esomeprazole magnesium
Nexium

Available forms
Available by prescription only
Capsules (delayed-release containing enteric-coated pellets): 20 mg or 40 mg (supplied as 22.3 or 44.5 mg esomeprazole magnesium)

Indications and dosages
 Gastroesophageal reflux disease (GERD), healing of erosive esophagitis. Adults: 20 or 40 mg P.O. daily for 4 to 8 weeks.
 Maintenance of healing in erosive esophagitis. Adults: 20 mg P.O. daily for no longer than 6 months.
 Symptomatic GERD. Adults: 20 mg P.O. daily for 4 weeks. If symptoms continue, treatment may continue 4 more weeks.
 Eradication of Helicobacter pylori (with other drugs) to reduce duodenal ulcer recurrence. Adults: Esomeprazole magnesium 40 mg P.O. daily plus amoxicillin 1,000 mg P.O. b.i.d. plus clarithromycin 500 mg P.O. b.i.d., all for 10 days.
≡ Dosage adjustment. For patients with severe hepatic failure, maximum daily dose is 20 mg.

Pharmacodynamics
Gastric secretion inhibitor action: Suppresses gastric secretion through proton pump inhibition. Inhibits the H⁺-K⁺-ATPase pump in gastric parietal cells, reducing gastric acidity by blocking the final step in acid production. Esomeprazole magnesium is the s-isomer of omeprazole.

Pharmacokinetics
Absorption: Esomeprazole is formulated as enteric-coated pellets in a gelatin capsule. Plasma levels peak 1 1/2 hours after oral administration. The plasma level following a 40-mg dose is threefold higher than after a 20-mg dose. Repeated once-daily dosing of 40 mg yields systemic bioavailability of 90% compared to a single 40-mg dose, which yields 64%. This may result from reduced hepatic metabolism and clearance with continued dosing. Giving esomeprazole with food reduces mean plasma level by 33% to 53%.
Distribution: Esomeprazole is about 97% protein-bound. The volume of distribution in healthy patients at steady state is 16 L.
Metabolism: Esomeprazole is extensively metabolized by cytochrome P-450 2C19 to form hydroxy and desmethyl metabolites that have no secretory activity. CYP2C19 exhibits polymorphism and people who are poor metabolizers have increased esomeprazole plasma levels. About 3% of whites and 15% to 20% of Asians lack cytochrome P-450 2C19. Cytochrome P-450 3A4 metabolizes the remaining amount of esomeprazole.
Excretion: Plasma elimination half-life is about 1 to 1 1/2 hours. Less than 1% of active parent drug is excreted in urine. About 80% of an oral dose is excreted as inactive metabolites in urine. Remaining inactive metabolites are excreted in feces. Systemic clearance of esomeprazole decreases with multiple dose administration.

Adverse reactions
CNS: headache.
GI: diarrhea, abdominal pain, nausea, flatulence, dry mouth, vomiting, constipation.

Effects on lab test results
None reported.

Interactions
Drug-drug. Amoxicillin, clarithromycin: Increases esomeprazole levels. Monitor patient for toxicity.
Diazepam: Decreases diazepam clearance. Monitor patient for diazepam toxicity.
Other drugs metabolized by cytochrome P-450 2C19: Alter esomeprazole clearance. Monitor patient closely, especially elderly patient or patient with hepatic insufficiency.
Drug-food. Any food: Reduces bioavailability. Advise patient to take drug 1 hour before eating.

Overdose and treatment
No antidote is known. Drug is highly protein-bound and therefore probably isn’t removed by dialysis. Supportive care is recommended.

Contraindications and precautions
Contraindicated in patients hypersensitive to any component of esomeprazole or omeprazole. Use cautiously when giving drug to pregnant patients, breast-feeding patients, or patients with hepatic insufficiency. Dosage adjustments are required in patients with severe disease.

Special considerations
• Symptomatic response to esomeprazole doesn’t rule out the presence of a gastric malignancy.
• Long-term therapy with omeprazole has caused atrophic gastritis.
• Food decreases the extent of absorption; give esomeprazole at least 1 hour before meals.
• Antacids won’t interfere with the absorption of esomeprazole.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Use cautiously, however, because omeprazole does appear in breast milk.

Patient education
• Tell patient to take drug exactly as prescribed and at least one hour before meals.
• Inform patient that antacids may be used while taking this drug.
• If patient has trouble swallowing the capsule, suggest that he open it, sprinkle contents into applesauce, and swallow applesauce immediately. Warn against crushing or chewing the drug pellets.
• Urge patient to store capsules at room temperature in a tight container.
• Tell patient to report continued or worsened symptoms; rash or other allergy symptoms; intended, suspected, or confirmed pregnancy; and breast-feeding or the intention to breast-feed.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use