Usage
Domperidone + Rabeprazole is prescribed for the treatment of gastroesophageal reflux disease (GERD), including symptomatic erosive or ulcerative GERD, long-term management of GERD, and symptomatic treatment of moderate to very severe GERD. It is also used for active duodenal ulcers, active benign gastric ulcers, Zollinger-Ellison syndrome, and in combination with antibacterial regimens for Helicobacter pylori eradication in peptic ulcer disease. It is specifically indicated for GERD that does not respond adequately to rabeprazole alone.
This combination medication falls under two pharmacological classifications:
- Domperidone: Prokinetic agent (increases gastrointestinal motility).
- Rabeprazole: Proton Pump Inhibitor (PPI) (reduces gastric acid secretion).
Domperidone works by blocking the effects of dopamine, which helps to increase the movement of the stomach and intestines. Rabeprazole works by irreversibly inhibiting the H+/K+ ATPase proton pump in gastric parietal cells, thereby suppressing gastric acid secretion. The combination provides both symptomatic relief and disease modification in GERD.
Alternate Names
There is no officially recognized alternate name for the combination itself. The components are sometimes referred to as:
- Domperidone: Sometimes called “Motilium” (a popular brand name).
- Rabeprazole: “AcipHex” is a common brand name.
Numerous brand names exist for this combination product, which vary regionally. Examples of brand names include Rablet D, Rantac RD, and Rabicip D.
How It Works
Pharmacodynamics: Domperidone acts as a dopamine antagonist, primarily at peripheral D2 receptors in the upper gastrointestinal tract, leading to increased gastric emptying and improved esophageal peristalsis. Rabeprazole inhibits H+/K+ ATPase, reducing gastric acid secretion.
Pharmacokinetics:
- Domperidone: Oral bioavailability is low due to extensive first-pass metabolism. Peak plasma levels are reached in approximately one hour. Metabolism is primarily hepatic. Excretion is via both renal and fecal routes.
- Rabeprazole: Absorbed following oral administration. It is converted to its active sulfenamide form in the acidic environment of parietal cells. Metabolized by CYP450 enzymes (primarily CYP2C19 and CYP3A4). Elimination is primarily via hepatic metabolism.
Mode of Action: Domperidone’s prokinetic action arises from D2 receptor antagonism, while Rabeprazole directly inhibits the proton pump, thereby reducing gastric acid production.
Receptor Binding/Enzyme Inhibition: Domperidone binds to dopamine D2 receptors. Rabeprazole irreversibly binds to and inhibits the H+/K+ ATPase proton pump.
Elimination Pathways: Domperidone is eliminated via hepatic and renal routes. Rabeprazole is primarily eliminated through hepatic metabolism.
Dosage
Standard Dosage
Adults: The usual dose is one capsule (containing 20 mg rabeprazole and 30 mg domperidone) once daily, taken in the morning before a meal, for 4 to 8 weeks. Treatment duration can be adjusted by the physician.
Children: The combination is generally not recommended for children due to limited safety and efficacy data.
Special Cases:
- Elderly Patients: Dose adjustment may be needed based on renal and hepatic function.
- Patients with Renal Impairment: Caution should be exercised in patients with renal impairment. Dose adjustment may be required.
- Patients with Hepatic Dysfunction: Contraindicated in moderate to severe hepatic impairment. Use with caution in mild hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with cardiac conditions, especially those with QT prolongation.
Clinical Use Cases
The provided sources do not list dosage guidelines specific to intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Dosage adjustments in these situations are at the discretion of the treating physician.
Dosage Adjustments
Dosage adjustments might be required based on patient factors such as renal or hepatic impairment, comorbidities, and concomitant medications. Close monitoring is crucial.
Side Effects
Common Side Effects
Headache, diarrhea, abdominal pain, nausea, vomiting, flatulence, dizziness, and dry mouth.
Rare but Serious Side Effects
Cardiac arrhythmias (including QT prolongation), extrapyramidal symptoms (movement disorders), hypersensitivity reactions, and severe hepatic dysfunction.
Long-Term Effects
The potential long-term side effects of this combination therapy require further investigation, but they could include potential vitamin B12 deficiency with extended use of PPIs.
Adverse Drug Reactions (ADR)
QT prolongation, torsades de pointes, ventricular arrhythmias, extrapyramidal symptoms (dyskinesias, dystonias), and anaphylaxis.
Contraindications
Absolute contraindications include hypersensitivity to either drug component, prolactin-releasing pituitary tumor (prolactinoma), gastrointestinal hemorrhage, mechanical obstruction or perforation, moderate or severe hepatic impairment, concomitant use with QT-prolonging drugs or potent CYP3A4 inhibitors, and pregnancy.
Drug Interactions
Clinically significant drug interactions exist with both components. Rabeprazole interacts with ketoconazole, itraconazole, atazanavir, and other drugs metabolized by CYP450 enzymes. Domperidone interacts with QT-prolonging drugs, potent CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin), and anticholinergic medications. Food, alcohol, and grapefruit juice can also affect drug absorption and metabolism.
Pregnancy and Breastfeeding
This drug combination is contraindicated during pregnancy and breastfeeding. Domperidone is excreted in breast milk and may pose risks to the neonate. Safer alternative options should be considered.
Drug Profile Summary
- Mechanism of Action: Domperidone enhances GI motility, Rabeprazole reduces acid secretion.
- Side Effects: Common: Headache, diarrhea, abdominal pain; Serious: QT prolongation, arrhythmias, extrapyramidal symptoms.
- Contraindications: Hypersensitivity, prolactinoma, GI bleeding/obstruction, hepatic impairment, QT-prolonging drugs, potent CYP3A4 inhibitors, pregnancy.
- Drug Interactions: CYP450 interactions, QT-prolonging agents, anticholinergics.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: One capsule (20mg/30mg) daily before a meal. Not recommended for children.
- Monitoring Parameters: ECG (for QT interval), liver function tests, electrolyte levels.
Popular Combinations
Frequently co-prescribed with antibiotics for H. pylori eradication (e.g., clarithromycin, amoxicillin).
Precautions
Screen for allergies, cardiac disease, electrolyte imbalances, renal/hepatic dysfunction. Caution in elderly and patients with other comorbidities. Avoid alcohol and other CNS depressants. Driving restrictions may be necessary.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Domperidone + Rabeprazole?
A: One capsule (containing 20mg rabeprazole and 30mg domperidone) once daily, usually before a meal.
Q2: Can this combination be used in children?
A: Generally not recommended due to limited safety and efficacy data in pediatric populations.
Q3: What are the major contraindications for Domperidone + Rabeprazole?
A: Hypersensitivity, prolactinoma, GI bleeding/obstruction, moderate-severe hepatic impairment, concurrent use with QT prolonging drugs or potent CYP3A4 inhibitors, and pregnancy.
Q4: What are the most important drug interactions to be aware of?
A: QT-prolonging drugs, potent CYP3A4 inhibitors (ketoconazole, itraconazole), and drugs metabolized by CYP2C19.
Q5: Is Domperidone + Rabeprazole safe during pregnancy and breastfeeding?
A: No, it’s contraindicated in both pregnancy and breastfeeding.
Q6: What are the common side effects?
A: Headache, diarrhea, abdominal pain, nausea, and dizziness.
Q7: What should be monitored in patients taking this combination?
A: ECG (QT interval), liver function tests, and electrolyte levels.
Q8: What are the serious/rare side effects to watch out for?
A: QT prolongation, cardiac arrhythmias, extrapyramidal symptoms, and severe allergic reactions.
Q9: How does Domperidone + Rabeprazole work in treating GERD?
A: Domperidone improves gastric motility and reduces reflux, while Rabeprazole suppresses gastric acid production, providing dual action against GERD symptoms.
Q10: Can this medication be taken with food?
A: Yes, it can be taken with or without food, although taking it before a meal is usually recommended.
