Esomeprazole

Generic Name

Esomeprazole

Brand Names

Nexium

Nexium Control

Esomac

EsoSure

Zoleri

Emizole

Available as tablets, capsules, granules for oral suspension, and intravenous injection

Drug Class

Proton Pump Inhibitor (PPI)

A selective and irreversible inhibitor of the H+/K+ ATPase enzyme system in the gastric parietal cell

Mechanism of Action

Esomeprazole is the S-isomer of omeprazole

It irreversibly inhibits the H+/K+ ATPase (proton pump) in gastric parietal cells

This inhibition blocks the final step in gastric acid secretion regardless of the stimulus (acetylcholine, histamine, or gastrin)

Inhibits both basal and stimulated gastric acid secretion

Provides a longer duration of action and higher bioavailability than omeprazole due to its stereoselective metabolism and binding efficiency

Indications

Gastroesophageal Reflux Disease (GERD)

Short-term treatment of erosive esophagitis

Maintenance of healing of erosive esophagitis

Symptomatic GERD without esophagitis

Peptic Ulcer Disease

Duodenal and gastric ulcer treatment and prevention

Part of combination therapy for Helicobacter pylori eradication with antibiotics (e.g., amoxicillin + clarithromycin)

NSAID-Associated Ulcers

Treatment and prevention of gastric and duodenal ulcers in NSAID users at risk

Zollinger-Ellison Syndrome

Treatment of pathological hypersecretory conditions including Zollinger-Ellison syndrome

Stress Ulcer Prophylaxis (IV use)

In intensive care units for high-risk patients

Upper GI Bleeding (IV use)

After endoscopic hemostasis to reduce risk of rebleeding in peptic ulcer hemorrhage

Over-the-Counter Use (e.g., Nexium Control)

Short-term relief of frequent heartburn in adults

Off-Label Uses

Eosinophilic esophagitis

Barrett's esophagus management

Chronic laryngitis due to reflux

Pancreatic enzyme therapy adjunct

Functional dyspepsia

Dosage and Administration

Adults

GERD

20–40 mg once daily for 4–8 weeks

Maintenance: 20 mg once daily

H. pylori Eradication (Triple Therapy)

Esomeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 7–10 days

NSAID-Associated Ulcers

20–40 mg daily for 4–8 weeks

Prevention: 20–40 mg daily

Zollinger-Ellison Syndrome

Initial: 40 mg twice daily

Adjust dose based on patient response

Doses up to 240 mg/day used

IV Administration

20–40 mg once daily for GERD

80 mg bolus followed by 8 mg/hour infusion for 72 hours post-endoscopic control of ulcer bleeding

Pediatric Dosage

Approved for children ≥1 year depending on indication and formulation

Doses adjusted by weight

Onset and Duration

Onset of action: 1–2 hours

Maximal effect: after 3–4 days of continuous therapy

Duration of acid suppression: up to 24 hours

Pharmacokinetics

Bioavailability: ~64% (increased with repeated dosing)

Metabolized in the liver by CYP2C19 and CYP3A4

Terminal half-life: 1–1.5 hours

Elimination: primarily renal as inactive metabolites

Food delays absorption but does not significantly affect efficacy

Contraindications

Hypersensitivity to esomeprazole, substituted benzimidazoles, or any component

Concurrent use with rilpivirine (contraindicated due to pH-dependent absorption of rilpivirine)

Caution in patients with severe hepatic impairment

Avoid long-term use without clear indication

Warnings and Precautions

May mask symptoms of gastric malignancy

Risk of Clostridium difficile-associated diarrhea

Long-term use increases risk of:

– Hypomagnesemia

– Bone fracture (especially in older adults or high-dose therapy)

– Vitamin B12 deficiency

– Chronic kidney disease and acute interstitial nephritis

May reduce absorption of pH-dependent drugs

Caution in patients with osteoporosis or taking corticosteroids

Hepatic dose adjustments: not required for mild to moderate hepatic impairment, maximum 20 mg/day in severe hepatic disease

Adverse Effects

Common

Headache

Abdominal pain

Nausea

Diarrhea

Constipation

Flatulence

Dry mouth

Uncommon

Dizziness

Peripheral edema

Insomnia

Skin rash or pruritus

Elevated liver enzymes

Rare

Agranulocytosis

Interstitial nephritis

Pancreatitis

Stevens-Johnson syndrome

Anaphylaxis

Severe hypomagnesemia (muscle cramps, arrhythmias)

Subacute cutaneous lupus erythematosus

Microscopic colitis

Long-Term Risks

Chronic PPI use linked with increased risks of:

– Kidney injury

– Vitamin and mineral deficiencies (B12, iron, magnesium)

– Enteric infections (e.g., C. difficile)

– Rebound acid hypersecretion

– Gastric polyps

– Dementia (in some observational studies)

Pregnancy and Lactation

Pregnancy

Category B (US FDA): animal studies do not show harm, but no controlled human studies

Generally considered safe during pregnancy

Lactation

Unknown whether esomeprazole is excreted in breast milk

Use with caution; omeprazole considered a safer alternative

Drug Interactions

Drugs with pH-Dependent Absorption

Reduced absorption of:

– Ketoconazole

– Itraconazole

– Atazanavir

– Rilpivirine (contraindicated)

– Erlotinib

CYP450 Interactions

Esomeprazole is metabolized by and may inhibit CYP2C19

May affect plasma levels of:

– Clopidogrel (reduces its activation; avoid combination if possible)

– Diazepam (increased levels)

– Warfarin (monitor INR)

– Phenytoin (monitor serum levels)

– Methotrexate (especially high doses; may delay elimination)

– Digoxin (risk of increased levels via altered absorption)

Herbal and Food Interactions

St John's Wort and rifampin may decrease esomeprazole levels

No significant food interactions but best taken 30–60 minutes before meals

Monitoring Parameters

Symptom control (heartburn, ulcer pain)

Endoscopic evaluation for ulcers or esophagitis if indicated

Magnesium levels with prolonged use

Vitamin B12 levels in long-term use

Serum creatinine and kidney function (especially in high-risk populations)

Signs of gastrointestinal infection in long-term users

Counseling Points

Take on an empty stomach, ideally in the morning 30–60 minutes before a meal

Swallow capsule whole with water

Do not crush or chew delayed-release formulations

May take several days for full symptom relief

Do not discontinue abruptly after long-term use due to risk of rebound acid hypersecretion

Notify provider if new or worsening symptoms like weight loss, vomiting, or difficulty swallowing occur

Use the lowest effective dose for the shortest duration

Comparative Notes

Esomeprazole vs Omeprazole

Esomeprazole is the S-isomer of omeprazole

Higher bioavailability and more consistent acid suppression

Slightly greater healing rates in erosive esophagitis

More expensive than omeprazole

Esomeprazole vs H2 Blockers (e.g., ranitidine)

Esomeprazole provides more potent and prolonged acid suppression

H2 blockers act faster but are less effective overall

PPI preferred for healing ulcers, treating GERD, and preventing NSAID-induced ulcers

Esomeprazole vs Other PPIs (pantoprazole, lansoprazole, rabeprazole)

Similar efficacy among PPIs

Choice often based on availability, cost, patient response, or interaction profile

Esomeprazole has higher CYP2C19 interaction potential than pantoprazole

Legal and Regulatory Status

Prescription-only for most indications

Available over-the-counter in some countries for short-term relief of heartburn (e.g., Nexium Control 20 mg for up to 14 days)

Included in national formularies and treatment guidelines globally

Listed on WHO Model List of Essential Medicines