Usage
Domperidone + Omeprazole is prescribed for the treatment of gastroesophageal reflux disease (GERD), dyspepsia, and other gastrointestinal motility disorders where delayed gastric emptying contributes to symptoms like nausea, vomiting, bloating, and epigastric discomfort. It is also indicated for the treatment of heartburn, acid reflux, and stomach ulcers.
This combination medication falls under the following pharmacological classifications:
- Domperidone: Dopamine antagonist, antiemetic, prokinetic.
- Omeprazole: Proton pump inhibitor (PPI).
Mechanism of Action: Omeprazole reduces gastric acid secretion by irreversibly inhibiting the H+/K+ ATPase enzyme system (proton pump) in the parietal cells of the gastric mucosa. Domperidone, on the other hand, is a peripheral dopamine receptor antagonist that blocks the inhibitory effects of dopamine on gastrointestinal motility. This increases lower esophageal sphincter pressure and accelerates gastric emptying and transit.
Alternate Names
This drug combination is most commonly referred to as Domperidone + Omeprazole. There isn’t a single international non-proprietary name (INN) for the combination. It is generally identified by the names of its two active constituents.
Brand Names: Limzer, Omez-DSR. Other brand names may exist regionally.
How It Works
Pharmacodynamics: Omeprazole suppresses gastric acid secretion, leading to a decrease in gastric acidity. Domperidone increases lower esophageal sphincter tone, improves antral and duodenal motility, and coordinates gastroduodenal activity to promote gastric emptying. It does not affect gastric secretions.
Pharmacokinetics:
- Omeprazole: Absorption begins after it leaves the stomach (due to enteric coating), reaching peak plasma levels in 0.5-3.5 hours. Bioavailability is 30-40% due to first-pass metabolism. It is highly protein-bound (95%) and metabolized by CYP450 enzymes. Elimination half-life is 0.5-1 hour, primarily via hepatic metabolism and renal excretion.
- Domperidone: Absorption is rapid, but bioavailability is low due to extensive first-pass metabolism. Peak plasma levels are achieved in about an hour. It is also highly protein-bound and extensively metabolized in the liver, predominantly by CYP3A4. Elimination is primarily through hepatic metabolism with some renal excretion.
Mode of Action: Omeprazole irreversibly blocks the H+/K+-ATPase enzyme system in parietal cells, reducing acid secretion. Domperidone antagonizes peripheral dopamine D2 receptors in the gastrointestinal tract, facilitating motility.
Receptor Binding, Enzyme Inhibition: Omeprazole inhibits the proton pump (H+/K+-ATPase). Domperidone antagonizes dopamine D2 receptors.
Elimination Pathways: Both drugs are primarily metabolized by the liver (CYP450 enzymes) and excreted via the kidneys.
Dosage
Standard Dosage
Adults:
The usual recommended dose is one capsule of Omeprazole 20mg + Domperidone 30mg once daily before meals. For domperidone monotherapy, the dosage can be 10mg three or four times a day, and may increase up to 20 mg three to four times daily if needed.
Children:
Safety and efficacy have not been established in children.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required.
- Patients with Renal Impairment: No dosage adjustment is generally required.
- Patients with Hepatic Dysfunction: Caution should be used in patients with severe liver impairment. Liver enzymes should be monitored regularly during treatment.
- Patients with Comorbid Conditions: Dose adjustments might be needed based on coexisting conditions. Consult current clinical guidelines and consider drug interactions.
Clinical Use Cases
The combination of domperidone and omeprazole is not typically indicated for use in clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Other medications might be more appropriate in these scenarios.
Dosage Adjustments
Dosage adjustments may be necessary based on individual patient factors like hepatic or renal dysfunction, other metabolic disorders, or pharmacogenetic variations affecting drug metabolism.
Side Effects
Common Side Effects:
Headache, diarrhea, abdominal pain, nausea, dizziness, dry mouth, and fatigue.
Rare but Serious Side Effects:
Cardiac arrhythmias (QT prolongation), extrapyramidal symptoms (e.g., tardive dyskinesia), hyperprolactinemia, gynecomastia, galactorrhea.
Long-Term Effects:
Potential long-term effects are primarily associated with Domperidone, including the aforementioned extrapyramidal effects and endocrine disturbances with prolonged high doses. Long-term use of PPIs like Omeprazole has been associated with an increased risk of certain infections (e.g., Clostridium difficile), vitamin B12 deficiency, and potentially, fractures.
Adverse Drug Reactions (ADR):
Any signs of cardiac arrhythmias, extrapyramidal reactions, or severe hypersensitivity should prompt immediate discontinuation and medical attention.
Contraindications
- Hypersensitivity to either domperidone or omeprazole.
- Gastrointestinal hemorrhage, mechanical obstruction, or perforation.
- Prolactin-releasing pituitary tumor (prolactinoma).
- Concomitant use with drugs that prolong the QT interval.
- Conditions where increased gastrointestinal motility could be harmful (e.g., gastrointestinal bleeding).
Drug Interactions
- Omeprazole: May interact with drugs metabolized by CYP450 enzymes, potentially altering their efficacy. Can affect the absorption of drugs whose bioavailability is pH-dependent (e.g., ketoconazole).
- Domperidone: Interacts with drugs that prolong the QT interval, increasing the risk of arrhythmias. May interact with dopamine agonists and anticholinergic drugs.
- Concomitant use of Domperidone with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, ritonavir, atazanavir, nelfinavir, saquinavir) should be avoided as these inhibit the metabolism of domperidone, which can increase the risk of serious ventricular arrhythmias.
Pregnancy and Breastfeeding
- Pregnancy: Domperidone is generally considered low risk during pregnancy but should only be used if the benefits outweigh the potential risks. Omeprazole should only be used during pregnancy if clearly needed. Data from large-scale studies indicate no adverse effects of Omeprazole on pregnancy outcome. Omeprazole is excreted in breast milk, but the risk of effects on the infant at therapeutic doses seem unlikely. Domperidone is contraindicated during breastfeeding.
Drug Profile Summary
- Mechanism of Action: Omeprazole: Proton pump inhibitor, reduces gastric acid. Domperidone: Dopamine antagonist, improves GI motility.
- Side Effects: Common: Headache, diarrhea, abdominal pain. Serious: Cardiac arrhythmias (QT prolongation), Extrapyramidal symptoms.
- Contraindications: Hypersensitivity, GI bleeding/obstruction, prolactinoma, QT-prolonging drugs.
- Drug Interactions: CYP450 substrates, QT prolonging drugs, Dopamine agonists.
- Pregnancy & Breastfeeding: Omeprazole: Use only if clearly needed. Domperidone: Caution advised during pregnancy, contraindicated while breastfeeding.
- Dosage: Adults: Omeprazole 20mg + Domperidone 30mg once daily before meals.
- Monitoring Parameters: Liver enzymes (especially in patients with hepatic impairment), ECG (for QT prolongation), symptoms of extrapyramidal reactions.
Popular Combinations
This combination itself is a popular pairing for dyspepsia and GERD with associated motility problems.
Precautions
- General Precautions: Evaluate for hypersensitivity, underlying cardiac conditions, liver and kidney function.
- Specific Populations: Use cautiously in the elderly and those with hepatic or renal impairment. Avoid in breastfeeding mothers. Not established for pediatric use.
- Lifestyle Considerations: Alcohol may worsen GERD symptoms.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Domperidone + Omeprazole?
A: The standard adult dosage is Omeprazole 20mg + Domperidone 30mg once daily, taken before meals.
Q2: How does this combination work differently from using just Omeprazole?
A: Omeprazole reduces acid production, while Domperidone addresses motility issues like slow gastric emptying, nausea, and vomiting, which Omeprazole alone would not resolve.
Q3: What are the serious side effects to watch out for?
A: Cardiac arrhythmias (QT prolongation), extrapyramidal reactions (movement disorders), and hyperprolactinemia are rare but serious potential side effects.
Q4: Can this combination be used in pregnancy or while breastfeeding?
A: Omeprazole should only be used if clearly needed. Domperidone should be used with caution during pregnancy and is contraindicated during breastfeeding.
Q5: Are there any specific drug interactions I should be aware of?
A: Yes. Both drugs interact with several medications. Omeprazole may affect CYP450 substrates and drugs dependent on gastric pH. Domperidone interacts with QT-prolonging medications, dopamine agonists, and anticholinergic drugs. Inform patients to disclose all medications, supplements, and herbal products they are taking.
Q6: What should I do if a patient experiences side effects?
A: Discontinue the medication and provide supportive care as needed. For serious side effects like cardiac arrhythmias or extrapyramidal symptoms, seek urgent medical consultation.
Q7: Can this drug combination be crushed or chewed?
A: No. The capsules should be swallowed whole. Crushing or chewing can alter the release profile and potentially increase side effects.
Q8: How should I monitor patients on Domperidone + Omeprazole long term?
A: Monitor liver enzymes in patients with hepatic impairment. Periodic ECGs might be considered to assess for QT prolongation, especially in patients at risk. Be vigilant for any signs of extrapyramidal reactions.
Q9: What patient education should I provide?
A: Counsel patients about common side effects, the importance of taking the medication as prescribed, and the need to report any unusual symptoms promptly. Advise against crushing or chewing the capsules. Encourage lifestyle modifications that can improve GERD symptoms.
Q10: Are there any specific contraindications for the use of this combination?
A: Yes. Contraindications include hypersensitivity to the components, gastrointestinal obstruction or bleeding, prolactinoma, and concomitant use of QT-prolonging medications.
