Esomeprazol

Additional information

Esomeprazole is the (S)-enantiomer of omeprazole.

Pharmacokinetics and dosing

A small pharmacokinetic study of healthy volunteers (3 men, 3 women) showed plasma protein binding of omeprazole, esomeprazole and (R)-omeprazole to be similar (97%) in men and women [1,2].Pooled data from several studies showed that, women had 33% higher AUC and 27% higher Cmax after a single-dose of 40 mg esomeprazole compared to men. At steady-state, no sex difference was seen [1, 6]. Esomeprazole is extensively metabolized by CYP2C19 which has lower activity in women than in men leading to a lower elimination. With repeated doses, first pass metabolism and systemic clearance diminish probably due to inhibition of CYP2C19 [2,8]. Esomeprazole is to some extent metabolized by CYP3A4 which in general has a lower activity in men [9]. However, in elderly patients (70-80 years old), AUC and Cmax are similar in men and women [1]. Although there are minor sex differences in esomeprazole pharmacokinetics, dosage adjustment based on sex has not been considered to be necessary [6].

Effects

Factors associated with decreased heartburn in patients with reflux esophagitis have been identified in a randomized, double-blind trial (1981 men, 1170 women). Patients received 40 mg esomeprazole or 40 mg pantoprazole for at least 4 weeks. Men were more likely than women to have good effect of the medication (odds ratio 1.35 men vs. women) [10].

The effect of long-term proton-pump inhibitor (PPI) treatment on serum gastrin concentrations after a meal has been evaluated in PPI users (56 men, 44 women) and PPI non-users (25 men, 25 women). Female patients had higher gastrin levels than males before and after the meal, whereas such sex differences were not found in the control group. Female patients also had higher chromogranin A values than males. High chromogranin A levels are seen in patients using proton-pump inhibitors. Female sex was the only independent predictor of elevated fasting gastrin values (OR 2.50, 95%CI: 1.08-5.76). No difference was observed between men and women in terms of BMI or dosage and the duration of PPI therapy. This indicates that women could be more sensitive than men to the inhibitory effects of acid secretion on gastrin release. However, it is unclear whether this is a clinically important sex difference [3].

Adverse effects

Hypersensitivity reactions to PPIs (omeprazole, lansoprazole, pantoprazole, esomeprazole and rabeprazole) have been evaluated in a literature review. Omeprazole was most frequently associated with hypersensitivity reactions. Overall, most hypersensitivity reactions were reported in women (61%) [4]. Sex-stratified data were not presented for each PPI.A retrospective study of PPI-induced subacute cutaneous lupus erythematosus (SCLE) has been carried out over a 19-year period. Nineteen women and two men were identified through medical records. PPIs associated with SCLE were lansoprazole (12 patients), omeprazole (6 patients), esomeprazole (4 patients) and pantoprazole (2 patients) [5].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Other information

Treatment patterns of PPI in patients with newly diagnosed gastroesophageal reflux disease have been analyzed in a British study. PPI prevalence was higher in women (25.2/1000 inhabitants vs 21.7/1000 inhabitants) [7].In 2005, esomeprazole was changed to non-preferred formulary status in the U.S., which was leading to increased copayment when purchasing from a community pharmacy. The change was aimed to encourage the use of other PPIs. Changes in the utilization of esomeprazole relative to other PPIs after the formulary change were examined in an observational study of claims data. In this cohort, men were more likely than women to switch to a preferred PPI (18.0% vs. 13.3%) or to discontinue all acid-reducing therapy (12.3% vs. 10.4%) [11].