Jump to content

Esomeprazole

From Wikipedia, the free encyclopedia
"Nexium" redirects here. For the defunct cult with the same pronunciation, seeNXIVM.
For the similarly named medication esomeprazole is derived from, seeomeprazole.

Esomeprazole
Clinical data
Pronunciation/ˌɛsoʊˈmɛprəˌzoʊl,-ˈmiː-,-ˌzɒl/[1]
Trade namesNexium, others[2]
AHFS/Drugs.comMonograph
MedlinePlusa699054
License data
Pregnancy
category
Routes of
administration		By mouth,intravenous
Drug classProton pump inhibitor
ATC code
Legal status
Legal status
Pharmacokineticdata
Bioavailability50 to 90%
MetabolismLiver(CYP2C19,CYP3A4)
Eliminationhalf-life1–1.5 hours
Excretion80%Kidney
20%Feces
Identifiers
  • (S)-(−)-5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H-benzoimidazole
CAS Number
PubChemCID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.149.048Edit this at Wikidata
Chemical and physical data
FormulaC17H19N3O3S
Molar mass345.42g·mol−1
3D model (JSmol)
  • COc1ccc2nc([nH]c2c1)[S@](=O)Cc1ncc(C)c(OC)c1C
  • 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/s1checkY
  • Key:SUBDBMMJDZJVOS-XMMPIXPASA-NcheckY
☒NcheckY(what is this?)(verify)

Esomeprazole,sold under the brand nameNexium[orNeksium] among others,[2]is a medication which reducesstomach acid.[11]It is used to treatgastroesophageal reflux disease,peptic ulcer disease,andZollinger–Ellison syndrome.[11][12]Its effectiveness is similar to that of otherproton pump inhibitors(PPIs).[13]It is taken by mouth orinjection into a vein.[11]

Common side effects include headache, constipation, dry mouth, and abdominal pain.[11]Serious side effects may includeangioedema,Clostridium difficileinfection,andpneumonia.[11]Use inpregnancyappears to be safe, while safety duringbreastfeedingis unclear.[3]Esomeprazole is the (S)-(−)-enantiomer(or less specifically the S-isomer) ofomeprazole.[11]It works by blockingH+/K+-ATPasein theparietal cellsof the stomach.[11]

It was patented in 1993 and approved for medical use in 2000.[14]It is available as ageneric medicationand soldover the counterin a number of countries.[15][12]In 2021, it was the 125th most commonly prescribed medication in the United States, with more than 4million prescriptions.[16][17]It is also available in lower dose formulations without a prescription in the United States,[18]the United Kingdom[19]as well as Australia, Canada, and New Zealand.[20]

Medical use[edit]

The primary uses of esomeprazole are gastroesophageal reflux disease, treatment and maintenance oferosive esophagitis,treatment ofduodenal ulcerscaused byH. pylori,prevention ofgastric ulcersin those on chronicNSAIDtherapy, and treatment of gastrointestinal ulcers associated withCrohn's disease.[21][22]

Gastroesophageal reflux disease[edit]

Gastroesophageal reflux disease(GERD) is a condition in which the digestive acid in the stomach comes in contact with theesophagus.The irritation caused by this disorder is known asheartburn.[23]Long-term contact between gastric acids and the esophagus can cause permanent damage to the esophagus and is associated with Barrett's esophagus.[24]Esomeprazole reduces the production of digestive acids, thus reducing their effect on the esophagus.

Duodenal ulcers[edit]

Esomeprazole is combined with the antibioticsclarithromycinandamoxicillin(ormetronidazoleinstead of amoxicillin in penicillin-hypersensitive patients) in a 10-day eradication triple therapy forHelicobacter pylori.Infection byH. pyloriis a causative factor in the majority ofpeptic and duodenal ulcers.

Efficacy[edit]

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[clarification needed]), but appeared more in those with severe disease (number needed to treat 8[clarification needed]).[25]A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations.[26]A 2017 study found esomeprazole to be among a number of effective PPIs.[27]

Adverse effects[edit]

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.[28]

Proton pump inhibitors may be associated with a greater risk of hip fractures[29]andClostridium difficile-associateddiarrhoea.[30]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 ofpneumonia.[31]

Long-term use of proton pump inhibitors in patients treated forHelicobacter pylorihas been shown to dramatically increase the risk of gastric cancer.[32]

Acute tubulointerstitial nephritis is a possible adverse reaction when using proton pump inhibitors.[9]

Interactions[edit]

Esomeprazole is acompetitive inhibitorof the enzymeCYP2C19,and may thereforeinteractwith drugs that depend on it formetabolism,such asdiazepamandwarfarin;the concentrations of these drugs may increase if they are used concomitantly with esomeprazole.[33]Conversely,clopidogrel(Plavix) is an inactiveprodrugthat partially depends on CYP2C19 for conversion to its active form; inhibition of CYP2C19 blocks the activation of clopidogrel, thus reducing its effects.[34][35]

Drugs that depend on stomach pH for absorption may interact with esomeprazole; drugs that depend on an acidic environment (such asketoconazoleoratazanavir) will be poorly absorbed, whereas drugs that are broken down in acidic environments (such aserythromycin) will be absorbed to a greater extent than normal.[33]

Pharmacokinetics[edit]

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.[36]

Dosage forms[edit]

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 40mg, as delayed-release capsules in the United States (containing esomeprazole strontium) in a 49.3mg strength (delivering the equivalent of 40mg of esomeprazole,[37]and as esomeprazole sodium forintravenousinjection/infusion. Oral esomeprazole preparations areenteric-coated,due to the rapid degradation of the drug in theacidicconditions of thestomach.This is achieved by formulating capsules using the multiple-unit pellet system.

The combinationnaproxen/esomeprazole magnesium(brand name Vimovo) is used for the prevention of gastric ulcers associated with chronicNSAIDtherapy. 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.[38]The FDA has added warnings to the label for Vimovo concerningacute interstitial nephritisand risk ofkidneyproblems in some patients.[39]

Multiple-unit pellet system[edit]

Esomeprazole capsules, as well as Losec/Prilosec tablets, are formulated as a "multiple-unit pellet system" (MUPS). Essentially, thecapsuleconsists 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 byosmosis.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 requiringnasogastric tubefeeding and those with difficulty swallowing (dysphagia).[40][41][42][43]

Society and culture[edit]

Global distribution[edit]

In 2010, AstraZeneca announced a co-promotion agreement withDaiichi Sankyoto distribute Nexium in Japan.[44]In September 2011, Nexium was approved for sale and was launched by Daiichi Sankyo in Japan.[45]Esomeprazole was approved for use in the United States in February 2001.[46][47]

Economics[edit]

Between the launch of esomeprazole in 2001 and 2005, the drug netted AstraZeneca about $14.4billion.[48]

Controversy[edit]

Main article:AstraZeneca's marketing of Nexium

There has been some controversy aboutAstraZeneca's behaviour in creating, patenting, and marketing the drug. Esomeprazole's successful predecessor,omeprazole,is a mixture of twomirror-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.[49]

Brand names[edit]

Generic versions of esomeprazole magnesium are available worldwide.[2]It is availableover-the-counterunder the brand name Nexium in the United States[18][50]and the UK.[51]

Veterinary use[edit]

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.[52]In that study the sulfone metabolite was detectable for several hours after injection of the parent drug.

Other uses[edit]

Esomeprazole can be used as aparasiticide.[53]Gokmenet al.,2016 screen for efficacy againstTrichomonas vaginalisisolates fromhorses.[53]They found esomeprazole to be effective as a veterinary antiparasitic.[53]

References[edit]

  1. ^"Esomeprazole".Merriam-Webster.com Dictionary.Retrieved21 January2016.
  2. ^abc"Esomeprazole Brand Names".BDdrugs.com.Bangladesh. 2011. Archived fromthe originalon 7 February 2012.
  3. ^ab"Esomeprazole Pregnancy and Breastfeeding Warnings".Drugs.com.Retrieved3 March2019.
  4. ^"Esomeprazole".Therapeutic Goods Administration (TGA).15 September 2017.Retrieved19 July2020.
  5. ^"Toreso/Esocolam/Meprator/Esotor/Nesed/Esome/Esotrack (Torrent Australasia Pty Ltd)".Therapeutic Goods Administration (TGA).16 February 2023.Retrieved9 April2023.
  6. ^"Product monograph brand safety updates".Health Canada.February 2024.Retrieved24 March2024.
  7. ^"Nexium- esomeprazole magnesium capsule, delayed release Nexium- esomeprazole magnesium granule, delayed release".DailyMed.U.S. Library of Medicine. 7 June 2018.Retrieved7 December2020.
  8. ^"Nexium 24HR- esomeprazole magnesium capsule, delayed release Nexium 24HR ClearMinis- esomeprazole magnesium capsule, delayed release".DailyMed.26 May 2020.Retrieved7 December2020.
  9. ^ab"Nexium I.V.- esomeprazole sodium injection".DailyMed.U.S. Library of Medicine. 27 November 2020.Retrieved7 December2020.
  10. ^"Nexium Control EPAR".European Medicines Agency(EMA).17 September 2018.Retrieved14 January2021.
  11. ^abcdefg"Esomeprazole Magnesium Monograph for Professionals".Drugs.com.American Society of Health-System Pharmacists.Retrieved3 March2019.
  12. ^abBritish national formulary: BNF 76(76 ed.). Pharmaceutical Press. 2018. p. 78.ISBN978-0-85711-338-2.
  13. ^"[99] Comparative effectiveness of proton pump inhibitors | Therapeutics Initiative".28 June 2016.Retrieved14 July2016.
  14. ^Fischer J, Ganellin CR (2006).Analogue-based Drug Discovery.John Wiley & Sons. p. 445.ISBN978-3-527-60749-5.
  15. ^Jones & Bartlett Learning (2017).2018 Nurse's Drug Handbook.Jones & Bartlett Learning. p. 394.ISBN978-1-284-12134-6.
  16. ^"The Top 300 of 2021".ClinCalc.Archivedfrom the original on 15 January 2024.Retrieved14 January2024.
  17. ^"Esomeprazole - Drug Usage Statistics".ClinCalc.Retrieved14 January2024.
  18. ^ab"Esomeprazole".MedlinePlus.United States National Library of Medicine.Retrieved2 March2020.
  19. ^"About esomeprazole".13 January 2022.
  20. ^"Australian TGA Scheduling of Esomeprazole".15 September 2017.Retrieved1 August2023.
  21. ^"Esomeprazole Magnesium".The American Society of Health-System Pharmacists.Retrieved3 April2011.
  22. ^Li J, Zhao J, Hamer-Maansson JE, Andersson T, Fulmer R, Illueca M, Lundborg P (March 2006). "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.doi:10.1016/j.clinthera.2006.03.010.PMID16750456.
  23. ^"Gastroesophageal Reflux Disease".The Lecturio Medical Concept Library.Retrieved23 July2021.
  24. ^"Barrett's Esophagus".The Mayo Clinic.8 February 2023.Retrieved1 August2023.
  25. ^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.PMID17162239.
  26. ^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.PMID16918878.S2CID23189853.
  27. ^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.ISSN0025-7974.PMC5626283.PMID28953640.
  28. ^"Nexium side effects".Drug information online.Drugs.com.Retrieved23 June2009.
  29. ^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.PMID17190895.
  30. ^"Proton pump inhibitors and Clostridium difficile".Bandolier. 2003. Archived fromthe originalon 23 December 2012.Retrieved13 July2007.
  31. ^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.PMID19470989.
  32. ^Cheung KS, Chan EW, Wong AY, Chen L, Wong IC, Leung WK (January 2018)."Long-term proton pump inhibitors and risk of gastric cancer development after treatment forHelicobacter pylori:a population-based study ".Gut.67(1): 28–35.doi:10.1136/gutjnl-2017-314605.PMID29089382.
  33. ^abStedman 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.PMID10930890.S2CID45337685.
  34. ^Lau WC, Gurbel PA (March 2009)."The drug-drug interaction between proton pump inhibitors and clopidogrel".CMAJ.180(7): 699–700.doi:10.1503/cmaj.090251.PMC2659824.PMID19332744.
  35. ^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.PMID19470853.S2CID13227312.
  36. ^Baselt RC (2008).Disposition of toxic drugs and chemicals in man(8th ed.). Foster City, Ca: Biomedical Publications. pp. 388–389.ISBN978-0-9626523-7-0.
  37. ^"esomeprazole strontium capsule, delayed release".DailyMed.U.S. Library of Medicine.
  38. ^"VIMOVO (naproxen and esomeprazole magnesium) delayed release tablets, for oral use"(PDF).Horizon Pharma USA.U.S. Food and Drug Administration. December 2014.
  39. ^"Vimovo (naproxen/esomeprazole magnesium) tablets".U.S. Food and Drug Administration. December 2014. Archived fromthe originalon 11 February 2015.Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
  40. ^Ullah MA, Maruf AA, Azad MA, Shohag MH, Sultana R, Latif AH, Hasnat A (July 2010). "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.doi:10.1016/j.clinthera.2010.07.007.PMID20678688.
  41. ^Vegesna V, Li J, Pollack C, Moreira S (February 2018). "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.doi:10.5414/CP203075.PMID29292694.
  42. ^Talpes S, Knoerzer D, Huber R, Pfaffenberger B (January 2005). "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.doi:10.5414/CPP43051.PMID15704615.
  43. ^Hamman H, Hamman J, Wessels A, Scholtz J, Steenekamp J (February 2019). "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.doi:10.1080/10837450.2018.1435691.PMID29394129.S2CID3596776.
  44. ^"AstraZeneca announces co-promotion agreement with Daiichi Sankyo for NEXIUM in Japan"(Press release). AstraZeneca. 29 October 2010.Retrieved15 July2019.
  45. ^"Daiichi Sankyo and AstraZeneca Launch NEXIUM 10mg and 20mg Capsules in Japan"(Press release). Daiichi Sankyo. 15 September 2011.Retrieved15 July2019.
  46. ^"Drug Approval Package: Nexium (Esomeprazole Magnesium) NDA #21-153 & 21-154".U.S.Food and Drug Administration(FDA).24 December 1999.Retrieved4 April2020.
  47. ^"Nexium: FDA-Approved Drugs".U.S.Food and Drug Administration(FDA).Retrieved4 April2020.
  48. ^Financial impact information:
  49. ^Gladwell M(25 October 2004)."High Prices: How to think about prescription drugs".The New Yorker.Retrieved23 June2006.
  50. ^"Nonprescription Nexium Heartburn Medicine Launches".ABC News.27 May 2014.
  51. ^"Esomeprazole: medicine to lower stomach acid".nhs.uk.29 August 2018.Retrieved9 December2019.
  52. ^Fladung R, Smith JS, Hines M, Soto-Gonzalez WM, Fayne B, Rahn RR, et al. (December 2022)."Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration".Frontiers in Veterinary Science.9:968973.doi:10.3389/fvets.2022.968973.PMC9797722.PMID36590808.
  53. ^abcMarchiondo AA, Cruthers LR, Fourie JJ, eds. (2019).Parasiticide screening - In Vitro and in Vivo Tests with Relevant Parasite Rearing and Host Infection/Infestation Methods.Vol. 1.London:Academic Press.pp. xxxi+576.ISBN978-0-12-813890-8.OCLC1104533040.

Further reading[edit]

Retrieved from "https://en.wikipedia.org/w/index.php?title=Esomeprazole&oldid=1233409798"