Cinitapride (1mg)

Cinitapride is a gastroprokinetic agent and antiulcer benzamide with agonist activity at 5-HT1 and 5-HT4 receptors and antagonist activity at 5-HT2 receptors.

CT PRIDE 1, a brand name for Cinitapride (1mg), is a prokinetic agent primarily used to treat gastrointestinal disorders. This medication is known for its efficacy in managing conditions like gastroesophageal reflux disease (GERD), functional dyspepsia, and other related digestive issues.

Cinitapride has three pronged mechanisms of action; it acts as an agonist at 5HT4 serotonergic receptor and antagonists at 5HT2 serotonergic and D2 dopaminergic receptors.

Brand Names Around the World

Marketed under trade names such as Cintapro, Cinitil, and Cidine, this drug has shown promise in alleviating symptoms associated with conditions like gastroesophageal reflux disease (GERD), functional dyspepsia, and delayed gastric emptying.

Cinitapride (trade names Cintapro, Pemix, Gapulsid) is a gastroprokinetic agent and antiemetic agent of the benzamide class which is marketed in India, Mexico, Pakistan, Spain, Croatia and the Czech Republic.

Cinitapride is available in India, Pakistan, Peru, Argentina, Spain, Paraguay, Ecuador, Uruguay, and Mexico. A combination preparation of cinitapride and pantoprazole is available in some countries.

How Does CT PRIDE 1 Work? (Mechanism of Action)

Understanding how CT PRIDE 1 works helps patients appreciate its effectiveness in treating gastrointestinal disorders.

Primary Mechanism

Cinitapride, a benzamide derivative, stimulates 5-HT4 and 5-HT1 and blocks the 5-HT2 and D2 receptors. The gastrointestinal motility effect of cinitapride is mainly achieved by enhancing acetylcholine release via stimulating 5-HT4 receptors and antagonizing the dopamine D2 receptor.

Cinitapride works by increasing the concentration of a chemical known as acetylcholine that helps in increasing the contractions of the stomach muscles.7 This helps in faster emptying of the food contents from the stomach to the intestine.

Dual Action on Serotonin Receptors

The activation of the 5-HT4 receptors results in enhanced release of acetylcholine, a neurotransmitter that stimulates smooth muscle contractions. These muscle contractions facilitate the movement of the stomach contents through the gastrointestinal tract, thereby promoting gastric emptying and improving motility.

By antagonizing the 5-HT2 receptors, Cinitapride helps reduce the release of serotonin, which can otherwise cause smooth muscle relaxation and slow down gastrointestinal transit. This dual action of Cinitapride—stimulating 5-HT4 receptors and inhibiting 5-HT2 receptors—creates a balanced environment that supports efficient and timely movement of food through the digestive system.

Effect on Lower Esophageal Sphincter

Another significant aspect of Cinitapride's mechanism is its ability to enhance lower esophageal sphincter (LES) tone. The LES is a ring of muscle that regulates the passage of food from the esophagus into the stomach and prevents the backflow of stomach contents into the esophagus. By increasing LES tone, Cinitapride helps prevent acid reflux, a common issue in GERD patients, thus alleviating heartburn and other related symptoms.

Antiemetic Properties

Cinitapride also exerts antiemetic effects, which can be attributed to its antagonistic action on dopamine D2 receptors.

Comparison with Other Prokinetics

Cisapride and cinitapride are drugs in the benzamide class that share the peripheral 5-HT4 agonist effect of metoclopramide (also a benzamide) without the dopamine D2 antagonist action that is primarily responsible for the potentially troublesome central side effects of metoclopramide.

Cinitapride demonstrates greater in vitro stimulatory activity on guinea pig intestinal smooth muscle than metoclopramide, suggesting a mechanism involving enhanced acetylcholine release from intramural cholinergic neurons.

Clinical Uses and Indications

CT PRIDE 1 is prescribed for a wide range of gastrointestinal conditions:

Primary Indications

It is indicated to treat gastrointestinal disorders associated with motility disturbances like gastroesophageal reflux disease (GERD), non-ulcer dyspepsia and delayed gastric emptying.

A. Gastroesophageal Reflux Disease (GERD)

Cinitapride is used to treat gastro-oesophageal reflux disease and symptoms of indigestion. Gastroesophageal reflux disease occurs when stomach acid frequently flows back into the food pipe (oesophagus). Indigestion is the feeling of fullness in the stomach due to excess acid and gas formation.

Gastroesophageal Reflux Disease (GERD): Cinitapride reduces acid reflux and heartburn by enhancing gastric motility.

B. Functional Dyspepsia (Indigestion)

Cinitapride, a gastrointestinal prokinetic, is commonly used for treating functional dyspepsia.

Functional Dyspepsia (Indigestion): Cinitapride eases bloating, nausea, and discomfort after meals.

C. Gastroparesis (Delayed Gastric Emptying)

Gastroparesis: Cinitapride helps in delayed gastric emptying, often seen in diabetic patients.

D. Irritable Bowel Syndrome (IBS) and Constipation

It has been proved that it is also effective for IBS and FC (functional constipation) symptoms.

Constipation & Irritable Bowel Syndrome (IBS): Cinitapride improves bowel movement regularity and reduces abdominal discomfort.

E. Nausea and Vomiting

It may be also used in the management of nausea and vomiting.

How CT PRIDE 1 Provides Relief

Cinitapride works by increasing the movement of esophagus, stomach, and intestines during digestion. It also increases the strength of muscle between esophagus and stomach to prevent reflux conditions.

Dosage and Administration Guidelines

Recommended Dosage

The usual daily dosage for adults is 1mg orally thrice a day, 15 minutes before meals.

Cinitapride is analogous to cisapride, but at a dose of 1 mg orally three times daily has not been associated with cardiac arrhythmias.

Administration Tips

Take it 15 minutes before each meal.

It is advised to take Cinitapride 3 times a day; however, follow your doctor's recommendation regarding the dosage and duration. Swallow the medicine as a whole with water. Do not crush, break or chew it.

Take Cinitapride as instructed by your doctor. You should take this medicine at least 15 minutes before your meals. Do not take in larger or lower dosages than advised. Do not break, crush or chew the tablet/capsule.

Missed Dose

If you forget to take the dose of Cinitapride at the given time, then take it as soon as you remember.However, if it is almost time for your next dose, skip the missed dose and continue with your regular schedule. Do not double the dose.

Pharmacokinetics: How the Body Processes CT PRIDE 1

Absorption

Cinitapride is rapidly absorbed after oral administration and is metabolized by CYP3A4 and CYP2C8.

The maximum plasma levels are reached two hours after the oral administration of cinitapride.

Metabolism

Cinitapride is rapidly absorbed and primarily metabolized by CYP3A4 and CYP2C8, which may reduce the risk of drug interactions.

Half-Life

Its elimination half-life is 3 to 5 hours for the first 8 hours, with a residual half-life of over 15 hours with extremely low plasma levels after that time.

Duration of Action

The amount of time for which Cinitapride remains active in your body is around 8 hours.

Clinical Efficacy and Research Evidence

Real-World Study Results

At weeks 2 and 4, the overall symptom improvement rate was 62.4 and 90.9%, respectively.

In this single-arm, prospective, multicentric study, 1,012 Chinese outpatients with functional dyspepsia and functional dyspepsia overlapping with gastroesophageal reflux disease, irritable bowel syndrome, and/or functional constipation were treated with cinitapride (1 mg t.i.d.) from May 2019 to March 2021. Symptom improvement was assessed at weeks 2 and 4, with adverse events recorded. At weeks 2 and 4, the overall symptom improvement rate was 62.4 and 90.9%, respectively.

Comparison with Domperidone

This randomized, double-blind, double-dummy, positive-controlled study compared the efficacy and safety of cinitapride (1 mg) and domperidone (10 mg) tid for 4 weeks in 383 consecutive patients with mild to moderate, postprandial distress syndrome-predominant dyspeptic symptoms according to Rome III criteria. The rates of symptom relief by cinitapride and domperidone after 4 weeks did not differ significantly on intension-to-treat analysis (85.8% vs. 81.8%, P=0.332).

Cinitapride, a 5-HT4 agonist and D2 antagonist, was compared with domperidone in PDS; although rates of overall symptom relief were similar at 85.8% versus 81.8%, respectively, cinitapride produced greater decreases in the severity of post-prandial fullness, early satiation, and bloating.9

Network Meta-Analysis Results

Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16–4.14) and placebo (OR: 3.52, 95%CI: 2.01–6.24). Cinitapride had lower risk of total adverse events than domperidone.

Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events.

Phase III Clinical Trial Confirmation

A Phase III trial confirmed cinitapride's non-inferiority to domperidone in patients with mild-to-moderate postprandial distress syndrome-predominant FD.

Additionally, a Phase IV study in Pakistan showed that cinitapride effectively controlled dyspepsia symptoms and improved patients' quality of life.

Benefits of CT PRIDE 1

1. Effective Symptom Relief

Its ability to enhance gastric motility provides significant relief from symptoms associated with these conditions.

2. Better Safety Profile Than Similar Drugs

Traditional prokinetic agents such as domperidone, mosapride, and cisapride were withdrawn due to cardiac safety concerns, making cinitapride's safety profile particularly important. In this real-world study, cinitapride was well tolerated, with no signs of hepatorenal or cardiac toxicity. Mild ECG abnormalities were reported in eight cases, but none were symptomatic, and no QT interval prolongation was observed.

3. No Cardiac Arrhythmia Risk at Standard Doses

The drug is free of QT segment prolongation.

No patient experienced QT interval prolongation. This phase III trial has confirmed a noninferior efficacy of cinitapride over domperidone for patients with mild to moderate, postprandial distress syndrome-predominant FD.

4. Fewer Central Side Effects

Although cisapride and cinitapride lack central depressant effects, they retain antiemetic properties because of some 5-HT3 properties.

5. Lower Risk of Adverse Events

Additionally, Cinitapride exhibited a lower hazard of total adverse events in comparison with Domperidone.

6. Effective for Overlapping Conditions

Cinitapride, a benzamide-derived molecule, which exhibits agonistic activity at 5-hydroxytryptamine1 (HT1) and 5-hydroxytryptamine4 (5HT4) receptors and antagonistic activity at 5HT2 and D2 dopaminergic receptors, has been widely used in mild-to-moderate FD and GERD. It has been proved that it is also effective for IBS and FC symptoms.

Side Effects

Like all medications, CT PRIDE 1 may cause side effects in some patients.

Common Side Effects

Cinitapride shows some common side effects like headache, dizziness, nausea, and vomiting. This medicine can also cause diarrhoea (loose stools), which may lead to dehydration. Hence, drink plenty of water to prevent dehydration. These side effects are temporary and resolve with time. However, it is advised to consult your doctor if the side effects persist or do not go away.

Common Side Effects: May include mild gastrointestinal symptoms such as nausea, abdominal pain, or diarrhea. Severe Side Effects: Though rare, can include neurological symptoms like tremors or extrapyramidal reactions.

Rare/Serious Side Effects

Adverse reactions to cinitapride, such as exanthema, sore throat, extrapyramidal symptoms, and unexplained increases in globulin levels, have been reported in previous studies.

Overdose Symptoms

The symptoms of overdose include drowsiness, confusion and extrapyramidal effects.

Never take more than the prescribed dose of Cinitapride. If you suspect that you might have taken an overdose of this medicine, go to the emergency department of your local hospital.

Precautions and Warnings

General Precautions

Before starting CT PRIDE 1, it is crucial to discuss your medical history and any existing health conditions with your doctor. Here are some precautions to consider: Pregnancy and Breastfeeding: The safety of Cinitapride during pregnancy and breastfeeding is not well established. Medical History: Disclose any history of gastrointestinal bleeding, obstruction, or perforation to your healthcare provider. Other Medications: Provide a complete list of all medications, including prescription, over-the-counter drugs, and herbal supplements, to avoid potential drug interactions.

Driving and Machinery

Use caution while driving or doing anything that requires concentration as Cinitapride can cause dizziness and sleepiness.

Cinitapride may cause drowsiness. It is advised that you do not perform activities that require high mental alertness such as driving vehicles or operating machines if you experience drowsiness during treatment with this medicine.

Gastrointestinal Conditions

Cinitapride is not recommended if you have gastrointestinal bleeding (a condition in which bleeding occurs in your food pipe, stomach, or intestine), obstruction (blockage in your intestine), and perforation (hole in the wall of stomach or intestine).

Tardive Dyskinesia

Tardive dyskinesia is a condition that involves abnormal movements of the jaw, lips and tongue. The condition is caused by prolonged use of some psychiatric medicines. Cinitapride is not recommended if you have tardive dyskinesia, as it can worsen your condition.

Stomach Ulcers

Stomach ulcers are sores present in the wall or lining of your stomach. The most common symptoms are stomach pain, nausea, vomiting, bloating, etc. Do not take Cinitapride if you have stomach ulcers as this medicine may worsen your condition.

When to Seek Medical Attention

Inform your doctor if you get watery diarrhea, fever, or stomach pain that does not go away.

Contraindications

CT PRIDE 1 should NOT be used in the following conditions:

Absolute Contraindications

Avoid using Cinitapride if you have a known allergy to cinitapride or any other ingredients present in this medicine.

Cinitapride is not recommended if you have gastrointestinal bleeding (a condition in which bleeding occurs in your food pipe, stomach, or intestine), obstruction (blockage in your intestine), and perforation (hole in the wall of stomach or intestine).

Allergic Reactions

Avoid using Cinitapride if you have a known allergy to cinitapride or any other ingredients present in this medicine. Seek immediate medical attention if you notice symptoms of serious allergic reactions such as skin rashes, itching/swelling (especially of the face/tongue/throat), severe dizziness, breathing difficulty, etc.

Drug Interactions

CT PRIDE 1 can interact with other medications, potentially altering their effects or increasing the risk of adverse reactions.

Major Drug Interactions

Some known interactions include: Anticholinergic Drugs: These medications can reduce the effectiveness of Cinitapride. CNS Depressants: Combining CT PRIDE 1 with central nervous system depressants like alcohol, sedatives, or tranquilizers can enhance sedative effects.

Drugs that influence the cytochrome P450 enzyme system, particularly CYP3A4 inhibitors such as erythromycin and ketoconazole, may increase the plasma concentration of Cinitapride, thereby intensifying its effects and side effects. Conversely, CYP3A4 inducers like rifampicin can decrease the effectiveness of Cinitapride by lowering its plasma concentration. It is also important to note that the concurrent use of Cinitapride with anticholinergic medications may counteract the prokinetic effects of Cinitapride.

Interaction with Ketoconazole

At steady state, co-administration with ketoconazole 200 mg bd increased its mean Cmax and AUC during a dosage interval by 1.63 and 1.98 times, respectively. There were small increases in the mean QTc interval and baseline-corrected QT interval on day 7, due to the effects of ketoconazole alone.

However, it has been demonstrated that concurrent administration of 200 mg ketoconazole twice daily with cinitapride, a prokinetic agent, has no effect on QT interval.

Food and Alcohol Interactions

Alcohol

Do not consume alcohol while taking Cinitapride as it can increase dizziness and the risk of stomach damage.

Avoid consumption of alcohol while taking Cinitapride. Alcohol intake leads to increased production of stomach acid, thereby increasing acidity and heartburn.

Avoid alcohol consumption while taking Cinitapride. It may lead to excessive drowsiness.

Food

Take CT PRIDE 1 on an empty stomach, 15 minutes before meals for optimal absorption and effectiveness.

Special Populations

Pregnancy

The safety of Cinitapride in pregnant women has not yet been determined. Hence, this medicine is not recommended during pregnancy. If you are pregnant or planning, inform your doctor before taking this medicine. Your doctor may prescribe Cinitapride only if the potential benefits exceed the risks.

Breastfeeding

Avoid taking Cinitapride if you are breastfeeding as it is unknown if the medicine passes into your breastmilk. You should consult your doctor before using this medicine to understand its risks and benefits.

Elderly Patients

Cinitapride should be used with extreme caution in elderly people due to the increased risk of serious side effects. This medicine may also increase the risk of tardive dyskinesia (a condition characterized by abnormal, involuntary movements of the jaw, lips and tongue) in these people. Appropriate dosage adjustments or replacement with a suitable alternative may be required.

Pediatric Population

Cinitapride is not recommended for patients below 18 years of age since the safety and efficacy of this medication is not clinically known in these patients.

Cinitapride should not be given to children as safety and effectiveness have not been established.

Patients with Liver Disease

Cinitapride may have mild side effects on the liver. Most people will never see any effect on the liver.

Patients with Kidney Disease

Cinitapride rarely harms the kidneys.

Storage Instructions

• Store at room temperature (15-30°C)

• Keep away from direct sunlight and moisture

• Keep in original packaging until use

• Keep out of reach of children

• Do not use after expiry date

Conclusion

CT PRIDE 1, containing Cinitapride (1mg), is a valuable medication for managing various gastrointestinal disorders, including GERD and functional dyspepsia. Its ability to enhance gastric motility provides significant relief from symptoms associated with these conditions. While generally well-tolerated, it is essential to adhere to the prescribed dosage and be aware of potential side effects and drug interactions. Consulting a healthcare provider before starting CT PRIDE 1 ensures safe and effective use, ultimately improving the quality of life for those affected by digestive disorders.1

Frequently Asked Questions 

Q1: What is CT PRIDE 1 used for?

Cinitapride is used in the treatment of Gastro-oesophageal reflux disease, Gastrointestinal motility disorders.

Q2: When should I take CT PRIDE 1?

Cinitapride is usually taken 15 minutes before each meal. It is suggested to take this medicine as prescribed by your doctor. Do not self-medicate as this can lead to certain complications.

Q3: Is CT PRIDE 1 habit-forming?

No habit forming tendency has been reported for Cinitapride.

Q4: Can I drive while taking CT PRIDE 1?

Cinitapride may cause drowsiness. Do not drive or operate machinery unless you are alert.

Q5: How long does it take for CT PRIDE 1 to work?

The amount of time required for Cinitapride to show its action is not clinically known.However, clinical studies show significant improvement within 2 weeks of treatment.

Q6: Can I take CT PRIDE 1 during pregnancy?

Inform your doctor if you are pregnant or breastfeeding as this medicine may not be safe during pregnancy and for the infant.

Q7: What should I do if I experience side effects?

Most side effects do not require any medical attention and disappear as your body adjusts to the medicine. Consult your doctor if they persist or if you're worried about them.

Q8: Can CT PRIDE 1 cause diarrhea?

Yes, diarrhea is a possible side effect. This medicine can also cause diarrhoea (loose stools), which may lead to dehydration.Drink plenty of water if you experience this side effect.

Q9: Is CT PRIDE 1 safe for the heart?

Cinitapride is rarely harmful for the heart.Clinical studies have shown no QT interval prolongation at standard doses.

Q10: How does CT PRIDE 1 compare to other prokinetics?

The findings suggest that both Metoclopramide and Cinitapride could emerge as frontrunners in functional dyspepsia treatment, showcasing enhanced effectiveness over other prokinetics. Importantly, Cinitapride's potential for a lower risk of adverse events adds another layer to its appeal.