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| Clinical data | |
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| Pronunciation | /ˌɛsoʊˈmɛprəˌzoʊl,-ˈmiː-,-ˌzɒl/[1] |
| Trade names | Nexium, others[2] |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a699054 |
| License data | |
| Pregnancy category | |
| Routes of administration | By mouth,intravenous |
| Drug class | Proton pump inhibitor |
| ATC code | |
| Legal status | |
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| Pharmacokinetic data | |
| Bioavailability | 50 to 90% |
| Metabolism | Liver (CYP2C19,CYP3A4) |
| Eliminationhalf-life | 1–1.5 hours |
| Excretion | 80%Kidney 20%Feces |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.149.048 |
| Chemical and physical data | |
| Formula | C17H19N3O3S |
| Molar mass | 345.42 g·mol−1 |
| 3D model (JSmol) | |
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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,Clostridioides difficile infection, andpneumonia.[11] Use inpregnancy appears to be safe, while safety duringbreastfeeding is unclear.[3] Esomeprazole is the (S)-(−)-enantiomer (or less specifically the S-isomer) ofomeprazole.[11] It works by blockingH+/K+-ATPase in theparietal cells of the stomach.[11]
It was patented in 1993 and approved for medical use in 2000.[14] It is available as ageneric medication and soldover the counter in several countries.[15][12] In 2022, it was the 122nd most commonly prescribed medication in the United States, with more than 5 million prescriptions.[16][17] In Australia, it was one of the top 10 most prescribed medications between 2017 and 2023.[18] It is also available in lower dose formulations without a prescription in the United States,[19] the United Kingdom[20] as well as Australia, Canada, and New Zealand.[21]
The primary uses of esomeprazole are gastroesophageal reflux disease, treatment and maintenance oferosive esophagitis, treatment ofduodenal ulcers caused byH. pylori, prevention ofgastric ulcers in those on chronicNSAID therapy, and treatment of gastrointestinal ulcers associated withCrohn's disease.[22][23]
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.[24] Long-term contact between gastric acids and the esophagus can cause permanent damage to the esophagus and is associated withBarrett's esophagus.[25] Esomeprazole reduces the production of digestive acids, thus reducing their effect on the esophagus.
Esomeprazole is combined with the antibioticsclarithromycin andamoxicillin (ormetronidazole instead of amoxicillin in penicillin-hypersensitive patients) in a 10-day eradication triple therapy forHelicobacter pylori. Infection byH. pylori is a causative factor in the majority ofpeptic and duodenal ulcers.
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]).[26] A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations.[27] A 2017 study found esomeprazole to be among a number of effective PPIs.[28]
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.[29]
Proton pump inhibitors may be associated with a greater risk of hip fractures[30] andClostridioides difficile-associateddiarrhoea.[31] 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.[32]
Long-term use of proton pump inhibitors in patients treated forHelicobacter pylori has been shown to dramatically increase the risk of gastric cancer.[33]
Acutetubulointerstitial nephritis is a possible adverse reaction when using proton pump inhibitors.[9]
Esomeprazole is acompetitive inhibitor of the enzymeCYP2C19, and may thereforeinteract with drugs that depend on it formetabolism, such asdiazepam andwarfarin; the concentrations of these drugs may increase if they are used concomitantly with esomeprazole.[34] Conversely,clopidogrel (Plavix) is an inactiveprodrug that partially depends on CYP2C19 for conversion to its active form; inhibition of CYP2C19 blocks the activation of clopidogrel, thus reducing its effects.[35][36]
Drugs that depend on stomach pH for absorption may interact with esomeprazole; drugs that depend on an acidic environment (such asketoconazole oratazanavir) will be poorly absorbed, whereas drugs that are broken down in acidic environments (such aserythromycin) will be absorbed to a greater extent than normal.[34]
Single 20 to 40 mg oral doses generally give rise to peak plasma esomeprazole concentrations of 0.5-1.0 mg/L within 1–4 hours, but after several days of once-daily administration, these levels may increase by about 50%. A 30-minute intravenous infusion of a similar dose usually produces peak plasma levels on the order of 1–3 mg/L. The drug is rapidly cleared from the body, largely by urinary excretion of pharmacologically inactive metabolites such as 5-hydroxymethylesomeprazole and 5-carboxyesomeprazole. Esomeprazole and its metabolites are analytically indistinguishable from omeprazole and the corresponding omeprazole metabolites unless chiral techniques are employed.[37]
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Esomeprazole is available as delayed-release capsules in the United States or as delayed-release tablets in Australia, the United Kingdom, and Canada (containing esomeprazole magnesium) in strengths of 20 and 40 mg, as delayed-release capsules in the United States (containing esomeprazole strontium) in a 49.3 mg strength (delivering the equivalent of 40 mg of esomeprazole,[38] and as esomeprazole sodium forintravenous injection/infusion. Oral esomeprazole preparations areenteric-coated, due to the rapid degradation of the drug in theacidic conditions 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 chronicNSAID therapy. Vimovo is available in two dosage strengths: 500/20 mg and 375/20 mg. Clinical trials of naproxen/esomeprazole demonstrated an incidence of GI ulcer in 24% of patients on naproxen (alone) versus 7% on naproxen/esomeprazole.[39] The FDA has added warnings to the label for Vimovo concerningacute interstitial nephritis and risk ofkidney problems in some patients.[40]
Esomeprazole capsules, as well as Losec/Prilosec tablets, are formulated as a "multiple-unit pellet system" (MUPS). Essentially, thecapsule 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 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 tube feeding and those with difficulty swallowing (dysphagia).[41][42][43][44]
In 2010, AstraZeneca announced a co-promotion agreement withDaiichi Sankyo to distribute Nexium in Japan.[45] In September 2011, Nexium was approved for sale and was launched by Daiichi Sankyo in Japan.[46] Esomeprazole was approved for use in the United States in February 2001.[47][48]
Between the launch of esomeprazole in 2001 and 2005, the drug netted AstraZeneca about $14.4 billion.[49]
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.[50]
Generic versions of esomeprazole magnesium are available worldwide.[2] It is availableover-the-counter under the brand name Nexium in the United States[19][51] and the UK.[52]
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.[53] In that study the sulfone metabolite was detectable for several hours after injection of the parent drug.
Esomeprazole can be used as aparasiticide.[54] Gokmenet al., 2016 screen for efficacy againstTrichomonas vaginalis isolates fromhorses.[54] They found esomeprazole to be effective as a veterinary antiparasitic.[54]
Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
$4.6 billion;
$3.9 billion;
$3.3 billion;
$2 billion;
launch and $580 million[dead link]
