Usage
Ondansetron + Rabeprazole is a combination drug prescribed for conditions involving both gastric acid hypersecretion and nausea/vomiting. It’s commonly used for:
- Gastroesophageal reflux disease (GERD)
- Peptic ulcers
- Zollinger-Ellison syndrome
- Nausea and vomiting associated with cancer treatments (chemotherapy and radiotherapy), surgery, and gastroenteritis.
- Prevention of nausea and vomiting after intubation, during surgical procedures, and for patients on mechanical ventilation or in ICU.
Pharmacological Classification:
- Rabeprazole: Proton Pump Inhibitor (PPI)
- Ondansetron: Serotonin 5-HT3 Receptor Antagonist (Antiemetic)
Mechanism of Action: This combination works through two distinct mechanisms:
- Rabeprazole inhibits the H+/K+ ATPase pump in parietal cells, thereby reducing gastric acid secretion.
- Ondansetron blocks serotonin 5-HT3 receptors in the central nervous system (chemoreceptor trigger zone) and peripherally on vagal nerve terminals in the gut. This prevents serotonin from inducing nausea and vomiting.
Alternate Names
While “Ondansetron + Rabeprazole” is the standard generic name, specific formulations might have regional variations.
Brand Names: Some examples include RABEVA-O, INORAB-O, RYPRAZ O, Rabistrum Odin, and Arpent O, although brand availability varies by region.
How It Works
Pharmacodynamics:
- Rabeprazole: Suppresses gastric acid secretion by irreversibly binding to the H+/K+ ATPase pump.
- Ondansetron: Blocks the binding of serotonin to 5-HT3 receptors. This inhibits activation of the vomiting reflex pathway involving the vagal afferents and the chemoreceptor trigger zone in the brainstem.
Pharmacokinetics:
- Rabeprazole:
- Absorption: Rapidly absorbed after oral administration.
- Metabolism: Extensively metabolized in the liver primarily by CYP2C19 and CYP3A4.
- Elimination: Excreted via the kidneys and in bile.
- Ondansetron:
- Absorption: Well absorbed orally.
- Metabolism: Metabolized by multiple hepatic CYP enzymes (CYP3A4, CYP1A2, CYP2D6) and flavin-containing monooxygenase 3 (FMO3).
- Elimination: Primarily eliminated through hepatic metabolism and renal excretion.
Mode of Action:
- Rabeprazole irreversibly binds to and inhibits the H+/K+ ATPase pump (proton pump) on the luminal surface of gastric parietal cells. This blocks the final step of acid secretion into the stomach.
- Ondansetron competitively and selectively antagonizes 5-HT3 receptors both centrally (CTZ) and peripherally (vagal afferents), preventing serotonin-induced nausea and vomiting.
Dosage
Dosage is dependent on the indication and patient factors.
Standard Dosage
Adults: The typical dose is one tablet containing 20 mg rabeprazole and 4 mg ondansetron once daily, usually taken before a meal.
Children: Dosage needs to be adjusted by a physician for those under 12 years old. Safety and efficacy haven’t been established in very young children. Ondansetron is generally avoid in children under 4.
Special Cases:
- Elderly Patients: Generally, no specific dose adjustment is needed, but individual patient conditions should be considered.
- Patients with Renal Impairment: Dose adjustments may be necessary in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: Dosage adjustments are required for ondansetron in patients with severe hepatic impairment (Child-Pugh C). Rabeprazole should be used with caution in patients with any degree of hepatic impairment.
- Patients with Comorbid Conditions: Consider existing medical conditions such as osteoporosis, autoimmune diseases, or Vitamin B12 deficiency. PPI use may increase fracture risk with long term use and/or conditions such as osteoporosis.
Clinical Use Cases
Dosing for specific indications is generally as above. For prevention of nausea and vomiting in the perioperative period, IV Ondansetron may be administered instead. Specific dosage and timing should be determined according to established protocols and patient factors.
Side Effects
Common Side Effects:
Headache, constipation, diarrhea, abdominal pain, nausea, vomiting, dizziness, fatigue, sore throat.
Rare but Serious Side Effects:
Allergic reactions (anaphylaxis, bronchospasm), severe dizziness, irregular heartbeat (QT prolongation with Ondansetron), Clostridium difficile-associated diarrhea, pancreatitis, interstitial nephritis, rhabdomyolysis.
Long-Term Effects:
Long-term PPI use can increase the risk of osteoporosis-related fractures, hypomagnesemia, vitamin B12 deficiency, and atrophic gastritis.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include hypersensitivity reactions, QT prolongation with ondansetron (especially at higher doses), and drug-induced liver injury with rabeprazole.
Contraindications
- Hypersensitivity to rabeprazole, ondansetron, or substituted benzimidazoles.
- Concomitant use of rilpivirine.
- Concomitant use of apomorphine.
Drug Interactions
Rabeprazole can interact with drugs dependent on gastric pH for absorption (e.g., ketoconazole, atazanavir, itraconazole). It can also affect the metabolism of drugs metabolized by CYP2C19 and CYP3A4.
Ondansetron can interact with drugs that prolong the QT interval. Its metabolism can be affected by inducers or inhibitors of CYP3A4, CYP1A2, CYP2D6, or FMO3.
Some specific interactions include:
- Atazanavir
- Ketoconazole
- Itraconazole
- Clopidogrel
- Methotrexate
- Warfarin
Pregnancy and Breastfeeding
Use during pregnancy is generally not recommended unless the benefits outweigh the potential risks. Consult a physician for personalized advice.
While Rabeprazole is considered safe during breastfeeding, the safety profile of ondansetron during breastfeeding isn’t fully established, although there is some evidence to suggest it can be used with caution.
Drug Profile Summary
- Mechanism of Action: Rabeprazole inhibits gastric acid secretion; Ondansetron blocks serotonin receptors to reduce nausea and vomiting.
- Side Effects: Headache, constipation, diarrhea, abdominal pain; rarely, QT prolongation, hypersensitivity reactions.
- Contraindications: Hypersensitivity, concomitant use of rilpivirine or apomorphine.
- Drug Interactions: CYP450 interactions (especially CYP3A4 and CYP2C19), drugs affecting gastric pH.
- Pregnancy & Breastfeeding: Use with caution; consult a physician.
- Dosage: Typically, 20 mg rabeprazole and 4 mg ondansetron once daily.
- Monitoring Parameters: Electrolytes (especially magnesium, potassium), liver function tests, complete blood count for long term use.
Popular Combinations
Often combined with antibiotics (amoxicillin and clarithromycin) for H. pylori eradication.
Precautions
Assess for allergies, liver/kidney function, and underlying medical conditions. Long-term PPI use requires monitoring for potential adverse effects like osteoporosis, B12 deficiency and hypomagnesemia. Caution advised during pregnancy and breastfeeding. Avoid alcohol and driving if experiencing side effects like dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ondansetron + Rabeprazole?
A: One tablet containing 20 mg rabeprazole and 4 mg ondansetron once daily before a meal. Dosage may vary in special populations.
Q2: What are the common side effects?
A: Headache, constipation, diarrhea, abdominal pain, nausea, dizziness.
Q3: Can this medication be used in pregnancy?
A: Generally not recommended. Consult a physician for individual assessment.
Q4: How does this combination work?
A: Rabeprazole reduces stomach acid, and ondansetron prevents nausea and vomiting.
Q5: Are there any drug interactions I should be aware of?
A: Yes, several drug interactions are possible. Inform your doctor about all medications you are taking.
Q6: Can this combination be used long-term?
A: Long-term use should be monitored by a physician due to potential side effects like decreased bone density and B12 deficiency.
Q7: What should I do 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.
Q8: Can I drink alcohol while taking this medication?
A: It’s best to avoid alcohol as it may worsen GERD symptoms and interact with the medications.
Q9: Can I take antacids with this medication?
A: Antacids can be taken but inform your physician for proper administration advice and/or to avoid any interactions.
Q10: How should this medication be stored?
A: Store at room temperature away from moisture and heat.
