Esomeprazole

Esomeprazole
Names
Pronunciation/ˌɛsoʊˈmɛprəˌzoʊl, -ˈmiː-, -ˌzɒl/[1]
Trade namesNexium, others[2]
IUPAC name
  • (S)-(−)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzoimidazole
Clinical data
Drug classProton pump inhibitor
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
    Routes of
    use    		By mouth, IV
    Defined daily dose30 mg[3]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa699054
    Legal
    License data
    Legal status
    Pharmacokinetics
    Bioavailability50 to 90%
    MetabolismLiver (CYP2C19, CYP3A4)
    Elimination half-life1–1.5 hours
    Excretion80% Kidney
    20% Faecal
    Chemical and physical data
    FormulaC17H19N3O3S
    Molar mass345.42 g·mol−1
    3D model (JSmol)
    SMILES
    • COc1ccc2nc([nH]c2c1)S(=O)Cc1ncc(C)c(OC)c1C
    InChI
    • InChI=1S/C17H19N3O3S/c1-10-8-18-15(11(2)16(10)23-4)9-24(21)17-19-13-6-5-12(22-3)7-14(13)20-17/h5-8H,9H2,1-4H3,(H,19,20)/t24-/m1/s1 checkY
    • Key:SUBDBMMJDZJVOS-XMMPIXPASA-N checkY

    Esomeprazole, sold under the brand names Nexium among others,[2] is a medication which reduces stomach acid.[5] It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome.[5][6] Effectiveness is similar to other proton pump inhibitors (PPIs).[7] It is taken by mouth or injection into a vein.[5]

    Common side effects include headache, constipation, dry mouth, and abdominal pain.[5] Serious side effects may include angioedema, Clostridium difficile infection, and pneumonia.[5] Use in pregnancy appears to be safe, while safety during breastfeeding is unclear.[8] Esomeprazole is the (S)-(−)-isomer of omeprazole.[5] It works by blocking H+/K+-ATPase in the parietal cells of the stomach.[5]

    It was patented in 1993 and approved for medical use in 2000.[9] It is available as a generic medication and sold over the counter in a number of countries.[10][6] A month supply in the United Kingdom costs the NHS about £3 as of 2019.[6] In the United States the wholesale cost of this amount is about US$10.[11] In 2017, it was the 88th most commonly prescribed medication in the United States, with more than nine million prescriptions.[12][13] It is also available without a prescription in the United States.[14]

    Medical use

    The primary uses of esomeprazole are gastroesophageal reflux disease, treatment and maintenance of erosive esophagitis, treatment of duodenal ulcers caused by H. pylori, prevention of gastric ulcers in those on chronic NSAID therapy, and treatment of gastrointestinal ulcers associated with Crohn's disease.[15][16]

    Gastroesophageal reflux disease

    Gastroesophageal reflux disease (GERD) is a condition in which the digestive acid in the stomach comes in contact with the esophagus. The irritation caused by this disorder is known as heartburn.[17] Esomeprazole reduces the production of digestive acids, thus reducing their effect on the esophagus[14]

    Stomach ulcers

    Esomeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole instead of amoxicillin in penicillin-hypersensitive patients[18]) over several days- eradication triple therapy for Helicobacter pylori.[19] Infection by H. pylori is a causative factor in the majority of peptic and duodenal ulcers.[20]

    Efficacy

    A 2006 meta analysis concluded that compared to other proton pump inhibitors, esomeprazole confers a modest overall benefit in esophageal healing and symptom relief. When broken down by disease severity, the benefit of esomeprazole relative to other proton pump inhibitors was negligible in people with mild disease (number needed to treat 50), but appeared more in those with severe disease (number needed to treat 8).[21] A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations.[22] A 2017 study found esomeprazole to be among a number of effective doses of PPIs.[23]

    Dosage

    The defined daily dose is 30 mg by mouth or by injection.[3]

    Side effects

    Painful hand lesions appeared 6 hours after dose of esomeprazole

    Common side effects include headache, diarrhea, nausea, flatulence, decreased appetite, constipation, dry mouth, and abdominal pain. More severe side effects are severe allergic reactions, chest pain, dark urine, fast heartbeat, fever, paresthesia, persistent sore throat, severe stomach pain, unusual bruising or bleeding, unusual tiredness, and yellowing of the eyes or skin.[24]

    Proton pump inhibitors may be associated with a greater risk of hip fractures[25] and Clostridium difficile-associated diarrhoea.[26] Patients are frequently administered the drugs in intensive care as a protective measure against ulcers, but this use is also associated with a 30% increase in occurrence of pneumonia.[27]Long-term use of PPIs in patients treated for Helicobacter pylori has been shown to dramatically increase the risk of gastric cancer.[28]

    Interactions

    Esomeprazole is a competitive inhibitor of the enzyme CYP2C19, and may therefore interact with drugs that depend on it for metabolism, such as diazepam and warfarin; the concentrations of these drugs may increase if they are used concomitantly with esomeprazole.[29] Conversely, clopidogrel (Plavix) is an inactive prodrug that partially depends on CYP2C19 for conversion to its active form; inhibition of CYP2C19 blocks the activation of clopidogrel, thus reducing its effects.[30][31]

    Drugs that depend on stomach pH for absorption may interact with omeprazole; drugs that depend on an acidic environment (such as ketoconazole or atazanavir) will be poorly absorbed[32]

    Pharmacokinetics

    Single 20 to 40 mg oral doses generally give rise to peak plasma esomeprazole concentrations of 0.5-1.0 mg/l within 1–4 hours, but after several days of once-daily administration, these levels may increase by about 50%. A 30-minute intravenous infusion of a similar dose usually produces peak plasma levels on the order of 1–3 mg/l. The drug is rapidly cleared from the body, largely by urinary excretion of pharmacologically inactive metabolites such as 5-hydroxymethylesomeprazole and 5-carboxyesomeprazole. Esomeprazole and its metabolites are analytically indistinguishable from omeprazole and the corresponding omeprazole metabolites unless chiral techniques are employed.[33]

    Society and culture

    Cost

    A month supply in the United Kingdom costs the NHS about £3 as of 2019.[6] In the United States the wholesale cost of this amount is about US$10.[11] In 2017, it was the 88th most commonly prescribed medication in the United States, with more than nine million prescriptions.[12][13]

    • Esomeprazole costs (US)
      Esomeprazole costs (US)
    • Esomeprazole prescriptions (US)
      Esomeprazole prescriptions (US)

    Dosage forms

    Esomeprazole strontium delayed-release capsules, 49.3 mg
    40 mg Nexium (esomeprazole magnesium) capsules

    Esomeprazole is available as delayed-release capsules in the United States or as delayed-release tablets in Australia, the United Kingdom, and Canada (containing esomeprazole magnesium) in strengths of 20 and 40 mg, as delayed-release capsules in the United States (containing esomeprazole strontium) in a 49.3 mg strength (delivering the equivalent of 40 mg of esomeprazole,[34] and as esomeprazole sodium for intravenous injection/infusion.

    Oral esomeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic conditions of the stomach. This is achieved by formulating capsules using the multiple-unit pellet system.[35]The combination naproxen/esomeprazole (brand name Vimovo) is used for the prevention of gastric ulcers associated with long term NSAID therapy. It is available in two dosage strengths: 500/20 mg and 375/20 mg. Clinical trials of naproxen/esomeprazole demonstrated an incidence of GI ulcer in 24% of patients on naproxen (alone) versus 7% on naproxen/esomeprazole.[36] The FDA has added warnings to the label for Vimovo concerning acute interstitial nephritis and risk of kidney problems in some patients.[37]

    Multiple-unit pellet system

    Esomeprazole capsules are formulated as a "multiple-unit pellet system" (MUPS). Essentially, the capsule consists of extremely small enteric-coated granules (pellets) of the esomeprazole formulation inside an outer shell. When the capsule is immersed in an aqueous solution, as happens when the capsule reaches the stomach. The contents swell from water absorption, causing the shell to burst, and releasing the enteric-coated granules. For most patients, the multiple-unit pellet system is of no advantage over conventional enteric-coated preparations.[35] Patients for whom the formulation is of benefit include those requiring nasogastric tube feeding and those with difficulty swallowing.[38]

    Global distribution

    In 2010, AstraZeneca announced a co-promotion agreement with Daiichi Sankyo to distribute Nexium in Japan.[39] In September 2011, Nexium was approved for sale and was launched by Daiichi Sankyo in Japan.[40] Esomeprazole was approved for use in the United States in February 2001.[41][42]

    Economics

    Between the launch of esomeprazole in 2001 and 2005, the drug netted AstraZeneca about $14.4 billion.[43]

    Controversy

    There has been some controversy about AstraZeneca's behaviour in creating, patenting, and marketing of the drug. Esomeprazole's successful predecessor, omeprazole, is a mixture of two mirror-imaged molecules (esomeprazole which is the S-enantiomer, and R-omeprazole); critics said the company was trying to "evergreen" its omeprazole patent by patenting the pure esomeprazole and aggressively marketing to doctors that it is more effective than the mixture.[44]

    Thomas A. Scully, head of the Centers for Medicare and Medicaid Services (CMS), also criticized AstraZeneca for their aggressive marketing of Nexium.[45]

    Brand names

    Generic versions of esomeprazole magnesium are available worldwide.[2] It is available over-the-counter under the brand name Nexium in the United States[14][46] and the UK.[47]

    References

    1. ↑ "Esomeprazole". Merriam-Webster Dictionary. Retrieved 21 January 2016.
    2. 1 2 3 "Esomeprazole brand names". Archived from the original on 18 June 2020. Retrieved 7 December 2014.
    3. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 17 June 2020. Retrieved 7 September 2020.
    4. ↑ "1.4 Esomeprazole". Therapeutic Goods Administration (TGA). 15 September 2017. Archived from the original on 19 July 2020. Retrieved 19 July 2020.
    5. 1 2 3 4 5 6 7 "Esomeprazole Magnesium Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Archived from the original on 10 August 2020. Retrieved 3 March 2019.
    6. 1 2 3 4 British national formulary : BNF 76 (76 ed.). Pharmaceutical Press. 2018. p. 78. ISBN 9780857113382.
    7. ↑ "[99] Comparative effectiveness of proton pump inhibitors | Therapeutics Initiative". 28 June 2016. Archived from the original on 30 October 2020. Retrieved 14 July 2016.
    8. ↑ "Esomeprazole Pregnancy and Breastfeeding Warnings". Drugs.com. Archived from the original on 6 March 2019. Retrieved 3 March 2019.
    9. ↑ Fischer, Jnos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 445. ISBN 9783527607495. Archived from the original on 28 February 2019. Retrieved 28 February 2019.
    10. ↑ Learning, Jones & Bartlett (2017). 2018 Nurse's Drug Handbook. Jones & Bartlett Learning. p. 394. ISBN 9781284121346. Archived from the original on 6 March 2019. Retrieved 3 March 2019.
    11. 1 2 "NADAC as of 2019-02-27". Centers for Medicare and Medicaid Services. Archived from the original on 6 March 2019. Retrieved 3 March 2019.
    12. 1 2 "The Top 300 of 2020". ClinCalc. Archived from the original on 12 February 2021. Retrieved 11 April 2020.
    13. 1 2 "Esomeprazole - Drug Usage Statistics". ClinCalc. Archived from the original on 29 November 2020. Retrieved 11 April 2020.
    14. 1 2 3 "Esomeprazole". MedlinePlus. United States National Library of Medicine. Archived from the original on 28 November 2020. Retrieved 2 March 2020.
    15. ↑ "Esomeprazole Magnesium". The American Society of Health-System Pharmacists. Archived from the original on 10 August 2020. Retrieved 3 April 2011.
    16. ↑ "Esomeprazole: MedlinePlus Drug Information". medlineplus.gov. Archived from the original on 28 November 2020. Retrieved 30 October 2020.
    17. ↑ "GERD". medlineplus.gov. Archived from the original on 15 November 2011. Retrieved 26 October 2020.
    18. ↑ Hauser, Stephen. Mayo Clinic Gastroenterology and Hepatology Board Review. Oxford University Press. p. 47. ISBN 978-0-19-937335-2. Archived from the original on 28 August 2021. Retrieved 26 October 2020.
    19. ↑ Domino, Frank J. The 5-Minute Clinical Consult 2011. Lippincott Williams & Wilkins. p. 975. ISBN 978-1-60831-259-7. Archived from the original on 28 August 2021. Retrieved 26 October 2020.
    20. ↑ Narayanan, Mechu; Reddy, Kavya M.; Marsicano, Elizabeth (2018). "Peptic Ulcer Disease and Helicobacter pylori infection". Missouri Medicine. 115 (3): 219–224. ISSN 0026-6620. Archived from the original on 28 August 2021. Retrieved 26 October 2020.
    21. ↑ Gralnek IM, Dulai GS, Fennerty MB, Spiegel BM (December 2006). "Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials". Clin. Gastroenterol. Hepatol. 4 (12): 1452–8. doi:10.1016/j.cgh.2006.09.013. PMID 17162239.
    22. ↑ Edwards SJ, Lind T, Lundell L (September 2006). "Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis - a comparison of esomeprazole with other PPIs". Aliment. Pharmacol. Ther. 24 (5): 743–50. doi:10.1111/j.1365-2036.2006.03074.x. PMID 16918878.
    23. ↑ Li MJ, Li Q, Sun M, Liu LQ (2017). "Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis". Medicine. 96 (39): e8120. doi:10.1097/md.0000000000008120. ISSN 0025-7974. PMC 5626283. PMID 28953640.
    24. ↑ "Nexium side effects". Drug information online. Drugs.com. Archived from the original on 20 June 2020. Retrieved 23 June 2009.
    25. ↑ Yang YX, Lewis JD, Epstein S, Metz DC (2006). "Long-term proton pump inhibitor therapy and risk of hip fracture". JAMA. 296 (24): 2947–53. doi:10.1001/jama.296.24.2947. PMID 17190895.
    26. ↑ Research, Center for Drug Evaluation and (26 June 2019). "FDA Drug Safety Communication: Clostridium difficile associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs)". FDA. Archived from the original on 22 December 2020. Retrieved 23 October 2020.
    27. ↑ Herzig SJ, Howell MD, Ngo LH, Marcantonio ER (2009). "Acid-suppressive medication use and the risk for hospital-acquired pneumonia". JAMA. 301 (20): 2120–8. doi:10.1001/jama.2009.722. PMID 19470989.
    28. ↑ Cheung, Ka Shing; Chan, Esther W.; Wong, Angel Y. S.; Chen, Lijia; Wong, Ian C. K.; Leung, Wai Keung (18 September 2017). "Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study". Gut. 67 (1): gutjnl–2017–314605. doi:10.1136/gutjnl-2017-314605. ISSN 0017-5749. PMID 29089382. Archived from the original on 9 March 2018. Retrieved 1 November 2017.
    29. ↑ Stedman CA, Barclay ML (August 2000). "Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors". Aliment. Pharmacol. Ther. 14 (8): 963–78. doi:10.1046/j.1365-2036.2000.00788.x. PMID 10930890.
    30. ↑ Cronenwett, Jack L.; Johnston, K. Wayne. Rutherford's Vascular Surgery E-Book. Elsevier Health Sciences. p. 553. ISBN 978-0-323-24306-3. Archived from the original on 28 August 2021. Retrieved 30 October 2020.
    31. ↑ Norgard NB, Mathews KD, Wall GC (July 2009). "Drug-drug interaction between clopidogrel and the proton pump inhibitors". Ann Pharmacother. 43 (7): 1266–74. doi:10.1345/aph.1M051. PMID 19470853.
    32. ↑ Lahner, E.; Annibale, B.; Fave, G. Delle (2009). "Systematic review: impaired drug absorption related to the co-administration of antisecretory therapy". Alimentary Pharmacology & Therapeutics. 29 (12): 1219–1229. doi:10.1111/j.1365-2036.2009.03993.x. ISSN 1365-2036. Archived from the original on 7 January 2022. Retrieved 26 October 2020.
    33. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 388-389.
    34. ↑ "esomeprazole strontium capsule, delayed release". DailyMed. Archived from the original on 29 April 2014. Retrieved 28 April 2014.
    35. 1 2 "Oral pharmaceutical formulations of esomeprazole in the form of mups (multi unit pellets system) tablets". patents.google. 5 August 2011. Archived from the original on 28 August 2021. Retrieved 29 October 2020.
    36. ↑ "Viomo label" (PDF). Archived (PDF) from the original on 24 October 2020. Retrieved 23 January 2015.
    37. ↑ "VIMOVO" (PDF). accessdata. FDA. Archived (PDF) from the original on 24 October 2020. Retrieved 29 October 2020.
    38. ↑ Scarpignato, C.; Porro, Gabriele Bianchi. Clinical Pharmacology and Therapy of Helicobacter Pylori Infection. Karger Medical and Scientific Publishers. p. 220. ISBN 978-3-8055-7658-1. Archived from the original on 28 August 2021. Retrieved 30 October 2020.
    39. ↑ "AstraZeneca announces co-promotion agreement with Daiichi Sankyo for NEXIUM in Japan" (Press release). AstraZeneca. 29 October 2010. Archived from the original on 21 October 2020. Retrieved 15 July 2019.
    40. ↑ "Daiichi Sankyo and AstraZeneca Launch NEXIUM 10mg and 20mg Capsules in Japan" (Press release). Daiichi Sankyo. 15 September 2011. Archived from the original on 25 August 2016. Retrieved 15 July 2019.
    41. ↑ "Drug Approval Package: Nexium (Esomeprazole Magnesium) NDA #21-153 & 21-154". U.S. Food and Drug Administration (FDA). 24 December 1999. Archived from the original on 3 May 2019. Retrieved 4 April 2020.
    42. ↑ "Nexium: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Archived from the original on 20 October 2020. Retrieved 4 April 2020.
    43. ↑ Financial impact information: 2005, $4.6 billion Archived 17 October 2006 at the Wayback Machine; 2004, $3.9 billion Archived 2007-02-02 at the Wayback Machine; 2003, $3.3 billion Archived 2004-07-28 at the Wayback Machine; 2002, $2 billion Archived 2003-06-08 at the Wayback Machine; 2001, launch and $580 million.
    44. ↑ Gladwell, Malcolm (25 October 2004). "High Prices: How to think about prescription drugs". The New Yorker. Archived from the original on 5 May 2014. Retrieved 23 June 2006.
    45. ↑ Pear, Robert (21 April 2003). "U.S. Limiting Costs of Drugs For Medicare (Published 2003)". The New York Times. Archived from the original on 11 February 2021. Retrieved 26 October 2020.
    46. ↑ "Nonprescription Nexium Heartburn Medicine Launches". ABC News. 27 May 2014. Archived from the original on 3 June 2014. Retrieved 27 June 2020.
    47. ↑ "Esomeprazole: medicine to lower stomach acid". nhs.uk. 29 August 2018. Archived from the original on 23 November 2020. Retrieved 9 December 2019.
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