Cimetidine nephrotoxicity

Carboplatin Myelosuppression (DLT), nephrotoxicity, nausea/ vomiting, electrolyte wasting, diarrhea, stomatitis, hypersensitivity reactions Prehydration not required. Give proper dosing for renal dysfunction. Premedicate dexamethasone, diphenhydramine, and cimetidine. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

Concurrent use of nephrotoxic agents may enhance the potential for nephrotoxicity. Probenecid and cimetidine decrease acyclovir clearance and increase exposure. Somnolence and lethargy may occur in patients receiving zidovudine and acyclovir. 

Cimetidine may increase cyclosporine levels and cause nephrotoxicity. Famotidine, Ranitidine, and cimetidine are now available over the counter. 

CICLOSPORIN H2 RECEPTOR BLOCKERS -CIMETIDINE t plasma concentrations of ciclosporin, with risk of nephrotoxicity, myelosuppression, neurotoxicity, excessive immunosuppression, with risk of infection and post-transplant lymphoproliferative disease Inhibition of CYP3A4-mediated metabolism of ciclosporin these inhibitors vary in potency. Cimetidine is classified as a potent inhibitor Avoid co-administration with cimetidine. Consider an alternative H2-blocker, but need to monitor plasma ciclosporin levels to prevent toxicity... 

The nephrotoxicity of dsplatin is reduced in humans [132], mice [133] and dogs [134] by co-admin-istration of probenecid, suggesting that cisplatin is transported by the PAH transport system. It has been proposed that platinum, hke other nephrotoxic metal ions such as mercury and potassium dichromate, are taken up by tubular cells as sulphydryl conjugate through a probenecid-sensitive pathway [133]. However, cisplatin might also be transported by the organic cation transport system, since quinidine, cimetidine and ranitidine inhibited its net secretion flux in the dog kidney [134]. 

An impressive list of compounds has been used to decrease cisplatin nephrotoxicity [ANF, glycine, diethyldithiocarbamate, calcium channel blockers, cimetidine, sodium thiosulphate, glutathione, other sulfidryl compounds,. ..]. Among them only sodium thiosulphate has received a significant clinical application and has been reported to reduce the renal toxicity of cisplatin administered locally by either the intra-arterial, intra-peritoneal or intrathoracic routes [50, 51]. However, controversies still exists as to the effect of sodium thiosulphate on cisplatin antitumor activity. Thus sodium thiosulphate may be most useful in combination with intraperitoneal cisplatin where it confers renal protection without altering local effects of cisplatin [51]. 

Renal metabolism of isoproterenol [171], bumet-anide [163], cimetidine [172] and N-methylnicotina-mide [173] has been reported. Renal metabolites may have different mode of excretion [174], and may be more nephrotoxic than the original substance [175]. Renal glucuronidation may be substantial as in the case of morphine [176]. Xenobiotic glucuronidation can proceed by linkage through an ether or an ester bound. 

Haragsim L, Zima T, Nemecek K. Nephrotoxic effects of platinum cytostatics-freventive effects of nife pine and cimetidine. Sb Lek 994t) 95,173 3. 

Reports are inconsistent. Cimetidine and famotidine have been reported to increase cielosporin levels, whereas in other studies cimetidine, famotidine and ranitidine have been reported to not affect cielosporin levels. Both cimetidine and ranitidine have been reported to cause an increase in serum creatinine levels, in some but not all studies, but this may possibly not be a reliable indicator of increased nephrotoxicity. Isolated cases of thrombocytopenia and hepatotoxicity have been reported with ranitidine and cielosporin. 

Information about the possible interactions of ciclosporin and cimetidine, famotidine or ranitidine is inconsistent, but there appear to be very few reports of confirmed toxicity. Moreover the reported increases in serum creatinine levels seen with the H2-receptor antagonists may not be a reflection of increased nephrotoxicity (see Mechanism )- Thus there is little to suggest that concurrent use should be avoided, but good initial monitoring is advisable. 

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