CISAPRIDE

Chemistry - An oral GI prokinetic agent, cisapride is a substituted piperidinyl benzamide and isstructurally, but not pharmacologically, related to procainamide. It is available commercially as amonohydrate, but potency is expressed in terms of the anhydrate.

Storage, Stability, Compatibility

Unless otherwise instructed by the manufacturer, store cisapride tablets in tight, light-resistant containers at room temperature.

Pharmacology - CISAPRIDE

Cisapride increases lower esophageal peristalsis and sphincter pressure and accelerates gastric emptying. The proposed mechanism of action is that it enhances the release of acetylcholine at the myenteric plexus, but does not induce nicotinic or muscarinic receptor stimulation. Acetylcholinesterase activity is not inhibited. Cisapride blocks dopaminergic receptors to a lesser extent than does metoclopramide and does not increase gastric acid secretion.

Uses, Indications

Cisapride is a new agent. Proposed uses for it in small animals includeesophageal reflux and treatment of primary gastric stasis disorders.

Pharmacokinetics - CISAPRIDE

Human data: After oral administration, cisapride is rapidly absorbed with anabsolute bioavailability of 35-40%. The drug is highly bound to plasma proteins and apparentlyextensively distributed throughout the body. Cisapride is extensively metabolized and its elimination half life is about 8-10 hours.

Contraindications, Precautions, Reproductive Safety

Cisapride is contraindicated in patientsin whom increased gastrointestinal motility could be harmful (e.g., perforation, obstruction, GIhemorrhage) or those who are hypersensitive to the drug.
Cisapride at high dosages (> 40 mg/kg/day) caused fertility impairment in female rats. At doses 12to 100 times the maximum recommended, cisapride was embryotoxic and fetotoxic in rabbits andrats. Its use during pregnancy should occur only when the benefits outweigh the risks. Cisapride isexcreted in maternal milk in low levels; use with caution in nursing mothers.

Adverse Effects, Warnings

Usage in small animal medicine has been limited to this point and anadverse effect profile has not been determined. As expected in humans, the primary adverse effectsare gastrointestinal related with diarrhea and abdominal pain most commonly reported.
Dosage may need to be decreased in patients with severe hepatic impairment.

Overdosage, Acute Toxicity

In one reported human overdose of 540 mg, the patient developed
GI distress and urinary frequency. LD50 doses in various lab animals range from 160 - 4000 mg/kg. Significant overdoses should be handled using standard gut emptying protocols when appropriate; supportive therapy should be initiated when required.

Drug Interactions

Because cisapride can decrease GI transit times, absorption of other drugsgiven orally may be affected. Oral drugs with a narrow therapeutic index may need serumlevels monitored more closely when adding or discontinuing cisapride. Use of anticholinergicagents may diminish the effects of cisapride. Cimetidine (not ranitidine) may increase cisaprideserum levels and cisapride may accelerate cimetidine and ranitidine absorption thereby enhancing their effects. Cisapride may enhance anticoagulants' effects; additional monitoring and anticoagulant dosage adjustments may be required. Cisapride may enhance the sedative effects of alcohol or benzodiazepines.
Elevated concentrations of cisapride with resultant ventricular arrhythmias may result if coadministered with ketoconazole, itraconazole, IV miconazole or troleandomycin. At present, themanufacturer states that cisapride should not be used with these drugs.