Drugs for peptic ulcer and GORD. Proton pump inhibitors
ATC code: A02BC05 (Esomeprazole)
Brand names
Nexium, Nexium 24HR
The S-enantiomer of omeprazole, specifically and irreversibly inhibits the H+/K+-ATPase (proton pump) of gastric parietal cells. Reduces basal and stimulated hydrochloric acid secretion by 80–95% with daily dosing. The advantage over omeprazole is more consistent pharmacokinetics: the S-enantiomer is less dependent on CYP2C19 metabolism and less affected by genetic variability. With daily dosing, a steady antisecretory effect is reached by days 3–5.
First line
First-line therapy for GERD in adults and adolescents. CG184 (2014, updated 2019) and 2022 recommend PPIs as the baseline GERD therapy, with dose chosen by esophagitis severity. Erosive esophagitis is treated for 8 weeks, non-erosive disease for 4 weeks with reassessment. Esomeprazole shows efficacy comparable to other PPIs at equivalent doses; at 40 mg it outperforms 20 mg in healing of severe erosive esophagitis.
After the course, the patient attempts withdrawal or switches to on-demand dosing. Continuous use beyond 8 weeks is reviewed every 6–12 months.
Sources
First line
Esomeprazole is one of the PPIs used in H. pylori eradication. Maastricht VI/Florence 2022 and 2017 recommend triple or bismuth quadruple therapy for 14 days. Esomeprazole 40 mg twice daily within the regimen provides acid suppression that supports antibiotic activity and concentration stability in the stomach.
First line
Esomeprazole is used for gastric and duodenal ulcers in adults. Standard dose 20–40 mg daily for 4–8 weeks. PPIs accelerate healing and reduce recurrence. In H. pylori-associated ulcer, esomeprazole is part of eradication therapy. In NSAID-related ulcers, the NSAID is discontinued and a PPI course is given with reassessment in 4–8 weeks.
First line
In Barrett esophagus, PPIs are prescribed lifelong to suppress acid reflux and reduce metaplasia progression. 2022 supports continuous PPI therapy in confirmed Barrett esophagus. Adenocarcinoma prevention data are observational; randomized evidence of cancer risk reduction is lacking, but reflux control remains standard practice.
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Long-term PPI therapy for functional dyspepsia without H. pylori-associated gastritis, esophagitis or other indications is not clinically justified. CG184 recommends reassessing the need to continue after 4 weeks; if there is no clear effect, the drug is discontinued. PPI use «just in case» for general epigastric heaviness is in the overuse category.
Not recommended
PPI prophylaxis is not indicated in patients without risk factors for NSAID-induced gastropathy. Risk factors: age ≥ 65, history of peptic ulcer, history of GI bleeding, concurrent glucocorticoids or anticoagulants, high-dose or combined NSAID use, chronic kidney disease. Routine PPI «cover» without these factors is an overuse category.
Long-term (over 2 years) suppression of gastric secretion reduces release of B12 from dietary proteins, leading to subclinical or clinical deficiency in some patients. Annual serum B12 monitoring is recommended for continuous therapy beyond 2 years; oral or parenteral replacement is prescribed at levels below 200 pg/mL.
PPIs reduce gastric acidity and impair release of dietary B12 from proteins. Long-term use (>2 years) raises B12 deficiency risk 1.5–2 fold. Check B12 levels in PPI courses longer than 12 months, especially in the elderly.
Source: FDA: FDA Drug Safety Communication: PPIs and vitamin B12 deficiency (2010)
Calcium carbonate absorption is acid-dependent, and long-term PPI use lowers its bioavailability. Meta-analyses link long-term (> 1 year) PPI use to a modest increase in hip and vertebral fracture risk, mainly in older adults. For PPI users at osteoporosis risk, organic calcium salts (citrate) that do not require an acidic environment are preferred.
Iron salts (sulfate, fumarate) require gastric acid to convert to Fe2+ and be absorbed. On PPI therapy their bioavailability falls by 20–50%. In iron-deficiency anemia in PPI users, parenteral forms or chelated iron are preferred.
PPIs reduce magnesium absorption in the small intestine. Long-term therapy leads to hypomagnesemia in some patients, with clinical manifestations: seizures, tetany, arrhythmias, tremor. issued a dedicated warning in 2011. Monitor magnesium every 12 months; every 3–6 months with concurrent diuretics.
6 pairs found. Sorted from critical to minor.
Mechanism
Esomeprazole is the S-isomer of omeprazole, the same CYP2C19 inhibitor. Citalopram plasma levels rise by 40–50%. The caps citalopram at 20 mg/day with CYP2C19 inhibitors.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Cap citalopram at 20 mg/day when combined. Alternative PPIs without CYP2C19 effect: pantoprazole or rabeprazole.
Mechanism
Esomeprazole inhibits CYP2C19, the key enzyme that converts clopidogrel to its active metabolite. Active clopidogrel levels fall by about 35%, weakening antiplatelet effect.
Symptoms
The patient feels no symptoms – the weakened antiplatelet effect is silent. The combination raises recurrent myocardial infarction and stent thrombosis risk in patients with prior stenting or acute coronary syndrome.
Management
Replace esomeprazole with pantoprazole (minimal CYP2C19 impact). Among other PPIs, rabeprazole is an alternative. If a PPI is not required, switch to famotidine (H2-blocker) or stop acid suppression.
Mechanism
Proton pump inhibitors block the renal BCRP transporter and reduce methotrexate clearance. At high oncologic doses, risk of delayed elimination and severe toxicity.
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases: fatal pancytopenia, nephrotoxicity.
Management
At oncologic methotrexate doses, stop esomeprazole 5 days before and resume 5 days after dosing. Alternative: famotidine (H2-blocker, no BCRP effect). At low rheumatologic doses, esomeprazole is acceptable with blood count monitoring.
Mechanism
Esomeprazole inhibits CYP2C19. Tacrolimus is minimally metabolised by CYP2C19, but in patients with slow metabolism (CYP2C19 genetic polymorphism) this route becomes the main one. In such patients tacrolimus plasma levels rise.
Symptoms
Acute nephrotoxicity: rising creatinine and falling glomerular filtration rate. Tremor, headache, hypertension, hyperglycaemia, hyperkalaemia. In transplant patients: accelerated graft function decline.
Management
In most patients, no clinically significant effect. In East Asian patients (high frequency of CYP2C19 slow metabolisers), alternative PPIs: pantoprazole or rabeprazole (weaker CYP2C19 effect). Check tacrolimus trough (C0) 1 week after starting esomeprazole.
Mechanism
Esomeprazole weakly affects CYP3A4 (mainly via CYP2C19). Atorvastatin levels are essentially unchanged. DDInter notes rare myalgia.
Symptoms
Usually no changes. Rare muscle pain cases, especially in patients with myopathy risk factors.
Management
The combination is acceptable without dose change. In patients with myopathy risk factors (older age, chronic kidney disease, hypothyroidism), check creatine kinase on muscle symptoms.
Mechanism
Esomeprazole suppresses gastric acidity, reducing release of B12 from food (which requires HCl and pepsin). With over 2 years of therapy, B12 deficiency risk is reported.
Symptoms
Fatigue, pallor, paraesthesias in hands and feet, gait instability, memory decline. Develops over 2–4 years of unrecognised therapy.
Management
On long-term PPIs (over 2 years), check B12 yearly. Oral cyanocobalamin tablets or drops can be given regardless of acidity (passive diffusion absorption at high doses). Alternative: H2-blockers (famotidine) for short-term acid suppression.
Sources
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FDA category B. Large cohort studies show no increased risk of congenital malformations. During pregnancy, used on indication, preferably after the first trimester, at the minimum effective dose. Alternatives: antacids and H2 blockers for episodic symptoms.
Passes into breast milk in minimal amounts. LactMed classifies it as compatible with breastfeeding. Monitor the infant for gastrointestinal symptoms.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Esomeprazole is evaluated for the following indications with varying evidence strength: Peptic ulcer disease (evidence tier A), GERD pharmacological treatment (evidence tier A), Helicobacter pylori infection (evidence tier A). See the full indication matrix with dosing and citations above on this page.
Common side effects of Esomeprazole (≥ 1 in 100): Headache, Diarrhea, constipation, flatulence, Nausea, abdominal discomfort, Dry mouth. See the Safety section for uncommon and serious reactions.
FDA category B. FDA category B. Large cohort studies show no increased risk of congenital malformations. During pregnancy, used on indication, preferably after the first trimester, at the minimum effective dose. Alternatives: antacids and H2 blockers for episodic symptoms.
Passes into breast milk in minimal amounts. LactMed classifies it as compatible with breastfeeding. Monitor the infant for gastrointestinal symptoms.
Esomeprazole is contraindicated in: Hypersensitivity to esomeprazole or substituted benzimidazoles; Co-administration with rilpivirine; Age under 1 year for most formulations. Full list in the Safety section.
long-term therapy is linked to B12 and magnesium deficiency, increased fracture and C. difficile infection risk. Prescriptions must be justified, and duration reviewed.
40 mg esomeprazole is roughly equivalent to 40 mg omeprazole but more pharmacokinetically stable. The advantage is predictability, not «power».
PPIs suppress acid but do not eliminate the cause. After withdrawal, symptoms often return.