No

Gastrointestinal Agent, Prokinetic

Treatment of nocturnal symptoms of gastroesophageal reflux disease (GERD), also demonstrated effectiveness for gastroparesis, refractory constipation, and nonulcer dyspepsia

C

Hypersensitivity to cisapride or any of its components; GI hemorrhage, mechanical obstruction, GI perforation, or other situations when GI motility stimulation is dangerous

Serious cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsade de pointes, and Q-T prolongation have been reported in patients taking cisapride with other drugs that inhibit CYP3A4. Some of these events have been fatal. Concomitant oral or intravenous administration of the following drugs with cisapride may lead to elevated cisapride blood levels and is contraindicated:

Antibiotics: Oral or I.V. erythromycin, clarithromycin, troleandomycin

Antidepressants: Nefazodone

Antifungals: Oral or I.V. fluconazole, itraconazole, miconazole, oral ketoconazole

Protease inhibitors: Indinavir, ritonavir, amprenavir

Cisapride is also contraindicated for patients with a prolonged electrocardiographic Q-T intervals (QTc > 450 milliseconds), a history o fQTc prolongation, or known family history of congenital long Q-T syndrome; clinically significant bradycardia, renal failure, history of ventricular arrhythmias, ischemic heart disease, and congestive heart failure; uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); respiratory failure; and concomitant medications known to prolong the Q-T interval and increase the risk of arrhythmia, such as certain antiarrhythmics, certain antipsychotics, certain antidepressants, astemizole, bepridil, sparfloxacin, and terodiline. The preceding lists of drugs are not comprehensive. Cisapride should not be used in patients with uncorrected hypokalemia or hypomagnesemia or who might experience rapid reduction of plasma potassium such as those administered potassium-wasting diuretics and/or insulin in acute settings.

On March 24, 2000 the FDA announced that the manufacturer of cisapride would voluntarily withdraw its product from the US market on July 14, 2000. This decision was based on 341 reports of heart rhythm abnormalities including 80 reports of deaths. The company will continue to make the drug available to patients who meet specific clinical eligibility criteria for a limited-access protocol (Contact 1-800-JANSSEN). Serious cardiac arrhythmias including ventricular tachycardia, ventricular fibrillation, torsade de pointes, and QT prolongation have been reported in patients taking this drug. Many of these patients also took drugs expected to increase cisapride blood levels by inhibiting the cytochrome P-450 3A4 enzymes that metabolize cisapride. These drugs include clarithromycin, erythromycin, troleandomycin, nefazodone, fluconazole, itraconazole, ketoconazole, indinavir and ritonavir. Some of these events have been fatal. Cisapride is contraindicated in patients taking any of these drugs. QT prolongation, torsade de pointes (sometimes with syncope), cardiac arrest and sudden death have been reported in patients taking cisapride without the above-mentioned contraindicated drugs. Most patients had disorders that may have predisposed them to arrhythmias with cisapride. Cisapride is contraindicated for those patients with: history of prolonged electrocardiographic Q-T intervals; renal failure; history of ventricular arrhythmias, ischemic heart disease, and congestive heart failure; uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); respiratory failure; and concomitant medications known to prolong the Q-T interval and increase the risk of arrhythmia, such as certain antiarrhythmics, including those of Class 1A (such as quinidine and procainamide) and Class III (such as sotalol); tricyclic antidepressants (such as amitriptyline); certain tetracyclic antidepressants (such as maprotiline); certain antipsychotic medications (such as certain phenothiazines and sertindole),protease inhibitors, astemizole, bepridil, sparfloxacin and terodiline. (The preceding lists of drugs are not comprehensive.) Recommended doses of cisapride should not be exceeded.

>5%:

Central nervous system: Headache

Dermatologic: Rash

Gastrointestinal: Diarrhea, GI cramping, dyspepsia, flatulence, nausea, xerostomia

Respiratory: Rhinitis

<5%:

Cardiovascular: Tachycardia

Central nervous system: Extrapyramidal effects, somnolence, fatigue, seizures, insomnia, anxiety

Hematologic: Thrombocytopenia, increased LFTs, pancytopenia, leukopenia, granulocytopenia, aplastic anemia

Respiratory: Sinusitis, coughing, upper respiratory tract infection, increased incidence of viral infection

CYP3A3/4 enzyme substrate

Nefazodone and maprotiline may increase the risk of malignant arrhythmias; concurrent use is contraindicated

Protease inhibitors (amprenavir, indinavir, nelfinavir, ritonavir) increase cisapride's concentration. Increased risk of malignant arrhythmias; concurrent use is contraindicated.

Cimetidine increases the bioavailability of cisapride; use an alternative H₂ antagonist

Macrolides (clarithromycin, erythromycin, troleandomycin) increase cisapride. Risk of arrhythmias; concurrent use is contraindicated.

Sertindole may increase the risk of malignant arrhythmias; concurrent use is contraindicated

Phenothiazines (prochlorperazine, promethazine) may increase the risk of malignant arrhythmias; concurrent use is contraindicated

Class Ia (quinidine, procainamide) and Class III (amiodarone, sotalol) antiarrhythmics increase the risk of malignant arrhythmias; concurrent use is contraindicated

TCAs increase the risk of malignant arrhythmias; concurrent use is contraindicated

Bepridil increases the risk of malignant arrhythmias; concurrent use is contraindicated

Quinolone antibiotics: Sparfloxacin, gatifloxacin, moxifloxacin increase the risk of malignant arrhythmias; concurrent use is contraindicated

Warfarin: Isolated cases of increased INR; monitor closely

Increased bioavailability of cisapride with grapefruit juice; concomitant use should be avoided.

Enhances the release of acetylcholine at the myenteric plexus. In vitro studies have shown cisapride to have serotonin-4 receptor agonistic properties which may increase gastrointestinal motility and cardiac rate; increases lower esophageal sphincter pressure and lower esophageal peristalsis; accelerates gastric emptying of both liquids and solids.

Onset of effect: 0.5-1 hour

Bioavailability: 35% to 40%

Protein binding: 97.5% to 98%

Metabolism: Extensively to norcisapride, which is eliminated in urine and feces

Half-life: 6-12 hours

Elimination: <10% of dose excreted into feces and urine

Oral:

Adults: Initial: 10 mg 4 times/day at least 15 minutes before meals and at bedtime; in some patients the dosage will need to be increased to 20 mg to obtain a satisfactory result

Concomitant use with grapefruit juice should be avoided as it increases the bioavailability of cisapride

May cause sedation, insomnia, anxiety, or extrapyramidal effects

Contraindicated with nefazodone; may increase cisapride levels which have been associated with Q-T prolongation and torsade de pointes

No information available to require special precautions

No effects or complications reported

Take before meals. Avoid alcohol and other CNS depressants. May cause increased sedation. Report severe abdominal pain, prolonged diarrhea, weight loss, or extreme fatigue. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Safety and effectiveness in children have not been established. Although cisapride does not affect psychomotor function nor induce sedation or drowsiness when used alone, advise patients that the sedative effects of benzodiazepines and of alcohol may be accelerated.

Suspension, oral (cherry cream flavor): 1 mg/mL (450 mL)

Tablet, scored: 10 mg, 20 mg

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