Esomeprazole, sold under the brand name Nexium r Neksiumamong others, is a medication which reduces

stomach acid Gastric acid or stomach acid is the acidic component – hydrochloric acid – of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other an ...

. It is used to treat

gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or ...

peptic ulcer disease Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

, and

Zollinger–Ellison syndrome Zollinger–Ellison syndrome (Z-E syndrome) is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea. The syndrome is caused by the formation of a gastrinoma ...

. Its effectiveness is similar to that of other

proton pump inhibitors Proton-pump inhibitors (PPIs) are a class of medications that cause a profound and prolonged reduction of gastric acid, stomach acid production. They do so by irreversibly inhibiting the stomach's H+/K+ ATPase, H+/K+ ATPase proton pump. The body ...

(PPIs). It is taken by mouth or injection into a vein. Common side effects include headache, constipation, dry mouth, and abdominal pain. Serious side effects may include

angioedema Angioedema is an area of swelling (edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which are ...

Clostridioides difficile infection ''Clostridioides difficile'' infection (CDI or C-diff), also known as ''Clostridium difficile'' infection, is a symptomatic infection due to the bacterial spores, spore-forming bacterium ''Clostridioides difficile''. Symptoms include watery di ...

, and

pneumonia Pneumonia is an Inflammation, inflammatory condition of the lung primarily affecting the small air sacs known as Pulmonary alveolus, alveoli. Symptoms typically include some combination of Cough#Classification, productive or dry cough, ches ...

. Use in

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

appears to be safe, while safety during

breastfeeding Breastfeeding, also known as nursing, is the process where breast milk is fed to a child. Infants may suck the milk directly from the breast, or milk may be extracted with a Breast pump, pump and then fed to the infant. The World Health Orga ...

is unclear. Esomeprazole is the (''S'')-(−)-

enantiomer In chemistry, an enantiomer (Help:IPA/English, /ɪˈnænti.əmər, ɛ-, -oʊ-/ Help:Pronunciation respelling key, ''ih-NAN-tee-ə-mər''), also known as an optical isomer, antipode, or optical antipode, is one of a pair of molecular entities whi ...

(or less specifically the S-

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

) of

omeprazole 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. It is also used to prevent up ...

. It works by blocking H⁺/K⁺-ATPase in the

parietal cell Parietal cells (also known as oxyntic cells) are epithelial cells in the stomach that secrete hydrochloric acid (HCl) and intrinsic factor. These cells are located in the gastric glands found in the lining of the fundus and body regions o ...

s of the stomach. It was patented in 1993 and approved for medical use in 2000. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

and sold

over the counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

in several countries. In 2022, it was the 122nd most commonly prescribed medication in the United States, with more than 5million prescriptions. In Australia, it was one of the top 10 most prescribed medications between 2017 and 2023. It is also available in lower dose formulations without a prescription in the United States, the United Kingdom as well as Australia, Canada, and New Zealand.

Medical use

The primary uses of esomeprazole are gastroesophageal reflux disease, treatment and maintenance of erosive esophagitis, treatment of duodenal ulcers caused by ''H. pylori'', prevention of gastric ulcers in those on chronic

NSAID Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of ...

therapy, and treatment of gastrointestinal ulcers associated with

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

Gastroesophageal reflux disease

Gastroesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is a chronic upper gastrointestinal disease in which stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/or ...

(GERD) is a condition in which the digestive acid in the stomach comes in contact with the

esophagus The esophagus (American English), oesophagus (British English), or œsophagus (Œ, archaic spelling) (American and British English spelling differences#ae and oe, see spelling difference) all ; : ((o)e)(œ)sophagi or ((o)e)(œ)sophaguses), c ...

. The irritation caused by this disorder is known as

heartburn Heartburn is a burning sensation felt behind the breastbone. It is a symptom that is commonly linked to acid reflux and is often triggered by food, particularly fatty, sugary, spicy, chocolate, citrus, onion-based and tomato-based products. Ly ...

. Long-term contact between gastric acids and the esophagus can cause permanent damage to the esophagus and is associated with

Barrett's esophagus Barrett's esophagus is a condition in which there is an abnormal ( metaplastic) change in the mucosal cells that line the lower part of the esophagus. The cells change from stratified squamous epithelium to simple columnar epithelium, intersper ...

. Esomeprazole reduces the production of digestive acids, thus reducing their effect on the esophagus.

Duodenal ulcers

Esomeprazole is combined with the antibiotics

clarithromycin Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, '' H. pylori'' infection, and Lyme disease, among others. Clari ...

and amoxicillin (or

metronidazole Metronidazole, sold under the brand name Flagyl and Metrogyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vagino ...

instead of amoxicillin in penicillin-hypersensitive patients) in a 10-day eradication triple therapy for ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, Flagellum#bacterial, flagellated, Bacterial cellular morphologies#Helical, helical bacterium. Mutants can have a rod or curved rod shape that exhibits l ...

''. Infection by ''H. pylori'' is a causative factor in the majority of peptic and duodenal ulcers.

Efficacy

A 2006 meta analysis concluded that compared to other proton pump inhibitors, esomeprazole confers a modest overall benefit in esophageal healing and symptom relief. When broken down by disease severity, the benefit of esomeprazole relative to other proton pump inhibitors was negligible in people with mild disease (number needed to treat 50), but appeared more in those with severe disease (number needed to treat 8). A second meta analysis also found increases in erosive esophageal healing (>95% healing rate) when compared to standardized doses in broadly selected patient populations. A 2017 study found esomeprazole to be among a number of effective PPIs.

Adverse effects

Common side effects include headache,

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

flatulence Flatulence is the expulsion of gas from the Gastrointestinal tract, intestines via the anus, commonly referred to as farting. "Flatus" is the medical word for gas generated in the stomach or bowels. A proportion of intestinal gas may be swal ...

, decreased appetite,

constipation Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The Human feces, stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the ...

, dry mouth, and abdominal pain. More severe side effects are severe allergic reactions, chest pain, dark urine, fast heartbeat, fever,

paresthesia Paresthesia is a sensation of the skin that may feel like numbness (''hypoesthesia''), tingling, pricking, chilling, or burning. It can be temporary or Chronic condition, chronic and has many possible underlying causes. Paresthesia is usually p ...

, persistent sore throat, severe stomach pain, unusual bruising or bleeding, unusual tiredness, and yellowing of the eyes or skin. Proton pump inhibitors may be associated with a greater risk of hip fractures and ''

Clostridioides difficile ''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as ''C. difficile'', or ''C. diff'' (), and is a Gram-positive spec ...

''-associated

diarrhoea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

. Patients are frequently administered the drugs in intensive care as a protective measure against ulcers, but this use is also associated with a 30% increase in occurrence of

. Long-term use of proton pump inhibitors in patients treated for ''

'' has been shown to dramatically increase the risk of gastric cancer. Acute tubulointerstitial nephritis is a possible adverse reaction when using proton pump inhibitors.

Interactions

Esomeprazole is a

competitive inhibitor Competitive inhibition is interruption of a chemical pathway owing to one chemical substance inhibiting the effect of another by competing with it for binding or bonding. Any metabolic or chemical messenger system can potentially be affected b ...

of the enzyme

CYP2C19 Cytochrome P450 2C19 (abbreviated CYP2C19) is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some ...

, and may therefore interact with drugs that depend on it for

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

, such as

diazepam Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety disorder, anxiety, seizures, alcohol withdrawal syndr ...

and

warfarin Warfarin, sold under the brand name Coumadin among others. It is used as an anticoagulant, anticoagulant medication. It is commonly used to prevent deep vein thrombosis and pulmonary embolism, and to protect against stroke in people who ha ...

; the concentrations of these drugs may increase if they are used concomitantly with esomeprazole. Conversely,

clopidogrel Clopidogrel, sold under the brand name Plavix among others, is an antiplatelet drug, antiplatelet medication used to reduce the risk of Cardiovascular disease, heart disease and stroke in those at high risk. It is also used together with aspi ...

(Plavix) is an inactive

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

that partially depends on CYP2C19 for conversion to its active form; inhibition of CYP2C19 blocks the activation of clopidogrel, thus reducing its effects. Drugs that depend on stomach pH for absorption may interact with esomeprazole; drugs that depend on an acidic environment (such as

ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

or atazanavir) will be poorly absorbed, whereas drugs that are broken down in acidic environments (such as

erythromycin Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used ...

) will be absorbed to a greater extent than normal.

Pharmacokinetics

Single 20 to 40mg oral doses generally give rise to peak plasma esomeprazole concentrations of 0.5-1.0mg/L within 1–4 hours, but after several days of once-daily administration, these levels may increase by about 50%. A 30-minute intravenous infusion of a similar dose usually produces peak plasma levels on the order of 1–3mg/L. The drug is rapidly cleared from the body, largely by urinary excretion of pharmacologically inactive metabolites such as 5-hydroxymethylesomeprazole and 5-carboxyesomeprazole. Esomeprazole and its metabolites are analytically indistinguishable from omeprazole and the corresponding omeprazole metabolites unless chiral techniques are employed.

Dosage forms

Esomeprazole is available as delayed-release capsules in the United States or as delayed-release tablets in Australia, the United Kingdom, and Canada (containing esomeprazole magnesium) in strengths of 20 and 40mg, as delayed-release capsules in the United States (containing esomeprazole strontium) in a 49.3mg strength (delivering the equivalent of 40mg of esomeprazole, and as esomeprazole sodium for

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

injection/infusion. Oral esomeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the

acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...

ic conditions of the

stomach The stomach is a muscular, hollow organ in the upper gastrointestinal tract of Human, humans and many other animals, including several invertebrates. The Ancient Greek name for the stomach is ''gaster'' which is used as ''gastric'' in medical t ...

. This is achieved by formulating capsules using the multiple-unit pellet system. The combination naproxen/esomeprazole magnesium (brand name Vimovo) is used for the prevention of gastric ulcers associated with chronic

therapy. Vimovo is available in two dosage strengths: 500/20mg and 375/20mg. Clinical trials of naproxen/esomeprazole demonstrated an incidence of GI ulcer in 24% of patients on naproxen (alone) versus 7% on naproxen/esomeprazole. The FDA has added warnings to the label for Vimovo concerning

acute interstitial nephritis Interstitial nephritis, also known as tubulointerstitial nephritis, is inflammation of the area of the kidney known as the renal interstitium, which consists of a collection of cells, extracellular matrix, and fluid surrounding the renal tubules ...

and risk of

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

problems in some patients.

Multiple-unit pellet system

Esomeprazole capsules, as well as Losec/Prilosec tablets, are formulated as a "multiple-unit pellet system" (MUPS). Essentially, the capsule consists of extremely small enteric-coated granules (pellets) of the esomeprazole formulation inside an outer shell. When the capsule is immersed in an aqueous solution, as happens when the capsule reaches the stomach, water enters the capsule by

osmosis Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively permeable membrane, selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of ...

. The contents swell from water absorption, causing the shell to burst, and releasing the enteric-coated granules. For most patients, the multiple-unit pellet system is of no advantage over conventional enteric-coated preparations. Patients for whom the formulation is of benefit include those requiring

nasogastric tube Nasogastric intubation is a medical process involving the insertion of a plastic tube (nasogastric tube or NG tube) through the nose, down the esophagus, and down into the stomach. Orogastric intubation is a similar process involving the insertion ...

feeding and those with difficulty swallowing (

dysphagia Dysphagia is difficulty in swallowing. Although classified under " symptoms and signs" in ICD-10, in some contexts it is classified as a condition in its own right. It may be a sensation that suggests difficulty in the passage of solids or l ...

Society and culture

Global distribution

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

Economics

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

Controversy

There has been some controversy about

AstraZeneca AstraZeneca plc () (AZ) is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, UK. It has a portfolio of products for major diseases in areas includi ...

's behaviour in creating, patenting, and marketing the drug. Esomeprazole's successful predecessor,

, is a mixture of two mirror-imaged molecules (esomeprazole which is the S-enantiomer, and R-omeprazole); critics said the company was trying to "

evergreen In botany, an evergreen is a plant which has Leaf, foliage that remains green and functional throughout the year. This contrasts with deciduous plants, which lose their foliage completely during the winter or dry season. Consisting of many diffe ...

" its omeprazole patent by patenting the pure esomeprazole and aggressively marketing to doctors that it is more effective than the mixture.

Brand names

Generic versions of esomeprazole magnesium are available worldwide. It is available

over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...

under the brand name Nexium in the United States and the UK.

Veterinary use

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

Other uses

Esomeprazole can be used as a parasiticide. Gokmen ''et al.'', 2016 screen for efficacy against ''

Trichomonas vaginalis ''Trichomonas vaginalis'' is an Anaerobic organism, anaerobic, flagellated protozoan parasite and the causative agent of a Sexually transmitted infection, sexually transmitted disease called trichomoniasis. It is the most common pathogenic protoz ...

'' isolates from

horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 mi ...

s. They found esomeprazole to be effective as a veterinary antiparasitic.