esomeprazole/naproxen 

Action and Spectrum

Actions and Spectrum 

Action: 

esomeprazole, a proton pump inhibitor (PPI), acts by irreversibly inhibiting the H+/K+-ATPase enzyme system located on the gastric parietal cells. This inhibition leads to a reduction in gastric acid secretion, thereby providing effective acid suppression. esomeprazole’s mechanism of action helps alleviate symptoms associated with gastroesophageal reflux disease (GERD) and promotes the healing of erosive esophagitis. 

naproxen, a nonsteroidal anti-inflammatory drug (NSAID), exerts its pharmacological effects through the inhibition of cyclooxygenase (COX) enzymes, specifically COX-1 and COX-2. By inhibiting these enzymes, naproxen suppresses the synthesis of prostaglandins, mediators involved in inflammation, pain, and fever. This anti-inflammatory action of naproxen provides relief from symptoms associated with various conditions, such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and acute musculoskeletal disorders. 

Spectrum: 

The spectrum of esomeprazole/naproxen encompasses a broad range of indications, including the treatment of erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), and the prevention of gastric ulcers associated with chronic NSAID therapy in patients at risk. It effectively mitigates pain and inflammation associated with conditions such as osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, thereby improving the quality of life for individuals affected by these disorders. 

Drug Interaction

Adverse Reaction

Frequency defined  

>10% 

Gastritis (17%) 

Dyspepsia (18%) 

Gastric erosion (19%)   

1-10% 

Headache (3%) 

Hiatal hernia (4%) 

Abdominal distension (4%) 

Diarrhea (6%) 

Flatulence (4%) 

Esophagitis (4%) 

Constipation (3%) 

Erosive duodenitis (2%) 

Hemorrhagic gastritis (1%) 

Abdominal pain (6%) 

Dysgeusia (2%)  

<1% 

Erosive esophagitis 

GERD 

Duodenal ulcer 

Black Box Warning

Black Box Warning:  

None  

Contraindication / Caution

Contraindication/Caution:  

Known Hypersensitivity: Patients with a known hypersensitivity or allergy to esomeprazole, naproxen, or any components of the formulation should not be prescribed esomeprazole/naproxen combination therapy.  

History of Asthma, Rhinitis, or Urticaria: Patients with a history of asthma, rhinitis (including allergic rhinitis), or urticaria should not receive esomeprazole/naproxen combination therapy.  

Active Gastrointestinal Bleeding, Peptic Ulcer Disease, or Perforation: The concurrent use of esomeprazole/naproxen combination therapy is contraindicated in patients with active gastrointestinal bleeding, peptic ulcer disease, or perforation.  

Severe Liver Impairment:  

The combination therapy of esomeprazole/naproxen should be avoided in patients with severe liver impairment due to the potential compromise of hepatic metabolism associated with the medication. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: C 

Lactation:  

esomeprazole: 

Excreted into human milk is unknown 

naproxen: 

Excreted into human milk is known 

Pregnancy Categories:         

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester. 

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.   

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.   

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:  

The drug is a pharmaceutical combination composed of esomeprazole, a proton pump inhibitor (PPI), and naproxen, a nonsteroidal anti-inflammatory drug (NSAID). This drug combination is primarily prescribed for the management of pain and inflammation associated with osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis. 

Pharmacodynamics:  

esomeprazole acts by specifically blocking the final step in the production of gastric acid, preventing the release of hydrogen ions into the stomach lumen. This inhibition occurs through the covalent binding of the active form of esomeprazole to the proton pump, resulting in long-lasting suppression of acid secretion. naproxen, on the other hand, inhibits cyclooxygenase enzymes, thereby reducing the production of prostaglandins involved in the mediation of pain, inflammation, and fever.   

Pharmacokinetics: 

Absorption 

esomeprazole is acid-labile and is formulated as an enteric-coated compound to prevent premature degradation in the acidic environment of the stomach. Upon reaching the small intestine, where the pH is less acidic, the enteric coating dissolves, allowing for esomeprazole absorption. On the other hand, naproxen is absorbed rapidly in the upper gastrointestinal tract. 

Distribution 

esomeprazole and naproxen enter systemic circulation and are distributed to various tissues throughout the body. The distribution of both drugs is not restricted to plasma, as they can penetrate into tissues such as the liver, kidney, and gastrointestinal mucosa.  

Metabolism 

esomeprazole undergoes extensive hepatic metabolism via the cytochrome P450 (CYP) enzyme system, predominantly CYP2C19. It undergoes oxidative metabolism, primarily forming hydroxyesomeprazole, which exhibits minimal pharmacological activity. naproxen, on the other hand, is primarily metabolized in the liver by CYP2C9, undergoing oxidative metabolism to form 6-desmethylnaproxen, as well as various minor metabolites.  

Excretion and elimination 

The metabolites of esomeprazole and naproxen, along with a portion of the unchanged drugs, are eliminated from the body through renal excretion. The main route of elimination for esomeprazole is via the urine, primarily as conjugated metabolites. naproxen is excreted in both urine and feces, primarily as unchanged drug and its metabolites. 

Adminstartion

Administration:  

When administering esomeprazole/naproxen, it is important to adhere to the recommended dosage regimen.  

The tablets should be swallowed whole without crushing or chewing, as this may affect the drug’s release characteristics. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: esomeprazole/naproxen 

Why do we use esomeprazole/naproxen?  

esomeprazole: The drug belongs to a class of medications called proton pump inhibitors (PPIs). It works by reducing the amount of acid produced in the stomach. esomeprazole is primarily used for the following conditions:  

Gastroesophageal Reflux Disease (GERD): The drug is commonly prescribed for the treatment of GERD.  

Peptic Ulcers: It is also used to heal and prevent the recurrence of peptic ulcers.  

Zollinger-Ellison Syndrome: This is a rare condition in which tumors in the pancreas or duodenum produce excessive amounts of a hormone called gastrin. esomeprazole is used to reduce the production of stomach acid in individuals with this syndrome.  

naproxen: naproxen is a nonsteroidal anti-inflammatory drug (NSAID) that helps reduce pain, inflammation, and fever. It is commonly used for the following conditions:  

Pain and Inflammation: naproxen is effective in relieving mild to moderate pain associated with conditions such as arthritis, menstrual cramps, muscle aches, dental pain, and minor injuries. 

Osteoarthritis and Rheumatoid Arthritis: It is often prescribed for the management of chronic conditions like osteoarthritis and rheumatoid arthritis to reduce pain, swelling, and joint stiffness.  

Tendonitis and Bursitis: naproxen can help alleviate pain and inflammation associated with tendonitis and bursitis.