Potentiation of nephrotoxicity by H2-antagonists in patients receiving cyclosporine.
The literature does not support a pharmacodynamic interaction between H2-antagonists and cyclosporine that would result in potentiation of cyclosporine's nephrotoxicity. The increase in serum creatinine associated with cimetidine, in the majority of cases, is due to competition with creatinine for tubular secretion. Ranitidine is unlikely to produce a change in serum creatinine. Additionally, there is no support for a pharmacokinetic interaction. However, cimetidine may influence peak concentrations of cyclosporine. Besides the clinical data reviewed here, two abstracts concur with these findings. Information was unavailable regarding interactions between cyclosporine and either famotidine or nizatidine that potentiate nephrotoxicity in transplant patients. Furthermore, the drug manufacturers state that no evidence is available to support any interaction of their products with cyclosporine. Thus, interpretation of renal function may be confusing with concomitant administration of cimetidine and cyclosporine unless GFR is accurately monitored. On the basis of the information available at this time, ranitidine may be considered the H2-antagonist of choice in a patient treated with cyclosporine.
Lewis
S M
SM
Pharmacy Service, Department of Veterans Affairs Medical Center, Pittsburgh, PA 15240, USA.
McCloskey
W W
WW
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002927:Cimetidine / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D004357:Drug Synergism; D006635:Histamine H2 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D016030:Kidney Transplantation
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D007166:Immunosuppressive Agents; D002927:Cimetidine; D016572:Cyclosporine