ITONORM

Itopride Hydrochloride 50mg SR Capsules

Itopride Hydrochloride 50 mg Tablets

The Active Ingredient of ITONORM is Itopride Hydrochloride, Drugs for functional gastrointestinal disorders. Which improves motility (automatic bowel and stomach movements, which are necessary to pass food through Digestive tract) and prevent from Nausea and Vomiting.

PRESENTATION

Each Capsule Contains Itopride Hydrochloride 150mg.

Each Tablets Contains Itopride Hydrochloride 50 mg

Pack Size: 10*10 Blisters.

CLINICAL PHARMACOLOGY

Pharmacodynamics properties

Pharmacotherapeutic Group: Drugs for functional Gastrointestinal Disorders.

Mechanism of Action:  Itopride activates the gastrointestinal propulsive motility by Dopamine D2 receptors Antagonistic action and Acetylcholine Esterase inhibitory action. Itopride activates Acetylcholine release and inhibits its degradation.

In addition Itopride has an Antiemetic effect which is based on interaction with Dopamine D2 receptors in Chemoreceptor zone. This effect was demonstrated by dose dependent inhibition of Apo Morphine induced vomiting in dogs.  Itopride accelerates Stomach Emptying in Humans.

In animal studies in dogs with a single dose administration Itopride supported Stomach emptying. Itopride has high specific action in upper part of Gastrointestinal Tract. Itopride does not influence plasma concentrations of Gastrin.

 Pharmacokinetic properties

Absorption: Itopride is absorbed rapidly and almost completely from Gastrointestinal Tract. Relative bioavailability is about 60% due to first-pass effect. Food does not affect bioavailability of the medicinal product. Maximum plasma concentrations are reached in 30 to 50 minutes after administration of 50 mg of Itopride. After repeated administration of doses in the range of 50 to 200 mg 3 times a day for period of 7 days, Itopride and its metabolites have shown pharmacokinetics of linear type with minimal accumulation.

Distribution:  About 96% of Itopride is bound to plasma proteins, mainly Albumin. Alpha-1-Acidglycoprotein accounts for less than 15% of binding.

In rats Itopride is distributed extensively in the tissues (Vdß = 6.1 l/kg) except for central nervous system; high concentrations are reached in Kidneys, Small Intestine, Liver, Adrenal Glands and Stomach. Protein binding in rats was lower than in Humans (78% vs. 96%). Penetration into the Central Nervous System was minimal. Itopride is excreted in milk of Lactating rats.

Metabolism:  In humans, Itopride is extensively metabolized in Liver. Three metabolites were identified of which only one manifests minor activity without pharmacological significance (about 2 to 3% of Itopride effect). The main metabolite is N-oxide, which is product of oxidation of the tertiary Amine-N-Dimethyl group.

Itopride is metabolized by Flavine Mono oxygenase (FMO3). The amount and efficacy of human FMO Iso enzymes can be associated with genetic polymorphisms which can result in rare autosomal recessive condition known as Trimethylaminuria (fish odor syndrome). Biological half-life in patient’s withTrimethylaminuria can be longer.

Pharmacokinetic in vivo studies of CYP-mediated reactions did not prove inhibition or induction of CYP2C19 and CYP2E1 caused by Itopride. Administration of Itopride did not influence content of CYP or the activity of Uridine-Diphosphate-Glucuronyl Transferase.

Excretion:  Itopride and its metabolites are primarily excreted by urine. The amount of excreted Itopride and N-oxide after oral single therapeutic dose to healthy volunteers was 3.7% and 75.4%, respectively. Half-life of Itopride is about 6 hours.

DRUG-DRUG INTERACTIONS

• No interactions on level of cytochrome P450 are expected to occur because Itopride is metabolized mainly by Flavine Monooxygenase. No interaction was detected when Itopride was administered concomitantly with Warfarin, Diazepam, Diclofenac, Ticlopidine, Nifedipine and Nicardipine.
• Itopride has Gastro-Kinetic effect that could influence the absorption of concomitantly orally administered medicinal products. Particular attention should be taken to drugs with a narrow therapeutic index, drugs with prolonged-release of active substance and enteric-coated drug formulations.
• Anticholinergic agents may reduce the action of Itopride.
• Substances as Cimetidine, Ranitidine, Teprenone and Cetrexate do not affect Prokinetic activity of Itopride.

INDICATIONS

• Treatment of Gastrointestinal symptoms of functional Non-Ulcer Dyspepsia, like feelings of Bloating, Gastric Fullness, Upper Abdominal pain, Anorexia, Heartburn, Nausea and Vomiting. 
• The medicinal product is indicated in Adults.

DOSAGE AND METHOD OF ADMINISTRATION

• The recommended dose for adults is 150 mg daily, i.e. 1 capsule of 150 mg 1 times a day or 50 mg Tablets 3 times a day before meal.
• The exact dosage and duration of treatment depends on the clinical state of the patient.
• The duration of the administration in clinical trials was maximally 8 weeks.

Pediatrics population:  The safety and efficacy of Itopride in Pediatric population has not been established.

Patients with Hepatic or Renal Impairment: Itopride is metabolized in Liver and the primary way of Excretion is via Kidneys. Patients with Impaired Hepatic or Renal function taking this medicinal product should be carefully monitored and in case of adverse reactions it is necessary to take appropriate measures, e.g. reduction of the dose or discontinuation of the therapy.

Elderly: It was shown in clinical trials that the incidence of adverse effects in patients aged 65 years and older was not higher than in younger patients. Itopride should be administered in elderly with adequate caution because of increased incidence in Hepatic and Renal Function Disorders, concomitant disease or treatment with additional drugs. Elderly using this medicinal product should be monitored closely and in case of Adverse reactions appropriate measures, such as reduction of the dose or discontinuation of the treatment should be taken. 

Method of Administration:  Capsules or Tablets should be swallowed with a sufficient amount of liquid.

SIDE-EFFECTS

Common (may affects 1 in 10 People)

• Swelling of the Hands, Feet, Ankles, Face, Lips or Throat, which can cause troubles with swallowing or breathing. You can see also Rash or Itching.

Uncommon (may affect less than 1 in 100 people)

• Diarrhea,
• Stomach ache,
• Constipation,
• Increased salivation
• Headache,
• Impaired sleeping,
• Dizziness,
• Back pain or pain on chest,

• Fatigue,
• Irritability

• Increased level of substances called Creatinine and Blood Urea Nitrogen (BUN)
• Decreased level of leukocytes (white blood cells) – leukopenia
• Increased level of Hormone Prolactin in Blood (can lead to excretion of milk or enlargement of Mammary gland)

Rare (may affect less than 1 in 1000 people)

• • Rash,
  • Redness of skin,
  • Itching

Unknown (frequency cannot be estimated from the available data)

• • Decreased Blood Platelet (as Bruise or Bleeding)
  • Trembling, Nausea (feeling to Vomit)
  • Enlargement of Mammary Gland (Gynecomastia),
  • Yellow skin (Jaundice)
  • Increased level of certain enzymes in blood – AST, ALT, GGT, alkaline phosphatase and coloring matter bilirubin
  • Anaphylactic reaction (severe allergic reaction)

In case of production or excretion of milk from mammary gland besides breast-feeding (Galactorrhea) or enlargement of mammary gland in men (Gynecomastia) stop the treatment and contact your doctor.  

WARNING AND PRECAUTIONS

Itopride potentiates Acetylcholine action and can induce side cholinergic effects.  Data about long-term administration of Itopride is not available

• Pregnancy: Safety of Itopride in pregnancy has not been established. Therefore Itopride can be used in pregnant women or women in whom pregnancy cannot be excluded only if therapeutic benefits considerably outweigh possible risks. No known effect during delivery is observed.
• Lactation: Itopride is excreted in the milk of lactating rats. Due to lack of experience with use of Itopride during breast-feeding in human, a decision must be made whether to discontinue breastfeeding or to discontinue Itopride therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the women.

CONTRAINDICATIONS

• Hypersensitivity to the Active substance or to any of the Excipients.
• ITONORM   must not be used in patients in whom increased Gastrointestinal motility could be harmful, e.g. in patients with gastrointestinal Haemorrhage, mechanical obstruction or perforation.