Itopride

Usage

Itopride hydrochloride is prescribed for the symptomatic treatment of gastrointestinal disorders associated with gastric dysmotility, such as functional dyspepsia (non-ulcer dyspepsia) and chronic gastritis. These symptoms can include bloating, early satiety, postprandial fullness, upper abdominal pain or discomfort, anorexia, heartburn, nausea, and vomiting.

It is pharmacologically classified as a gastroprokinetic agent.

Itopride’s mechanism of action involves a dual effect: dopamine D2 receptor antagonism and acetylcholinesterase inhibition. This leads to increased acetylcholine levels, which stimulates motility in the upper gastrointestinal tract.

Alternate Names

Itopride may also be referred to as Itopride hydrochloride.

Brand names for Itopride include: Ganaton, Itoplat, Itopid, Itopa, Regasta, and Etopride.

How It Works

Pharmacodynamics: Itopride enhances gastric motility and accelerates gastric emptying by increasing acetylcholine levels. It achieves this through dopamine D2 receptor antagonism in the gastrointestinal tract, which prevents the inhibitory effects of dopamine on acetylcholine release. Simultaneously, it inhibits acetylcholinesterase, the enzyme responsible for breaking down acetylcholine, thus further increasing acetylcholine concentrations. This leads to increased peristalsis and improved gastro-duodenal coordination. Itopride also increases lower esophageal sphincter pressure, which can help reduce reflux symptoms.

Pharmacokinetics: Itopride is rapidly and almost completely absorbed after oral administration. Its bioavailability is around 60% due to first-pass metabolism in the liver. Peak plasma concentrations are reached within approximately 30-45 minutes. It is extensively metabolized in the liver, primarily by flavin-containing monooxygenase 3 (FMO3). Itopride and its metabolites are mainly excreted in the urine. The elimination half-life is approximately 6 hours.

Mode of Action: At the cellular level, Itopride acts on D2 receptors and acetylcholinesterase within the enteric nervous system of the gastrointestinal tract. By antagonizing D2 receptors, Itopride removes the inhibitory influence of dopamine on acetylcholine release. The concurrent inhibition of acetylcholinesterase prevents the breakdown of acetylcholine, leading to its accumulation and enhanced stimulation of muscarinic receptors, resulting in increased gastrointestinal motility.

Elimination Pathways: Itopride is primarily eliminated through hepatic metabolism, with subsequent renal excretion of metabolites.

Dosage

Standard Dosage

Adults: The usual adult dose is 50 mg three times daily, taken orally before meals. Dosages may be reduced based on patient age and symptom severity.

Children: The safety and efficacy of Itopride in children under 16 years of age have not been established. It is not recommended for pediatric use.

Special Cases:

• Elderly Patients: Caution should be exercised when administering Itopride to elderly patients due to the higher likelihood of decreased hepatic and renal function. Close monitoring for adverse effects is recommended, and dosage adjustments may be necessary.
• Patients with Renal Impairment: Dosage adjustment may be required based on the degree of renal impairment. Close monitoring is necessary.
• Patients with Hepatic Dysfunction: As Itopride is primarily metabolized in the liver, dosage adjustments may be necessary in patients with hepatic impairment. Close monitoring is crucial.
• Patients with Comorbid Conditions: Careful consideration should be given to patients with Parkinson’s disease or other conditions involving dopamine regulation.

Clinical Use Cases Itopride’s primary indication is for the management of dyspepsia symptoms. It is not indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, intensive care unit (ICU) use, or emergency situations.

Dosage Adjustments Dosage adjustments are based on individual patient characteristics, including age, symptom severity, renal function, and hepatic function.

Side Effects

Common Side Effects: Diarrhea, abdominal pain, constipation, increased salivation, nausea, headache, dizziness, tremor.

Rare but Serious Side Effects: Leukopenia, thrombocytopenia, anaphylactoid reactions, gynecomastia, jaundice, rash, itching, increased liver enzymes (AST, ALT, γ-GTP, alkaline phosphatase, bilirubin).

Long-Term Effects: Data on long-term effects are limited.

Adverse Drug Reactions (ADR): Anaphylactoid reactions, severe liver dysfunction, blood dyscrasias.

Contraindications

Itopride is contraindicated in patients with hypersensitivity to Itopride or any of its components. It is also contraindicated in conditions where increased gastrointestinal motility could be harmful, such as gastrointestinal hemorrhage, mechanical obstruction, or perforation.

Drug Interactions

Itopride can interact with anticholinergic drugs, potentially reducing its prokinetic effects. It may affect the absorption of other orally administered medications due to its gastrokinetic action. Particular caution is advised for drugs with a narrow therapeutic index or modified-release formulations.

Pregnancy and Breastfeeding

The safety of Itopride during pregnancy has not been established. Its use should be avoided unless the potential benefits outweigh the risks. It is recommended to avoid Itopride during breastfeeding or discontinue breastfeeding if Itopride is necessary.

Drug Profile Summary

• Mechanism of Action: Dopamine D2 receptor antagonist and acetylcholinesterase inhibitor, leading to increased acetylcholine and enhanced gastrointestinal motility.
• Side Effects: Diarrhea, abdominal pain, headache, nausea, dizziness; rarely, leukopenia, thrombocytopenia, anaphylactoid reactions, jaundice.
• Contraindications: Hypersensitivity, gastrointestinal hemorrhage, mechanical obstruction, perforation.
• Drug Interactions: Anticholinergic drugs.
• Pregnancy & Breastfeeding: Avoid unless benefits outweigh risks.
• Dosage: Adults: 50 mg three times daily before meals. Adjustments may be necessary based on individual patient characteristics.
• Monitoring Parameters: Liver function tests, complete blood count.

Popular Combinations

No specific popular combinations of Itopride with other medications are widely established.

Precautions

• General Precautions: Monitor for any signs of hypersensitivity, liver dysfunction, or blood dyscrasias.
• Specific Populations: Use with caution in elderly patients, those with renal or hepatic impairment, and avoid or monitor closely in pregnant or breastfeeding women.
• Lifestyle Considerations: No specific lifestyle considerations are consistently reported.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Itopride?

A: The standard adult dosage is 50 mg taken orally three times daily before meals. The dose may be adjusted based on the patient’s age, symptoms, and hepatic or renal function.

Q2: What are the common side effects of Itopride?

A: Common side effects include diarrhea, abdominal pain, constipation, nausea, headache, and dizziness.

Q3: Is Itopride safe to use during pregnancy?

A: The safety of Itopride during pregnancy has not been established. It is generally recommended to avoid its use unless the benefits outweigh the potential risks to the fetus.

Q4: Can Itopride interact with other medications?

A: Yes, Itopride can interact with anticholinergic drugs, reducing its effectiveness. It may also alter the absorption of other oral medications.

Q5: How does Itopride work?

A: Itopride acts as a dopamine D2 receptor antagonist and acetylcholinesterase inhibitor, which increases acetylcholine levels and promotes gastric motility.

Q6: What conditions is Itopride used to treat?

A: Itopride is primarily used to treat the symptoms of functional dyspepsia and chronic gastritis related to impaired gastric motility.

Q7: Are there any contraindications for using Itopride?

A: Yes, Itopride is contraindicated in patients with hypersensitivity to the drug, gastrointestinal bleeding, mechanical obstruction, or perforation.

Q8: What should patients know before taking Itopride?

A: Patients should inform their doctor about all other medications they are taking, any pre-existing medical conditions, and if they are pregnant or breastfeeding. They should also be aware of potential side effects and report any unusual symptoms to their doctor.

Q9: What should doctors monitor in patients taking Itopride?

A: Doctors should monitor liver function tests and complete blood counts, especially in patients with pre-existing hepatic or hematological conditions.

Q10: How long can Itopride be taken?

A: Clinical trials have typically administered Itopride for up to 8 weeks. Long-term use should be carefully considered and guided by patient response and the presence of any adverse effects.