Drug products: Losec, Losec®, Omecat, OMEP, Omeprazol ABECE, Omeprazol Actavis, Omeprazol AGP, Omeprazol Alternova, Omeprazol Apofri, Omeprazol Arrow, Omeprazol Aurobindo, Omeprazol Bijon, Omeprazol Bluefish, Omeprazol Distriquimica, Omeprazol Ebb, Omeprazol Evolan, Omeprazol Mylan, Omeprazol Orifarm, Omeprazol Pensa, Omeprazol ratiopharm, Omeprazol Sandoz, Omeprazol Teva, Omeprazole, Omestad, Omezolmyl, Omezyl, Omona, Pedippi
ATC code: A02BC01
Substances: omeprazole, omeprazole magnesium, omeprazole sodium
Proton pump inhibitors (PPI) decrease the acid secretion leading to increase in the serum levels of gastrin. One study has shown that women treated with PPI had higher serum levels of gastrin compared to men both before and after meals. In persons not treated with PPI this differences between men and women was not found. This indicates that women are more sensitive to the acid secretion effect of PPI. The clinical relevance of this is unknown.
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]. No studies with a clinically relevant sex analysis regarding the dosing of omeprazole have been found.
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 .Another study (18 men, 14 women) evaluated the effect of long-term treatment with omeprazole on serum gastrin in patients with reflux esophagitis. All patients were initially treated with 40 mg omeprazole for 1-2 months and subsequently treated with 20 mg omeprazole to prevent relapse of esophagitis. Follow up time was at least 12 months. Women had significantly higher basal gastrin levels than men at 18 and 21 months .
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%) . 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) .
Reproductive health issues
Oral contraceptives may induce changes in clinical effects of drugs metabolized by CYP2C19. Omeprazole is metabolized through CYP2C19 to 5-hydroxyomeprazole. A Swedish study (391 men, 428 women) found that the mean omeprazole/hydroxyomeprazole ratio was twice as high in women taking oral contraceptives as in women not taking oral contraceptives or men. The metabolite is inactive . Regarding drug-drug interactions aspects, please consult Janusmed Interactions (in Swedish, Janusmed interaktioner).Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Regression of Barrett’s esophagus, a consequence of long-standing gastro-esophageal reflux, with long-term PPI therapy has been analyzed (188 patients). Patients were either taking a lower PPI dose (20 mg omeprazole daily or 30 mg lansoprazole daily) or a higher PPI dose (40 mg omeprazole or 60 mg lansoprazole). Partial re-epithelialization in the form of squamous islands was related to the duration of PPI therapy (risk ratio 0.43) and male sex (risk ratio 1.4) .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) .
Date of litterature search: 2015-03-19
- Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - NEXIUM (esomeprazole) [updated 2001-02-20]. länk
- Andersson T, Hassan-Alin M, Hasselgren G, Röhss K, Weidolf L. Pharmacokinetic studies with esomeprazole, the (S)-isomer of omeprazole. Clin Pharmacokinet. 2001;40:411-26. PubMed
- Helgadóttir H, Metz DC, Yang YX, Rhim AD, Björnsson ES. The effects of long-term therapy with proton pump inhibitors on meal stimulated gastrin. Dig Liver Dis. 2014;46:125-30. PubMed
- Bose S, Guyer A, Long A, Banerji A. Evaluation and management of hypersensitivity to proton pump inhibitors. Ann Allergy Asthma Immunol. 2013;111:452-7. PubMed
- Sandholdt LH, Laurinaviciene R, Bygum A. Proton pump inhibitor-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2014;170:342-51. PubMed
- Cooper BT, Chapman W, Neumann CS, Gearty JC. Continuous treatment of Barrett's oesophagus patients with proton pump inhibitors up to 13 years: observations on regression and cancer incidence. Aliment Pharmacol Ther. 2006;23:727-33. PubMed
- Hall J, Dodd S, Durkin M, Sloan S. Impact of proton pump inhibitor utilization patterns on gastroesophageal reflux disease-related costs. Manag Care. 2002;11:14-8. PubMed
- Jansen JB, Klinkenberg-Knol EC, Meuwissen SG, De Bruijne JW, Festen HP, Snel P et al. Effect of long-term treatment with omeprazole on serum gastrin and serum group A and C pepsinogens in patients with reflux esophagitis. Gastroenterology. 1990;99:621-8. PubMed
- Laine K, Tybring G, Bertilsson L. No sex-related differences but significant inhibition by oral contraceptives of CYP2C19 activity as measured by the probe drugs mephenytoin and omeprazole in healthy Swedish white subjects. Clin Pharmacol Ther. 2000;68:151-9. PubMed
- Läkemedelsstatistik. Stockholm: Socialstyrelsen 2015 [cited 2016-03-14.] Socialstyrelsens statistikdatabas
- Conicse. Stockholm: eHälsomyndigheten. 2015 [cited 2016-03-23.] länk
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson