What is Cisapride?
Cisapride belongs to the group of prokinetics. Prokinetics are active ingredients that promote motility, that is, motility of the gastrointestinal tract.
What is Cisapride used for?
Cisapride stimulates gastrointestinal motility and is therefore used to treat:
- gastroesophageal reflux disease (GERD);
- mild to moderate reflux esophagitis for maintenance therapy;
- gastroparesis (e.g., idiopathic, drug-induced, diabetic, or postoperative gastroparesis);
- irritable stomach (non-ulcer dyspepsia) by the type of motility disorders;
- intestinal pseudo-pulmonary obstruction.
Mechanism of action of Cisapride
Mechanism of Action Cisapride Propulsid is a partial agonist of serotonin receptors of subtype 5-HT4. It increases motility throughout the digestive tract by increasing the release of acetylcholine in the Auerbach plexus (plexus myentericus).
However, it has no direct parasympathomimetic properties and has no effect on gastric juice secretion. Cisapride stimulates esophageal peristalsis and increases esophageal sphincter tone, it prevents the reflux of gastric contents into the esophagus.
The drug promotes propulsive contraction of the stomach and duodenum, as well as gastroduodenal coordination. Gastric emptying is accelerated, and bile reflux is prevented.
Cisapride promotes both small and large intestine motility. Intestinal transit time and transit time through the large intestine are shortened.
Cisapride vs Metoclopramide
Metoclopramide is also a prokinetic and is used to treat the same conditions.
However, Cisapride, in comparison with Metoclopramide, does not exhibit any antidopaminergic properties and the release of prolactin (dopamine, a hormone that inhibits prolactin) is not increased by the administration of Cisapride. Long-term studies of the treatment of diabetic gastroparesis have shown that the prokinetic effect of Cisapride persists with long-term therapy and that tachyphylaxis is not expected.
It has also been shown that Cisapride at a dose (10 mg) resulted in significantly more rapid gastric emptying than Metoclopramide.
How long does Cisapride stay in the system?
Cisapride is rapidly and completely absorbed and undergoes extensive presystemic metabolism in the liver and small intestine wall. Bioavailability is 50% on an empty stomach, 65% when taken with food, and decreases with decreased gastric juice secretion.
The onset of action is 30-60 minutes after oral administration.
Because of the intensive metabolism of Cisapride, 90% is excreted as biotransformation products. Only 1% of the unchanged initial substance is excreted by the kidneys and 6% by the feces. The elimination half-life is about 10 hours, complete elimination takes 40 to 70 hours.
The usual dose for adults with gastroparesis and gastroesophageal reflux disease: 10 mg orally 4 times daily 15 min before meals and before bedtime, if necessary, can be increased to 20 mg per dose.
The usual dose for adults with dyspepsia: 5 mg orally 3 times a day 15 minutes before meals, if necessary, can be increased to 10 mg.
The usual pediatric dose for gastroesophageal reflux disease: for children from one year of age is 0.2-0.3 mg/kg/dose orally 3-4 times a day. Maximum: 10 mg per dose.
Cisapride: Side effects
The most common side effects are allergic reactions such as skin rash, urticaria, abdominal cramps, upset stomach, and diarrhea. In individual cases: mild headache, somnolence, reversible liver dysfunction with or without cholestasis, central nervous system effects such as central seizures or extrapyramidal effects and increased frequency of urination, changes in heart function.
- Hypersensitivity to Cisapride.
- In pregnancy and in patients with epilepsy only after the strictest indication and careful assessment of risk and benefit.
- Lactation. In case of an undesirable increase in gastrointestinal motility, such as gastrointestinal bleeding, mechanical obstruction, or perforation.
- Cisapride is contraindicated when used concomitantly with ketoconazole, itraconazole, miconazole, fluconazole, erythromycin, clarithromycin, or troleandomycin due to increased plasma levels (risk of arrhythmia).
- Since protease inhibitors such as ritonavir, saquinavir, indinavir, fluvoxamine, and nefazodone are also biotransformed by cytochrome CYP3A4 isoforms, concomitant use with Cisapride should be avoided because of the risk of increased plasma levels.
- There is insufficient experience with use in infants less than 4 weeks of age. Premature infants should not be treated with Cisapride until 3 months after birth.
- Patients with risk factors or conditions such as coronary heart disease, arrhythmias, renal failure, electrolyte imbalance, concomitant proarrhythmogenic drug therapy, or concomitant therapy with CYP3A4 inhibitors should be monitored for QT interval prolongation on ECG, pirouette tachycardia or ventricular arrhythmias for careful observation.
Cisapride stimulates gastrointestinal motility, which may affect the absorption rate of other drugs. Absorption of other drugs from the stomach may be reduced. On the other hand, the rate of absorption from the small intestine, such as benzodiazepines or paracetamol, may be increased. Thus, the sedative effect of benzodiazepines and alcohol, and antidepressants may be increased.
In the case of drugs requiring particularly precise dosage (e.g. antiepileptic drugs), it is recommended to monitor the plasma concentration.
When concomitant use of anticoagulants, prolongation of prothrombin time should be expected. Therefore, it should be monitored for several days at the beginning and termination of therapy with Cisapride and the anticoagulant dose should be adjusted accordingly.
Anticholinergic agents and possibly also opioid analgesics counteract the effects of Cisapride. H2-receptor antagonists increase the bioavailability of Cisapride, and their own bioavailability (shown for cimetidine and ranitidine) is reduced.
Ketoconazole inhibits extensive biotransformation of Cisapride in the liver, which leads to a significant increase in its plasma levels, which may lead to prolonged QT interval on ECG, pirouette tachycardia, and ventricular arrhythmias.
Does Cisapride need to be refrigerated?
Cisapride preparations should be stored according to the manufacturer's instructions and used only up to the date stated on the label. The tablets should be kept away from moisture. Suspension may be stored up to 3 months after opening the bottle. Store only in a refrigerator.read more