Nastilox
Nastilox Uses, Dosage, Side Effects, Food Interaction and all others data.
In many countries (including Canada) cisapride has been either withdrawn or has had its indications limited due to reports about long QT syndrome due to cisapride, which predisposes to arrhythmias. The FDA issued a warning letter regarding this risk to health care professionals and patients.
Nastilox 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. Nastilox stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Nastilox 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. Nastilox does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity.
| Trade Name | Nastilox |
| Availability | Discontinued |
| Generic | Cisapride |
| Cisapride Other Names | Cisaprid, Cisaprida, Cisapride, Cisapridum |
| Related Drugs | omeprazole, famotidine, pantoprazole, Nexium, Pepcid, metoclopramide, Protonix, Prilosec, ranitidine, calcium carbonate |
| Type | |
| Formula | C23H29ClFN3O4 |
| Weight | Average: 465.945 Monoisotopic: 465.183062343 |
| Protein binding | 97.5% |
| Groups | Approved, Investigational, Withdrawn |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Greece |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Nastilox is a medication used to treat heartburn associated with GERD.
For the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease.
Nastilox is also used to associated treatment for these conditions: Gastrointestinal Disorder
How Nastilox works
Nastilox acts through the stimulation of the serotonin 5-HT4 receptors which increases acetylcholine release in the enteric nervous system (specifically the myenteric plexus). This results in increased tone and amplitude of gastric (especially antral) contractions, relaxation of the pyloric sphincter and the duodenal bulb, and increased peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit.
Food Interaction
- Avoid grapefruit products.
- Exercise caution with St. John's Wort.
- Take before a meal. Take at least 15 minutes before meals.
[Major] CONTRAINDICATED: Coadministration with grapefruit juice may increase the plasma concentrations of cisapride.
The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.
In a study of 14 healthy volunteers, administration with 250 mL of grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of cisapride (10 mg single dose) by 34% and 39%, respectively, compared to water.
A second single-dose study involving 12 healthy volunteers demonstrated an increase of 68% and 51% in cisapride Cmax and AUC, respectively, compared to water.
In another 10 healthy volunteers, repeated ingestion of double-strength grapefruit juice (200 mL three times a day for 2 days, then with a 10 mg dose of cisapride and at 0.5 and 1.5 hours afterwards) resulted in an 81% and 144% increase in mean cisapride Cmax and AUC, respectively, compared to water.
A high degree of intersubject variability in the grapefruit juice effect was observed in all three studies, but no patient experienced any changes in heart rate, blood pressure, or QT interval.
However, high plasma levels of cisapride have been associated with prolongation of the QT interval on the ECG; ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes; cardiac arrest; and sudden death.
GENERALLY AVOID: Coadministration with red wine may increase the plasma concentrations of cisapride in susceptible individuals.
The exact mechanism of interaction is unknown but is believed to involve inhibition of CYP450 3A4 in the gut wall similar to grapefruit juice.
In 12 healthy volunteers, administration with 250 mL of red wine (cabernet sauvignon) produced only minor and statistically insignificant changes in cisapride pharmacokinetics compared to water.
However, one subject had a doubling in cisapride AUC and Cmax with red wine.
The same subject also had the largest interaction with grapefruit juice, which suggests that a significant interaction may occur in certain individuals, perhaps those with a preexisting high intestinal CYP450 3A4 content.
MANAGEMENT: Patients receiving cisapride therapy should avoid the consumption of grapefruits and grapefruit juice.
Because a significant interaction may occur with red wine in the occasional patient, red wine should preferably be avoided also during cisapride therapy.
Nastilox Drug Interaction
Moderate: glycerin, glycerin, albuterol, albuterolMinor: sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprimUnknown: ubiquinone, ubiquinone, copper gluconate, copper gluconate, levocarnitine, levocarnitine, acetaminophen, acetaminophen, bioflavonoids, bioflavonoids, valproic acid, valproic acid, cholecalciferol, cholecalciferol
Nastilox Disease Interaction
Major: cardiac disease, GI hemorrhage/obstruction/perforation
Elimination Route
Nastilox is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%.
Half Life
6-12 hours
Innovators Monograph
You find simplified version here Nastilox
