Esomeprazole Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:477167063
Width:245
Width2:250
Tradename:Nexium, others[1]
Dailymedid:Esomeprazole
Pregnancy Au:B3
Routes Of Administration:By mouth, intravenous
Class:Proton pump inhibitor
Atc Prefix:A02
Atc Suffix:BC05
Legal Au:S2
Legal Au Comment:/  S4 (Prescription Only Medicine)[2] [3]
Legal Ca:Rx-only
Legal Ca Comment:[4]
Legal Uk:GSL
Legal Us:OTC
Legal Us Comment:/ Rx-only[5] [6] [7]
Legal Eu:OTC
Legal Eu Comment:[8]
Bioavailability:50 to 90%
Metabolism:Liver (CYP2C19, CYP3A4)
Elimination Half-Life:1–1.5 hours
Excretion:80% Kidney
20% Feces
Index2 Label:as salt
Cas Number:119141-88-7
Pubchem:9579578
Drugbank:DB00736
Chemspiderid:7843323
Unii:N3PA6559FT
Kegg:D07917
Kegg2:D01984
Chebi:50275
Chembl:1201320
Iupac Name:(S)-(−)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzoimidazole
C:17
H:19
N:3
O:3
S:1
Smiles:COc1ccc2nc([nH]c2c1)[S@](=O)Cc1ncc(C)c(OC)c1C
Stdinchi: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
Stdinchikey:SUBDBMMJDZJVOS-XMMPIXPASA-N

Esomeprazole, sold under the brand name Nexium [or '''Neksium'''] among others,[1] is a medication which reduces stomach acid. It is used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome.[9] Its effectiveness is similar to that of other proton pump inhibitors (PPIs).[10] It is taken by mouth or injection into a vein.

Common side effects include headache, constipation, dry mouth, and abdominal pain. Serious side effects may include angioedema, Clostridium difficile infection, and pneumonia. Use in pregnancy appears to be safe, while safety during breastfeeding is unclear.[11] Esomeprazole is the (S)-(−)-enantiomer (or less specifically the S-isomer) of omeprazole. It works by blocking H+/K+-ATPase in the parietal cells of the stomach.[12]

It was patented in 1993 and approved for medical use in 2000.[13] It is available as a generic medication and sold over the counter in a number of countries.[14] [9] In 2021, it was the 125th most commonly prescribed medication in the United States, with more than 4million prescriptions.[15] [16] It is also available in lower dose formulations without a prescription in the United States, the United Kingdom[17] as well as Australia, Canada, and New Zealand.[18]

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.[19] [20]

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.[21] Long-term contact between gastric acids and the esophagus can cause permanent damage to the esophagus and is associated with Barrett's esophagus.[22] Esomeprazole reduces the production of digestive acids, thus reducing their effect on the esophagus.

Duodenal ulcers

Esomeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole instead of amoxicillin in penicillin-hypersensitive patients) in a 10-day eradication triple therapy for Helicobacter pylori. Infection by H. pylori is a causative factor in the majority of peptic and duodenal ulcers.

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).[23] A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations.[24] A 2017 study found esomeprazole to be among a number of effective PPIs.[25]

Adverse effects

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.[26]

Proton pump inhibitors may be associated with a greater risk of hip fractures[27] and Clostridium difficile-associated diarrhoea.[28] 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.[29]

Long-term use of proton pump inhibitors in patients treated for Helicobacter pylori has been shown to dramatically increase the risk of gastric cancer.[30]

Acute tubulointerstitial nephritis is a possible adverse reaction when using proton pump inhibitors.

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.[31] 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.[32] [33]

Drugs that depend on stomach pH for absorption may interact with esomeprazole; drugs that depend on an acidic environment (such as ketoconazole or atazanavir) will be poorly absorbed, whereas drugs that are broken down in acidic environments (such as erythromycin) will be absorbed to a greater extent than normal.[31]

Pharmacokinetics

Single 20 to 40mg oral doses generally give rise to peak plasma esomeprazole concentrations of 0.5-1.0mg/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 1–3mg/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.[34]

Dosage forms

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 40mg, as delayed-release capsules in the United States (containing esomeprazole strontium) in a 49.3mg strength (delivering the equivalent of 40mg of esomeprazole,[35] 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.

The combination naproxen/esomeprazole magnesium (brand name Vimovo) is used for the prevention of gastric ulcers associated with chronic NSAID therapy. Vimovo is available in two dosage strengths: 500/20mg and 375/20mg. 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, as well as Losec/Prilosec tablets, 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, water enters the capsule by osmosis. 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. Patients for whom the formulation is of benefit include those requiring nasogastric tube feeding and those with difficulty swallowing (dysphagia).[38] [39] [40] [41]

Society and culture

Global distribution

In 2010, AstraZeneca announced a co-promotion agreement with Daiichi Sankyo to distribute Nexium in Japan.[42] In September 2011, Nexium was approved for sale and was launched by Daiichi Sankyo in Japan.[43] Esomeprazole was approved for use in the United States in February 2001.[44] [45]

Economics

Between the launch of esomeprazole in 2001 and 2005, the drug netted AstraZeneca about $14.4billion.[46]

Controversy

There has been some controversy about AstraZeneca's behaviour in creating, patenting, and marketing 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.[47]

Brand names

Generic versions of esomeprazole magnesium are available worldwide.[1] It is available over-the-counter under the brand name Nexium in the United States[48] [49] and the UK.[50]

Veterinary use

Injection formulations of esomeprazole are used for gastroprotection in veterinary medicine. In goats administered the drug by intravenous or subcutaneous injection rapid elimination was noted.[51] In that study the sulfone metabolite was detectable for several hours after injection of the parent drug.

Other uses

Esomeprazole can be used as a parasiticide. Gokmen et al., 2016 screen for efficacy against Trichomonas vaginalis isolates from horses. They found esomeprazole to be effective as a veterinary antiparasitic.[52]

Further reading

Notes and References

  1. Web site: Esomeprazole Brand Names . 2011 . BDdrugs.com . Bangladesh . https://web.archive.org/web/20120207193751/http://www.bddrugs.com/product5.php?idn=5&prev=&prev1=&prev2= . 7 February 2012 .
  2. Web site: Esomeprazole . Therapeutic Goods Administration (TGA) . 15 September 2017 . 19 July 2020.
  3. Web site: Toreso/Esocolam/Meprator/Esotor/Nesed/Esome/Esotrack (Torrent Australasia Pty Ltd) . Therapeutic Goods Administration (TGA) . 16 February 2023 . 9 April 2023.
  4. Web site: Product monograph brand safety updates . . February 2024 . 24 March 2024.
  5. Web site: Nexium- esomeprazole magnesium capsule, delayed release Nexium- esomeprazole magnesium granule, delayed release . DailyMed . U.S. Library of Medicine . 7 June 2018 . 7 December 2020.
  6. Web site: Nexium 24HR- esomeprazole magnesium capsule, delayed release Nexium 24HR ClearMinis- esomeprazole magnesium capsule, delayed release . DailyMed . 26 May 2020 . 7 December 2020.
  7. Web site: Nexium I.V.- esomeprazole sodium injection. DailyMed . U.S. Library of Medicine . 27 November 2020 . 7 December 2020.
  8. Web site: Nexium Control EPAR . European Medicines Agency (EMA) . 17 September 2018 . 14 January 2021.
  9. Book: British national formulary : BNF 76. 2018. Pharmaceutical Press. 978-0-85711-338-2 . 78. 76.
  10. Web site: [99] Comparative effectiveness of proton pump inhibitors Therapeutics Initiative]. 14 July 2016. 28 June 2016.
  11. Web site: Esomeprazole Pregnancy and Breastfeeding Warnings . Drugs.com . 3 March 2019 .
  12. Web site: Esomeprazole Magnesium Monograph for Professionals . Drugs.com . American Society of Health-System Pharmacists . 3 March 2019 .
  13. Book: Fischer J, Ganellin CR . Analogue-based Drug Discovery . 2006 . John Wiley & Sons . 978-3-527-60749-5 . 445 .
  14. Book: ((Jones & Bartlett Learning)) . 2018 Nurse's Drug Handbook . 2017 . Jones & Bartlett Learning . 978-1-284-12134-6 . 394 .
  15. Web site: The Top 300 of 2021 . ClinCalc . 14 January 2024 . 15 January 2024 . https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx . live .
  16. Web site: Esomeprazole - Drug Usage Statistics . ClinCalc . 14 January 2024.
  17. Web site: About esomeprazole . 13 January 2022 .
  18. Web site: Australian TGA Scheduling of Esomeprazole . 15 September 2017 . 1 August 2023 .
  19. Web site: Esomeprazole Magnesium . The American Society of Health-System Pharmacists . 3 April 2011 .
  20. Li J, Zhao J, Hamer-Maansson JE, Andersson T, Fulmer R, Illueca M, Lundborg P . Pharmacokinetic properties of esomeprazole in adolescent patients aged 12 to 17 years with symptoms of gastroesophageal reflux disease: A randomized, open-label study . Clin Ther . 28 . 3 . 419–27 . March 2006 . 16750456 . 10.1016/j.clinthera.2006.03.010 .
  21. Web site: Gastroesophageal Reflux Disease. The Lecturio Medical Concept Library . 23 July 2021.
  22. Web site: Barrett's Esophagus. 8 February 2023 . The Mayo Clinic . 1 August 2023.
  23. Gralnek IM, Dulai GS, Fennerty MB, Spiegel BM . Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials . Clin. Gastroenterol. Hepatol. . 4 . 12 . 1452–8 . December 2006 . 17162239 . 10.1016/j.cgh.2006.09.013 .
  24. Edwards SJ, Lind T, Lundell L . 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 . September 2006 . 16918878 . 10.1111/j.1365-2036.2006.03074.x . 23189853 . free .
  25. Li MJ, Li Q, Sun M, Liu LQ . Comparative effectiveness and acceptability of the FDA-licensed proton pump inhibitors for erosive esophagitis . Medicine . 96 . 39 . 2017 . 0025-7974 . 28953640 . 5626283 . 10.1097/md.0000000000008120 . e8120.
  26. Web site: Nexium side effects . Drug information online . Drugs.com . 23 June 2009 .
  27. Yang YX, Lewis JD, Epstein S, Metz DC . Long-term proton pump inhibitor therapy and risk of hip fracture . JAMA . 296 . 24 . 2947–53 . 2006 . 17190895 . 10.1001/jama.296.24.2947 . free .
  28. Web site: Proton pump inhibitors and Clostridium difficile . https://archive.today/20121223071436/http://www.medicine.ox.ac.uk/bandolier/booth/Pharmacy/PPIcdiff.html . dead . 23 December 2012 . 2003 . 13 July 2007 . Bandolier .
  29. Herzig SJ, Howell MD, Ngo LH, Marcantonio ER . Acid-suppressive medication use and the risk for hospital-acquired pneumonia . JAMA . 301 . 20 . 2120–8 . 2009 . 19470989 . 10.1001/jama.2009.722 .
  30. Cheung KS, Chan EW, Wong AY, Chen L, Wong IC, Leung WK . Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study . Gut . 67 . 1 . 28–35 . January 2018 . 29089382 . 10.1136/gutjnl-2017-314605 . free .
  31. Stedman CA, Barclay ML . Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors . Aliment. Pharmacol. Ther. . 14 . 8 . 963–78 . August 2000 . 10930890 . 10.1046/j.1365-2036.2000.00788.x . 45337685 .
  32. Lau WC, Gurbel PA . The drug-drug interaction between proton pump inhibitors and clopidogrel . CMAJ . 180 . 7 . 699–700 . March 2009 . 19332744 . 2659824 . 10.1503/cmaj.090251 .
  33. Norgard NB, Mathews KD, Wall GC . Drug-drug interaction between clopidogrel and the proton pump inhibitors . Ann Pharmacother . 43 . 7 . 1266–74 . July 2009 . 19470853 . 10.1345/aph.1M051 . 13227312 .
  34. Book: Baselt RC . Disposition of toxic drugs and chemicals in man . 2008 . Biomedical Publications . Foster City, Ca . 978-0-9626523-7-0 . 8th . 388–389 .
  35. Web site: esomeprazole strontium capsule, delayed release . DailyMed . U.S. Library of Medicine .
  36. Web site: VIMOVO (naproxen and esomeprazole magnesium) delayed release tablets, for oral use . Horizon Pharma USA . U.S. Food and Drug Administration . December 2014 .
  37. Web site: Vimovo (naproxen/esomeprazole magnesium) tablets . https://web.archive.org/web/20150211053608/https://www.fda.gov/Safety/MedWatch/SafetyInformation/ucm262248.htm . 11 February 2015 . Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER) . U.S. Food and Drug Administration . December 2014 .
  38. Ullah MA, Maruf AA, Azad MA, Shohag MH, Sultana R, Latif AH, Hasnat A . Relative bioavailability and pharmacokinetic properties of two different enteric formulations of esomeprazole in healthy Bangladeshi male volunteers: An open-label, single-dose, randomized-sequence, two-way crossover study . Clinical Therapeutics . 32 . 7 . 1419–1426 . July 2010 . 20678688 . 10.1016/j.clinthera.2010.07.007 .
  39. Vegesna V, Li J, Pollack C, Moreira S . Assessing the bioequivalence of over-the-counter esomeprazole banded capsules and multiple-unit pellet system tablets . International Journal of Clinical Pharmacology and Therapeutics . 56 . 2 . 92–99 . February 2018 . 29292694 . 10.5414/CP203075 .
  40. Talpes S, Knoerzer D, Huber R, Pfaffenberger B . Esomeprazole MUPS 40 mg tablets and esomeprazole MUPS 40 mg tablets encapsulated in hard gelatine are bioequivalent . International Journal of Clinical Pharmacology and Therapeutics . 43 . 1 . 51–56 . January 2005 . 15704615 . 10.5414/CPP43051 .
  41. Hamman H, Hamman J, Wessels A, Scholtz J, Steenekamp J . Development of multiple-unit pellet system tablets by employing the SeDeM expert diagram system II: pellets containing different active pharmaceutical ingredients . Pharmaceutical Development and Technology . 24 . 2 . 145–156 . February 2019 . 29394129 . 10.1080/10837450.2018.1435691 . 3596776 .
  42. AstraZeneca announces co-promotion agreement with Daiichi Sankyo for NEXIUM in Japan . AstraZeneca . 29 October 2010 . 15 July 2019.
  43. Daiichi Sankyo and AstraZeneca Launch NEXIUM 10mg and 20mg Capsules in Japan . Daiichi Sankyo . 15 September 2011 . 15 July 2019.
  44. Web site: Drug Approval Package: Nexium (Esomeprazole Magnesium) NDA #21-153 & 21-154 . U.S. Food and Drug Administration (FDA) . 24 December 1999 . 4 April 2020.
  45. Web site: Nexium: FDA-Approved Drugs . U.S. Food and Drug Administration (FDA) . 4 April 2020.
  46. Financial impact information:
    • Web site: Annual Review 2005 . AstraZeneca . $4.6 billion. https://web.archive.org/web/20060312000637/http://www.astrazeneca.com/sites/7/imagebank/typeArticleparam511672/astrazeneca-2005-annual-review.pdf . 12 March 2006 .
    • Web site: Annual Review 2004 . AstraZeneca . $3.9 billion . https://web.archive.org/web/20070202143327/http://www.astrazeneca.com/sites/7/imagebank/typeArticleparam511562/astrazeneca-2004-annual-report.pdf . 2 February 2007 .
    • Web site: Annual Review 2003 . AstraZeneca . $3.3 billion . https://web.archive.org/web/20040728120928/http://www.astrazeneca.com/sites/7/imagebank/typearticleparam503063/AstraZeneca%20Annual%20Report%202003.pdf . 28 July 2004 .
    • Web site: Annual Review 2002 . AstraZeneca . $2 billion . https://web.archive.org/web/20030608161027/http://www.astrazeneca.com/annualrep2002/pdf/694617_Report_front.pdf . 8 June 2003 .
  47. High Prices: How to think about prescription drugs . Gladwell M . Malcolm Gladwell . . 25 October 2004 . 23 June 2006 .
  48. Web site: Esomeprazole. . . 2 March 2020 .
  49. Web site: Nonprescription Nexium Heartburn Medicine Launches . 27 May 2014 . ABC News.
  50. Web site: Esomeprazole: medicine to lower stomach acid . nhs.uk . 9 December 2019 . 29 August 2018.
  51. Fladung R, Smith JS, Hines M, Soto-Gonzalez WM, Fayne B, Rahn RR, Escher OG, Harvill L, Garcia JD, Kreuder AJ, Cox S . 6 . Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration. . Frontiers in Veterinary Science . December 2022 . 9. 968973. 10.3389/fvets.2022.968973 . 36590808 . 9797722 . free .
  52. Book: Marchiondo AA, Cruthers LR, Fourie JJ . 2019 . 1 . xxxi+576 . . . Parasiticide screening - In Vitro and in Vivo Tests with Relevant Parasite Rearing and Host Infection/Infestation Methods . 978-0-12-813890-8 . 1104533040.