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Esomeprazol

Klassificering: A

Preparat: Axagon, Axiago, Esomeprazol Actavis, Esomeprazol Apofri, Esomeprazol Jubilant, Esomeprazol Krka, Esomeprazol Mylan, Esomeprazol Orion, Esomeprazol Pensa, Esomeprazol ratiopharm, Esomeprazol Sandoz, Esomeprazol Stada, Esomeprazol STADA, Esomeprazol SUN, Esomeprazol SUN Pharma, Esomeprazole Accord, Esomeprazole SUN, Esopral, Inexium, Nexiam, Nexium, Nexium Control, Nexium®, Nexium® HP, Ulcerex, Vimovo

ATC kod: A02BC05, A02BD06, M01AE52

Substanser: esomeprazol, esomeprazolmagnesium, esomeprazolmagnesiumdihydrat, esomeprazolmagnesiumtrihydrat, esomeprazolnatrium

Sammanfattning

Protonpumpshämmare (PPI) minskar syrasekretionen vilket ökar nivåerna av serumgastrin. En studie har visat att kvinnor som behandlas med PPI hade högre gastrinnivåer före och efter måltid än män. Hos personer som inte behandlades med PPI sågs inte denna könsskillnad. Detta kan tyda på att kvinnor är mer känsliga för den syrasekretionshämmande effekten av PPI. Den kliniska betydelsen är dock oklar.
 
Kunskapsunderlaget avseende skillnader mellan kvinnor och män är begränsat och motiverar inte olika dosering eller behandling.

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].

Försäljning på recept

Fler kvinnor än män hämtade ut läkemedel innehållande esomeprazol (ATC-kod A02BC05) på recept i Sverige år 2015, totalt 81 430 kvinnor och 58 255 män. Det motsvarar 17 respektive 12 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70 år och äldre hos båda könen. I genomsnitt var läkemedel innehållande esomeprazol 1,5 gånger vanligare hos kvinnor [12].

Kombinationsprodukter,,Fler kvinnor än män hämtade ut tabletter innehållande kombination av esomeprazol, amoxicillin och klaritromycin (ATC-kod A02BD06) på recept i Sverige år 2015, totalt 7 867 kvinnor och 6 694 män. Det motsvarar 1,6 respektive 1,4 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 70-79 år hos kvinnor och i åldersgruppen 75-84 år hos män. Totalt sett var tabletter innehållande kombination av esomeprazol, amoxicillin och klaritromycin 1,2 gånger vanligare hos kvinnor.,,Något fler kvinnor än män hämtade ut tabletter innehållande kombination av naproxen och esomeprazol (ATC-kod M01AE52) på recept i Sverige år 2015, totalt 1 775 kvinnor och 1 151 män. Det motsvarar 0,4 respektive 0,2 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 45-64 år hos båda könen. I genomsnitt var tabletter innehållande kombination av naproxen och esomeprazol 1,6 gånger vanligare hos kvinnor [12].

 

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2015-03-19

Referenser

  1. Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - NEXIUM (esomeprazole) [updated 2001-02-20]. länk
  2. 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
  3. 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
  4. 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
  5. Sandholdt LH, Laurinaviciene R, Bygum A. Proton pump inhibitor-induced subacute cutaneous lupus erythematosus. Br J Dermatol. 2014;170:342-51. PubMed
  6. NEXIUM (esomeprazole). Summary of Product Characteristics. European Medicines Agency (EMA); 2014.
  7. Martindale: The Complete Drug Reference. Pharmaceutical Press.
  8. 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
  9. Harris RZ, Benet LZ, Schwartz JB. Gender effects in pharmacokinetics and pharmacodynamics. Drugs. 1995;50:222-39. PubMed
  10. Labenz J, Armstrong D, Zetterstrand S, Eklund S, Leodolter A. Clinical trial: factors associated with resolution of heartburn in patients with reflux oesophagitis--results from the EXPO study. Aliment Pharmacol Ther. 2009;29:959-66. PubMed
  11. Linton A, Bacon T, Peterson M. Proton-pump inhibitor utilization associated with the change to nonpreferred formulary status for esomeprazole in the TRICARE formulary. J Manag Care Pharm. 2009;15:42-54. PubMed
  12. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson