Omeprazole

Template:Short description Template:For Template:Use dmy dates Template:Cs1 config Template:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

|preview=

}}{{Infobox drug/maintenance categoriesTemplate:Yesno | drug_name = | INN = | _drugtype =

| _has_physiological_data= | _has_gene_therapy=

| vaccine_type= | mab_type= | _number_of_combo_chemicals={{#invoke:ParameterCount |main |component1 |component2 |component3 |component4|component5|component6 }} | _vaccine_data= | _mab_data= | _mab_vaccine_data= | _mab_other_data=171933CC1=CN=C(C(=C1OC)C)CS(=O)C2=NC3=C(N2)C=C(C=C3)OCRacemic mixture1S/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)SUBDBMMJDZJVOS-UHFFFAOYSA-NTemplate:StdinchiciteTemplate:Stdinchicite1.4±0.1<ref name="chemsrc">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>156 | _combo_data= | _physiological_data= | _clinical_data=Template:Drugs.coma693050Omeprazole <ref name="Drugs.com pregnancy">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>B3By mouth, intravenousLosec, Prilosec, others<ref name=AHFS2015/><ref name="Drugs.com international" />Proton-pump inhibitorA02Template:ATC | _legal_data=S4<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>Rx-only<ref name="Omeprazole TriviumVet PI" />Rx-onlyPOM/ Rx-onlyOTC

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

| _image_0_or_2 = Omeprazole enantiomers labelled.svgOmeprazole enantiomers ball-and-stick models from xtal 2015.png | _image_LR =

| _datapage = Omeprazole (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=S4Rx-onlyPOMOTCRx-only | _ATC_prefix_supplemental=A02Template:ATC | _has_EMA_link = | CAS_number=73590-58-6 | PubChem=4594 | ChemSpiderID=4433 | ChEBI=7772 | ChEMBL=1503 | DrugBank=DB00338 | KEGG=D00455 | _hasInChI_or_Key={{#if: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)SUBDBMMJDZJVOS-UHFFFAOYSA-N |yes}} | UNII=KG60484QX9 | _hasJmol02 = |_hasMultipleCASnumbers = |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields= |Watchedfields=changed |verifiedrevid=462265}}

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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It can be taken by mouth or by injection into a vein.<ref name=AHFS2015/><ref name=UK2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is also available in the fixed-dose combination medication omeprazole/sodium bicarbonate as Zegerid<ref name="Zegerid FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Zegerid OTC FDA label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and as Konvomep.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Common side effects include nausea, vomiting, headaches, abdominal pain, and increased intestinal gas.<ref name=AHFS2015/><ref name=Dav2015 /> Serious side effects may include Clostridioides 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/>

Omeprazole was patented in 1978 and approved for medical use in 1988.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">Template:Cite book</ref> It is available as a generic medication.<ref name=AHFS2015/> In 2022, it was the ninth most commonly prescribed medication in the United States, with more than 52Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is also available without a prescription in the United States.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

Template:See also Omeprazole can be used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcers, erosive esophagitis, Zollinger–Ellison syndrome, and eosinophilic esophagitis.<ref>Template:Cite journal</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>Template:Cite journal</ref> Amoxicillin may be replaced with metronidazole in patients who are allergic to penicillin.<ref name="Maastricht_2_Consensus_Report">Template:Cite journal</ref>

Adverse effects

Adverse effects occurring in at least 1% of people include:<ref>Template:Cite journal</ref>Template:Failed verification

• 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 Clostridioides difficile associated diarrhea<ref>Template:Cite journal</ref>
• Osteoporosis-related fractures<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
• Hypomagnesemia<ref>Template:Cite journal</ref>

Concern has been expressed regarding vitamin B₁₂<ref>Template:Cite journal</ref> and iron malabsorption,<ref>Template:Cite journal</ref> but effects seem to be insignificant, especially when supplement therapy is provided.<ref>Template:Cite journal</ref>

Since their introduction, proton-pump inhibitors (PPIs, especially omeprazole) have also been associated with several cases of acute interstitial nephritis,<ref>Template:Cite journal</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 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">Template:Cite journal</ref>

There is a possible association between long term use and dementia which requires further study to confirm.<ref>Template:Cite journal</ref>

A review article in U.S. Pharmacist in 2013 states that long-term use of PPIs is associated with decreased calcium absorption (causing increased risk of osteoporosis and fractures), decreased magnesium absorption (causing 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>Template:Cite journal</ref>

Pregnancy and breastfeeding

The safety of using omeprazole has not been established in pregnant or breastfeeding women.<ref name=Dav2015>Template:Cite book</ref> Epidemiological data do not show an increased risk of major birth defects after maternal use of omeprazole during pregnancy.<ref>Template:Cite journal</ref>

Interactions

File:Omeprazol Activis bottle.jpg

Omeprazol Actavis 20 mg, bottle and pills in Sweden

Important drug interactions are rare.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> However, the most significant major drug interaction concern is the decreased activation of clopidogrel when taken together with omeprazole.<ref>Template:Cite journal</ref> Although still controversial,<ref>Template:Cite journal</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 inhibitor of the enzymes CYP2C19 and CYP3A4.<ref>Template:Cite journal</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>Template:Cite journal</ref><ref>Template:Cite journal</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 (i.e., the total effect over time of a given dose). Other examples of drugs dependent on CYP3A4 for their metabolism are escitalopram,<ref>Template:EMedicine</ref> warfarin,<ref name="pmid12724615">Template:Cite journal</ref> oxycodone, tramadol, and oxymorphone. The concentrations of these drugs may increase if they are used concomitantly with omeprazole.<ref name=Stedman>Template:Cite journal</ref>

Omeprazole is also a competitive inhibitor of p-glycoprotein, as are other PPIs.<ref>Template:Cite journal</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 induction of CYP3A4 and CYP2C19.<ref>Template:Cite journal</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⁺/K⁺ATPase inhibitor. This is the enzyme needed for the final step in the secretion of gastric acid.<ref name=":0">Template:Cite journal</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>Template:Cite journal</ref> Omeprazole has a volume of distribution of 0.4 L/kg. It has high plasma protein binding of 95%.<ref name="Omeprazole"/>

Omeprazole is completely metabolized by the cytochrome P450 system, mainly in the liver, by CYP2C19 and CYP3A4 isoenzymes.<ref name=Dav2015 /> Identified metabolites are the sulfone, the sulfide, and hydroxy-omeprazole. 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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Bioactivation

As with all structually-similar benzimidazole proton pump inhibitors, omeprazole is a prodrug. A basic molecule, it accumulates in the acidic canaliculi of parietal cells in a protonated form where the S=O group becomes S-OH, which in turn is interconvertible with an achiral, reactive sulfonamide form. The sulfonamide form is able to attach onto the cysteine residue on the H⁺/K⁺-ATPase, thereby irreversibly inhibiting it.<ref name=Huttunen>Template:Cite journal</ref>

Omeprazol rearrangement in the body

This process is not affected by chirality, by AstraZeneca's own admission.<ref name="www1.astrazeneca-us.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Chirality

The two different chiralities of omeprazole are both metabolized into inactive products by cytochrome P450 enzymes, but each chirality are differently inactivated by specific isozymes. Compared to the (R)-enantiomer, the (S)-enantiomer is relatively more resistant to metabolism, especially metabolism by CYP2C19<ref>Template:Cite journal</ref> (if it's processed by CYP2C19 at all).<ref>Template:Cite journal</ref> As a result, among people with a more active version of CYP2C19 ("extensive metabolizers"), the (R) half of a dose of omeprazole is likely to perform more poorly. Conversely, among those with a less active version of CYP2C19 ("poor metabolizers"), more the (R) half is expected to survive metabolism and end up useful. 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 tailored according to CYP2C19 metabolism status.<ref>Template:Cite journal</ref>

AstraZeneca also developed esomeprazole (Nexium) which is a eutomer, purely the (S)-enantiomer, rather than a racemate like omeprazole.<ref name="www1.astrazeneca-us.com"/>

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-competitively so it has a dose-dependent effect.<ref name="Omeprazole">Template:Cite journal</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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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>Template:Cite journal</ref> Additionally, most sources recommend that after taking omeprazole, at least 30 minutes should be allowed to elapse before eating<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> (at least 60 minutes for immediate-release omeprazole plus sodium bicarbonate products, such as Zegerid).<ref name="Zegerid OTC FDA label" />

Chemistry

Omeprazole contains a tricoordinated sulfinyl sulfur in a pyramidal structure and therefore can exist as either the (S)- or (R)-enantiomers. Omeprazole is a racemate, an equal mixture of the two.<ref name=Huttunen/>

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 mg/L in persons receiving the drug therapeutically by the oral route and 1–6 mg/L in people with acute overdose. Enantiomeric 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. Template:ISBN.</ref>

History

{{#invoke:Labelled list hatnote|labelledList|Main article|Main articles|Main page|Main pages}} 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>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Fellenius 1981">Template:Cite journal</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 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>Template:Cite journal</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>Template:Cite news</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>Template:Cite press release</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 coatings was obvious, the patent was found valid, because the source of the problem was non-obvious and was discovered by the patentee.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

In September 2023, AstraZeneca announced it would pay $425 million to settle product liability litigations against Prilosec in the United States.<ref>Template:Cite news</ref>

Brand names

Brand names include Losec, Prilosec, Zegerid, Miracid, and Omez.<ref name="Drugs.com international">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name=AHFS2015/>

Veterinary uses

In February 2025, the Committee for Veterinary Medicinal Products of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the veterinary medicinal product Omeprazole TriviumVet, gastro-resistant capsule, hard, intended for dogs.<ref name="Omeprazole TriviumVet EPAR" /> The applicant for this veterinary medicinal product is TriviumVet DAC.<ref name="Omeprazole TriviumVet EPAR">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Omeprazole TriviumVet was authorized for veterinary use in the European Union in April 2025.<ref name="Omeprazole TriviumVet PI">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Further reading

• Template:Cite book

External links

1. REDIRECT Template:Drugs for peptic ulcer and GORD