Generic Name

Nexium

Mechanism

Nexium (esomeprazole) is a *potent, irreversible proton‑pump inhibitor (PPI)* that selectively blocks the H⁺/K⁺‑ATPase (the gastric proton pump) on gastric parietal cells.
• Binds covalently to a cysteine thiol group on the enzyme, producing a 10‑to‑30‑fold reduction in basal acid secretion that is maintained for approximately 24 h.
• Attenuates the residual acid secretion caused by histamine, gastrin, or acetylcholine.
• Compared with other PPIs, esomeprazole’s S‑enantiomer configuration yields higher bioavailability and more consistent acid suppression.

Pharmacokinetics

• Administration: Oral tablets, delayed‑release (≥ AcME ®).
• Absorption: ~80 % bioavailability; maximal plasma concentrations (Tmax) at ~1 h post‑dose (fasted state).
• Distribution: Highly protein‑bound (~81 %), mainly to albumin; sparse penetration into gastric mucus.
• Metabolism: Primarily via CYP‑2C19 (*∼ 70 %*) and CYP‑3A4 (*∼ 24 %*).
• Elimination: Renal (∼ 22 %) and fecal (∼ 30 %); terminal half‑life 1.2 – 1.5 h.
• Drug interactions:
• *CYP‑2C19* polymorphisms influence clearance → extensive and poor metabolizers.
• *Clopidogrel*: moderate inhibition → reduced antiplatelet efficacy (use cautiously).
• *Ritonavir*, *cimetidine*, *ketoconazole*: inhibit CYP‑2C19 → ↑ esomeprazole exposure.
• *Warfarin*: negligible effect.

Indications

• Gastroesophageal reflux disease (GERD) – erosive and non‑erosive forms.
• Erosive esophagitis – healing and maintenance.
• Zollinger‑Ellison syndrome – hypersecretion of gastric acid.
• Peptic ulcer disease – for ulcer healing or maintenance.
• Prevention of ulcer recurrence in patients on low‑dose aspirin or COX‑2 inhibitors.
• Adjunct in Helicobacter pylori triple or quadruple therapy (when combined with amoxicillin, clarithromycin, and a PPI).

Contraindications

• Contraindicated:
• Severe hypersensitivity to esomeprazole or any excipients.
• Warnings:
• Long‑term use (>12 weeks) → increased risk of *Clostridioides difficile* colitis, *vitamin B12* deficiency, *magnesium* deficiency, and bone fractures.
• Hepatic impairment (Child‑Pugh B and C) → reduced clearance → higher exposure.
• Hyponatremia: potential *hyponatremic* events reported with prolonged use.
• Subclinical kidney disease: monitor renal function; dose reduction may be required.

Dosing

Monitoring

• Baseline: CBC; electrolytes; liver enzymes; renal function.
• Periodic:
• Electrolytes (Mg²⁺, K⁺, Ca²⁺) if therapy > 12 weeks.
• Serum B12 after > 1 year therapy.
• Bone density in patients ≥ 50 yrs or long‑term therapy.
• Drug interaction: Re‑evaluate clopidogrel or other CYP‑2C19 substrates.

Clinical Pearls

• Timing Matters: Administer 30–60 min before the first meal; maximum acid suppression occurs 1–1.5 h after dosing.
• PPI‑Clopidogrel: Recent data suggests clopidogrel efficacy is not clinically compromised by esomeprazole at usual doses. Nevertheless, consider generic clopidogrel or alternative PPI if patients require high‑dose clopidogrel (e.g., Post‑PCI).
• Dose Optimization: For refractory GERD, incrementally add 10 mg (or switch to 20 mg BID) before escalating dose; target is often 20 mg BID, not just changing brands.
• Fasting vs. Fed: While esomeprazole’s absorption is less affected by food than omeprazole, the *delayed‑release* formulation tolerates meals better—make patient aware to keep the tablet in the mouth for ≥ 45 s.
• Drug Delivery: In ICU settings, enteric‑coated tablets are preferable over granules to reduce aspiration risk.
• Long‑term Use Recall: Patients on > 12 weeks long‑term therapy should be screened for hypomagnesemia (serum Mg²⁺  6‑month courses.

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• Keywords: Nexium, esomeprazole, proton pump inhibitor, GERD therapy, gastric acid suppression, long‑term PPI complications, drug interactions with clopidogrel, dosing schedule, monitoring guidelines.