Gasmotin

See Table 1:
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Generic name: Mosapride citrate.
Chemical name: (±)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl] benzamide citrate dihydrate.
Molecular formula: C₂₁H₂₅ClFN₃O₃·C₆H₈O₇·2H₂O.
Molecular weight: 650.05.
Partition coefficient: 9.1 x 10² (chloroform/water solvent, pH 7.0, at room temperature).
Mosapride citrate occurs as white to yellowish white crystalline powder.
It is odorless and has a slightly bitter taste.
It is freely soluble in N, N-dimethylformamide, in pyridine and in acetic acid (100), sparingly soluble in methanol, slightly soluble in ethanol (95) and acetic anhydride, and practically insoluble in water and in diethyl ether.

Pharmacotherapeutic Group: Gastroprokinetic drug.
Pharmacology: Mechanism of Action: This drug is a selective 5-HT₄ receptor agonist. It is considered that this drug stimulates 5-HT₄ receptors in the gastrointestinal nerve plexus, which increases the release of acetylcholine, resulting in enhancement of gastrointestinal motility and gastric emptying.
Clinical Pharmacology: In the gastric emptying test for healthy adults and patients with chronic gastritis, single administration of 5 mg of this drug enhanced gastric emptying.
Gastroprokinetic Effect: This drug increased gastric and duodenal motility after meals in conscious dogs.
Gastric Emptying Enhancing Effect: This drug enhances gastric emptying of liquid (in mice and rats) and solid (in rats) content. The gastric emptying enhancing effect was decreased after one-week repeated administration (in rats).
Clinical Studies: The results of clinical studies on 435 cases in total including a double-blind comparative study are summarized as follows. (see Table 2)

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Pharmacokinetics: Plasma Concentration: (5 healthy adults under fasting conditions, single administration of 5 mg of mosapride citrate): See Table 3.

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Plasma Protein Binding Rate: 99.0% [in vitro, human serum, at a concentration of 1 μg/mL, methods of ultrafiltration or equilibrium dialysis].
Main Metabolites and Metabolic Pathway: Main Metabolite: des-4-fluorobenzyl compound.
Metabolic pathway: Mosapride citrate is metabolized mainly in the liver, where the 4-fluorobenzyl group is removed, followed by oxidation of the morpholine ring at position 5, and hydroxylation of the benzene ring at position 3.
Excretion Route and Excretion Rate: Excretion route: In urine and feces.
Excretion rate: In urine collected for 48 hours after administration, 0.1% was excreted as unchanged compound and 7.0% was excreted as the main metabolite (des-4-fluorobenzyl compound). (Healthy adults, single administration of 5 mg of mosapride citrate under fasting conditions.)
Metabolic Enzyme: Cytochrome P-450 sub-family: mainly CYP3A4.
Drug Interactions: When erythromycin at 1,200 mg/day was concomitantly administered with this drug at 15 mg/day, in comparison with a single administration of mosapride, maximum blood concentration of mosapride increased from 42.1 ng/mL to 65.7 ng/mL, the half-life was prolonged from 1.6 hours to 2.4 hours and AUC_0-4 increased from 62 ng·hr/mL to 114 ng·hr/mL. (Healthy adult.)

Gastrointestinal symptoms associated with functional dyspepsia (chronic gastritis) (heartburn, nausea/vomiting).

For adults, 15 mg of mosapride citrate as anhydrous form is usually administered daily in 3 divided oral doses before or after meals.

Important Precautions: If any improvement of gastrointestinal symptoms is not observed after the administration for a given period of time (usually for 2 weeks), this drug should not be administered aimlessly for a long period.
Other Precautions: When 100 to 330 times of the recommended clinical dose (30 to 100 mg/kg/day) of mosapride citrate was orally administered in rodents for long period (104 weeks in rats, 92 weeks in mice), increased incidence of hepatocellular adenoma and thyroid follicular cell adenoma were observed.
Use in Children: Safety of this drug in children has not been established [no clinical experience].
Use in the Elderly: Since in the elderly patients their physiological function in the kidneys and the liver are reduced in general, this drug should be administered with care by monitoring patients' condition. If any adverse reactions are found, appropriate measures such as reducing the dose (e.g. to 7.5 mg daily) should be given.

This drug should not be used in pregnant women, women who may possibly be pregnant, only if the expected therapeutic benefits outweigh the possible risks associated with the treatment. [Safety of this drug in pregnant women has not been established.]
Administration of this drug to nursing mothers should be avoided. If administration is essential, nursing mothers should discontinue breastfeeding during the treatment. [Animal (rat) experiments have shown that this drug is excreted in breast milk.]

Adverse reactions were found in 40 of 998 cases (4.0%) in clinical trials. The main adverse reactions were diarrhea/loose stools (1.8%), dry mouth (0.5%), malaise (0.3%), etc. Abnormal clinical laboratory test values were observed in 30 of 792 cases (3.8%), which were mainly eosinophilia (1.1%), elevations of triglyceride (1.0%), AST (GOT), ALT (GPT), ALP and gamma-GTP (0.4% each) (at the time of approval).
Clinically Significant Adverse Reactions: Fulminant hepatitis, hepatic dysfunction and jaundice (less than 0.1%, each).
Since fulminant hepatitis, serious hepatic dysfunction accompanied with marked elevations of AST (GOT), ALT (GPT) and gamma-GTP, etc. and jaundice may occur and some of them were fatal, the patient should be monitored carefully and if any abnormalities are found, discontinue the administration immediately and give appropriate measures.
Other Adverse Reactions: See Table 4.

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Inform the doctor in case of any adverse reactions related to drug use.

Precautions for coadministration (GASMOTIN should be administered with care when coadministered with the following drugs.) (See Table 5.)

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When dispensing the drug: For drugs that are dispensed in a press-through package (PTP), instruct the patient to remove the drug from the package prior to use. (It has been reported that, if the PTP sheet is swallowed, the sharp corners of the sheet may puncture the esophageal mucosa, resulting in severe complications such as mediastinitis.)

Store at room temperature not exceeding 30°C.
Shelf life: 5 years.

GIT Regulators, Antiflatulents & Anti-Inflammatories

A03FA09 - mosapride ; Belongs to the class of propulsives. Used in the treatment of functional gastrointestinal disorders.

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