Full Prescribing Info
Itopride HCl.
Pharmacology: Pharmacokinetics: Absorption: Itopride HCl is rapidly and almost completely absorbed from the gastrointestinal tract. Relative bioavailability is calculated to be 60% due to liver first-pass metabolism. There is no effect of food on bioavailability. Peak plasma levels (Cmax=0.28 mcg/mL) are reached after 0.5-0.75 hrs after itopride HCl 50 mg. Following multiple oral doses ranging from 50-200 mg 3 times daily, itopride HCl and its metabolites showed linear pharmacokinetics over a treatment period of 7 days, with minimal accumulation.
Distribution: Approximately 96% of itopride HCl is bound to plasma proteins. Albumin accounts for most of the binding. Alpha1-acid glycoprotein accounts for <15% of binding.
In rats, itopride is distributed extensively (Vdβ=6.1 L/kg) with high concentrations in the kidneys, small intestines, liver, adrenal glands and stomach. Protein-binding in the rat was lower than that seen in humans (78% vs 96%). The transfer into the central nervous system (CNS), including brain and spinal cord, was minimal. Itopride distributes into the breast milk of rats.
Metabolism: Itopride undergoes extensive hepatic metabolism in humans. Three (3) metabolites have been identified, of which only 1 exerts minor activity without pharmacological relevance (approximately 2-3% of that of itopride). The primary metabolite in humans is the N-oxide, generated by oxidation of the tertiary amine N-dimethyl group.
Itopride is metabolized by a flavin-dependent monooxygenase (FMO3). The abundance and efficiency of the human FMO-isozymes can be subject to genetic polymorphisms, which can lead to a rare autosomal recessive condition known as trimethylaminuria (fish odor syndrome). The half-life (t½) of itopride may therefore, be longer in trimethylaminuria patients.
In vivo pharmacokinetic studies on CYP-mediated reactions revealed that itopride showed neither inhibitory nor inductory effect on CYP2C19 and CYP2E1. CYP content and uridine diphosphate glucuronosyl transferase activity were not altered with the administration of itopride.
Excretion: Itopride hydrochloride and its metabolites are primarily excreted in the urine. The urinary excretions of itopride and its N-oxide were 3.7% and 75.4%, respectively, in healthy subjects after oral administration of a single therapeutic dose.
The terminal phase t½ of itopride hydrochloride was approximately 6 hrs.
Treatment of chronic gastritis or non-ulcer dyspepsia ie, feeling of abdominal bloatedness, upper abdominal pain, heartburn, nausea and vomiting.
Dosage/Direction for Use
Adult: Recommended Dose: 1 tablet (50 mg) taken orally 3 times daily before meals. The dose may be reduced according to the patient's age and symptoms. In the clinical studies, Ganaton has been administered up to 8 weeks.
There have been no reported cases of overdosage in humans. In case of excessive overdosage, the usual measures of gastric lavage and symptomatic therapy should be applied.
Hypersensitivity to itopride hydrochloride or any of the excipients of Ganaton.
Patients in whom an increase in gastrointestinal motility could be harmful eg, gastrointestinal hemorrhage, mechanical obstruction or perforation.
Special Precautions
Itopride hydrochloride enhances the action of acetylcholine and may produce cholinergic side effects.
Adverse Reactions
Clinical Trials: In clinical trials (phase I-III), itopride hydrochloride was well-tolerated and no serious adverse reactions were reported. A total of 19 adverse drug reactions in 14 patients were reported out of 572 cases with an incidence of 2.4%. The majority of these adverse reactions occurring in >1 patient consisted of diarrhea in 4 cases (0.7%), headache in 2 cases (0.3%) and abdominal pain in 2 cases (0.3%).
Abnormal laboratory findings observed in the trials include decreased white blood cells (leukocytopenia) in 4 cases (0.7%), increased prolactin in 2 cases (0.3%).
Post Marketing Experience: The following adverse events have been reported in patients receiving itopride hydrchloride.
Blood and Lymphatic System Disorders: Leukopenia and thrombocytopenia.
Immune System Disorders: Anaphylactoid reaction.
Endocrine Disorders: Increased prolactin level and gynecomastia.
Nervous System Disorders: Dizziness, headache and tremor.
Gastrointestinal Disorders: Diarrhea, constipation, abdominal pain, increased saliva and nausea.
Hepatobiliary Disorders: Jaundice.
Skin and Subcutaneous Tissue Disorders: Rash, redness and itching.
Investigations: Increased aspartate aminotransferase (AST) [serum glutamic oxaloacetic transaminase (SGOT)], alanine aminotransferase (ALT) [serum glutamic pyruvic transaminase (SGPT)], γ-glutamyl transpeptidase (γ-GTP), alkaline phosphatase and bilirubin.
Drug Interactions
Metabolic interactions are not expected since itopride is primarily metabolized by flavine monooxygenase and not by CYP450. No changes in protein-binding have been seen with co-administration of warfarin, diazepam, diclofenac sodium, ticlopidine hydrochloride, nifedipine and nicardipine hydrochloride. Since itopride has gastrokinetic effects, it could influence the absorption of concomitantly orally administered drugs. Particular caution should be taken with drugs with a narrow therapeutic index, sustained-release or enteric-coated formulations. Antiulcer drugs eg, cimetidine, ranitidine, teprenone and cetraxate do not affect the prokinetic action of itopride. Anticholinergic drugs may reduce the action of itopride.
Store at temperatures not exceeding 30°C.
ATC Classification
A03FA - Propulsives ; Used in the treatment of functional gastrointestinal disorders.
FC tab 50 mg x 30's.
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