Foscamet nephrotoxicity

Deray G, Martinez F, Katlama C, Levaltier B, Beaufils H, Danis M, Rozenheim M, Baumelou A, Dohin E, Gentihni M, et al Foscamet nephrotoxicity mechanism, incidence and prevention. Am J Nephrol 1989 9(4) 316-21. 

Increased risk of nephrotoxicity with acyclovir, aminoglycoside, cyclosporine, flucytosine, foscamet, gancyclovrr, mitomycin, penicillamine, sirolimus, vancomycin... 

Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid fe.g., /i-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin foscamet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses. 

Foscamet s major dose-limiting toxicities are nephrotoxicity and hypocalcemia. Increases in semm creatinine occur in up to one-half of patients but usually are reversible after dmg cessation. High doses, rapid infusion, volume depletion, prior renal insufficiency, and concurrent nephrotoxic dmgs are risk factors. Acute tubular necrosis, crystalline glomerulopathy, nephrogenic diabetes insipidus, and interstitial nephritis have been described. Saline loading may reduce the risk of nephrotoxicity. 

A man with a kidney transplant taking corticosteroids and ciclosporin developed a cytomegalovirus infection that was treated with foscarnet 85 mg/kg daily. Despite efforts to minimise the nephrotoxic effects of the foscarnet (hydration with 2.5 litres of isotonic saline daily and nifedipine 80 mg the day before and during treatment) the patient developed non-ol-iguric worsening of his renal function after 8 days. Nine days after stopping the foscamet, the former renal function was restored. ... 

Not understood. It seems that the nephrotoxic effects of the ciclosporin and foscamet may be additive. 

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