Cisapride

465.95

465.95

279-689-7

DTXSID3022825

White to slightly biege powder

A - Alimentary tract and metabolism

2942000000

86

4.26810

white solid

1.3±0.1 g/cm3

109.8 °C

605.4°C at 760 mmHg

319.9±31.5 °C

1.593

DMSO: ~30 mg/mL

Store at RT

Odorless

Crystals from 2-propanol /monohydrate/|109.8 °C /monohydrate/

2

41

26-39

CU9372000

Xi

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

Both cisapride and tegaserod were linked to occasional instances of serum enzyme elevations during therapy (1% to 9%), but these elevations were generally mild and asymptomatic, resolving rapidly with or without discontinuing drug. While moderate serum enzyme elevations during 5-HT4 receptor agonist therapy have been described, there have been have been no convincing reports of clinically apparent acute liver injury with jaundice attributed to these agents. Plucalopride has not been linked to increased rates of serum enzyme elevations nor to instances of acute liver injury with jaundice, but experience with its long-term use has been limited.

Cispride has been reported to increase the rate of absorption of /alcohol or benzodiazepines/.|Concurrent use /with anticholinergics or other medications with anticholinergic activity/ may antagonize the effects of cisapride on gastrointestinal motility.|Cisapride accelerates the absorption of cimetidine and rantidine.|Concurrent use of itraconazole, ketoconazole, or intravenous miconazole with cisapride is contraindicated; concurrent use may result in elevated plasma concentrations of cisapride through inhibition of the cytochrome p450 metabolic pathways by these antifungals; this has led to ventricular arrhythmias, including torsades des pointes, in patients taking cisapride and ketoconazole.|For more Interactions (Complete) data for CISAPRIDE (8 total), please visit the HSDB record page.

The serotonin type 4 (5-HT4) receptor agonists are potent prokinetic agents that act on serotonin receptors in the intestine and promote intestinal peristalsis, increase gastric emptying and decrease esophageal reflux. Two 5-HT4 receptor agonists have been developed and were approved for use in the United States, but both were found to have significant serious adverse effects and have been withdrawn (cisapride) or placed under restricted use (tegaserod). Both cisapride and tegaserod have been associated with a low rate of transient serum enzyme elevations during therapy, but neither has been implicated convincing in cases of clinically apparent liver injury with jaundice.

Anti-Ulcer Agents; Gastrointestinal Agents; Serotonin Agonists|Cisapride is indicated for the symptomatic treatment of nocturnal (and daytime /Not included in US product labeling/) heartburn, and of esophagitis due to reflux and delayed gastric emptying. Treatment may continue for up to 8 weeks; however, tolerance to cisapride may develop at some point in therapy. /Included in US product labeling/|Cisapride is indicated in the treatment of gastroparesis, including idiopathic, diabetic, and intestinal pseudo-obstruction. Treatment may continue for up to 8 weeks; however, tolerance to cisapride may develop at some point in therapy. /NOT included in US product labeling/|... Reduce the consumption of laxatives in patients who chronically abuse these agents.|For more Therapeutic Uses (Complete) data for CISAPRIDE (7 total), please visit the HSDB record page.

Cisapride generally is well tolerated. Adverse effects on the GI tract and nervous system are most common and those most frequently requiring discontinuance of the drug(usually because of intolerable diarrhea and/or abdominal pain). The most common adverse GI effects (e.g., diarrhea) are extensions of the drug's pharmacologic activity. Because of differences in the pharmacologic profiles of the drugs, adverse nervous system effects are less common with cisapride than with metoclopramide whereas diarrhea is more common with cisapride.|In adults receiving cisapride for motility disorder in US placebo-controlled clinical trials, including those with gastroesophageal reflux disease, the most frequent adverse effects of cisapride were headache, diarrhea, abdominal pain, nausea, constipation, and rhinitis. The frequency of diarrhea, abdominal pain, constipation, flatulence, and rhinitis appears to be dose dependent, occurring more frequently in patients receiving oral cisapride 20 mg 4 times daily than in those receiving 10 mg 4 times daily. Many adverse effects reported with cisapride occurred at a frequency similar to that associated with placebo, and a causal relationship to the drug often could not be established.|Dehydration was reported in more than 1% of patients receiving cisapride in controlled clinical trials. Limited evidence indicates that cisapride does not adversely affect glycemic control in insulin-dependent (type I) diabetic patients with delayed gastric emptying.|Viral infection occurred in about 4% of patients receiving cisapride in controlled clinical trails and required discontinuance of the drug in 0.2% of patients. Fever was reported in about 2% of patients receiving cisapride in controlled clinical trials and required discontinuance in 0.1%.|For more Drug Warnings (Complete) data for CISAPRIDE (6 total), please visit the HSDB record page.

Endogenous compounds and drugs that bind to and activate SEROTONIN RECEPTORS. Many serotonin receptor agonists are used as ANTIDEPRESSANTS; ANXIOLYTICS; and in the treatment of MIGRAINE DISORDERS. (See all compounds classified as Serotonin Receptor Agonists.)|Various agents with different action mechanisms used to treat or ameliorate PEPTIC ULCER or irritation of the gastrointestinal tract. This has included ANTIBIOTICS to treat HELICOBACTER INFECTIONS; HISTAMINE H2 ANTAGONISTS to reduce GASTRIC ACID secretion; and ANTACIDS for symptomatic relief. (See all compounds classified as Anti-Ulcer Agents.)|Drugs used for their effects on the gastrointestinal system, as to control gastric acidity, regulate gastrointestinal motility and water flow, and improve digestion. (See all compounds classified as Gastrointestinal Agents.)

The placental transfer of cisapride, a new prokinetic agent, was studied in a sheep model. The pharmacokinetics of cisapride were studied in the lamb, the pregnant ewe, and the fetus by obtaining blood samples from chronically implanted arterial catheters. Comparable pharmacokinetic parameters were found in the lamb and the adult sheep: half-life, 1.39-1.83 hr; total plasma clearance, 1998-2160 ml/kg/hr; AUC, 92.6-100.1 ng.hr/ml. Cisapride plasma concentrations after continuous infusion were predicted correctly based on the parameters obtained after IV bolus. There was a materno-fetal transfer of cisapride following a single IV bolus administered to the mother. Cisapride crossed the placenta within 5 min and equilibrated with maternal plasma within 20 to 30 min after dosing. The average fetal-to-maternal plasma concentration ratio was 0.71. The amniotic fluid also contained measurable amounts of cisapride. The protein binding of cisapride in maternal and fetal plasma is 89.0% and 88.4%, respectively; the free fraction is 4 times larger than in humans. Cisapride crosses the ovine placental barrier. The sheep placenta is less permeable than the human placenta, but the higher free fraction of cisapride facilitates placental transfer.

IPA COPYRIGHT: ASHP The metabolism of cisapride in vitro using Liver fractions of dogs, rabbits, and rats and the metabolites identified by high performance LC and by MS are described. Main bi otransformat i on routes were oxi dat i ve N-dealkylat i on at the pi peri di ne ni trogen and aron at i c hydroxylat i on at the fluorophenyl or at the benzami de moi ety. ENG ~21 nq~_~n_~.|(+-)-Cisapride has known human metabolites that include 3-Fluoro-4-hydroxycisapride, 4-Fluoro-2-hydroxycisapride, and Norcisapride.

Cisapride exerts its effect by increasing the release of acetylcholine from the postganglionic nerve endings of the myenteric plexus. This release of acetylcholine increases esophageal activity and increases esophageal sphincter tone, thereby improving esophageal clearance and decreasing reflux of gastric and duodenal emptying as a result of increased gastric and duodenal contractility and antroduodenal coordination. Duodenogastric reflux is also decreased. Cisapride improves transit in both small and large bowel.

For treatment of overdose: Recommended treatment consists of the following: Stopping administration of medication. Use of gastric lavage and/or administration of activated charcoal. Supportive therapy.

No mutagenicity was demonstrated in the following in vitro and in vivo models: ... chromosomal aberration assay on human lymphocytes ... .

Cisapride

VanDaele, Eur. Pat. Appl. 76,530 (1983 to Janssen)

IPA COPYRIGHT: ASHP An accurate and reproducible HPLC method with UV detection is described for the determination of cisapride in human plas~na and rat liver tissue. Typical chromatograms from plas~na from a healthy subject 12 hr after oral intake of 10 mg of the drug, and fro~n liver from a rat 24 hr after a repeated oral dosing schedule of 10 mg/kg per day for 7 days, are presented. F Nl::

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients