Introduction
Nexium (esomeprazole magnesium) is a proton pump inhibitor (PPI) that reduces gastric acid secretion through irreversible inhibition of the hydrogen-potassium adenosine triphosphatase (H+/K+ ATPase) enzyme system in gastric parietal cells. It is the S-isomer of omeprazole and represents a significant advancement in acid suppression therapy. Nexium is widely prescribed for various acid-related disorders and has become one of the most commonly used medications in gastroenterology practice.
Mechanism of Action
Nexium exerts its therapeutic effects through irreversible inhibition of the H+/K+ ATPase enzyme system (proton pump) at the secretory surface of gastric parietal cells. This enzyme is responsible for the final step in gastric acid production, exchanging intracellular hydrogen ions for extracellular potassium ions. Esomeprazole is a weak base that accumulates in the acidic compartment of parietal cells, where it undergoes conversion to active sulfenamide derivatives. These active forms form disulfide bonds with cysteine residues on the proton pump, leading to prolonged inhibition of acid secretion. The drug specifically targets the stimulated proton pumps, providing more effective acid control than previous generations of acid-suppressing medications.
Indications
FDA-approved indications:
- Healing of erosive esophagitis
- Maintenance of healing of erosive esophagitis
- Symptomatic gastroesophageal reflux disease (GERD)
- Risk reduction of NSAID-associated gastric ulcers
- Helicobacter pylori eradication in combination with antibiotics
- Pathological hypersecretory conditions including Zollinger-Ellison syndrome
Non-FDA approved uses (off-label):
- Prevention of stress ulcer bleeding in critically ill patients
- Treatment of upper gastrointestinal bleeding
- Management of Barrett's esophagus
- Eosinophilic esophagitis
Dosage and Administration
Standard adult dosing:- Erosive esophagitis healing: 20 mg or 40 mg once daily for 4-8 weeks
- Maintenance of healed erosive esophagitis: 20 mg once daily
- Symptomatic GERD: 20 mg once daily for 4 weeks
- H. pylori eradication: 40 mg once daily with amoxicillin 1000 mg and clarithromycin 500 mg twice daily for 10-14 days
- NSAID ulcer risk reduction: 20 mg or 40 mg once daily
- Should be taken at least 30-60 minutes before the first meal of the day
- Capsules should be swallowed whole; not to be crushed or chewed
- For patients with difficulty swallowing, capsules may be opened and contents mixed with applesauce
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Maximum dose of 20 mg daily in severe impairment
- Geriatric patients: No dosage adjustment necessary
- Pediatric patients: FDA-approved for ages 1-17 with weight-based dosing
Pharmacokinetics
Absorption: Rapidly absorbed with peak plasma concentrations occurring at approximately 1.5 hours. Bioavailability is 64% after first dose and increases to 89% with repeated once-daily dosing. Food decreases bioavailability significantly when administered with meals. Distribution: Volume of distribution is approximately 0.22 L/kg. Protein binding is 97%, primarily to albumin. Metabolism: Extensively metabolized in the liver via the cytochrome P450 system, primarily by CYP2C19 and CYP3A4. Esomeprazole is metabolized to hydroxy, desmethyl, and sulfone metabolites. Elimination: Plasma elimination half-life is approximately 1-1.5 hours. However, the acid inhibitory effect persists much longer due to irreversible binding to proton pumps. Excretion is primarily via urine (80%) as metabolites, with the remainder in feces.Contraindications
- Hypersensitivity to esomeprazole, substituted benzimidazoles, or any component of the formulation
- Concomitant use with rilpivirine-containing products due to potential for reduced antiviral efficacy
- Patients taking atazanavir due to significantly reduced plasma concentrations
Warnings and Precautions
Bone fracture: Long-term (≥1 year) and high-dose PPI therapy may be associated with increased risk of osteoporosis-related fractures of hip, wrist, or spine. Hypomagnesemia: Prolonged PPI use may cause hypomagnesemia, which can present with tetany, arrhythmias, and seizures. Clostridium difficile-associated diarrhea: PPI use may increase risk of C. difficile infection. Acute interstitial nephritis: Has been observed with PPI use and may occur at any time during therapy. Cutaneous and systemic lupus erythematosus: New onset or exacerbation of existing disease has been reported. Vitamin B12 deficiency: Long-term PPI use may lead to malabsorption of vitamin B12. Fundic gland polyps: Long-term use (≥1 year) may increase risk of fundic gland polyps.Drug Interactions
Clinically significant interactions:- Clopidogrel: Reduced antiplatelet effect due to CYP2C19 inhibition
- Methotrexate: May increase methotrexate levels due to renal tubular competition
- Ketoconazole, itraconazole: Reduced absorption due to increased gastric pH
- Digoxin: Possible increased digoxin absorption
- Saquinavir, atazanavir: Significantly reduced plasma concentrations
- Tacrolimus: Possible increased tacrolimus levels
- Warfarin: Increased INR monitoring recommended due to potential CYP2C19 inhibition
- St. John's Wort, rifampin: May decrease esomeprazole levels
Adverse Effects
Common adverse reactions (≥1%):- Headache (5-10%)
- Diarrhea (4-5%)
- Abdominal pain (3-4%)
- Nausea (3-4%)
- Flatulence (2-3%)
- Constipation (2%)
- Dry mouth (1%)
- Acute interstitial nephritis
- Clostridium difficile-associated diarrhea
- Bone fracture
- Hypomagnesemia
- Vitamin B12 deficiency
- Cutaneous and systemic lupus erythematosus
- Fundic gland polyps
Monitoring Parameters
- Symptom improvement and resolution
- Endoscopic healing in erosive esophagitis
- Magnesium levels with prolonged therapy
- Vitamin B12 levels with long-term use
- Bone density assessment with long-term high-dose therapy
- Renal function in patients with pre-existing renal impairment
- Signs of hypersensitivity reactions
- Signs of C. difficile infection with persistent diarrhea
Patient Education
- Take medication 30-60 minutes before the first meal of the day
- Swallow capsules whole; do not crush or chew
- Report any signs of allergic reaction (rash, itching, swelling)
- Inform healthcare provider of all medications being taken
- Report persistent diarrhea, abdominal pain, or bloody stools
- Discuss long-term therapy risks with healthcare provider
- Do not discontinue medication abruptly without medical supervision
- Be aware of potential interactions with other medications
- Report any new or worsening symptoms promptly
- Understand that this medication may affect absorption of certain nutrients
References
1. Katz PO, Gerson LB, Vela MF. Guidelines for the diagnosis and management of gastroesophageal reflux disease. Am J Gastroenterol. 2013;108(3):308-328. 2. Shi S, Klotz U. Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol. 2008;64(10):935-951. 3. Nexium (esomeprazole magnesium) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2021. 4. Strand DS, Kim D, Peura DA. 25 Years of Proton Pump Inhibitors: A Comprehensive Review. Gut Liver. 2017;11(1):27-37. 5. FDA Drug Safety Communication: Low magnesium levels can be associated with long-term use of Proton Pump Inhibitor drugs. U.S. Food and Drug Administration. 2011. 6. Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of Proton Pump Inhibitors Based on a Large, Multi-Year, Randomized Trial of Patients Receiving Rivaroxaban or Aspirin. Gastroenterology. 2019;157(3):682-691. 7. Schoenfeld AJ, Grady D. Adverse Effects Associated With Proton Pump Inhibitors. JAMA Intern Med. 2016;176(2):172-174.