Esomeprazole Magnesium Capsules (Nexium — AstraZeneca)
March 30, 2001 4 minutes read
Pharmacology Update
Esomeprazole Magnesium Capsules (Nexium—AstraZeneca)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Astrazeneca is launching its new proton pump inhibitor (PPI) esomeprazole (Nexium). The new drug is coming to market just as AstraZeneca is losing patent protection on its multibillion dollar PPI omeprazole (Prilosec). Esomeprazole, the S-isomer of omeprazole, is touted as being the most potent PPI available.
Indications
Esomeprazole is indicated for the healing of erosive esophagitis, treatment of heartburn and other symptoms associated with gastroesophageal reflux disease (GERD) and the maintenance of healing of erosive esophagitis. It is also indicated for the eradication of Helicobacter pylori in combination with amoxicillin and clarithromycin.1
Dosage
The recommended dose for the treatment of erosive esophagitis is 20 or 40 mg once daily for 4-8 weeks. For the treatment of heartburn and other symptoms associated with GERD, the recommended dose is 20 mg once daily for 4-8 weeks. The dose for maintenance of healing of erosive esophagitis is 20 mg once daily. For the eradication of H pylori the dose is esomeprazole 40 mg once daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 10 days. Esomeprazole should be taken at least 1 hour before a meal. If the patient has difficulty in swallowing the capsule, the contents may be mixed with a tablespoon of apple sauce. The pellets should not be chewed or crushed.1
Potential Advantages
At the recommended doses, esomeprazole appears to be the most potent PPI on the market. It has greater acid suppression than omeprazole, lansoprazole, or pantoprazole.4 Esomeprazole has greater systemic bioavailability than omeprazole due to a lower first-pass metabolism and nonlinear pharmacokinetics.3,4 The systemic bioavailability is about 80% higher for esomeprazole 20 mg compared to omeprazole 20 mg and about 5 times greater with esomeprazole 40 mg. This results in greater acid suppression throughout the day. The mean duration for maintaining gastric pH more than 4 for esomeprazole 40 mg, esomeprazole 20 mg, and omeprazole 20 mg is 16.8 hours (95% CI, 15.0-18.4), 12.7 hours (95% CI, 11.0-14.4), and 10.5 hours (95% CI, 8.8-12.2), respectively.
More than 55% of patients maintain intragastric pH more than 4 with esomeprazole 40 mg compared to 24% for esomeprazole 20 mg and 14% for omeprazole 20 mg.3
Potential Disadvantages
Food decreases the extent of absorption of esomeprazole by 33-53%. The drug should be taken at least 1 hour before a meal. Esomeprazole may inhibit the metabolism of drugs which are metabolized via cytochrome P450 2C19. A 45% decrease in the clearance of diazepam has been reported.1 The side effects of esomeprazole appear to be similar to those reported for omeprazole with headache, diarrhea, and abdominal pain being the most common with a frequency of 4-6%.
Comments
Esomeprazole is the S-isomer of omeprazole which is a racemic mixture (S- and R-isomers). They both have the same mechanism of action but differ in their pharmacokinetic and pharmacodynamic properties. Greater acid suppression throughout the day has been reported with esomeprazole compared to other PPIs.3 The improved potency has resulted in modest improvements in the healing of erosive esophagitis. Four large studies (from 572-1216 subjects/arm) were reported by the manufacturer, 2 reported statistical differences between esomprazole and omeprazole and 2 did not.1,2 Generally, the efficacy of esomeprazole and omeprazole did not differ dramatically. Healing rates were 64.7-69.5% for omeprazole 20 mg, 68.7-70.5% for esomprazole 20 mg, and 71.5-81.7% for esomeprazole 40 mg at 4 weeks. Healing rates at 8 weeks were 84.2-89.8%, 89.9-90.6%, and 92.2-94.1% for esomeprazole. One published study reported faster time to sustained resolution of symptoms.2 Median time to sustained resolution for esomeprazole 40 mg, 20 mg, and omeprazole 20 mg were 5, 8, and 9 days, respectively. No real differences were seen in the median time to first symptom resolution, 2 days for each regimen. Esomeprazole is effective for maintaining healed erosive esophagitis.
Healing after 6 months was maintained in about 93% of patients treated with esomeprazole 40 mg or 20 mg compared to 29% with placebo and 57% with esomeprazole 10 mg.6 Esomeprazole is approved for once daily dosing as part of a triple H pylori eradication regimen with amoxicillin and clarithromycin.1,7 Eradication rates, 84-85%, are similar to the twice daily PPI-based regimens. AstraZeneca is pricing esomeprazole 40 mg and 20 mg similar to that of omeprazole 20 mg.
Clinical Implications
GERD is a common chronic condition affecting about one-third of the population.5 PPIs are generally regarded as the treatment of choice for severe cases although antireflux surgery is also an option. Esomeprazole appears to be marginally more potent than the available PPIs and may offer some benefit to those who have not adequately responded to existing PPIs.
References
1. Nesium Product Information. AstraZeneca. February 2001.
2. Kahrilas PJ, et al. Aliment Pharmacol Ther. 2000; 14(10):1249-1258.
3. Lind T, et al. Aliment Pharmacol Ther. 2000;14(7):861-867.
4. Spencer CM, Faulds D. Drugs. 2000;60(2):321-329.
5. DiPalma JA. J Clin Gastroenterol. 2001;32(1):19-26.
6. Johnson DA, et al. Am J Gastroenterol. 2001;96(1):27-34.
7. Line L, et al. Am J Gastroenterol. 2000;95(12): 3393-3398.
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