Since itopride is not metabolised by the cytochrome P450 (CYP) 3A4) enzyme system but by the flavin mono-oxygenase enzyme system, enzyme system, it is unlikely to alter the pharmacokinetics of other concomitantly administered drugs like cisapride and mosapride.

Oral CYP 3A4 inhibitor dosing along with cisapride significantly inhibits the metabloism of cisapride resulting in markedly elevated plasma concentrations of cisapride in patients

Anticholinergic agents like atropine may reduce the action of itopride, and caution may be requird in case the two need to be administered concomittantly.

Itopride hydrochloride is well tolerated and and adverse reactions infrequently reported include-

diarrhea, constipation, headache, abdominal pain, irritated feeling and dizziness.

Not indicated

Special precautions:

Itopride should be used with caution because it enhances the action of acetylcholine

Approved on    2002/2006

Indication-

Antiemetic Prokinetic agent

Dosage-

50mg tid

Gastro Osephageal Reflux Disease (GORD)

Evidence Based Medicine (MIMS- March 2003)

Beneficial

1. Proton Pump Inhibitors such as omeprazole, Lansoprazole, pantoprazole

2. H-2 Antagonists such as cimetidine, ranitidine, famotidine, (less than proton pump inhibitors)

3. Fundoplication

Likely to be beneficial

1. Medical and surgical tretment of GORD in selected patients with extraoesophageal manifestations.

Unknown effectiveness

1. Medical and surgical treatment of GORD in patients with Barrets oesophagus

2. Surgical treatment for non erosive oesophagitis

Key Points

1. One systemic review of randomised clinical trials has found proton inhibitors to be more effective than H-2 antagonists in both erosive and non-erosive oesophagitis. One trial has found no significant differences in the effectiveness of different proton pump inhibitors

2. Surgical treatment has not been adequately evaluated in controlled clinical trials. Medical and surgical treatments have not been adequately compared

3. It is not clear whether patients with Barretts oesophagitis benefit from medical or surgical treatment of their gastro oesophageal reflux

4. There is limited, conflicting evidence on the basis on the benefits of treating gastro oesophageal reflux in patients with extra oesophageal manifestations (such as asthma)

Pharmacology

Itopride has a dual mode of action. It inhibits the dopamine D2 receptor at the parasympathetic nerve ends and thereby increases the release of acetylcholine and decreases the metabolism of acetylcholine by inhibiting the enzyme acetylcholinesterase(AChE).

By maintaining higher acetylcholine levels. Itopride increases the esophageal and gastrointestinal peristalisis, increases the lower oesophageal sphincter pressure, stimulates gastric motility, accelrates gastric emptying, and improves gastro-duodenal co-ordination.

By virtue of its dopamine D2 receptor antagonistic action on the chemoreceptor trigger zone (CTZ), itopride also exerts anti-emetic actions.

Pharmacokinetics:

On oral administration of a single dose of 50mg of itopride in normal healthy adults, it was observed that the drug is rapidly and extensively absorbed (96%- 98%). The peak serum concentrations are acheived within 35 minutes after oral dosing. Itopride is readily and extensively distributed except in the central nervous system and spinal cord.

The drug is metabolized in the liver by N-oxidation to inactive metabolites by the enzyme flavin-containing mono-oxygenase. The half-life of itopride is about 6 hours, thus necessiating a tid dose. On repeated dosing, itopride does not accumulate in the body.

The pharmacokinetic profile after repeated doses is similar to that after the first dose, Food does not significantly affect the absorption of itopride.

Clinical experience Studies have shown that Itopride was effective in providing moderate to complete relief of gastrointestinal symptoms caused by reduced gastric motility, like gastric fullness, upper abdominal pain, anorexia, heartburn, nausea, and vomiting.

Treatment with itopride did not cause prolongation of QTc interval on ECG or ventricular arrhythmias in any of these studies.

Food does not significantly affect the absorption of itopride

Not reported