universitaires St-Luc, B-1200 Brussels (Belgium) Dear Sir, In their comprehensive editorial on the nephrological aspects of liver transplantation, Delaney and Nasir [1] mention the deleterious effect of several drugs potentiating ciclosporin (CS) nephrotoxicity. Unfortunately, their table listing the incriminated drugs includes several drugs without clinically significant interaction with CS. As these drugs may be of benefit to CS-treated patients, we provide here some additional information. Contrary to the claim of Delaney and Nasir [1] neither H2 blockers nor oral trimethoprim increase CS nephrotoxicity. As recently shown by us and others, the serum creatinine concentration is not affected by ranitidine administration to CS-treated patients [2, 3]. The increase in serum creatinine observed under cimetidine treatment merely reflects an impaired tubular secretion of creatinine, whereas glomerular filtration rate, determined by inulin clearance, remains unchanged [3]. The same phenomenon has been demonstrated for oral trimethoprim in this journal [4]. There is thus no reason to withhold either H2 blockers or trimethoprim whenever they are indicated. The assertion that ciprofloxacin enhances CS toxicity is based on a single case report better interpreted as an example of acute interstitial nephritis unrelated to CS therapy. Indeed, in this observation CS whole blood levels failed to rise under ciprofloxacin [5]. Several larger studies have clearly demonstrated that neither ciprofloxacin nor other fluoroquinolones such as norfloxacin and ofloxacin interact with CS [6–8]. These antibiotics may thus be confidently prescribed to CS-treated patients. Finally, we would like to complete the information concerning calcium channel blockers. Besides diltiazem [9] and verapamil [10], nicardipine also increases CS levels [11, 12]. Fortunately, other calcium channel blockers like nifedipine, nitrendipine and isradipine do not significantly interact with CS, [13,14, unpubl. observations] and may thus be safely prescribed. Delaney and Nasir [1] quite rightly point out the importance of being aware of possible drug interactions potentiating CS nephrotoxicity. The simultaneous use of CS and investigational or newly released drugs should prompt close monitoring of CS levels and glomerular filtration rate (rather than only serum creatinine), particularly if this drug is also extensively metabolized by the liver. References