Nephrotoxicity and hepatotoxicity of histamine H-2 receptor antagonists

The extensive use of selective histamine H-2 receptor antagonists provides a unique opportunity to describe very rare adverse drug reactions. Although mild elevation of serum creatinine level following the administrat ion of cimetidine is relatively common, acute interstitial nephritis (AIN) is a rare hypersensitivity reaction. There have been 25 published reports o f AIN associated with H-2 antagonist therapy and we also identified 16 case s from the Australian Adverse Drug Reaction Advisory Committee (ADRAC) data base. AIN was reported most commonly following cimetidine administration. A IN was supported by renal biopsy in 28 patients and by rechallenge in 6. H- 2 antagonist-induced AIN was more commonly reported in men older than 50 ye ars. In the majority of cases the onset was within 2 weeks of initiation of therapy (1 day to ii months). The clinical manifestations were nonspecific including sterile pyuria, elevated erythrocyte sedimentation rate, fatigue , proteinuria and leucocytosis whereas rash, arthralgia and flank pain were rarely reported. There were 170 cases of hepatotoxicity following H-2 antagonist administrat ion reported to ADRAC. These were more common following ranitidine and incl uded cholestatic, hepatocellular and mixed reactions. Hepatotoxicity was pr oven following liver biopsy in several cases published in the literature an d in 15 cases reported to ADRAC. Hepatotoxicity recurred upon rechallenge i n 6 cases. Generally, renal and hepatic adverse effects resolved quickly after cessati on of H-2 antagonist therapy and did not require specific treatment. Nephro toxicity and hepatotoxicity following administration of an H-2 antagonist i s rare and a high index of suspicion is necessary for early detection. Now that many H-2 antagonists are available over the counter, awareness of thes e conditions and early detection with cessation of antagonist therapy would appear paramount.