- symptomatic management of gastrointestinal (gi) motility disorders which include gastroesophageal reflux disease, gastroparesis and intestinal pseudo-obstruction.
- cisapride is a gastrokinetic drug that increases esophageal peristaltic activity and lower esophageal sphincter tone.
- gastric and duodenal contractility and emptying are increased.
- both small and large bowel transit is improved.
- cisapride is believed to act by increasing the release of acetylcholine at nerve endings in the myenteric plexus of the GI tract; it does not possess dopamine antagonist activity.
- cisapride differs from 2 other gastrokinetic drugs, domperidone and metoclopramide, in the following:
- cisapride enhances motility in both the upper and lower sections of the GI tract
- cisapride lacks anti-emetic properties
- cisapride does not increase serum prolactin concentration
- cisapride does not appear to possess the CNS side effects and extrapyramidal reactions which result from dopamine antagonism
- because of the "first-pass" effect in the liver, and gut wall, only 40 to 50% of an oral dose reaches the systemic circulation.
- extensively metabolized in the liver; metabolites are eliminated in urine and feces.
- very highly (98%) protein bound, mainly to albumin.
- GI mostly - diarrhea, borborygmi (rumbling noise caused by the propulsion of gas through the intestines) transient abdominal cramping, abdominal distension, flatulence
- small incidence (< 2%) of somnolence, drowsiness, lethargy, fatigue
- NOTE: In July of 1997 Janssen - Ortho Inc (Canada) issued a letter stating "Prepulsid is contraindicated in prematurely born infants (born at a gestational age of less than 36 weeks), from 0 through three months after the delivery date."(128)
This follows case reports of prolongation of the QT interval in infants and pediatric patients. (129 - 132) In addition, a prospective study of 49 neonates demonstrated an increased QT interval (above an arbitrary interval of 0.45, n=7). (133) The prolonged QT interval was inversely correlated to birth weight and gestational age and was most frequent in infants < 33 weeks gestation.
- cisapride is contraindicated in conditions where stimulation of the GI tract may be dangerous (eg. gastrointestinal hemorrhage, mechanical obstruction or perforation, Hirschsprung's disease, or following an episode of necrotizing enterocolitis)
- initial dosage should be reduced in hepatic or renal insufficiency
- 0.2 mg/kg po tid-qid
- administer 15 min before feeds
- Krogh CME et al (ed): Compendium of Pharmaceuticals and Specialties, Canadian Pharmaceutical Association, 1992.
- Verlinden M and Wellburn P: The use of prokinetic agents in the treatment of gastrointestinal motility disorders in childhood, in Disorders of Gastrointestinal Motility in Childhood, Milla PJ (Ed), John Wiley and Sons Ltd, p 125-140,1988.
- Vandenplas Y, Deneyer M, Verlinden M et al: Gastroesophageal reflux incidence and respiratory dysfunction during sleep in infants, Journal of Pediatric Gastroenterology and Nutrition 1989: 8:31-36.
- Murdoch J: Cisapride, Pharmacy Practice 1990 (June): 23-25.
- Raoult A (Vice-President, Scientific Affairs, Janssen-Ortho Inc, Canada), Letter to Healthcare Professionals, July 22, 1997.
- Lewin MB, Bryant RM, Fenrich AL et al : Cisapride-induced long QT interval. The Journal of Pediatrics 1996; 128: 279-81.
- Bedu A, Lupoglazoff JM, Faure C et al : Cisapride high dosage and long QT interval (Letter). The Journal of Pediatrics 1997; 130: 164.
- Hanson R, Browne G, Fasher B et al : Cisapride-induced prolonged QT interval:too much of a good thing (Letter). The Journal of Pediatrics 1997; 130 : 164-166.
- Vervaet et al. Unpublished data base of Janssen-Ortho Inc. November 1996.
- Bernardini S, Semama DS, Huet F et al: Effects of cisapride on QTc interval in neonates. Archives of Disease in Childhood (Fetal Neonatal Edition)1997; 77(3) : F 241-3
Last Updated: 1 November 1999