Cisapride

Cisapride belongs to Serotonin 5-HT₄ receptors stimulator the acts as a Gastrointestinal Agent.

Cisapride is readily absorbed in the GI tract. The time taken to reach peak plasma concentrations is approximately 1-2 hours after oral administration. Cisapride is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%. Cisapride primarily metabolized via hepatic via cytochrome P450 3A4 enzyme.

Cisapride shows side effects like Diarrhea, upset stomach, stomach discomfort, headache, stuffy nose, constipation, coughing.

Cisapride is available in the form of Oral tablet and oral suspension.

Cisapride is available in India, Canada, US, Australia, France, Italy, China, Spain, and Germany.

Cisapride belongs to the Gastrointestinal Agent acts as a Serotonin 5-HT₄ receptors stimulator.

Cisapride 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.

The Onset of action of Cisapride is about 0.5-1 hour.

The Tmax of Cisapride is approximately 1-2 hours.

Cisapride is available in the form of Oral tablet and oral suspension.

Cisapride tablet and suspension is taken orally, usually 3-4 times a day.

Cisapride is an effective medicine, used to increase the mobility of food in the stomach and intestine. It is used for the treatment of diseases like non-ulcer dyspepsia, Gastro-intestinal reflux disease etc.

Cisapride belongs to the Gastrointestinal Agent acts as a Serotonin 5-HT₄ receptors stimulator.

Cisapride increases GI motility by enhancing the release of acetylcholine at the myenteric plexuses in the gut plain muscle. It increases lower oesophageal sphincter pressure, shortens gastric transit time, reduces oesophageal reflux, and facilitates healing of oesophageal ulcers. It also increases small intestine activity.

Cisapride is approved for use in the following clinical indications

• GERD or gastrointestinal dysmotility

Cisapride is a medication used to treat heartburn associated with GERD.

• GERD or gastrointestinal dysmotility

Adult Oral Dose:

Initial: 5-10 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.

Pediatric Oral Dose:

Infants, Children, and Adolescents: 0.15 to 0.2 mg/kg/dose 3 to 4 times/day; maximum dose: 10 mg/dose.

• Dosage Adjustment in Hepatic impairment Patient

Initiate at 50% usual dose.

Cisapride is contraindicated in patients with

• 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.

• Cisapride should not be used in patients in whom an increase in gastrointestinal motility could be harmful, e.g., in the presence of gastrointestinal hemorrhage, mechanical obstruction, or perforation. Cisapride is contraindicated in patients with known sensitivity or intolerance to the drug.

• History of prolonged electrocardiographic QT intervals or known family history of congenital long QT syndrome; renal failure; history of ventricular arrhythmias, ischemic heart disease, and congestive heart failure; clinically significant bradycardia; uncorrected electrolyte disorders (hypokalemia, hypomagnesemia); respiratory failure; and concomitant medications known to prolong the QT interval and increase the risk of arrhythmia, such as certain antiarrhythmics, certain antipsychotics, certain antidepressants, astemizole, bepridil, sparfloxacin, and terodiline.

• ECG should be considered prior to initiation of cisapride. Cisapride should not be used in patients with a prolonged QT interval at baseline, those with a history of torsades de pointes, or those with long QT syndrome. Cisapride should also be avoided in patients with sinus node dysfunction, and in those with second or third degree atrioventricular block.
• Cisapride should not be used concomitantly with other drugs known to prolong the QT interval: certain antiarrhythmics, including those of Class IA (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); astemizole, bepridil, sparfloxacin, and terodiline.

Cisapride is excreted in human milk at concentrations approximately 1/20 of those observed in plasma. Caution should be exercised when cisapride is administered to a nursing woman, and particular care must be taken if the nursing infant or the mother is taking a drug that might alter cisapride's metabolism in the infant.

Animal studies have failed to reveal evidence of teratogenicity, although embryo- and fetotoxicity are seen in rats and rabbits at high doses (150 mg/kg/day and 20 mg/kg/day, respectively). There are no controlled data in human pregnancy. Cisapride should only be given during pregnancy when benefit outweighs risk.

Common Adverse effects

• Headache, Skin rash, Abdominal cramps, diarrhea, dyspepsia, flatulence, nausea, xerostomia, Rhinitis, Tachycardia, Anxiety, drowsiness, extrapyramidal reaction, fatigue, insomnia, seizure, Aplastic anemia, granulocytopenia, leukopenia, pancytopenia, thrombocytopenia, Increased liver enzymes, Viral infection (increased incidence), Cough, sinusitis, upper respiratory tract infection.

Rare Adverse effects

• Apnea, bronchospasm, gynecomastia, hyperprolactinemia, methemoglobinemia, psychiatric disturbance, skin photosensitivity.

• Antibiotics:

In vitro and/or in vivo data show that clarithromycin, erythromycin, and troleandomycin markedly inhibit the metabolism of cisapride, which can result in an increase in plasma cisapride levels and prolongation of the QT interval on the ECG.

• Anticholinergics:

Concurrent administration of certain anticholinergic compounds, such as belladonna alkaloids and dicyclomine, would be expected to compromise the beneficial effects of cisapride.

• Anticoagulants (Oral):

In patients receiving oral anticoagulants, the coagulation times were increased in some cases. It is advisable to check coagulation time within the first few days after the start and discontinuation of cisapride therapy, with an appropriate adjustment of the anticoagulant dose, if necessary.

• Antidepressants:

In vitro data indicate that nefazodone inhibits the metabolism of cisapride, which can result in an increase in plasma cisapride levels and prolongation of the QT interval on the ECG.

• Antifungals:

In vitro and/or in vivo data indicate that fluconazole, itraconazole, and oral ketoconazole markedly inhibit the metabolism of cisapride, which can result in an increase in plasma cisapride levels and prolongation of the QT interval on the ECG. Human pharmacokinetic data indicate that oral ketoconazole markedly inhibits the metabolism of cisapride, resulting in a mean eight-fold increase in AUC of cisapride. A study in 14 normal male and female volunteers suggests that coadministration of cisapride and ketoconazole can result in prolongation of the QT interval on the ECG.

• H₂ Receptor Antagonists:

Cimetidine coadministration leads to an increased peak plasma concentration and AUC of cisapride, there is no effect on cisapride absorption when it is coadministered with ranitidine. The gastrointestinal absorption of cimetidine and ranitidine is accelerated when they are co-administered with Cisapride.

• Protease Inhibitors:

In vitro data indicate that indinavir and ritonavir markedly inhibit the metabolism of cisapride which can result in an increase in plasma cisapride levels and prolongation of the QT interval on the ECG.

The common side effect of Cisapride include the following

Common

• Diarrhea, Upset stomach, Stomach discomfort, Headache, Stuffy nose, Constipation, Coughing.

Rare

• Vision changes, Chest pain.

• Pregnancy

Pregnancy Category C

Oral teratology studies have been conducted in rats (doses up to 160 mg/kg/day) and rabbits (doses up to 40 mg/kg/day). There was no evidence of a teratogenic potential of cisapride in rats or rabbits. Cisapride was embryotoxic and fetotoxic in rats at a dose of 160 mg/kg/day (100 times the maximum recommended human dose on a mg/kg basis and 14 times the maximum recommended human dose on a mg/m² basis) and in rabbits at a dose of 20 mg/kg/day (approximately 12 times the maximum recommended human dose on a mg/kg basis) or higher. It also produced reduced birth weights of pups in rats at 40 and 160 mg/kg/day and adversely affected the pup survival. There are no adequate and well-controlled studies in pregnant women. Cisapride should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the mother and the fetus.

• Nursing Mothers

Cisapride is excreted in human milk at concentrations approximately 1/20 of those observed in plasma. Caution should be exercised when cisapride is administered to a nursing woman, and particular care must be taken if the nursing infant or the mother is taking a drug that might alter cisapride's metabolism in the infant.

• Pediatric Use

Safety and effectiveness in pediatric patients under the age of 16 years have not been established for any indication. Although causality has not been established, serious adverse events, including death, have been reported in infants and children treated with cisapride. Several pediatric deaths were due to cardiovascular events (third degree heart block and ventricular tachycardia).

• Geriatric Use

Steady-state plasma levels are generally higher in older than in younger patients, due to a moderate prolongation of the elimination half-life. Therapeutic doses, however, are similar to those used in younger adults. The rate of common adverse experiences in patients greater than 65 years of age in clinical trials was similar to that in younger adults.

In instances of overdose, patients should be evaluated for possible QT prolongation and ventricular arrhythmias, including torsades de pointes. Treatment should include gastric lavage and/or activated charcoal, close observation and general supportive measures.

Pharmacodynamic

Cisapride is a parasympathomimetic which acts as a serotonin 5-HT₄ agonist; upon activation of the receptor signaling pathway, cisapride promotes the release of acetylcholine neurotransmitters 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.

Pharmacokinetics

• Absorption

It is Readily absorbed in the GI tract. Time taken to reach peak plasma concentrations is approximately 1-2 hours after oral administration.

• Distribution

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

• Metabolism and Excretion

Cisapride primarily metabolized via hepatic via cytochrome P450 3A4 enzyme.

• https://www.uptodate.com/contents/cisapride-united-states-available-via-limited-access-fda-investigational-drug-ind-protocol-only-drug-information?search=cisapride&source=panel_search_result&selectedTitle=1~107&usage_type=panel&kp_tab=drug_general&display_rank=1
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