What are the recommendations for long‑term use of Nexium (esomeprazole)?

Long-Term Nexium (Esomeprazole) Use: Recommendations and Risks

Long-term esomeprazole should only be continued when there is a clear, documented indication (such as erosive esophagitis, Barrett's esophagus, or Zollinger-Ellison syndrome), and patients without definitive indications should be considered for de-prescribing due to well-established risks of fractures, hypomagnesemia, iron deficiency, and enteric infections. 1

When Long-Term Use Is Appropriate

Documented Indications for Maintenance Therapy:

• Eosinophilic esophagitis (EoE): Long-term maintenance with esomeprazole 20 mg twice daily can be considered in patients who achieve clinical and histological remission, as 70-81% maintain sustained remission on continued therapy. 2
• NSAID-associated ulcer prevention: In patients requiring ongoing NSAIDs with a history of peptic ulcer, esomeprazole 20 mg once daily effectively prevents ulcer recurrence, with 95.9% remaining ulcer-free at 1 year. 3
• Erosive esophagitis maintenance: After achieving healing, maintenance therapy prevents relapse in patients with documented erosive disease. 4, 5

Critical caveat: In EoE patients who discontinue PPI after achieving remission, 87.5% experience symptom recurrence and all exhibit histological recurrence, supporting the need for indefinite therapy in responders. 2

When Long-Term Use Should Be Avoided

Inappropriate Indications:

• Unexplained chronic cough: Do not prescribe esomeprazole for chronic cough with a negative workup for acid reflux disease, as high-dose therapy shows no benefit on cough severity or quality of life. 2
• Absence of documented GERD or ulcer disease: The American College of Gastroenterology recommends trial de-prescribing in patients without definitive indications. 1

FDA labeling restrictions: Over-the-counter esomeprazole should not be used for more than 14 days or more than one course every 4 months without physician supervision. 6

Established Risks of Long-Term Use

Bone Health:

• Meta-analysis demonstrates a 20% increased risk of hip fracture (RR 1.20,95% CI 1.14-1.28) with long-term PPI use, attributed to reduced calcium absorption from decreased gastric acid. 1
• Patients with pre-existing fracture risk factors require bone health monitoring. 1

Electrolyte and Nutritional Deficiencies:

• Hypomagnesemia: 71% higher risk after ≥3 months of therapy (adjusted OR 1.71,95% CI 1.33-2.19), requiring magnesium level monitoring before starting and periodically during treatment. 1
• Iron deficiency: Reduced gastric acid impairs non-heme iron absorption in a dose-dependent manner. 1
• Vitamin B12 deficiency: Assess B12 status after 3+ years of continuous use. 1

Infectious Complications:

• Increased susceptibility to gastroenteritis and enteric infections due to reduced gastric acid barrier, particularly in vulnerable populations. 1

Rebound Acid Hypersecretion:

• Common after discontinuation, lasting 2-6 months as a physiological response to secondary hypergastrinemia, which can complicate de-prescribing efforts. 1

Monitoring Requirements for Long-Term Therapy

Baseline and Periodic Assessments:

• Check magnesium levels before initiating therapy and periodically during long-term use. 1
• Assess vitamin B12 status after 3+ years of continuous therapy. 1
• Monitor bone health in patients with pre-existing fracture risk factors. 1
• Reassess the risk-benefit profile at 6-month intervals. 2

De-Prescribing Strategy

When to Consider Discontinuation:

• Absence of documented indication (erosive esophagitis, Barrett's esophagus, pathological hypersecretion, or H. pylori eradication maintenance). 1
• Resolution of underlying condition requiring initial therapy. 1

Common Pitfall: Rebound acid hypersecretion lasting 2-6 months can mimic recurrent disease and lead to unnecessary resumption of therapy; counsel patients about this expected phenomenon. 1

Drug Interactions

Clopidogrel Interaction:

• European and US regulatory agencies issued warnings regarding diminished clopidogrel action when combined with esomeprazole, though post-hoc analyses of randomized trials did not show increased thromboembolic events. 2
• Practical approach: Do not withhold PPIs when gastrointestinal protection is indicated in patients on dual antiplatelet therapy, but be aware of the theoretical interaction. 2

Dosing for Specific Indications

Eosinophilic esophagitis: Esomeprazole 20 mg twice daily (or omeprazole equivalent) for both induction (8-12 weeks) and maintenance therapy. 2

NSAID-associated ulcer prevention: Esomeprazole 20 mg once daily. 3

Erosive esophagitis healing: Esomeprazole 40 mg once daily for up to 8 weeks. 4, 5