indication

For the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease.

pharmacology

Cisapride is a parasympathomimetic which acts as a serotonin 5-HT₄ agonist. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous system. Cisapride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Cisapride increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder. Cisapride does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity.

mechanism of action

Cisapride acts through the stimulation of the serotonin 5-HT₄ receptors which increases acetylcholine release in the enteric nervous system (specifically the myenteric plexus). This results in increased tone and amplitude of gastric (especially antral) contractions, relaxation of the pyloric sphincter and the duodenal bulb, and increased peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit.

biotransformation

Hepatic. Extensively metabolized via cytochrome P450 3A4 enzyme.

absorption

Cisapride is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%.

half life

6-12 hours

drug interactions

Acenocoumarol: Cisapride may increase the anticoagulant effect of acenocoumarol.

Acetophenazine: Increased risk of cardiotoxicity and arrhythmias

Amiodarone: Increased risk of cardiotoxicity and arrhythmias

Amitriptyline: Increased risk of cardiotoxicity and arrhythmias

Amoxapine: Increased risk of cardiotoxicity and arrhythmias

Amprenavir: Amprenavir may increase the effect and toxicity of cisapride.

Anisindione: Cisapride may increase the anticoagulant effect of anisindione.

Aprepitant: Increased risk of cardiotoxicity and arrhythmias

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Astemizole: Increased risk of cardiotoxicity and arrhythmias

Atazanavir: Increased risk of cardiotoxicity and arrhythmias

Bepridil: Increased risk of cardiotoxicity and arrhythmias

Bretylium: Increased risk of cardiotoxicity and arrhythmias

Chlorpromazine: Increased risk of cardiotoxicity and arrhythmias

Clarithromycin: Increased risk of cardiotoxicity and arrhythmias

Clomipramine: Increased risk of cardiotoxicity and arrhythmias

Delavirdine: Delavirdine, a strong CYP3A4 inhibitor, may increase the metabolism of cisapride. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of cisapride if delavirdine is initiated, discontinued or dose changed.

Desipramine: Increased risk of cardiotoxicity and arrhythmias

Dicumarol: Cisapride may increase the anticoagulant effect of dicumarol.

Dihydroquinidine barbiturate: Increased risk of cardiotoxicity and arrhythmias

Diltiazem: Diltiazem, a moderate CYP3A4 inhibitor, may increase the serum concentration of cisapride by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of cisapride if diltiazem is initiated, discontinued or dose changed.

Disopyramide: Increased risk of cardiotoxicity and arrhythmias

Doxepin: Increased risk of cardiotoxicity and arrhythmias

Efavirenz: Increased risk of cardiotoxicity and arrhythmias

Encainide: Increased risk of cardiotoxicity and arrhythmias

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Ethopropazine: Increased risk of cardiotoxicity and arrhythmias

Fexofenadine: Increased risk of cardiotoxicity and arrhythmias

Flecainide: Increased risk of cardiotoxicity and arrhythmias

Fluconazole: Increased risk of cardiotoxicity and arrhythmias

Fluphenazine: Increased risk of cardiotoxicity and arrhythmias

Fosamprenavir: Amprenavir increases the effect and toxicity of cisapride

Ibutilide: Increased risk of cardiotoxicity and arrhythmias

Imipramine: Increased risk of cardiotoxicity and arrhythmias

Indinavir: Increased risk of cardiotoxicity and arrhythmias

Itraconazole: Increased risk of cardiotoxicity and arrhythmias

Josamycin: Increased risk of cardiotoxicity and arrhythmias

Ketoconazole: Increased risk of cardiotoxicity and arrhythmias

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Maprotiline: Increased risk of cardiotoxicity and arrhythmias

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Methdilazine: Increased risk of cardiotoxicity and arrhythmias

Methotrimeprazine: Increased risk of cardiotoxicity and arrhythmias

Mibefradil: Mibefradil increases levels of cisapride

Nefazodone: Nefazodone increases serum levels of cisapride

Nelfinavir: Increased risk of cardiotoxicity and arrhythmias

Nifedipine: Cisapride may increase the effect and toxicity of nifedipine.

Nortriptyline: Increased risk of cardiotoxicity and arrhythmias

Perphenazine: Increased risk of cardiotoxicity and arrhythmias

Posaconazole: Contraindicated co-administration

Procainamide: Increased risk of cardiotoxicity and arrhythmias

Prochlorperazine: Increased risk of cardiotoxicity and arrhythmias

Promazine: Increased risk of cardiotoxicity and arrhythmias

Promethazine: Increased risk of cardiotoxicity and arrhythmias

Propafenone: Increased risk of cardiotoxicity and arrhythmias

Propiomazine: Increased risk of cardiotoxicity and arrhythmias

Protriptyline: Increased risk of cardiotoxicity and arrhythmias

Quinidine: Increased risk of cardiotoxicity and arrhythmias

Quinidine barbiturate: Increased risk of cardiotoxicity and arrhythmias

Quinupristin: This combination presents an increased risk of toxicity

Ritonavir: Increased risk of cardiotoxicity and arrhythmias

Saquinavir: Increased risk of cardiotoxicity and arrhythmias

Sotalol: Increased risk of cardiotoxicity and arrhythmias

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. Cisapride may also increase the concentration of Tacrolimus in the blood.

Telithromycin: Telithromycin may reduce clearance of Cisapride. Concomitant therapy is contraindicated.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Thiethylperazine: Increased risk of cardiotoxicity and arrhythmias

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Tipranavir: Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Cisapride. Concomitant therapy is contraindicated.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trifluoperazine: Increased risk of cardiotoxicity and arrhythmias

Triflupromazine: Increased risk of cardiotoxicity and arrhythmias

Trimeprazine: Increased risk of cardiotoxicity and arrhythmias

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Troleandomycin: Increased risk of cardiotoxicity and arrhythmias

Voriconazole: Voriconazole may increase the serum concentration and toxicity of cisapride likely by decreasing its metabolism. Additive QTc prolongation may also occur. Concomitant therapy is contraindicated.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Warfarin: Cisapride may increase the anticoagulant effect of warfarin.

Zafirlukast: Increased risk of cardiotoxicity and arrhythmias

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).