Usage
Cinitapride + Rabeprazole is indicated for the treatment of gastroesophageal reflux disease (GERD), peptic ulcers (gastric and duodenal), dyspepsia, gastroparesis, functional dyspepsia, and Zollinger-Ellison syndrome.
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Pharmacological Classification: This combination comprises a proton pump inhibitor (PPI) (Rabeprazole) and a prokinetic agent (Cinitapride).
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Mechanism of Action: Rabeprazole reduces gastric acid production by inhibiting the H+/K+ ATPase pump in parietal cells. Cinitapride, a substituted benzamide, increases gastrointestinal motility by enhancing the strength and frequency of contractions in the esophagus, stomach, and small intestine. This dual action addresses both acid secretion and impaired motility, which are contributing factors in GERD and other related conditions.
Alternate Names
This drug combination is available under various brand names such as Rabekind-CP, Cintarab, Rebizole-CP, and Reol-CTP. There isn’t a universally recognized non-proprietary name for the combination itself.
How It Works
- Pharmacodynamics: Rabeprazole binds irreversibly to the H+/K+ ATPase enzyme (proton pump) on gastric parietal cells, blocking hydrogen ion secretion into the stomach lumen and reducing acid production. Cinitapride acts as a serotonin 5-HT4 receptor agonist and possibly as a dopamine D2 receptor antagonist. This promotes acetylcholine release, stimulating gastrointestinal smooth muscle contraction and increasing motility.
- Pharmacokinetics: Rabeprazole is rapidly absorbed after oral administration. It undergoes hepatic metabolism primarily by CYP2C19, and its elimination is mainly via the biliary route. Cinitapride is well-absorbed orally and also undergoes hepatic metabolism and renal excretion.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Rabeprazole inhibits the proton pump (H+/K+ ATPase), directly reducing acid secretion. Cinitapride interacts with serotonin 5-HT4 receptors and potentially with dopamine D2 receptors, influencing cholinergic transmission in the gut.
- Elimination Pathways: Rabeprazole is eliminated primarily by hepatic metabolism (CYP2C19) followed by biliary excretion. Cinitapride is metabolized by the liver and excreted by the kidneys.
Dosage
Standard Dosage
Adults:
The usual recommended dosage is 20 mg Rabeprazole and 1 mg or 3 mg Cinitapride, administered orally once daily, preferably before a meal.
Children:
This combination is not recommended for children as safety and effectiveness haven’t been established in pediatric populations.
Special Cases:
- Elderly Patients: Use with caution due to potential age-related decline in renal and hepatic function. Dosage adjustments may be needed. Careful monitoring for side effects is recommended.
- Patients with Renal Impairment: Exercise caution. Dose adjustment may be necessary based on the degree of impairment.
- Patients with Hepatic Dysfunction: Use with caution, particularly in cases of severe liver disease. Dose adjustments may be necessary.
- Patients with Comorbid Conditions: Individual patient factors, including diabetes, cardiovascular disease, osteoporosis, lupus, and low magnesium levels, should be considered. Monitor magnesium levels with long-term therapy.
Clinical Use Cases
There are no specific established dosage guidelines for Cinitapride + Rabeprazole for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Rabeprazole alone may be used in perioperative or critical care settings for stress ulcer prophylaxis.
Dosage Adjustments
Dose reduction may be needed in patients with renal or hepatic impairment. Long-term use, particularly over one year, can increase the risk of bone fractures and requires monitoring. Although specific adjustments based on metabolic disorders or genetic polymorphisms are not mentioned for this combination, patient-specific factors should always be considered.
Side Effects
Common Side Effects
- Diarrhea
- Nausea
- Vomiting
- Headache
- Dizziness
- Flatulence
- Stomach pain
- Constipation
- Drowsiness
Rare but Serious Side Effects
- Severe allergic reactions (anaphylaxis)
- Severe stomach pain
- Liver problems (hepatotoxicity)
- Hypomagnesemia (low magnesium levels)
- Bone fractures (with prolonged use)
Long-Term Effects
Prolonged use, especially over one year, may increase the risk of bone fractures (osteoporosis-related fractures of the hip, wrist, or spine) and hypomagnesemia.
Adverse Drug Reactions (ADR)
Clinically significant ADRs requiring immediate intervention include severe allergic reactions, signs of liver dysfunction (jaundice, dark urine, abdominal pain), and symptoms of hypomagnesemia (muscle spasms, tremors, seizures, abnormal heart rhythms).
Contraindications
- Hypersensitivity to rabeprazole, cinitapride, or any component of the formulation
- Pregnancy (especially first trimester)
- Breastfeeding
- Concomitant use with rilpivirine or atazanavir
- Gastrointestinal bleeding
- Mechanical obstruction or perforation of the GI tract
- Movement disorders
Drug Interactions
- CYP450 Interactions: Rabeprazole is metabolized by CYP2C19. Concomitant use with CYP2C19 inhibitors (e.g., ketoconazole, fluconazole) may increase rabeprazole levels.
- Other Drug Interactions: Cinitapride can interact with medications that affect the QT interval (e.g., some antiarrhythmics) and drugs with anticholinergic properties. Rabeprazole can interact with drugs like methotrexate, digoxin, warfarin, and some antifungals. It may decrease the absorption of drugs dependent on gastric acidity. It may interact with St. John’s Wort.
- Interactions with Commonly Prescribed Medications: Interactions can occur with antifungals (ketoconazole, itraconazole), antiretrovirals (atazanavir, rilpivirine), methotrexate, digoxin, warfarin, clopidogrel, and others.
- Over-the-Counter (OTC) Drugs and Supplements: St. John’s wort may interact with Rabeprazole.
- Food and Lifestyle Factors: Alcohol should be avoided as it increases stomach acid production and may worsen symptoms.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Contraindicated in pregnancy, particularly during the first trimester, due to the potential risk of fetal harm.
- Breastfeeding: Not recommended as the safety is unknown.
Drug Profile Summary
- Mechanism of Action: Rabeprazole inhibits acid secretion; Cinitapride increases GI motility.
- Side Effects: Diarrhea, nausea, headache, dizziness. Rarely: hypomagnesemia, bone fractures.
- Contraindications: Hypersensitivity, pregnancy, breastfeeding, co-administration with rilpivirine/atazanavir.
- Drug Interactions: Antifungals, antiretrovirals, methotrexate, warfarin.
- Pregnancy & Breastfeeding: Contraindicated/not recommended.
- Dosage: Adults: 20 mg rabeprazole + 1mg/3mg cinitapride once daily before meals. Not for children.
- Monitoring Parameters: Magnesium levels (long-term use), liver enzymes, INR (if on warfarin).
Popular Combinations
Cinitapride is often combined with Rabeprazole for enhanced management of GERD as it addresses both the acid secretion and motility components. It can be combined with antibiotics like amoxicillin and clarithromycin for treating H. pylori infections.
Precautions
- General Precautions: Screen for allergies, metabolic disorders, and organ dysfunction.
- Pregnant Women: Contraindicated.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: Not recommended for children; use with caution in the elderly.
- Lifestyle Considerations: Avoid alcohol. Driving caution due to potential drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cinitapride + Rabeprazole?
A: The usual adult dose is 20 mg Rabeprazole and 1 mg/3 mg Cinitapride once daily before meals. Not recommended for children.
Q2: What are the common side effects?
A: Common side effects include diarrhea, nausea, headache, dizziness, flatulence, and constipation.
Q3: Can this combination be used during pregnancy?
A: No, it’s contraindicated in pregnancy, especially the first trimester.
Q4: Are there any drug interactions I should be aware of?
A: Yes, it can interact with antifungals, antiretrovirals, methotrexate, warfarin, and other drugs. It may also interfere with the absorption of some medications.
Q5: What conditions does this medication treat?
A: It is used to treat GERD, peptic ulcers, dyspepsia, gastroparesis, functional dyspepsia, and Zollinger-Ellison syndrome.
Q6: How does Cinitapride enhance the action of Rabeprazole?
A: Rabeprazole reduces acid secretion, while Cinitapride improves gastric emptying. This combined action provides more complete relief from symptoms.
Q7: Can I take this medicine with alcohol?
A: No, alcohol should be avoided as it can increase stomach acid production and worsen symptoms. It may also intensify the drug’s side effects like drowsiness.
Q8: What if I miss a dose?
A: Take the missed dose as soon as you remember, unless it’s close to your next scheduled dose. Do not double the dose to catch up.
Q9: Should I take this medicine with food?
A: It is generally recommended to take this combination before a meal.
Q10: What are the long-term safety considerations?
A: Long-term use may increase the risk of bone fractures and low magnesium levels (hypomagnesemia). Regular monitoring may be needed.
