Omeprazole is a medicine that reduces the production of acid in the stomach (proton pump inhibitor). It is used for frequent heartburn and, on prescription, for problems such as reflux and stomach and duodenal ulcers. For frequent heartburn (2 or more days a week), it may take 1 to 4 days for full effect.
Also known as: Losec
Rifampin accelerates Omeprazole metabolism and reduces its acid-suppressing effect.
Omeprazole is metabolised by CYP2C19 and CYP3A4; rifampicin induces these enzymes and can reduce its concentrations by more than 50%, decreasing gastric acid suppression (relevant in ulcer, severe GORD or stress prophylaxis). Monitor the clinical response and consider increasing the omeprazole dose or preferring a less affected PPI (e.g. pantoprazole) during the combination.
Omeprazole + rifampicin: rifampicin lowers omeprazole levels (CYP2C19/3A4 induction), reducing acid suppression. Monitor the response and consider adjustment.
CYP2C19 induction, the main Omeprazole metabolic pathway.
Symptom control (dyspepsia, GERD, ulcer).
Recurrent gastric symptoms.
Consider a higher dose or an alternative (e.g. a PPI less dependent on CYP2C19).
DailyMed/FDA (NIH/NLM) — approved Rifampin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Reduced Levothyroxine absorption with higher gastric pH.
The levothyroxine label states that gastric acidity is essential for adequate absorption and that proton pump inhibitors can cause hypochlorhydria, affect intragastric pH and reduce levothyroxine absorption, potentially raising dose requirements in some hypothyroid patients; appropriate patient monitoring is recommended. In practice, keep levothyroxine always on an empty stomach, 30–60 minutes before breakfast, separate it from the PPI as much as possible and monitor TSH, adjusting the dose if needed, especially when starting or stopping the PPI.
Levothyroxine + omeprazole: the PPI can reduce levothyroxine absorption (hypochlorhydria). Keep levothyroxine on an empty stomach, separate administration and monitor TSH.
Levothyroxine dissolution depends on gastric acid; the PPI reduces absorption.
TSH 6–8 weeks after starting the PPI.
Persistent fatigue, weight gain, cold intolerance — possible signs of hypothyroidism.
Give Levothyroxine 30–60 minutes before breakfast and monitor TSH.
DailyMed/FDA (NIH/NLM) — approved Levothyroxine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=55f4c679-86cb-b97f-e063-6294a90ad5ef ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Omeprazole (proton-pump inhibitor) reduces Ketoconazole absorption by raising gastric pH.
Ketoconazole (tablet) is a weak base whose dissolution and oral absorption depend strongly on acidic gastric pH. Omeprazole, by suppressing acid secretion, reduces ketoconazole plasma concentrations in a clinically significant way, potentially compromising the treatment of systemic fungal infections. The ketoconazole label and the Portuguese Prontuário Terapêutico recommend avoiding the combination or, if unavoidable, considering alternative formulations and monitoring the clinical response to the antifungal.
Omeprazole + ketoconazole: ketoconazole absorption depends on acidic pH and is drastically reduced by PPIs. Avoid the combination.
pH-dependent absorption: acid suppression reduces ketoconazole dissolution in the stomach.
Clinical response to the antifungal.
Persistent fungal infection.
Separate dosing (ketoconazole 2 h before omeprazole) or prefer a non-pH-dependent azole.
DailyMed/FDA (NIH/NLM) — approved Ketoconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f162e616-21b4-49b1-b437-15e21001a6f0 ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Omeprazole raises Voriconazole levels (CYP2C19 inhibition) and voriconazole raises omeprazole levels.
The interaction is bidirectional and mediated by CYP2C19: voriconazole inhibits CYP2C19 and can raise omeprazole concentrations (Cmax ≈2× and AUC ≈4× per the voriconazole label), while omeprazole increases voriconazole exposure by about 15% (Cmax) and 40% (AUC). The voriconazole label recommends halving the omeprazole dose when starting voriconazole in patients on omeprazole ≥40 mg (no voriconazole dose adjustment needed). In practice, monitor the adverse effects of both (headache, diarrhoea, PPI hypomagnesaemia; voriconazole photosensitivity, hepatotoxicity and visual disturbances) and consider voriconazole therapeutic drug monitoring.
Omeprazole + voriconazole: bidirectional interaction — voriconazole raises omeprazole (2–4×) and omeprazole increases voriconazole (~15–40%). Halve the omeprazole dose.
Bidirectional CYP2C19 interaction: omeprazole inhibits voriconazole metabolism; voriconazole inhibits omeprazole metabolism.
Voriconazole levels (if available), liver function tests, visual effects.
Photophobia, visual disturbances, elevated transaminases.
Monitor voriconazole response and adverse effects; consider reducing the voriconazole dose with long-term use.
DailyMed/FDA (NIH/NLM) — approved Voriconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f6a1a792-141b-42e8-8bd1-884e4408eb8a ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Combining Atazanavir with Omeprazole substantially reduces Atazanavir concentrations, with a risk of virological failure.
Atazanavir absorption depends on an acidic gastric pH: omeprazole, by suppressing acid secretion, reduces the solubility and plasma concentration of atazanavir in a clinically significant way, with a risk of loss of virologic response and development of resistance (the atazanavir label explicitly warns about this risk). If the combination is unavoidable, the label recommends not exceeding a PPI dose comparable to omeprazole 20 mg and taking it approximately 12 hours before atazanavir 300 mg with ritonavir 100 mg, with virological monitoring. In HIV patients, any drug that raises gastric pH must be managed carefully and reassessed.
Omeprazole + atazanavir: the PPI markedly reduces atazanavir exposure, with a risk of antiretroviral failure. Avoid; if needed, PPI ≤20 mg 12 hours before with boosting and monitoring.
Proton pump inhibitors such as Omeprazole raise gastric pH, reducing Atazanavir absorption and lowering its exposure.
Monitor viral load and, if available, CD4; reassess when Omeprazole is started or stopped.
Detectable viral load or signs of therapeutic failure after starting Omeprazole require reassessment of the antiretroviral regimen.
Avoid the combination when possible; if unavoidable, prefer H2-receptor antagonists and/or separate dosing times; do not use a PPI with low doses of Atazanavir.
DailyMed/FDA (NIH/NLM) — approved Atazanavir label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=165cff62-b284-4a27-a65d-9ec8a5bfcdd8 ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Long-term omeprazole may reduce absorption of dietary vitamin B12, but rarely affects supplemental cyanocobalamin.
Proton pump inhibitors such as omeprazole reduce the gastric acid secretion needed to release protein-bound vitamin B12 from food, so long-term use can reduce dietary B12 absorption and, in rare cases, lead to vitamin B12 deficiency. Supplemental cyanocobalamin at pharmacological doses is absorbed by passive diffusion, independent of intrinsic factor and pH, so oral supplementation maintains efficacy. In patients on chronic omeprazole with risk factors (elderly, vegetarian diet, atrophic gastritis), consider monitoring B12 and supplementing if needed.
Long-term omeprazole may reduce absorption of dietary vitamin B12, but rarely affects supplemental cyanocobalamin.
PPI-induced prolonged hypochlorhydria reduces release of food-bound B12.
Monitor blood count and B12 levels in elderly or malnourished patients.
Macrocytic anaemia or persistent neuropathic symptoms.
With long-term PPI use, monitor B12 levels in at-risk patients.
DailyMed (FDA) — approved Cyanocobalamin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3bb870d8-128d-75ea-e063-6394a90a707b ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Omeprazole may reduce the absorption of oral iron, particularly non-heme iron.
Non-haem iron absorption (present in oral supplements) depends on acidic gastric pH, which keeps iron in the more absorbable ferrous form; omeprazole, by suppressing acid secretion, can reduce absorption and the efficacy of supplementation in patients with iron deficiency anaemia. In patients on a PPI with an unsatisfactory response to oral iron, consider increasing the dose, separating administrations, preferring haem iron or alternate-day dosing, and assess the need for intravenous iron.
Iron + omeprazole: raised pH reduces non-haem iron absorption. Monitor the response to supplementation and consider parenteral iron if needed.
Gastric acid suppression by the PPI impairs the reduction of Fe3+ to Fe2+, essential for duodenal iron absorption.
Monitor the therapeutic response of iron-deficiency anaemia.
Persistent iron-deficiency anaemia despite treatment.
Consider monitoring the response to iron (haemoglobin, ferritin); separate administration times.
DailyMed (FDA) — approved Iron label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=73d1f079-d8eb-44f4-b33d-05fb25b80c8f ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
PPI + calcium: omeprazole reduces calcium carbonate absorption.
Calcium carbonate requires an acidic gastric pH to dissolve and be absorbed; proton pump inhibitors (PPIs) such as omeprazole raise gastric pH and reduce calcium absorption from carbonate. In patients on long-term PPIs taking calcium supplements (common in osteoporosis prevention), the efficacy of supplementation can be compromised. Alternatives: use calcium citrate (pH-independent absorption), increase the dose under serum calcium monitoring, or consider the clinical impact. The interaction is of moderate relevance — do not stop PPIs without indication, but consider the most appropriate calcium salt.
PPI + calcium: omeprazole reduces calcium carbonate absorption. Consider calcium citrate or monitor.
Calcium carbonate requires gastric acid to dissolve and be absorbed; omeprazole suppresses acidity.
Serum calcium and clinical response.
No acute symptoms; risk of deficiency with long-term use.
In PPI patients, prefer calcium citrate or adjust the calcium dose.
DailyMed (FDA) — approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 ; approved Calcium carbonate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=348d3dfa-6a52-4583-96e3-83c4bf2df45b — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Antacids may reduce omeprazole absorption when taken at the same time.
Omeprazole is a proton pump inhibitor (PPI) usually taken on an empty stomach, 30–60 minutes before breakfast. Antacids can be used concomitantly for symptomatic relief, but simultaneous administration can reduce omeprazole absorption (which depends on the enteric coating and the pH of the medium) and decrease its efficacy. The omeprazole label considers the combination acceptable, but in practice it is recommended to separate administration by 1–2 hours. In patients with refractory symptoms, assess adherence and timing before escalating the PPI dose.
Antacids + omeprazole: generally compatible, but separate administration (at least 1–2 hours) to avoid reducing omeprazole absorption.
Gastric pH change and altered dissolution of gastro-resistant capsules by the antacid.
Monitor response to antacid/anti-ulcer therapy.
Insufficient symptom control.
Separate administration times (2 hours).
DailyMed (FDA) — approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 ; approved Antacids label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5e346dc0-69ce-4cc5-bb5d-bfa833e11c1f — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Bisphosphonate + PPI: possible reduced alendronate absorption and effect.
Omeprazole reduces gastric acidity, which can decrease the absorption of some oral bisphosphonates and their efficacy in osteoporosis; additionally, long-term proton pump inhibitor use is associated with an increased risk of bone fractures (possibly through reduced calcium absorption and direct effects on bone metabolism). In patients taking alendronate, the PPI should be used only with a clear indication, at the lowest dose and for the shortest time possible; reassess the need for gastroprotection and ensure adequate calcium and vitamin D intake.
Omeprazole + alendronate: PPIs can reduce bisphosphonate absorption and long-term use is associated with a higher fracture risk. Reassess the PPI need.
Acid suppression may reduce alendronate dissolution/absorption.
Assess adherence and therapeutic response.
Fracture or lack of densitometric improvement.
Ensure correct schedule (fasting + water) and reassess the need for the PPI.
DailyMed (FDA) — approved Alendronate label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c7e470d6-508e-466e-a78d-060bbbc9745c ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Reduced Clopidogrel efficacy. Omeprazole inhibits CYP2C19, reducing pro-drug activation.
Clopidogrel is a prodrug that depends on CYP2C19 to be converted into the active metabolite; omeprazole is a potent inhibitor of this enzyme and reduces the formation of the active metabolite and platelet inhibition, with a documented increased risk of cardiovascular events. The clopidogrel label advises against co-administration with CYP2C19 inhibitors such as omeprazole and esomeprazole. Whenever gastroprotection is needed in patients taking clopidogrel, prefer pantoprazole (less CYP2C19 inhibition) or an H2 antagonist, and avoid the combination.
Clopidogrel + omeprazole: omeprazole inhibits CYP2C19 and reduces clopidogrel activation, decreasing antiplatelet protection. Avoid; prefer pantoprazole or an H2 antagonist.
Clopidogrel requires CYP2C19 for activation; Omeprazole potently inhibits that enzyme.
Watch for thrombotic events (chest pain, neurological symptoms).
New thrombotic events — chest pain, sudden unilateral weakness, speech changes.
Prefer Pantoprazole (less interaction) or another gastric protectant when needed.
DailyMed/FDA (NIH/NLM) — approved Clopidogrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9928956-bb7b-4ec2-bc38-d3c9c4199cae ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Omeprazole may reduce Chloroquine absorption by raising gastric pH.
Chloroquine is a weak base whose gastrointestinal absorption can be reduced when gastric pH is raised, as happens with proton pump inhibitors. Although the clinical impact is variable, reduced absorption can compromise malaria prophylaxis or treatment or use in autoimmune diseases. Separate administration (for example, omeprazole on an empty stomach and chloroquine at a distant time), ensure adherence and monitor the clinical response; in patients with unexplained therapeutic failure, reassess the combination.
Omeprazole + chloroquine: raised pH can reduce chloroquine absorption. Monitor response and separate administration.
Lower Chloroquine solubility at higher pH.
Response to treatment.
Malaria treatment failure.
Consider an alternative and monitor the clinical response.
DailyMed/FDA (NIH/NLM) — approved Chloroquine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06c69e2b-211b-4746-9f3a-f86d36520570 ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1
Combining Phenytoin with Omeprazole may increase Phenytoin concentrations and cause toxicity.
Phenytoin is metabolised in the liver, partly by CYP2C19, the same enzyme inhibited by omeprazole. Co-administration can raise phenytoin concentrations and precipitate toxicity (nystagmus, ataxia, sedation, dysarthria), especially at PPI start or at high doses. Monitor serum phenytoin levels and signs of toxicity when starting or stopping omeprazole, adjusting the dose as needed. In epileptic patients with stable control, prefer, if possible, a PPI with lower interaction potential.
Phenytoin + omeprazole: the PPI can raise phenytoin levels (CYP2C19 inhibition). Monitor levels and signs of toxicity.
Omeprazole is a CYP2C19 inhibitor, a pathway involved in Phenytoin metabolism, and may raise its levels.
Watch for nystagmus, ataxia and sedation after starting Omeprazole.
Nystagmus, ataxia or sedation after starting Omeprazole require level testing and adjustment.
Monitor signs of Phenytoin toxicity and serum levels, adjusting the dose if needed.
DailyMed/FDA (NIH/NLM) — approved Phenytoin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef4e97a7-cd18-47a9-a016-2eca5481a87e ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Omeprazole may slightly increase the effect of warfarin, with a risk of INR elevation.
Omeprazole inhibits CYP2C19, an enzyme involved in R-warfarin metabolism; the inhibition can reduce warfarin clearance and raise the INR, although the effect is generally modest and variable between patients. Other proton pump inhibitors with less CYP2C19 affinity (e.g. pantoprazole) are sometimes preferred in anticoagulated patients. The INR should be monitored when omeprazole is started or stopped, especially in patients with a borderline INR or relevant genetic polymorphisms, and the dose adjusted as needed.
Omeprazole inhibits CYP2C19 and can slightly raise the INR (usually modest, but relevant in sensitive patients). Monitor the INR when starting the PPI.
Omeprazole inhibits CYP2C19 and may alter warfarin metabolism (R-isomer).
Monitor the INR more frequently.
Bleeding from supratherapeutic INR.
Monitor the INR when starting or stopping omeprazole.
DailyMed (FDA) — approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6ea9a6f3-b756-4cdf-b3db-f666a2c17d66 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057 — additional reference: Prontuário Terapêutico do INFARMED (11th ed., 2012)
Omeprazole reduces Itraconazole absorption by raising gastric pH, compromising efficacy.
Itraconazole capsules require an acidic gastric medium to dissolve and absorb the drug; omeprazole, by raising the pH, reduces itraconazole plasma concentrations and can compromise antifungal treatment or prophylaxis. Separate administration (itraconazole with a meal and the PPI on an empty stomach) and, alternatively, use the itraconazole oral solution, which is less pH-dependent. Monitor the clinical response and, when available, the antifungal concentration.
Itraconazole (capsules) + omeprazole: absorption depends on acidic pH and is reduced by PPIs. Separate administration and consider the oral solution.
pH-dependent absorption: acid suppression reduces itraconazole dissolution in the stomach.
Clinical response to the antifungal.
Persistent fungal infection.
Separate dosing, switch omeprazole to a short-acting antacid outside the dosing window, or use another class.
DailyMed/FDA (NIH/NLM) — approved Itraconazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a4d555fa-787c-40fb-bb7d-b0d4f7318fd0 ; approved Omeprazole label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=37291cab-e350-d8e3-e063-6294a90a9cb1 — with additional reference: Prontuário Terapêutico do INFARMED, INFARMED (11th ed., 2012)
Food may delay omeprazole absorption; taking it before breakfast optimises acid suppression.
Take 30–60 minutes before breakfast.
EMC-UK (MHRA) — approved Omeprazole SmPC: https://www.medicines.org.uk/emc/product/1509/smpc
Long-term omeprazole may cause symptomatic hypomagnesaemia.
Check serum magnesium in long-term therapy (> 1 year), especially with diuretics or digoxin.
EMC-UK (MHRA) — approved Omeprazole SmPC: https://www.medicines.org.uk/emc/product/1509/smpc
Long-term proton pump inhibitor use is associated with an increased risk of fractures.
Use the lowest effective dose and duration; consider calcium/vitamin D supplementation when indicated.
EMC-UK (MHRA) — approved Omeprazole SmPC: https://www.medicines.org.uk/emc/product/1509/smpc
Omeprazole is widely used in pregnancy (reflux/heartburn); available evidence does not indicate an increased risk of malformations.
Can be used in all trimesters when indicated.
Excreted into breast milk in small amounts; compatible with breastfeeding.
No specific additional contraception.
EMC-UK (MHRA) — approved Omeprazole SmPC: https://www.medicines.org.uk/emc/product/1509/smpc
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Proton pump inhibitor: the antisecretory effect begins within one hour, with maximum within two hours; inhibition is about 50% of maximum at 24 hours and can last up to 72 hours, due to prolonged binding to the H+/K+-ATPase pump. After discontinuation, acid secretion returns gradually over 3 to 5 days.
Specifically inhibits the H+/K+-ATPase enzyme system (proton pump) at the secretory surface of the gastric parietal cell, blocking the final step of acid production; the effect is dose-related and inhibits both basal and stimulated acid secretion, irrespective of the stimulus.
Absorption begins only after the enteric-coated granules leave the stomach; peak plasma concentrations occur 0.5 to 3.5 hours after dosing. Absolute bioavailability is about 30 to 40% (20 to 40 mg), largely due to first-pass metabolism. Plasma protein binding is about 95%.
Extensively metabolised in the liver by the cytochrome P450 system: most depends on CYP2C19 (formation of hydroxyomeprazole) and the remainder on CYP3A4 (formation of omeprazole sulphone). About 77% of the dose is eliminated in urine as at least six metabolites; the remainder is recovered in faeces (significant biliary excretion).
The plasma half-life in healthy subjects is 0.5 to 1 hour; in patients with chronic hepatic disease it prolongs to about 3 hours. The short half-life contrasts with the prolonged duration of the antisecretory effect.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
