Usage
Cinitapride is prescribed for gastrointestinal disorders associated with motility disturbances. These include:
- Gastroesophageal reflux disease (GERD)
- Non-ulcer dyspepsia
- Delayed gastric emptying (Gastroparesis)
- Functional dyspepsia
Pharmacological Classification: Gastroprokinetic agent (5-HT4 receptor agonist, 5-HT2 receptor antagonist, and D2 receptor antagonist).
Mechanism of Action: Cinitapride enhances gastrointestinal motility by increasing acetylcholine concentrations, stimulating 5-HT4 receptors, and blocking 5-HT2 and dopamine D2 receptors. This leads to increased coordinated contractions of the stomach and intestinal muscles, promoting faster movement of food through the digestive tract. It also tightens the lower esophageal sphincter (LES), preventing acid reflux.
Alternate Names
There is no internationally recognized non-proprietary name other than Cinitapride.
Brand Names: Cinita, Cintapro, Cinmove, CT Pride, Biopride, Gasotin, Nupenta-CP, Acepride. (This list may not be exhaustive and can vary by region.)
How It Works
Pharmacodynamics: Cinitapride primarily acts on the gastrointestinal tract by increasing motility. This prokinetic effect is mediated through multiple mechanisms:
- 5-HT4 Receptor Agonism: Stimulates these receptors in the gut, enhancing acetylcholine release, which increases gut muscle contractions and improves motility.
- 5-HT2 Receptor Antagonism: Blocks these receptors, further contributing to enhanced gut motility and reducing some side effects associated with 5-HT2 agonism.
- Dopamine D2 Receptor Antagonism: Contributes to its antiemetic properties and plays a role in its prokinetic effects.
- Cholinergic effects: Enhances the action of acetylcholine
Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration.
- Metabolism: First-pass metabolism in the liver, primarily by CYP3A4 and CYP2C8 enzymes.
- Elimination: Primarily eliminated via biliary excretion, with some renal excretion. Elimination half-life of 3-5 hours initially, followed by a longer residual half-life of over 15 hours. No accumulation observed with repeated doses.
- Tmax: Approximately 2 hours after oral administration.
Dosage
Standard Dosage
Adults:
- 1 mg orally three times daily, 15 minutes before meals.
- Dosage may be reduced based on patient age and symptoms.
Children:
Not recommended due to lack of safety and efficacy data.
Special Cases:
- Elderly Patients: Use with caution due to increased risk of side effects. Dosage adjustment may be required.
- Patients with Renal Impairment: Caution advised. Dose adjustments may be required based on creatinine clearance.
- Patients with Hepatic Dysfunction: Use with caution, especially in severe cases. Dosage adjustments may be needed.
- Patients with Comorbid Conditions: Consider individual patient factors. Close monitoring is recommended.
Clinical Use Cases
Specific dosage recommendations for Cinitapride in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations haven’t been established.
Dosage Adjustments
Dose modifications should be considered based on individual patient factors, including renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms affecting drug metabolism.
Side Effects
Common Side Effects
- Headache
- Dizziness
- Nausea
- Diarrhea
- Drowsiness
- Dry mouth
- Abdominal discomfort
Rare but Serious Side Effects
- Extrapyramidal symptoms (involuntary muscle movements, spasms of face, neck, and tongue)
- Allergic reactions (rash, itching, angioedema)
- Gynecomastia
Long-Term Effects
Potential long-term effects are not well-established.
Adverse Drug Reactions (ADR)
Clinically significant ADRs requiring immediate intervention include severe allergic reactions, extrapyramidal symptoms, and cardiac arrhythmias (although rare).
Contraindications
- Hypersensitivity to cinitapride or any component of the formulation.
- Gastrointestinal hemorrhage, mechanical obstruction, or perforation.
- Tardive dyskinesia.
Drug Interactions
- CYP3A4 Inhibitors: May increase cinitapride levels, potentially increasing the risk of side effects.
- QT Prolonging Drugs: Concomitant use may increase the risk of cardiac arrhythmias.
- Drugs affecting electrolyte balance: Caution is advised, as these could enhance the effects of cinitapride.
Pregnancy and Breastfeeding
Cinitapride should not be used during the first trimester of pregnancy. Use in later trimesters and during breastfeeding should be considered only if the potential benefit outweighs the potential risk to the fetus or infant.
Drug Profile Summary
- Mechanism of Action: Prokinetic agent, 5-HT4 agonist, 5-HT2 antagonist, D2 antagonist.
- Side Effects: Headache, dizziness, nausea, diarrhea, drowsiness, extrapyramidal symptoms (rare).
- Contraindications: Hypersensitivity, GI bleeding/obstruction/perforation, tardive dyskinesia.
- Drug Interactions: CYP3A4 inhibitors, QT prolonging drugs.
- Pregnancy & Breastfeeding: Not recommended in the first trimester, use with caution in later stages and during breastfeeding.
- Dosage: 1 mg thrice daily before meals.
- Monitoring Parameters: Monitor for extrapyramidal symptoms and other adverse reactions.
Popular Combinations
Cinitapride is sometimes combined with proton pump inhibitors (PPIs) like pantoprazole or rabeprazole for enhanced efficacy in managing GERD and other acid-related disorders.
Precautions
- General Precautions: Assess for allergies, pre-existing GI conditions, and concomitant medications.
- Specific Populations: Use with caution in elderly patients, those with renal/hepatic impairment, and pregnant/breastfeeding women.
- Lifestyle Considerations: Avoid alcohol as it might exacerbate some side effects. Caution advised when driving or operating machinery due to potential drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cinitapride?
A: The standard adult dosage is 1 mg orally three times daily, 15 minutes before meals.
Q2: How does Cinitapride differ from other prokinetic agents?
A: Cinitapride has a multi-faceted mechanism involving 5-HT4 agonism, 5-HT2 antagonism, and D2 antagonism, potentially offering broader benefits in motility disorders compared to agents with a single mechanism.
Q3: What are the most serious side effects of Cinitapride?
A: Although rare, the most serious side effects include extrapyramidal symptoms (movement disorders) and allergic reactions.
Q4: Can Cinitapride be used in children?
A: Cinitapride is not recommended for use in children due to a lack of data on safety and efficacy.
Q5: Can Cinitapride be used during pregnancy?
A: Cinitapride should not be used during the first trimester. Use in later trimesters requires careful consideration of risks and benefits.
Q6: How should Cinitapride be administered?
A: Cinitapride should be taken orally as a tablet, ideally 15 minutes before meals.
Q7: Does Cinitapride interact with other medications?
A: Yes, it can interact with certain drugs like CYP3A4 inhibitors and QT prolonging agents. It’s crucial to review the patient’s medication list for potential interactions.
Q8: What should patients be monitored for while taking Cinitapride?
A: Patients should be monitored for any adverse reactions, especially extrapyramidal symptoms.
Q9: Is Cinitapride safe for patients with kidney or liver disease?
A: Cinitapride should be used with caution in patients with renal or hepatic impairment, and dosage adjustments may be necessary.
Q10: What should a patient do if they miss a dose of Cinitapride?
A: They should take the missed dose as soon as they remember, unless it’s close to the next scheduled dose. Do not double the dose.
