Sergel

Indications

Esomeprazole enteric coated capsule is indicated for relief of chronic heartburn and other symptoms associated with gastroesophageal reflux disease (GERD), healing of erosive esophagitis, maintenance of healing of erosive esophagitis, eradication of Helicobacter pylori infection in combination with amoxicillin and clarithromycin in patients with duodenal ulcer disease, treatment of Zollinger-Ellison syndrome, acid related dyspepsia, and duodenal and gastric ulcer.

Pharmacology

Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase enzyme in the gastric parietal cell. It is the S-isomer of omeprazole and provides better control of gastric acid secretion than the racemic proton pump inhibitors. The capsule contains enteric-coated pellets of esomeprazole magnesium that protect the drug from degradation in acid and allow absorption after passage into the intestine. After oral administration, peak plasma level (Cmax) is reached in about 1.5 hours (Tmax), Cmax increases proportionally with dose, and systemic exposure increases accordingly.

Dosage & Administration

• Healing of erosive esophagitis: 20 mg or 40 mg once daily for 4–8 weeks; an additional 4–8 weeks may be considered if healing is incomplete.
• Maintenance of healing of erosive esophagitis: 20 mg once daily; clinical studies did not extend beyond 6 months.
• Symptomatic GERD: 20 mg once daily for 4 weeks; if symptoms persist, an additional 4 weeks may be considered.
• Helicobacter pylori eradication (triple therapy): Esomeprazole 40 mg once daily for 10 days with amoxicillin 1000 mg twice daily and clarithromycin 500 mg twice daily for 10 days.
• Zollinger-Ellison syndrome: 20–80 mg once daily; dose should be adjusted individually and continued as long as clinically indicated.
• Acid-related dyspepsia: 20–40 mg once daily for 2–4 weeks according to clinical response.
• Duodenal ulcer: 20 mg once daily for 2–4 weeks; gastric ulcer: 20–40 mg once daily for 4–8 weeks.
• IV in GERD with erosive esophagitis (adults): 20 mg or 40 mg once daily by IV injection over >3 minutes or IV infusion over 10–30 minutes.
• IV in pediatric GERD with erosive esophagitis: 1 month to <1 year: 0.5 mg/kg once daily; 1–17 years <55 kg: 10 mg once daily; 1–17 years ≥55 kg: 20 mg once daily (IV infusion 10–30 minutes).
• Risk reduction of rebleeding of gastric or duodenal ulcers after therapeutic endoscopy (adults): 80 mg IV infusion over 30 minutes followed by continuous infusion of 8 mg/hour for 72 hours.
• Oral capsules should be swallowed whole with water and taken at least one hour before a meal. Do not crush or chew.
• For patients with difficulty swallowing, the capsule may be opened and the pellets mixed with a spoonful of soft, cool applesauce and swallowed immediately without chewing.

Interaction

Esomeprazole is extensively metabolized in the liver mainly by CYP2C19 and CYP3A4. It is not likely to inhibit CYP1A2, 2A6, 2C9, 2D6, 2E1 or 3A4 at clinically relevant concentrations, and clinically important interactions with drugs metabolized by these enzymes are not expected. Co-administration with diazepam, a CYP2C19 substrate, has resulted in about a 45% decrease in diazepam clearance with increased plasma levels after dosing. By inhibiting gastric acid secretion, esomeprazole may affect absorption of drugs whose bioavailability depends on gastric pH, such as ketoconazole, iron salts and digoxin. Combination therapy with clarithromycin and amoxicillin increases plasma levels of esomeprazole and 14-hydroxyclarithromycin. Oral contraceptives, phenytoin and quinidine do not appear to significantly change the pharmacokinetics of esomeprazole.

Contraindications

Esomeprazole is contraindicated in patients with known hypersensitivity to esomeprazole, substituted benzimidazoles or to any component of the formulation.

Side Effects

The most frequently reported adverse events include headache, diarrhoea, nausea, flatulence, abdominal pain, constipation and dry mouth. In clinical use there is no important difference in the type of adverse events between short-term therapy and maintenance treatment up to 12 months.

Pregnancy & Lactation

There are no adequate and well-controlled studies of esomeprazole use in pregnant women. Animal studies have not shown teratogenic effects. Because it is not known whether esomeprazole is excreted in human breast milk and a potential risk to the infant cannot be excluded, breast-feeding should be discontinued if treatment with esomeprazole is considered essential.

Precautions & Warnings

Symptomatic response to therapy with esomeprazole does not exclude the presence of gastric malignancy, so further evaluation should be considered in alarm features. Capsules should be taken at least one hour before meals and swallowed whole; pellets should not be crushed or chewed. For patients unable to swallow capsules, the pellets may be mixed with soft applesauce and swallowed immediately without chewing, and the mixture should not be stored. Antacids may be used concomitantly if needed. Use with caution in patients with severe hepatic impairment, in whom the dose should not exceed 20 mg once daily.

Overdose Effects

Very high single oral doses have produced toxicity in animals, including reduced motor activity, changes in respiratory rate, tremor, ataxia and intermittent clonic convulsions. There have been no well-documented cases of severe overdose in humans. There is no specific antidote for esomeprazole and, because it is highly protein bound, it is not expected to be removed by dialysis. Management of overdose should be symptomatic and supportive, with consideration of the possibility of multiple drug ingestion.

Storage Conditions

Store below 30°C in a dry place, protected from light and moisture. Keep out of the reach of children.