Nucleic acid and Omeprazole: Difference between pages

{{Short description|Medication to treat gastroesophageal reflux disease and other conditions}}

{{Use dmy dates|date=January 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{For|the similarly named medication derived from omeprazole|esomeprazole}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 462265

| image = Omeprazole.svg

| chirality = [[Racemic mixture]]

| width = 200

| alt =

| image2 = Omeprazole-3D-balls.png

| width2 = 200

| alt2 =

| caption =

<!-- Clinical data -->

| pronounce = {{IPAc-en|oʊ|ˈ|m|ɛ|p|r|ə|z|oʊ|l}}

| tradename = Losec, Prilosec, others<ref name=AHFS2015/><ref name="Drugs.com international" />

| Drugs.com = {{drugs.com|monograph|omeprazole}}

| MedlinePlus = a693050

| DailyMedID = Omeprazole

| pregnancy_AU = B3

| pregnancy_AU_comment = <ref name="Drugs.com pregnancy">{{cite web | title=Omeprazole Use During Pregnancy | website=Drugs.com | date=11 April 2019 | url=https://www.drugs.com/pregnancy/omeprazole.html | access-date=15 February 2020 | archive-date=15 February 2020 | archive-url=https://web.archive.org/web/20200215230433/https://www.drugs.com/pregnancy/omeprazole.html | url-status=live }}</ref>

| pregnancy_category=

| routes_of_administration = [[Oral administration|By mouth]], [[Intravenous therapy|intravenous]]

| class = [[Proton-pump inhibitor]]

| ATC_prefix = A02

| ATC_suffix = BC01

| ATC_supplemental = {{ATC|A02|BC51}}

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F-->

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=[[Health Canada]] | date=7 July 2016 | url=https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html | access-date=1 April 2024}}</ref>

| legal_DE = <!-- Anlage I, II, III or Unscheduled-->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = GSL

| legal_UK_comment =

| legal_US = OTC

| legal_US_comment = /&nbsp;Rx-only

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV-->

| legal_UN_comment =

| legal_status = <!--For countries not listed above-->

<!-- Pharmacokinetic data -->

| bioavailability= 35–76%<ref>{{cite web | title=Prilosec- omeprazole magnesium capsule, delayed release Prilosec- omeprazole magnesium granule, delayed release | website=DailyMed | date=22 December 2016 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1b077e6-b070-43f2-a98e-380cc635419d | access-date=15 February 2020 | archive-date=27 December 2019 | archive-url=https://web.archive.org/web/20191227184048/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a1b077e6-b070-43f2-a98e-380cc635419d | url-status=live }}</ref><ref>{{cite journal | vauthors = Vaz-da-Silva M, Loureiro AI, Nunes T, Maia J, Tavares S, Falcão A, Silveira P, Almeida L, Soares-da-Silva P | title = Bioavailability and bioequivalence of two enteric-coated formulations of omeprazole in fasting and fed conditions | journal = Clinical Drug Investigation | volume = 25 | issue = 6 | pages = 391–399 | year = 2005 | pmid = 17532679 | doi = 10.2165/00044011-200525060-00004 | url = http://www.medscape.com/viewarticle/508018 | url-status = live | access-date = 21 October 2018 | s2cid = 22082780 | archive-url = https://web.archive.org/web/20130313204630/http://www.medscape.com/viewarticle/508018 | archive-date = 13 March 2013 }}</ref>

| protein_bound = 95%

| metabolism = [[Liver]] ([[CYP2C19]], [[CYP3A4]])

| metabolites =

| >

| elimination_half-life= 1–1.2 hours

| duration_of_action =

| excretion = 80% (urine)<br />20% (bile via feces)

<!-- Identifiers -->

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 73590-58-6

| CAS_supplemental =

| PubChem = 4594

| IUPHAR_ligand = 4279

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB00338

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4433

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = KG60484QX9

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D00455

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 7772

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1503

| NIAID_ChemDB =

| PDB_ligand = 1C6

| synonyms =

<!-- Chemical and physical data -->

| IUPAC_name = 5-Methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methanesulfinyl]-1''H''-benzimidazole

| C = 17 | H = 19 | N = 3 | O = 3 | S = 1

| SMILES = CC1=CN=C(C(=C1OC)C)CS(=O)C2=NC3=C(N2)C=C(C=C3)OC

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| 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)

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = SUBDBMMJDZJVOS-UHFFFAOYSA-N

| density = 1.4±0.1<ref name="chemsrc">{{cite web |url=https://www.chemsrc.com/en/cas/73590-58-6_591579.html |title=Omeprazole MSDS |access-date=21 October 2018 |archive-date=19 April 2017 |archive-url=https://web.archive.org/web/20170419120322/http://www.chemsrc.com/en/cas/73590-58-6_591579.html |url-status=live }}</ref>

| density_notes =

| melting_point = 156

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

}}

<!-- Definition and medical uses -->

'''Omeprazole''', sold under the brand names '''Prilosec''' and '''Losec''', among others, is a medication used in the treatment of [[gastroesophageal reflux disease]] (GERD), [[peptic ulcer disease]], and [[Zollinger–Ellison syndrome]].<ref name="AHFS2015">{{cite web |title=Omeprazole |url=https://www.drugs.com/monograph/omeprazole.html |publisher=The American Society of Health-System Pharmacists |access-date=21 October 2018 |archive-date=19 February 2011 |archive-url=https://web.archive.org/web/20110219135631/http://www.drugs.com/monograph/omeprazole.html |url-status=live }}</ref> It is also used to prevent [[upper gastrointestinal bleeding]] in people who are at high risk.<ref name=AHFS2015/> Omeprazole is a [[proton-pump inhibitor]] (PPI) and its effectiveness is similar to that of other PPIs.<ref name=TI2016>{{cite web|title=[99] Comparative effectiveness of proton pump inhibitors {{!}} Therapeutics Initiative|url=http://www.ti.ubc.ca/2016/06/28/99-comparative-effectiveness-proton-pump-inhibitors/|access-date=14 July 2016|date=28 June 2016|archive-date=30 October 2020|archive-url=https://web.archive.org/web/20201030063031/https://www.ti.ubc.ca/2016/06/28/99-comparative-effectiveness-proton-pump-inhibitors/|url-status=live}}</ref> It can be taken by mouth or by [[intravenous|injection into a vein]].<ref name=AHFS2015/><ref name=UK2016>{{cite web |title=Omeprazole 40 mg Powder for Solution for Infusion |url=https://www.medicines.org.uk/emc/medicine/25259 |website=EMC |access-date=21 October 2018 |date=10 February 2016 |url-status=live |archive-url=https://web.archive.org/web/20160407193540/https://www.medicines.org.uk/emc/medicine/25259 |archive-date=7 April 2016}}</ref> It is also available in the fixed-dose [[combination medication]] omeprazole/sodium bicarbonate as Zegerid<ref name="Zegerid FDA label">{{cite web | title=Zegerid- omeprazole and sodium bicarbonate powder, for suspension Zegerid- omeprazole and sodium bicarbonate capsule | website=DailyMed | date=4 March 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cd6868b9-5824-442b-8d65-4db29ecb70a4 | access-date=16 December 2022}}</ref><ref name="Zegerid OTC FDA label">{{cite web | title=Zegerid OTC- omeprazole and sodium bicarbonate capsule, gelatin coated | website=DailyMed | date=5 December 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ad1ca2b-3119-b8c2-e053-2a91aa0a2f77 | access-date=16 December 2022}}</ref> and as Konvomep.<ref>{{cite web | title=Konvomep- omeprazole and sodium bicarbonate kit | website=DailyMed | date=30 August 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=688ed6f1-d78a-4006-a682-57021cb38a3e | access-date=21 January 2023}}</ref>

<!-- Side effects and mechanism -->

Common side effects include nausea, vomiting, headaches, abdominal pain, and [[flatulence|increased intestinal gas]].<ref name=AHFS2015/><ref name=Dav2015 /> Serious side effects may include [[Clostridium difficile colitis|''Clostridium difficile'' colitis]], an increased risk of [[pneumonia]], an increased risk of [[bone fractures]], and the potential of masking [[stomach cancer]].<ref name=AHFS2015/> Whether it is safe for use in [[pregnancy]] is unclear.<ref name=AHFS2015/> It works by blocking the release of [[stomach acid]].<ref name=AHFS2015/>

<!-- History, society and culture -->

Omeprazole was patented in 1978, and approved for medical use in 1988.<ref>{{cite web | title=Drug Approval Package: Prilosec (Omeprazole) NDA# 019-810s38s50s5 | website=U.S. [[Food and Drug Administration]] (FDA) | date=30 March 2001 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/019810s38s50s56.cfm | access-date=5 October 2022 | archive-date=1 April 2021 | archive-url=https://web.archive.org/web/20210401151454/https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/019810s38s50s56.cfm | url-status=live }}</ref><ref>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=445 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA445 |access-date=29 June 2020 |archive-date=3 August 2020 |archive-url=https://web.archive.org/web/20200803230101/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA445 |url-status=live }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> It is available as a [[generic medication]].<ref name=AHFS2015/> In 2021, it was the eighth-most commonly prescribed medication in the United States, with more than 54{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title=Omeprazole - Drug Usage Statistics, ClinCalc DrugStats Database | website=ClinCalc | url=https://clincalc.com/DrugStats/Drugs/Omeprazole | access-date=14 January 2024 }}</ref> It is also available without a prescription in the United States.<ref>{{cite web |title=Questions and Answers on Prilosec OTC (omeprazole) |url=https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/questions-and-answers-prilosec-otc-omeprazole |website=U.S. [[Food and Drug Administration]] (FDA) |access-date=2 March 2020 |date=3 November 2018 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828195503/https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/questions-and-answers-prilosec-otc-omeprazole |url-status=live }}</ref><ref>{{cite web | title=Drug Approval Package: Prilosec (Omeprazole Magnesium) NDA #021229 | website=U.S. [[Food and Drug Administration]] (FDA) | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-229_Prilosec.cfm | access-date=6 October 2022 | archive-date=24 January 2022 | archive-url=https://web.archive.org/web/20220124210732/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21-229_Prilosec.cfm | url-status=live }}</ref>

==Medical uses==

{{See also|Proton-pump inhibitor}}

Omeprazole can be used in the treatment of [[gastroesophageal reflux disease]] (GERD), [[peptic ulcers]], [[erosive esophagitis]], [[Zollinger–Ellison syndrome]], and [[eosinophilic esophagitis]].<ref>{{cite journal | vauthors = Cheng E | title = Proton pump inhibitors for eosinophilic oesophagitis | journal = Current Opinion in Gastroenterology | volume = 29 | issue = 4 | pages = 416–420 | date = July 2013 | pmid = 23449027 | pmc = 4118554 | doi = 10.1097/MOG.0b013e32835fb50e }}</ref><ref name=AHFS2015/>

===Peptic ulcers===

Peptic ulcers may be treated with omeprazole. Infection with ''[[Helicobacter pylori]]'' can be treated by taking omeprazole, [[amoxicillin]], and [[clarithromycin]] together for 7–14 days.<ref>{{cite journal | vauthors = Fuccio L, Minardi ME, Zagari RM, Grilli D, Magrini N, Bazzoli F | title = Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication | journal = Annals of Internal Medicine | volume = 147 | issue = 8 | pages = 553–562 | date = October 2007 | pmid = 17938394 | doi = 10.7326/0003-4819-147-8-200710160-00008 | s2cid = 11644009 }}</ref> Amoxicillin may be replaced with [[metronidazole]] in patients who are allergic to penicillin.<ref name="Maastricht_2_Consensus_Report">{{cite journal | vauthors = Malfertheiner P, Megraud F, O'Morain C, Bazzoli F, El-Omar E, Graham D, Hunt R, Rokkas T, Vakil N, Kuipers EJ | title = Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report | journal = Gut | volume = 56 | issue = 6 | pages = 772–781 | date = June 2007 | pmid = 17170018 | pmc = 1954853 | doi = 10.1136/gut.2006.101634 }}</ref>

==Adverse effects==

Adverse effects occurring in at least 1% of people include:<ref>{{cite journal | vauthors = McTavish D, Buckley MM, Heel RC | title = Omeprazole. An updated review of its pharmacology and therapeutic use in acid-related disorders | journal = Drugs | volume = 42 | issue = 1 | pages = 138–170 | date = July 1991 | pmid = 1718683 | doi = 10.2165/00003495-199142010-00008 }}</ref>{{Failed verification|date=February 2023}}

*Central nervous system: headache (7%), dizziness (2%)

*Respiratory: [[upper respiratory tract infection]] (2%), cough (1%)

*Gastrointestinal: abdominal pain (5%), diarrhea (4%), nausea (4%), vomiting (3%), flatulence (3%), acid regurgitation (2%), constipation (2%)

*Neuromuscular and skeletal: back pain (1%), weakness (1%)

*Dermatologic: rash (2%)

Other concerns related to adverse effects are:

*Recurrence of ''[[Clostridium difficile colitis|Clostridium difficile]]'' associated diarrhea<ref>{{cite journal | vauthors = Abou Chakra CN, Pepin J, Sirard S, Valiquette L | title = Risk factors for recurrence, complications and mortality in Clostridium difficile infection: a systematic review | journal = PLOS ONE | volume = 9 | issue = 6 | pages = e98400 | date = 21 June 2014 | pmid = 24897375 | pmc = 4045753 | doi = 10.1371/journal.pone.0098400 | bibcode = 2014PLoSO...998400A | doi-access = free }}</ref>

*[[osteoporosis#Fractures|Osteoporosis-related fractures]]<ref>{{cite journal | vauthors = Yang YX, Lewis JD, Epstein S, Metz DC | title = Long-term proton pump inhibitor therapy and risk of hip fracture | journal = JAMA | volume = 296 | issue = 24 | pages = 2947–2953 | date = December 2006 | pmid = 17190895 | doi = 10.1001/jama.296.24.2947 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yu EW, Bauer SR, Bain PA, Bauer DC | title = Proton pump inhibitors and risk of fractures: a meta-analysis of 11 international studies | journal = The American Journal of Medicine | volume = 124 | issue = 6 | pages = 519–526 | date = June 2011 | pmid = 21605729 | pmc = 3101476 | doi = 10.1016/j.amjmed.2011.01.007 }}</ref>

*[[Hypomagnesemia]]<ref>{{cite journal | vauthors = Hess MW, Hoenderop JG, Bindels RJ, Drenth JP | title = Systematic review: hypomagnesaemia induced by proton pump inhibition | journal = Alimentary Pharmacology & Therapeutics | volume = 36 | issue = 5 | pages = 405–413 | date = September 2012 | pmid = 22762246 | doi = 10.1111/j.1365-2036.2012.05201.x | s2cid = 9073390 | doi-access = free }}</ref>

Concern has been expressed regarding [[vitamin B12|vitamin B₁₂]]<ref>{{cite journal | vauthors = Neal K, Logan R | title = Potential gastrointestinal effects of long-term acid suppression with proton pump inhibitors | journal = Alimentary Pharmacology & Therapeutics | volume = 15 | issue = 7 | pages = 1085–1086 | date = July 2001 | pmid = 11421886 | doi = 10.1046/j.1365-2036.2001.0994a.x | s2cid = 39455836 | doi-access = free }}</ref> and [[iron]] [[malabsorption]],<ref>{{cite journal | vauthors = Sarzynski E, Puttarajappa C, Xie Y, Grover M, Laird-Fick H | title = Association between proton pump inhibitor use and anemia: a retrospective cohort study | journal = Digestive Diseases and Sciences | volume = 56 | issue = 8 | pages = 2349–2353 | date = August 2011 | pmid = 21318590 | doi = 10.1007/s10620-011-1589-y | s2cid = 33574008 }}</ref> but effects seem to be insignificant, especially when supplement therapy is provided.<ref>{{cite journal | vauthors = McColl KE | title = Effect of proton pump inhibitors on vitamins and iron | journal = The American Journal of Gastroenterology | volume = 104 | issue = Suppl 2 | pages = S5–S9 | date = March 2009 | pmid = 19262546 | doi = 10.1038/ajg.2009.45 | s2cid = 31455416 }}</ref>

Since their introduction, proton-pump inhibitors (PPIs, especially omeprazole) have also been associated with several cases of [[acute interstitial nephritis]],<ref>{{cite journal | vauthors = Härmark L, van der Wiel HE, de Groot MC, van Grootheest AC | title = Proton pump inhibitor-induced acute interstitial nephritis | journal = British Journal of Clinical Pharmacology | volume = 64 | issue = 6 | pages = 819–823 | date = December 2007 | pmid = 17635502 | pmc = 2198775 | doi = 10.1111/j.1365-2125.2007.02927.x }}</ref> an inflammation of the [[kidneys]] that often occurs as an adverse drug reaction.

=== Long-term use ===

Long-term use of PPIs is strongly associated with the development of benign [[polyp (medicine)|polyps]] from [[fundic glands]] (which is distinct from [[fundic gland polyposis]]); these polyps do not cause cancer and resolve when PPIs are discontinued. No association is seen between PPI use and cancer, but use of PPIs may mask gastric cancers or other serious gastric problems and physicians should be aware of this effect.<ref name="Corleto2014">{{cite journal | vauthors = Corleto VD, Festa S, Di Giulio E, Annibale B | title = Proton pump inhibitor therapy and potential long-term harm | journal = Current Opinion in Endocrinology, Diabetes, and Obesity | volume = 21 | issue = 1 | pages = 3–8 | date = February 2014 | pmid = 24310148 | doi = 10.1097/med.0000000000000031 | s2cid = 205791135 | hdl = 11573/618643 }}</ref>

There is a possible association between long term use and [[dementia]] which requires further study to confirm.<ref>{{cite journal | vauthors = Eusebi LH, Rabitti S, Artesiani ML, Gelli D, Montagnani M, Zagari RM, Bazzoli F | title = Proton pump inhibitors: Risks of long-term use | journal = Journal of Gastroenterology and Hepatology | volume = 32 | issue = 7 | pages = 1295–1302 | date = July 2017 | pmid = 28092694 | doi = 10.1111/jgh.13737 | doi-access = free }}</ref>

A review article in ''[[U.S. Pharmacist]]'' in 2013 states that long-term use of PPIs is associated with [[Hypocalcaemia|decreased calcium absorption]] (causing increased risk of [[osteoporosis]] and [[Bone fracture|fractures]]), [[Magnesium deficiency|decreased magnesium absorption]] (causing [[Electrolyte imbalance|electrolyte disturbances]]), and increased risk of certain infections such as ''[[C. difficile]]'' and [[community-acquired pneumonia]]. They hypothesize that this is due to decreased stomach acid production.<ref>{{cite journal | vauthors = O'Neill LW, Culpepper BL, Galdo JA |title=Long-Term Consequences of Chronic Proton Pump Inhibitor Use | journal = US Pharmacist | date = 2013 | volume = 38 | issue = 12 | pages = 38–42 |url= https://www.uspharmacist.com/article/longterm-consequences-of-chronic-proton-pump-inhibitor-use|access-date=28 December 2020 |archive-date=21 January 2021|archive-url=https://web.archive.org/web/20210121163435/https://www.uspharmacist.com/article/longterm-consequences-of-chronic-proton-pump-inhibitor-use|url-status=live}}</ref>

===Pregnancy and breastfeeding===

The safety of using omeprazole has not been established in pregnant or breastfeeding women.<ref name=Dav2015>{{cite book|title=Davis's Drug Guide for Nurses| vauthors = Vallerand AH, Sanoski CA, Deglin JH |publisher=F.A. Davis Company|year=2015|isbn=978-0-8036-4085-6|edition=14th|pages=924–925|oclc=881473728}}</ref> Epidemiological data do not show an increased risk of major birth defects after maternal use of omeprazole during [[pregnancy]].<ref>{{cite journal | vauthors = Pasternak B, Hviid A | title = Use of proton-pump inhibitors in early pregnancy and the risk of birth defects | journal = The New England Journal of Medicine | volume = 363 | issue = 22 | pages = 2114–2123 | date = November 2010 | pmid = 21105793 | doi = 10.1056/NEJMoa1002689 | s2cid = 10954538 | doi-access = free }}</ref>

== Interactions ==

[[File:Omeprazol Activis bottle.jpg|thumb|upright|Omeprazol Actavis 20 mg, bottle and pills in Sweden]]

Important drug interactions are rare.<ref>{{cite web | vauthors = Fitzakerley J |url= http://www.d.umn.edu/~jfitzake/Lectures/DMED/Antiulcer/Treatment/ReducePain/PPIs/PPIsSE.html |title=2014 Treatments for Acid-Peptic Diseases. |access-date=21 October 2018|url-status=dead | archive-url=https://web.archive.org/web/20140419014436/http://www.d.umn.edu/~jfitzake/Lectures/DMED/Antiulcer/Treatment/ReducePain/PPIs/PPIsSE.html |archive-date=19 April 2014 |publisher=University of Minnesota Medical School Duluth}}</ref><ref>{{cite web |url=http://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-Materials/Downloads/ppi-adult-factsheet.pdf |title=Proton Pump Inhibitor: Use in Adults |archive-url=https://web.archive.org/web/20131212143828/http://www.cms.gov/Medicare-Medicaid-Coordination/Fraud-Prevention/Medicaid-Integrity-Education/Pharmacy-Education-Materials/Downloads/ppi-adult-factsheet.pdf |archive-date=12 December 2013 |access-date=21 October 2018 |work=CMS Medicaid Integrity Program}}</ref> However, the most significant major drug interaction concern is the decreased activation of [[clopidogrel]] when taken together with omeprazole.<ref>{{cite journal | vauthors = Douglas IJ, Evans SJ, Hingorani AD, Grosso AM, Timmis A, Hemingway H, Smeeth L | title = Clopidogrel and interaction with proton pump inhibitors: comparison between cohort and within person study designs | journal = BMJ | volume = 345 | pages = e4388 | date = July 2012 | pmid = 22782731 | pmc = 3392956 | doi = 10.1136/bmj.e4388 }}</ref> Although still controversial,<ref>{{cite journal | vauthors = Focks JJ, Brouwer MA, van Oijen MG, Lanas A, Bhatt DL, Verheugt FW | title = Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review | journal = Heart | volume = 99 | issue = 8 | pages = 520–527 | date = April 2013 | pmid = 22851683 | doi = 10.1136/heartjnl-2012-302371 | s2cid = 23689175 }}</ref> this may increase the risk of stroke or heart attack in people taking clopidogrel to prevent these events.

This interaction is possible because omeprazole is an [[enzyme inhibitor|inhibitor]] of the enzymes [[CYP2C19]] and [[CYP3A4]].<ref>{{cite journal | vauthors = Shirasaka Y, Sager JE, Lutz JD, Davis C, Isoherranen N | title = Inhibition of CYP2C19 and CYP3A4 by omeprazole metabolites and their contribution to drug-drug interactions | journal = Drug Metabolism and Disposition | volume = 41 | issue = 7 | pages = 1414–1424 | date = July 2013 | pmid = 23620487 | pmc = 3684819 | doi = 10.1124/dmd.113.051722 }}</ref> [[Clopidogrel]] is an inactive [[prodrug]] that partially depends on CYP2C19 for conversion to its active form. Inhibition of CYP2C19 may block the activation of clopidogrel, which could reduce its effects.<ref>{{cite journal | vauthors = Lau WC, Gurbel PA | title = The drug-drug interaction between proton pump inhibitors and clopidogrel | journal = CMAJ | volume = 180 | issue = 7 | pages = 699–700 | date = March 2009 | pmid = 19332744 | pmc = 2659824 | doi = 10.1503/cmaj.090251 }}</ref><ref>{{cite journal | vauthors = Norgard NB, Mathews KD, Wall GC | title = Drug-drug interaction between clopidogrel and the proton pump inhibitors | journal = The Annals of Pharmacotherapy | volume = 43 | issue = 7 | pages = 1266–1274 | date = July 2009 | pmid = 19470853 | doi = 10.1345/aph.1M051 | s2cid = 13227312 }}</ref>

Almost all [[benzodiazepines]] are metabolised by the CYP3A4 and [[CYP2D6]] pathways, and inhibition of these enzymes results in a higher [[Area under the curve (pharmacokinetics)|area under the curve]] (i.e., the total effect over time of a given dose). Other examples of drugs dependent on CYP3A4 for their metabolism are [[escitalopram]],<ref>{{EMedicine|article|1879354|Selective Serotonin Reuptake Inhibitors and CYP2D6}}</ref> [[warfarin]],<ref name="pmid12724615">{{cite journal | vauthors = Daly AK, King BP | title = Pharmacogenetics of oral anticoagulants | journal = Pharmacogenetics | volume = 13 | issue = 5 | pages = 247–252 | date = May 2003 | pmid = 12724615 | doi = 10.1097/00008571-200305000-00002 }}</ref> [[oxycodone]], [[tramadol]], and [[oxymorphone]]. The concentrations of these drugs may increase if they are used concomitantly with omeprazole.<ref name=Stedman>{{cite journal | vauthors = Stedman CA, Barclay ML | title = Review article: comparison of the pharmacokinetics, acid suppression and efficacy of proton pump inhibitors | journal = Alimentary Pharmacology & Therapeutics | volume = 14 | issue = 8 | pages = 963–978 | date = August 2000 | pmid = 10930890 | doi = 10.1046/j.1365-2036.2000.00788.x | s2cid = 45337685 }}</ref>

Omeprazole is also a competitive inhibitor of [[p-glycoprotein]], as are other PPIs.<ref>{{cite journal | vauthors = Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF | title = Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein | journal = Naunyn-Schmiedeberg's Archives of Pharmacology | volume = 364 | issue = 6 | pages = 551–557 | date = December 2001 | pmid = 11770010 | doi = 10.1007/s00210-001-0489-7 | s2cid = 19990184 }}</ref>

Drugs that depend on an acidic stomach environment (such as [[ketoconazole]] or [[atazanavir]]) may be poorly absorbed, whereas acid-labile antibiotics (such as [[erythromycin]] which is a very strong CYP3A4 inhibitor) may be absorbed to a greater extent than normal due to the more alkaline environment of the stomach.<ref name=Stedman/>

[[St. John's wort]] (''Hypericum perforatum'') and ''[[Ginkgo biloba]]'' significantly reduce plasma concentrations of omeprazole through [[enzyme induction and inhibition|induction]] of CYP3A4 and CYP2C19.<ref>{{cite journal | vauthors = Izzo AA, Ernst E | title = Interactions between herbal medicines and prescribed drugs: an updated systematic review | journal = Drugs | volume = 69 | issue = 13 | pages = 1777–1798 | year = 2009 | pmid = 19719333 | doi = 10.2165/11317010-000000000-00000 | s2cid = 25720882 }}</ref>

Proton-pump inhibitors like omeprazole have been found to increase the plasma concentrations of [[methotrexate]].<ref name = MD>{{cite web |title=Methotrexate |work=Martindale: The Complete Drug Reference |publisher=Pharmaceutical Press |date=6 January 2014 |access-date=12 April 2014 |url=http://www.medicinescomplete.com/mc/martindale/current/ms-9550-n.htm | veditors = Brayfield A |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828170949/https://about.medicinescomplete.com/wp-content/plugins/revslider/public/assets/js/jquery.themepunch.revolution.min.js?ver=5.4.5.2 |url-status=live }}</ref>

==Pharmacology==

Omeprazole irreversibly blocks the enzyme system on parietal cells that is needed for the secretion of gastric acid. It is a specific H{{sup|+}}/K{{sup|+}}ATPase inhibitor. This is the enzyme needed for the final step in the secretion of gastric acid.<ref name=":0">{{cite journal | vauthors = Howden CW | title = Clinical pharmacology of omeprazole | journal = Clinical Pharmacokinetics | volume = 20 | issue = 1 | pages = 38–49 | date = January 1991 | pmid = 2029801 | doi = 10.2165/00003088-199120010-00003 | s2cid = 25855436 }}</ref>

===Mechanism of action===

Omeprazole is a selective and irreversible proton pump inhibitor. It suppresses stomach acid secretion by specific inhibition of the H⁺/K⁺-ATPase system found at the secretory surface of gastric [[parietal cells]]. Because this enzyme system is regarded as the acid (proton, or H⁺) pump within the [[gastric mucosa]], omeprazole inhibits the final step of acid production.<ref name=":0" />

Omeprazole also inhibits both basal and stimulated acid secretion irrespective of the stimulus<ref name=":1" /> as it blocks the last step in acid secretion.<ref name=":1" /> The drug binds [[Non-competitive inhibition|non-competitively]] so it has a dose-dependent effect.<ref name="Omeprazole">{{cite journal | vauthors = Clissold SP, Campoli-Richards DM | title = Omeprazole. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome | journal = Drugs | volume = 32 | issue = 1 | pages = 15–47 | date = July 1986 | pmid = 3527658 | doi = 10.2165/00003495-198632010-00002 }}</ref>

The inhibitory effect of omeprazole occurs within 1 hour after oral administration. The maximum effect occurs within 2 hours. The duration of inhibition is up to 72 hours. When omeprazole is stopped, baseline stomach acid secretory activity returns after 3 to 5 days. The inhibitory effect of omeprazole on acid secretion will plateau after 4 days of repeated daily dosing.<ref>{{cite web | url = http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bced816b-6927-49fb-851f-f83a678dac97#nlm34090-1 | title = Omeprazole package insert | archive-url = https://web.archive.org/web/20140419020303/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=bced816b-6927-49fb-851f-f83a678dac97 | archive-date=19 April 2014 | location = India | publisher = Dr. Reddy's Laboratories Limited | date = June 2013 }}</ref>

===Pharmacokinetics===

The absorption of omeprazole takes place in the small intestine and is usually completed within 3 to 6 hours. The systemic [[bioavailability]] of omeprazole after repeated doses is about 60%.<ref>{{cite journal | vauthors = Cederberg C, Andersson T, Skånberg I | title = Omeprazole: pharmacokinetics and metabolism in man | journal = Scandinavian Journal of Gastroenterology. Supplement | volume = 166 | issue = sup166 | pages = 33–40 | date = 1 January 1989 | pmid = 2690330 | doi = 10.3109/00365528909091241 }}</ref> Omeprazole has a volume of distribution of 0.4 L/kg. It has high plasma protein binding of 95%.<ref name="Omeprazole"/>

Omeprazole, as well as other PPIs, are only effective on active H⁺/K⁺-ATPase pumps. These pumps are stimulated in the presence of food to aid in digestion. For this reason, patients should be advised to take omeprazole with a glass of water, before a meal.<ref>{{cite journal | vauthors = Katz PO, Gerson LB, Vela MF | title = Guidelines for the diagnosis and management of gastroesophageal reflux disease | journal = The American Journal of Gastroenterology | volume = 108 | issue = 3 | pages = 308–28; quiz 329 | date = March 2013 | pmid = 23419381 | doi = 10.1038/ajg.2012.444 | s2cid = 8198975 | doi-access = free }}</ref> Additionally, most sources recommend that after taking omeprazole, at least 30 minutes should be allowed to elapse before eating<ref>{{cite web|url=http://medical-dictionary.thefreedictionary.com/omeprazole|title=Omeprazole, in The Free Medical Dictionary|access-date=11 November 2010|archive-date=12 June 2011|archive-url=https://web.archive.org/web/20110612172513/http://medical-dictionary.thefreedictionary.com/omeprazole|url-status=live}}</ref><ref>{{cite web|url=https://www.drugs.com/monograph/omeprazole.html|title=Omeprazole|publisher=Drugs.com|access-date=11 November 2010|url-status=live|archive-url=https://web.archive.org/web/20110219135631/http://www.drugs.com/monograph/omeprazole.html|archive-date=19 February 2011}}</ref> (at least 60 minutes for immediate-release omeprazole plus sodium bicarbonate products, such as Zegerid).<ref name="Zegerid OTC FDA label" />

Omeprazole is completely metabolized by the [[cytochrome P450]] system, mainly in the liver, by [[CYP2C19]] and [[CYP3A4]] [[Isozyme|isoenzymes]].<ref name=Dav2015 /> Identified metabolites are the [[sulfone]], the [[sulfide]], and hydroxy-omeprazole, which exert no significant effect on acid secretion. About 77% of an orally given dose is excreted as metabolites in the urine, and the remainder is found in the feces, primarily originating from bile secretion.<ref name=":1" /> Omeprazole has a half life of 0.5 to 1 hour.<ref name=":1">{{cite web |title=Omeprazole |url=https://www.drugbank.ca/drugs/DB00338 |website=www.drugbank.ca |access-date=29 January 2019 |archive-date=30 January 2019 |archive-url=https://web.archive.org/web/20190130053122/https://www.drugbank.ca/drugs/DB00338 |url-status=live }}</ref>

==Chemistry==

Omeprazole contains a tricoordinated sulfinyl sulfur in a pyramidal structure and therefore can exist as either the (''S'')- or (''R'')-[[enantiomer]]s. Omeprazole is a [[racemate]], an equal mixture of the two. In the acidic conditions of the [[canaliculus (parietal cell)|canaliculi]] of [[parietal cells]], both enantiomers are converted to [[achiral]] products ([[sulfenic acid]] and [[sulfenamide]] configurations) which react with a [[cysteine]] group in [[Hydrogen potassium ATPase|H⁺/K⁺ ATPase]], thereby inhibiting the ability of the parietal cells to produce [[gastric acid]].{{citation needed|date=March 2016}}

:[[File:Omeprazole Mechanism V1.svg|500px|Omeprazol rearrangement in the body]]

[[AstraZeneca]] also [[drug development|developed]] [[esomeprazole]] (Nexium) which is a [[eutomer]], purely the (''S'')-enantiomer, rather than a racemate like omeprazole.{{medcn|date=December 2022}}

Omeprazole undergoes a [[Chirality (chemistry)|chiral shift]] ''[[in vivo]]'' which converts the inactive (''R'')-enantiomer to the active (''S'')-enantiomer, doubling the concentration of the active form.<ref name="www1.astrazeneca-us.com">{{cite web | url = http://www1.astrazeneca-us.com/pi/Nexium.pdf | title = Nexium Prescribing Information | archive-url = https://web.archive.org/web/20091008000830/http://www1.astrazeneca-us.com/pi/Nexium.pdf | archive-date=8 October 2009 | publisher = AstraZeneca Pharmaceuticals }}</ref> This chiral shift is accomplished by the [[CYP2C19]] [[isozyme]] of [[cytochrome P450]], which is not found equally in all human populations. Those who do not metabolize the drug effectively are called "poor metabolizers". The proportion of the poor metabolizer [[phenotype]] varies widely between populations, from 2.0 to 2.5% in African Americans and white Americans to >20% in Asians. Several [[pharmacogenomics]] studies have suggested that PPI treatment should be [[personalized medicine|tailored]] according to CYP2C19 metabolism status.<ref>{{cite journal | vauthors = Furuta T, Shirai N, Sugimoto M, Nakamura A, Hishida A, Ishizaki T | title = Influence of CYP2C19 pharmacogenetic polymorphism on proton pump inhibitor-based therapies | journal = Drug Metabolism and Pharmacokinetics | volume = 20 | issue = 3 | pages = 153–167 | date = June 2005 | pmid = 15988117 | doi = 10.2133/dmpk.20.153 | s2cid = 19090952 }}</ref>

===Measurement in body fluids===

Omeprazole may be quantified in plasma or serum to monitor therapy or to confirm a diagnosis of poisoning in hospitalized patients. Plasma omeprazole concentrations are usually in a range of 0.2–1.2&nbsp;mg/L in persons receiving the drug therapeutically by the oral route and 1–6&nbsp;mg/L in people with acute overdose. Enantiomeric [[chromatography|chromatographic]] methods are available to distinguish esomeprazole from racemic omeprazole.<ref>Baselt RC, ''Disposition of Toxic Drugs and Chemicals in Man'', 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1146–7. {{ISBN|978-0-9626523-7-0}}.</ref>

==History==

{{main|Discovery and development of proton pump inhibitors }}

Omeprazole was first made in 1979 by Swedish AB Hässle, part of [[Astra AB]]. It was the first of the proton pump inhibitors (PPI).<ref>{{cite web|url=https://apps.who.int/medicinedocs/en/d/Js4915e/2.5.html|archive-url=https://web.archive.org/web/20101002080328/http://apps.who.int/medicinedocs/en/d/Js4915e/2.5.html|url-status=dead|archive-date=2 October 2010|title=Trends in Drug Patenting - Case Studies: THE CASES: 5. OMEPRAZOLE|website=apps.who.int|access-date=22 August 2019}}</ref><ref name="Fellenius 1981">{{cite journal | vauthors = Fellenius E, Berglindh T, Sachs G, Olbe L, Elander B, Sjöstrand SE, Wallmark B | title = Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+ + K+)ATPase | journal = Nature | volume = 290 | issue = 5802 | pages = 159–161 | date = March 1981 | pmid = 6259537 | doi = 10.1038/290159a0 | s2cid = 4368190 | bibcode = 1981Natur.290..159F }}</ref> [[Astra AB]], now AstraZeneca, launched it as an ulcer medicine under the name Losec in Sweden. It was first sold in the United States in 1989 under the brand name Losec. In 1990, at the request of the [[Food and Drug Administration|U.S. Food and Drug Administration]], the brand name Losec was changed to Prilosec to avoid confusion with the [[diuretic]] Lasix ([[furosemide]]).<ref name=farley>{{cite journal | vauthors = Farley D | title = Making it easier to read prescriptions | journal = FDA Consumer | volume = 29 | issue = 6 | pages = 25–27 | date = July–August 1995 | pmid = 10143448 | url = http://www.thebody.com/content/art13913.html | url-status = dead | access-date = 26 January 2011 | archive-url = https://web.archive.org/web/20120315172345/http://www.thebody.com/content/art13913.html | archive-date = 15 March 2012 }}</ref> The new name led to confusion between omeprazole (Prilosec) and [[fluoxetine]] (Prozac), an [[antidepressant]].<ref name=farley />

==Society and culture==

=== Economics ===

When Prilosec's U.S. patent expired in April 2001, AstraZeneca introduced esomeprazole (Nexium) as a patented replacement drug.<ref>{{cite news |title=Prilosec's Maker Switches Users To Nexium, Thwarting Generics | vauthors = Harris G |work=The Wall Street Journal |url=https://www.wsj.com/articles/SB1023326369679910840 |date=6 June 2002 |url-status=live |archive-url=https://web.archive.org/web/20170806181248/https://www.wsj.com/articles/SB1023326369679910840 |archive-date=6 August 2017}}</ref> Many companies introduced generics as AstraZeneca's patents expired worldwide, which are available under many brand names.

Omeprazole was a subject of a patent litigation in the U.S.<ref>{{cite press release | title=AstraZeneca awarded damages in Prilosec patent litigation | website=AstraZeneca | date=3 December 2013 | url=https://www.astrazeneca.com/media-centre/press-releases/2013/astrazeneca-prilosec-patent-litigation-ruling-03122013.html | access-date=4 October 2023}}</ref> The invention involved

application of two different coatings to a drug in pill form to ensure, that the omeprazole did not disintegrate before reaching its intended site of action in stomach. Although the solution by means of two coating was obvious, the patent was found valid, because the source of the problem was non-obvious and was discovered by the patentee.<ref>{{cite web | url=https://scholar.google.com/scholar_case?case=12553883911671736992&q=+In+re+Omeprazole+Patent+Litigation&hl=en&as_sdt=40000003 | title=IN RE OMEPRAZOLE PATENT LITIGATION, Court of Appeals, Federal Circuit 2011 - Google Scholar }}</ref>

In September 2023, AstraZeneca announced it would pay $425 million to settle product liability litigations against Prilosec in the United States.<ref>{{cite news |date=3 October 2023 |title=AstraZeneca to pay $425 mln to settle Nexium, Prilosec litigation in US |work=Reuters |url=https://www.reuters.com/legal/astrazeneca-pay-425-mln-settle-nexium-prilosec-litigation-us-2023-10-03/ |access-date=3 October 2023}}</ref>

=== Brand names ===

Brand names include Losec, Prilosec, Zegerid, Miracid, and Omez.<ref name="Drugs.com international">{{cite web | title=Omeprazole international | website=Drugs.com | date=3 February 2020 | url=https://www.drugs.com/international/omeprazole.html | access-date=27 February 2020 | archive-date=28 February 2020 | archive-url=https://web.archive.org/web/20200228060551/https://www.drugs.com/international/omeprazole.html | url-status=live }}</ref><ref name=AHFS2015/>

== References ==

{{Reflist}}

== Further reading ==

* {{cite book | title=Medical Genetics Summaries | chapter=Omeprazole Therapy and CYP2C19 Genotype | chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK100895/ | veditors=Pratt VM, McLeod HL, Rubinstein WS, Scott SA, Dean LC, Kattman BL, Malheiro AJ | display-editors=3 | publisher=[[National Center for Biotechnology Information]] (NCBI) | year=2012 | pmid=28520353 | id=Bookshelf ID: NBK100895 | vauthors=Dean L | url=https://www.ncbi.nlm.nih.gov/books/NBK61999/ }}

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