Esomeprazole

Esomeprazole, sold under the brand name Nexium (or Neksium) among others, Its effectiveness is similar to that of other proton pump inhibitors (PPIs). It is taken by mouth or injection into a vein. Esomeprazole is the (S)-(−)-enantiomer (or less specifically the S-isomer) of omeprazole.

It was patented in 1993 and approved for medical use in 2000. It is available as a generic medication and sold over the counter in several countries. In Australia, it was one of the top ten most-prescribed medications between 2017 and 2023. It is also available in lower dose formulations without a prescription in the United States, 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 therapy, and treatment of gastrointestinal ulcers associated with Crohn's disease.

Gastroesophageal reflux disease

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

Duodenal ulcers

Esomeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole instead of amoxicillin in penicillin-hypersensitive patients) in a 10-day eradication triple therapy for Helicobacter pylori. 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, 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.

Proton pump inhibitors may be associated with a greater risk of hip fractures and Clostridioides difficile-associated diarrhoea. 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 pneumonia.

Long-term use of proton pump inhibitors in patients treated for Helicobacter pylori has been shown to dramatically increase the risk of gastric cancer.

Acute tubulointerstitial nephritis is a possible adverse reaction when using proton pump inhibitors. Conversely, clopidogrel (Plavix) is an inactive prodrug 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 or atazanavir) will be poorly absorbed, whereas drugs that are broken down in acidic environments (such as erythromycin) will be absorbed to a greater extent than normal.

Dosage forms

thumb|Esomeprazole strontium delayed-release capsules, 49.3 mg

thumb|40 mg Nexium (esomeprazole magnesium) capsules

Esomeprazole is available as delayed-release capsules in the United States or as delayed-release tablets in Australia, the United Kingdom, and Canada (containing esomeprazole magnesium) in strengths of 20 and 40mg, as delayed-release capsules in the United States (containing esomeprazole strontium) in a 49.3mg strength (delivering the equivalent of 40mg of esomeprazole, and as esomeprazole sodium for intravenous injection/infusion. Oral esomeprazole preparations are enteric-coated, due to the rapid degradation of the drug in the acidic conditions of the stomach. 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 NSAID 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 and risk of kidney 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. 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 feeding and those with difficulty swallowing (dysphagia).

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