Omeprazole and St John's Wort: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
St John's Wort
No brand names on recordOmeprazole
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
St. John's Wort can make omeprazole (Prilosec) work less well. Omeprazole lowers stomach acid to treat heartburn, reflux, and ulcers. St. John's Wort speeds up the liver enzymes that break omeprazole down, so your body clears the medicine faster and there is less of it in your blood.
In practice, that means your heartburn or reflux symptoms could come back or not be controlled as well. The good news is this is very manageable. Don't stop or change anything on your own. Just let your pharmacist or doctor know you're taking both, and they can guide you on the safest plan.
Effect: Reduced omeprazole exposure (decreased Cmax and AUC) with possible loss of acid-suppression efficacy.
Mechanism: St John's Wort induces CYP3A4 and CYP2C19, the enzymes that extensively metabolize omeprazole, accelerating its clearance. Magnitude is influenced by CYP2C19 genotype.
- Direction: Enzyme induction lowers parent drug levels (omeprazole is active as-is, not a prodrug dependent on these enzymes).
- Evidence: Probable; supported by crossover PK studies in healthy subjects.
- Onset: Unspecified; induction typically develops over days to weeks.
- Management: Avoid concomitant use. If therapy overlaps, monitor symptom control and consider individualized adjustment or an alternative.
What happens
Reduced omeprazole exposure
Interaction Deep Dive
CYP2C19 and CYP3A4 are responsible for the extensive metabolism of omeprazole. Taking omeprazole together with St John's wort (an inducer of CYP3A4) can markedly lower omeprazole plasma levels. A crossover study conducted in healthy males found that giving St John's wort alongside omeprazole reduced both the Cmax and AUC of omeprazole 23. A separate study demonstrated that this combination significantly lowered omeprazole serum concentrations in healthy Chinese participants whose CYP2C19 genotype was established. During prolonged St John's wort use, the effect on omeprazole exposure varied according to the CYP2C19 genotype allelic variants present in the participants 4. Omeprazole should not be given concurrently with St John's wort 231.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism of omeprazole by St John's wort; induction of CYP2C19-mediated metabolism of omeprazole by St John's wort
How to manage this interaction
What your care team may do:
- Because St. John's Wort can substantially lower omeprazole levels, the usual guidance is to avoid using them together.
- Your team may look at whether the St. John's Wort can be stopped, or whether your reflux/ulcer treatment needs to be adjusted and individualized.
- They may monitor your symptoms more closely to be sure your acid control is still working.
What you should do: Keep taking your omeprazole as prescribed and don't stop either product on your own. Tell your pharmacist or prescriber that you use St. John's Wort (many people don't mention supplements), and ask them for the safest plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) Taking St John's Wort together with omeprazole markedly lowered omeprazole serum levels, with the effect varying according to the dominant variant of each individual's CYP2C19 genotype. In a randomized, placebo-controlled crossover study, healthy Chinese participants with known CYP2C19 genotype (n=12) were given a 14-day oral course of either placebo or St John's Wort 300 mg three times daily. Six participants had the 'wild-type' allele for the CYP2C19 genotype (extensive metabolizer phenotype) and six had 'mutant' CYP2C19 alleles corresponding to 'poor metabolizer' phenotypes. On day 15, each participant took a single oral 20 mg dose of omeprazole, following which blood samples were assessed over the subsequent 12 hours for omeprazole along with its metabolites 5-hydroxyomeprazole (5-HO; CYP2C19-dependent) and omeprazole sulfone (OS; CYP3A4-dependent). Participants then switched to the alternate study arm following a 5-week washout interval. Relative to placebo, concurrent St John's Wort in extensive metabolizers significantly lowered the mean Cmax of omeprazole from 1.64 mcmol/L to 0.76 mcmol/L and the AUC from 3.19 mcmol x hour/L to 1.63 mcmol x hour/L (-49.6% and 43.9%, respectively; p=0.017 and p=0.011, respectively). Mean maximum serum concentrations of 5-HO and OS were 38.1% and 155.5% higher, respectively, following St John's Wort exposure (p=0.028 and p=0.001, respectively). Omeprazole Cmax was likewise decreased in poor metabolizers given concurrent St John's Wort (-37.5% versus the placebo group; p less than 0.001), yet mean maximum serum concentrations of 5-HO were considerably lower in poor metabolizers than in extensive metabolizers (0.26 mcmol/L versus 1.21 mcmol/L; p less than 0.001) after St John's Wort exposure 4.
b) In a crossover study, giving St John's Wort (300 mg three times daily for 14 days) together with omeprazole in 12 healthy male participants reduced omeprazole Cmax and AUC by 37.5% and 37.9%, respectively, in CYP2C19 poor metabolizers, and by 49.6% and 43.9%, respectively, in extensive metabolizers 23.
Common questions
Can I take Omeprazole and St John's Wort together?
St. John's Wort speeds up how fast your body clears omeprazole, so the omeprazole may not control your acid symptoms as well. It's best to avoid the combination, so tell your pharmacist or doctor before using both. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Omeprazole and St John's Wort interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Omeprazole and St John's Wort interaction managed?
What your care team may do: Because St. John's Wort can substantially lower omeprazole levels, the usual guidance is to avoid using them together. Your team may look at whether the St. John's Wort can be stopped, or whether your reflux/ulcer treatment needs to be adjusted and individualized. They may monitor your symptoms more closely to be sure your acid control is still working. What you should… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Omeprazole or St John's Wort need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (4)
- Product Information: KONVOMEP(TM) powder for oral suspension, omeprazole sodium bicarbonate powder for oral suspension. Azurity Pharmaceuticals Inc (per manufacturer), Woburn, MA, 2022. DailyMed
- Product Information: PRILOSEC(R) oral delayed-release capsules, omeprazole oral delayed-release capsules. AstraZeneca Pharmaceuticals LP (Per FDA), Wilmington, DE, 2011. DailyMed
- Product Information: PRILOSEC(R) delayed-release oral suspension, omeprazole magnesium delayed-release oral suspension. AstraZeneca Pharmaceuticals LP (Per FDA), Wilmington, DE, 2011. DailyMed
- Wang L-S, Zhou G, Zhu B, et al: St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Ther 2004; 75(3):191-197. PubMed
Keep reading about St John's Wort
Keep reading about Omeprazole
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
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