Proton pump inhibitors
ATC code: A02BC01 (Omeprazole)
Brand names
Prilosec, Zegerid
Irreversibly inhibits the H+/K+-ATPase in gastric parietal cells — the final step of gastric acid secretion. Converted to its active form in the acidic environment of parietal cell canaliculi, where it binds the enzyme covalently. The effect persists until new H+/K+-ATPase molecules are synthesized (about 24 hours).
First line
PPIs are first-line for GERD in adults per 2022 and CG184. Standard dose: omeprazole 20 mg once daily for 4–8 weeks in non-erosive disease, 40 mg in erosive disease. If the response is inadequate, assess adherence, timing, functional heartburn, and alternative diagnoses. Long-term maintenance uses the lowest effective dose.
First line
A component of H. pylori eradication regimens per Maastricht VI/Florence Consensus 2022. In triple therapy: omeprazole 20 mg BID with amoxicillin and clarithromycin. In bismuth quadruple therapy: with tetracycline and metronidazole. Course duration 14 days. PPI is continued at least 4 more weeks after antibiotics for mucosal healing.
First line
Gastroprotection is indicated in long-term NSAID users with risk factors: age over 65, prior peptic ulcer or GI bleeding, concomitant anticoagulants, antiplatelet drugs, or glucocorticoids, and high NSAID doses. Routine gastroprotection in low-risk patients is not recommended.
First line
Standard therapy for peptic ulcer disease: omeprazole 20–40 mg once or twice daily for 4–8 weeks depending on ulcer location. In H. pylori-positive patients, as part of an eradication regimen. Maintenance therapy is used in recurrent ulcers, H. pylori-negative ulcers, and chronic NSAID users.
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
Omeprazole is widely prescribed as gastric protection for short NSAID courses in patients without GI-bleed risk factors, and for general post-meal discomfort. 2022 and 2022 recommend PPI plus NSAID only with risk factors: age over 60, ulcer history, anticoagulants, antiplatelets, high-dose NSAIDs. The Targownik 2010 BMJ analysis and subsequent systematic reviews show long-term PPI signals: B12 deficiency, hypomagnesemia, fractures ( Drug Safety Communications 2010, 2011) and Clostridioides difficile infection (FDA DSC 2012).
12 pairs found. Sorted from critical to minor.
Mechanism
Omeprazole raises gastric pH – atazanavir solubility drops, bioavailability falls 75%. ART fails with resistance risk.
Symptoms
Rising HIV viral load on apparently ongoing therapy.
Management
Combination contraindicated. Switch omeprazole to ranitidine (H2 blocker) given 12 hours apart from atazanavir.
Mechanism
Omeprazole is a potent CYP2C19 inhibitor, the main citalopram metabolic route. Citalopram plasma levels rise by 40–50%. The capped citalopram at 20 mg/day with CYP2C19 inhibitors in 2012 because of dose-dependent QT risk.
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
Clopidogrel is a prodrug. It must be converted in the liver via CYP2C19 into its active antiplatelet metabolite. Omeprazole strongly inhibits CYP2C19: active metabolite levels drop by 45% and platelet inhibition weakens. The issued a dedicated warning about this pair in 2009.
Symptoms
The patient feels no symptoms – the weakened antiplatelet effect is silent. The combination raises the risk of recurrent myocardial infarction, stent thrombosis, and stroke in patients with prior stenting or acute coronary syndrome.
Management
Replace omeprazole with pantoprazole, which has minimal effect on CYP2C19. Among other proton pump inhibitors, rabeprazole is an alternative. If a PPI is not required, switch to famotidine (an H2-blocker that does not affect CYP2C19) or stop acid suppression altogether.
Mechanism
Omeprazole blocks the renal BCRP transporter and reduces methotrexate clearance. At oncologic methotrexate doses, plasma levels rise 2- to 3-fold, with reported severe nephrotoxicity and pancytopenia.
Symptoms
Mouth ulcers (mucositis), nausea, diarrhoea, hair loss. Blood counts fall: leukocytes, platelets, erythrocytes. Severe cases include fatal pancytopenia, nephrotoxicity, and hepatotoxicity.
Management
At oncologic methotrexate doses, the combination is not prescribed. During methotrexate cycles, replace omeprazole with ranitidine or famotidine (H2-blockers, no BCRP effect). At low rheumatologic doses, risk is minimal; omeprazole is acceptable with full blood count monitoring.
Mechanism
Omeprazole blocks CYP2C19. In CYP2C19 slow metabolisers (genetic polymorphism), tacrolimus is predominantly metabolised by CYP2C19, and plasma levels may double.
Symptoms
Acute nephrotoxicity: rising creatinine, hypertension, tremor, headache. 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 omeprazole.
Mechanism
Omeprazole weakly blocks CYP3A4; alprazolam plasma levels may rise slightly. The effect is clinically weak.
Symptoms
Minimal changes: mild additional sedation in some patients. Older patients: rare ataxia.
Management
Dose adjustment is usually unnecessary. In older patients and prolonged therapy, monitor cognition and fall risk.
Sources
Mechanism
Omeprazole weakly blocks CYP3A4 – atorvastatin exposure rises modestly (by 10–20%). Clinically significant myopathy beyond baseline is rare.
Symptoms
Usually no changes. In patients with risk factors (older age, chronic kidney disease, hypothyroidism): muscle pain and weakness possible.
Management
The combination is acceptable without dose change. In patients with myopathy risk factors, check creatine kinase on muscle symptoms. Alternative PPI without CYP3A4 effect: pantoprazole or rabeprazole.
Sources
Mechanism
Ciprofloxacin absorbs better in acidic gastric environment. Omeprazole raises gastric pH — ciprofloxacin bioavailability drops by 20–30%. Clinically significant in infections with borderline pathogen sensitivity.
Symptoms
In severe infection: inadequate clinical response — persistent fever, symptoms, and inflammation markers 48–72 hours after antibiotic start.
Management
On the combination, take ciprofloxacin 2 hours before or 6 hours after omeprazole. If dosing cannot be separated, alternative antibiotics: amoxicillin-clavulanate for respiratory infections, a cephalosporin for UTIs. In urinary infections, ciprofloxacin still reaches adequate urine concentrations regardless of bioavailability.
Sources
Mechanism
Proton pump inhibitors raise gastric pH, reducing levothyroxine absorption. TSH may rise 2–4 weeks after starting omeprazole.
Symptoms
Return of hypothyroidism: fatigue, weight gain, cold intolerance, dry skin, low mood. In thyroid cancer (TSH suppression needed), loss of control.
Management
Take levothyroxine 30–60 minutes before food and omeprazole. Check TSH 6–8 weeks after starting or stopping omeprazole. If TSH rises, increase levothyroxine by 12.5–25 mcg.
Sources
Mechanism
Omeprazole inhibits CYP2C19, the enzyme responsible for sertraline metabolism. Sertraline levels rise by about 40%. Adverse effects may intensify: nausea, insomnia, sexual dysfunction.
Symptoms
Nausea, diarrhoea, insomnia or somnolence, tremor, anxiety, decreased libido. Symptoms appear in the first 1–2 weeks after starting omeprazole in patients on stable sertraline.
Management
For short omeprazole courses (2–4 weeks), no specific adjustment needed. For long-term therapy with significant adverse effects, reduce sertraline by 25–50% or switch to pantoprazole (minimal CYP2C19 effect).
Sources
Mechanism
Proton pump inhibitors suppress gastric acidity and reduce B12 release from food (which requires HCl and pepsin). For short courses (up to 8 weeks), clinically insignificant. With long-term therapy (over 2 years), B12 deficiency risk is reported.
Symptoms
On long-term therapy: fatigue, pallor, paraesthesias in hands and feet, gait instability, memory decline.
Management
For short omeprazole courses, no adjustment needed. On long-term therapy (over 2 years), check B12 yearly. If it falls below 200 pg/mL, give cyanocobalamin 500–1000 mcg/day orally — passive diffusion absorption at high doses works regardless of acidity.
Sources
Mechanism
Omeprazole weakly inhibits intestinal OCT1, the transporter mediating metformin absorption. Metformin bioavailability may rise slightly. Clinical significance is minimal.
Symptoms
The combination usually causes no specific symptoms. Each drug's individual side effects remain.
Management
No dose adjustment needed. On long-term PPI therapy (over 2 years), check B12 yearly — both drugs may reduce its absorption.
Sources
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FDA category C. Large cohort studies have not shown a significant increase in birth defects. Used when clinically necessary and benefits outweigh risks.
Passes into milk in minimal amounts. Considered compatible with breastfeeding in infants over 1 month old.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Omeprazole is evaluated for the following indications with varying evidence strength: Peptic ulcer disease (evidence tier A), Gastroesophageal reflux disease (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 Omeprazole (≥ 1 in 100): Headache, Diarrhea or constipation, Nausea, flatulence, Abdominal pain. See the Safety section for uncommon and serious reactions.
FDA category C. FDA category C. Large cohort studies have not shown a significant increase in birth defects. Used when clinically necessary and benefits outweigh risks.
Passes into milk in minimal amounts. Considered compatible with breastfeeding in infants over 1 month old.
Omeprazole is contraindicated in: Hypersensitivity to any component; Concomitant use with rilpivirine and nelfinavir. Full list in the Safety section.
long-term use is associated with hypomagnesemia, vitamin B12 deficiency, increased fracture risk, acute interstitial nephritis, C. difficile infection, and community-acquired pneumonia. Prescribing should be justified and periodically reviewed.
many patients do well with lifestyle changes (weight, meals, sleep position) and a short PPI course. Lifelong therapy is justified in severe erosive esophagitis, Barrett esophagus, or Zollinger-Ellison syndrome.