Cisapride drug interactions

BedfordTA, Rowbotham DJ. Cisapride. Drug interactions of clinical signi cSra Saf, 1996 15 167-175. 

Coadministration with cisapride, pimozide, or carbamazepine (see Warnings and Drug Interactions) patients who were withdrawn from nefazodone because of evidence of liver injury (see Warning box. Warnings) hypersensitivity to nefazodone or other phenylpiperazine antidepressants. 

Drug interactions Coadministration of cisapride, pimozide, dofetilide, orquinidine with itraconazole is contraindicated. Itraconazole is a potent inhibitor of the cytochrome P450 3A4 isoenzyme system and may raise plasma concentrations of... 

Do not administer concurrently with cisapride, midazolam, triazolam, or ergot derivatives. Competition for CYP3A4 by efavirenz could result in inhibition of metabolism of these drugs and create the potential for serious or life-threatening adverse events (eg, cardiac arrhythmias, prolonged sedation, respiratory depression see Drug Interactions). 

CYP3A4 is involved in the metabolism of 80%-90% of all currently available drugs (Table 2). Its presence accounts for the majority of the cytochrome enzymes in the liver. It has attracted attention from both physicians and pharmaceutical companies, as there have been incidences of fatal drug interactions, which have resulted in the withdrawal of these drugs from the market (terfena-dine in 1997, astemizole in 1999, and cisapride in 2000). Combinations ofpotent CYP3A4 inhibitors and substrates can drive drug levels to the toxic range. The... 

Michalets, E.L. and Williams, C.R. (2000) Drug interactions with cisapride clinical implications. Clin Pharmacokinet 39 49—75. 

Concomitant administration of KETEK with cisapride or pimozide is contraindicated (see Clinical Pharmacology Drug-Drug Interactions and Precautions )... 

Concomitant administration of clarithromycin with cisapride, pimozide, astemizole, or terfenadine is contraindicated. There have been postmarketing reports of drug interactions when clarithromycin and/ or erythromycin are coadministered with cisapride, pimozide, astemizole, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes). 

Drug Interactions Increased prothrombin time after warfarin administration Phenytoin Cyclosporine Tolbutamide Tacrolimus Glyburide Glipizide Rifampin Cisapride Terfenadine Astemizole Theophylline ... 

Tegaserod has no known effects on cytochrome P450 enzymes and no known drug interactions. Unlike cisapride, tegaserod does not inhibit cardiac repolarization and does not prolong the QT interval. 

Kirch W, Janisch HD, Qhnhaus EE, van Peer A. Cisapride-cimetidine interaction enhanced cisapride bioavailability and accelerated cimetidine absorption. Ther Drug Monit 1989 11(4) 411-14. 

Telithromycin has several clinically significant drug interactions similar to those for erythromycin. It is both a substrate and a strong inhibitor of CYP3A4. Coadministration of rifampin, a potent inducer of CYP, decreases the serum concentrations of telithromycin by 80%. CYP3A4 inhibitors (e.g., itraconazole) increase peak serum concentrations of telithromycin. Serum concentrations of CYP3A4 substrates (e.g., pimozide, cisapride, midazolam, statins, cyclosporine, phenytoin) are increased by telithromycin. Telithromycin also increases peak serum concentrations of metoprolol and digoxin. 

Fluconazole inhibits CYP3A4 and CYP2C9 and thus significantly increases plasma concentrations of amprenavir, cisapride, cyclosporine, phenytoin, sulfonylureas, tacrolimus, theophylline, telithromycin, and warfarin. Patients receiving >400 mg daily or azotemic patients may experience additional drug interactions. Rifampin decreases the fluconazole AUC by -25%. 

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). 

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