Itopride hydrochloride 50 mg Tablets
Each tablet contains:
Itopride hydrochloride SO mg
lactose monohydrate, Polyvinyl pyrrolidone k25, Croscarmellose sodium, Magnesium stearate & Silicon dioxide.
Pharmacological action :
– Itopride hydrochloride activates gastrointestinal propulsive motility due to its dopamine 02 antagonizing activity and acetyl cholinesterase inhibitory activity. It activates acetylcholine release and inhibits its degradation.
– Itopride hydrochloride also has antiemetic action through interaction with 02 receptors located in the chemoreceptor trigger zone.
– ltopride hydrochloride has been shown to accelerate gastric emptying in humans.
– The action of Itopride hydrochloride is highly specific for the upper gastrointestinal tract. Itoprlde hydrochloride does not affect serum gastrin levels.
Itopride hydrochloride 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 0.28mcg/mi) are reached after 05 to 0.75 hours after oral dose of SO mg ofltopride hydrochloride. Following multiple oral doses ranging from 50 mg to 200 mg tid, Itopride hydrochloride and its metabolites showed
linear pharmacokinetics over a treatment period of seven days, with minimal accumulation.
Approximately 96% of Itopride hydrochloride is bound to plasma proteins. Albumin accounts for most of the binding. Alpha-l-acid- glycoprotein accounts for less than 15% of binding.
Itopride hydrochloride undergoes extensive hepatic metabolism in humans. Three metabolites have been indentified, of which only one exerts minor activity whithout 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 hydrochloride is metabolized by a flavin-dependent mono-oxygenase (FM03). The abundance and efficiency of the human FMQ-isozymes can be subjected to genetic polymorph isms, which can lead to rare autosomal recessive condition known as trimethylaminuria (fish odor syndrome). The half life of Itopride hydrochloride may therefore be longer in trimethylaminuria patients. In vivo pharmacokinetic studies on CYP-mediated reactions revealed that Itopride hydrochloride showed neither inhibitory nor inductory effect CYP2C19 and CYP2E1. CYP content and uridine diphosphate glucuronosyl transferase activity were not altered with the administration of Itopride.
Itopride hydrochloride and its metabolites are primarily excreted in the urine. The urinary excretions ofltopride hydrochloride and its N.-oxidewere 3.7%and 75.4 % respectively, in healthy subjects after oral administration of a single therapeutic dose. The terminal phase half life of Itopride hydrochloride was approximately six hours.
Itopride hydrochloride is used in the treatment of gastrointestinal symptoms of:
– Functional dyspepsia.
– Non-ulcer dyspepsia (chronic gastritis) i.e : sensation of bloating, early satiety, upper abdominal pain or discomfort, anorexia, heartburn, nausea & vomiting.
Dosage & Administration :
– The recommended dose of Itopride hydrochloride for adult patients is 150 mg daily [one tablet (50 mg) taken orally three times a day before meals.] The dose may be reduced according to the patient’s age & symptoms.
Contra – indications :
-Itoprlde hydrochloride is contraindicated in patients with known hypersensitivity to Itopride hydrochloride or any of the excipients.
Itopride hydrochloride should not be used in patients in whom an increase in gastrointestinal motility could be harmful e.g gastrointestinal hemorrhage, mechanical obstruction or perforation.
Side effects :
The following adverse events have been reported in patients receiving Itopride hydrochloride:
– Blood and lymphatic system disorders: Leukopenia and thrombocytopenia .
– Immune system disorders: Anaphylactoid reaction.
– Endocrine disorders: increased prolactin level & gynecomastia.
– Nervous system disorders: Dizziness, headache & tremor.
– Gastrointestinal disorders: Diarrhea, constipation abdominal pain, increased saliva & nausea.
– Hepato- biliary disorders: Jaundice.
– Skin & subcutaneous tissue disorders: Rash, redness ~ itching.
– Investigations: increased AST (5GOn, increased ALT ( SGPD. increased gamma
– GTP, increased alkaline phosphatase & increased bilirubin.
Drug -Drug Interactions :
– Metabolic interactions are not expected since Itopride hydrochloride is primarily metabolized by flavine mono – oxygenase & not by CYP 450. -Since Itopride hydrochloride has gastrokinetic effects, it could influence the absorption of concomitantly orally administered drugs. particular caution should be taken with drugs with narrow therapeutic index, sustained release or enteric- coated formulations
– Anti-ulcer drugs: like cimetidine, ranitidine, teprenone and cetraxate do not affect the prokinetic action of itopride.
– Anticholinergic drugs may reduce the action of itopride hydrochloride.
– No changes in protein binding have been seen with coadministraion of warfarin, diazepam, diclofenac sodium, ticlopidine hydrochloride, nifedipene and nicardipine hydrochloride.
Pregnancy and Lactation :
-There are no adequate and well- controlled studies in pregnant women. Therefore, Itopride hydrochloride should not be used during. pregnancy unless the benefits outweigh the potential risks.
– Because Itopride hydrochloride is excreted in milk, and because of the potential for adverse reactions in nursinhg infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
– There are no known effects of Itopride hydrochloride on labor or delivery.
Precautions and warnings :
Itopride hydrochloride enhances the action of acetylcholine and may produce cholinergic side effects.
– Pediatric use: Safety of this product in children under the age of 16 has not been established .
– Geriatric use: In general, appropriate caution should be exercised in the administration and monitoring of Itopride hydrochloride in elderly patients reflecting the greater frequency of decreased hepatic, renal function, and of concomitant disease or
other drug therapy.
There have been no reported cases of overdose in humans. In case of excessive overdose the usual measures of gastric Lavage symptomatic therapy should be applied.
Patient information :
– The dose of this product is to be taken before meals.
– Inform your physician when any signs of side effects appear either those mentioned in the insert leaflet or not.
Package Br Storage :
– Box of 10, 20 or 30 tablets.
– Store at a temperature not exceeding 30 0(, in a dry place.
– Do not use unless under physician supervision.
Keep all medicaments out of reach of children
Produced by :
BORG PHARMACEUTICAL INO.
b0rg El-Arab new city Alexandria – Egypt