Dexrabeprazole

Usage

• Dexrabeprazole is prescribed for the treatment of conditions related to excess stomach acid production. These conditions include gastroesophageal reflux disease (GERD), erosive esophagitis, and duodenal ulcers. It is also used in combination therapy for Helicobacter pylori eradication to reduce the risk of duodenal ulcer recurrence and in the management of pathological hypersecretory conditions like Zollinger-Ellison syndrome. In adolescents, it’s used for short-term treatment of symptomatic GERD.
• Pharmacological Classification: Proton Pump Inhibitor (PPI)
• Mechanism of Action: Dexrabeprazole irreversibly binds to the H+/K+ ATPase enzyme (proton pump) in gastric parietal cells, inhibiting the final step of gastric acid secretion. This results in a profound and long-lasting reduction of stomach acid production.

Alternate Names

• (R)-Rabeprazole (The active isomer of Rabeprazole).
• Brand Name: Dexilant

How It Works

• Pharmacodynamics: Dexrabeprazole, by inhibiting the proton pump, effectively suppresses gastric acid secretion. This leads to symptom relief and promotes healing in conditions caused by excessive stomach acid.

• Pharmacokinetics:

  • Absorption: Dexrabeprazole is administered orally as a delayed-release formulation, meaning it’s designed to release the drug in the small intestine rather than the stomach. This ensures better absorption.
  • Metabolism: Primarily metabolized in the liver via CYP enzymes (mainly CYP2C19 and CYP3A4).
  • Elimination: Excreted through both renal and hepatic pathways.

• Mode of Action: Dexrabeprazole works at the cellular level by specifically targeting the H+/K+ ATPase enzyme in the parietal cells of the stomach lining. It irreversibly binds to this pump, preventing it from transporting hydrogen ions into the stomach lumen, thus reducing acid secretion.

• Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: The primary mechanism is the irreversible inhibition of the H+/K+ ATPase enzyme (proton pump).

• Elimination Pathways: Eliminated through both renal (urine) and hepatic (bile/feces) pathways. Some metabolites are generated by CYP2C19 and CYP3A4 enzymes.

Dosage

Standard Dosage

Adults:

• GERD, Erosive Esophagitis: 20 mg once daily for 4-8 weeks; if not healed after 8 weeks, an additional 8-week course may be considered.
• Maintenance of healed Erosive Esophagitis: 20 mg once daily for up to 12 months.
• Symptomatic GERD: 20 mg once daily for 4 weeks. If symptoms persist, an additional 4-week course can be considered.

Children:

• 12 years and older (Adolescents): 20 mg once daily for up to 8 weeks for symptomatic GERD.
• Under 12 years: Not recommended, safety and efficacy not established.

Special Cases:

• Elderly Patients: Dose adjustments may be required due to potentially decreased metabolism and clearance. Monitor closely for adverse effects.
• Patients with Renal Impairment: Caution is advised. Dosage adjustment might be necessary.
• Patients with Hepatic Dysfunction: For moderate hepatic impairment, the maximum dose is 30 mg per day. Use with caution in severe hepatic impairment.
• Patients with Comorbid Conditions: Individualized dosing is crucial. Consider comorbid conditions like diabetes, cardiovascular disease, and interactions with other medications.

Clinical Use Cases

Dexrabeprazole isn’t typically adjusted for procedures like intubation, surgical procedures, mechanical ventilation, or specifically for ICU use. The underlying condition being treated (e.g., GERD) would dictate the dosage. Consult guidelines for stress ulcer prophylaxis if applicable. The drug is not indicated for emergency situations like status epilepticus or cardiac arrest.

Dosage Adjustments

• Renal or hepatic impairment may require dose reductions.
• Monitor magnesium levels, especially with prolonged use.

Side Effects

Common Side Effects:

• Diarrhea
• Headache
• Nausea
• Abdominal pain
• Vomiting
• Flatulence

Rare but Serious Side Effects:

• Severe allergic reactions (anaphylaxis)
• Clostridium difficile associated diarrhea
• Hypomagnesemia (low magnesium levels)
• Fundic gland polyps (with prolonged use)
• Vitamin B12 deficiency (with prolonged use)
• Cutaneous lupus erythematosus (CLE)
• Stevens-Johnson Syndrome (SJS)

Long-Term Effects:

• Bone fractures (with prolonged use, especially over a year)
• Low magnesium levels

Adverse Drug Reactions (ADR): ADR requiring immediate intervention include severe allergic reactions, hypomagnesemia with associated symptoms (seizures, tetany), SJS, and CLE.

Contraindications

• Hypersensitivity to dexrabeprazole, substituted benzimidazoles or any components of the formulation.
• Gastric malignancy (symptomatic relief does not rule out the possibility).

Drug Interactions

• CYP450 Interactions: Dexrabeprazole is metabolized by CYP2C19 and CYP3A4. Drugs that inhibit these enzymes (e.g., ketoconazole, itraconazole, voriconazole) can increase dexrabeprazole levels. Inducers of these enzymes (e.g., rifampin, St. John’s wort) can decrease its levels.
• Other Clinically Significant Interactions:
  • Methotrexate
  • Digoxin
  • Warfarin
  • Clopidogrel
  • Atazanavir
  • Nelfinavir
  • Iron Supplements
• Food and Lifestyle Factors: Alcohol should be avoided as it can worsen GERD symptoms and interact with dexrabeprazole.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B. Use only if the benefits outweigh the risks to the fetus.
• Fetal Risks: Limited human data available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/fetal development, parturition or postnatal development.
• Breastfeeding: Not recommended as it is unknown if dexrabeprazole is excreted in human milk. Rabeprazole (the racemic mixture) is contraindicated during breastfeeding.

Drug Profile Summary

• Mechanism of Action: Proton pump inhibitor, reducing stomach acid production.
• Side Effects: Common: Diarrhea, headache, nausea, abdominal pain, vomiting. Serious: Hypomagnesemia, C. difficile infection, fundic gland polyps.
• Contraindications: Hypersensitivity to the drug or substituted benzimidazoles, gastric malignancy.
• Drug Interactions: CYP2C19 and CYP3A4 inhibitors/inducers, methotrexate, digoxin, warfarin, clopidogrel, some antiretrovirals.
• Pregnancy & Breastfeeding: Category B; not recommended while breastfeeding.
• Dosage: Adults: 20 mg daily. Children (12+): 20 mg daily for symptomatic GERD.
• Monitoring Parameters: Magnesium levels (especially with long-term use). Consider monitoring vitamin B12 and bone density with prolonged therapy.

Popular Combinations

• Antibiotics (amoxicillin, clarithromycin) for H. pylori eradication.
• Domperidone or levosulpiride for improved gastric motility in some cases of dyspepsia (off label use).

Precautions

• General Precautions: Evaluate for possible gastric malignancy before initiating therapy. Assess renal and hepatic function. Monitor magnesium levels with long-term use.
• Specific Populations: Use with caution in pregnancy, breastfeeding not recommended. Use with caution in patients with severe renal or hepatic impairment.
• Lifestyle Considerations: Avoid alcohol, and triggering foods.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Dexrabeprazole?

A: Adults: 20mg daily for GERD, erosive esophagitis, and duodenal ulcers. Maintenance: 20 mg daily for up to 12 months for erosive esophagitis. Adolescents (12+): 20mg daily for symptomatic GERD, up to 8 weeks.

Q2: How does Dexrabeprazole differ from other PPIs?

A: Dexrabeprazole is the R-enantiomer of rabeprazole, offering potentially improved efficacy at lower doses compared to its racemic counterpart.

Q3: What are the serious side effects to watch out for?

A: Hypomagnesemia, C. difficile infection, bone fractures (long-term use), vitamin B12 deficiency (long-term use).

Q4: Can Dexrabeprazole be used in pregnancy?

A: Pregnancy Category B: Only if the benefits outweigh the risks. Consult with a specialist.

Q5: Is it safe to take Dexrabeprazole while breastfeeding?

A: Not recommended. It is not known if dexrabeprazole is excreted in human milk.

Q6: What are the common drug interactions with Dexrabeprazole?

A: CYP2C19 and 3A4 inhibitors/inducers, methotrexate, digoxin, warfarin, clopidogrel, certain antiretrovirals.

Q7: How long can a patient take Dexrabeprazole?

A: Long-term use (up to 12 months) is approved for maintenance of healed erosive esophagitis. Longer durations should be assessed on a case-by-case basis, balancing benefits and risks like bone fractures and hypomagnesemia.

Q8: How should Dexrabeprazole be administered?

A: Orally, as a delayed-release tablet, with or without food.

Q9: What should I do if a patient misses a dose?

A: Take the missed dose as soon as remembered, unless it is close to the time for the next dose. Do not double the dose.

Q10: Can patients with liver problems take Dexrabeprazole?

A: Use cautiously, dose adjustments may be needed. In moderate hepatic impairment, maximum dose 30mg/day. In severe hepatic impairment, use with extreme caution.