Cisapride cardiotoxicity

Paakkari I. Cardiotoxicity of new antihistamines and cisapride. Toxicol Lett. 2002 127 279-284. 

GRAPEFRUIT JUICE CISAPRIDE T plasma concentrations and likely T risk of adverse effects (e.g. cardiotoxicity, Q-T prolongation, torsade de pointes) t oral bioavailability and slight but significant t elimination half-life Although a study in volunteers did not show any changes in heart rate, PR or Q-T prolongation, avoid concurrent use... 

SSRI drug interactions The SSRls are inhibitors of hepatic cytochrome P450 isozymes, an action that has led to increased activity of other drugs including tricyclic antidepressants and warfarin. Huvoxamine inhibits the metabolism of cisapride, astemizole, and terfena-dine, and the resultant cardiotoxicity has led to the withdrawal of the latter two thugs (see Table 30-3). Citalopram causes fewer drug interactions than other SSRls. 

Cardiotoxicity occurred when ketoconazole was used by patients taking astemizole or terfena-dine, a drug interaction that led to the withdrawal of the two nonsedating antihistamines in the United States. The same type of drug interaction has been reported between ketoconazole and cisapride as a result of the ability of ketoconazole to inhibit hepatic drug-metaholizing enzymes. The answer is (D). 

Cisapride is metabolized by a cytochrome P450 isozyme that is inhibited by erythromycin and by ketoconazole. Decreased clearance of the antihistaminic drugs astemizole and terfenadine (now withdrawn) may also result in cardiotoxicity. The answer is (E). 

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