What happens when you take omeprazole with st. john's wort?
St. John's wort (Hypericum perforatum) is one of the most potent natural enzyme inducers known. Its active constituents, primarily hyperforin, activate the pregnane X receptor (PXR), which upregulates expression of cytochrome P450 enzymes including CYP3A4 and CYP2C19, as well as the drug efflux transporter P-glycoprotein. After about 2 weeks of regular St. John's wort use, these systems are running at substantially higher capacity.
Omeprazole is metabolized by both CYP2C19 (primary, producing 5-hydroxyomeprazole) and CYP3A4 (secondary, producing omeprazole sulfone). St. John's wort induces both pathways simultaneously, which dramatically accelerates omeprazole clearance. A controlled study by Wang et al. (2004) showed that 14 days of St. John's wort 300 mg three times daily reduced omeprazole AUC by 38% in CYP2C19 wild-type subjects and increased clearance via both metabolic routes. The plasma concentration of omeprazole dropped substantially, with corresponding loss of acid-suppressing effect.
Why is this important?
Omeprazole is prescribed for serious conditions where loss of acid suppression has real consequences: peptic ulcer disease (risk of bleeding and perforation), severe GERD with esophagitis (risk of progression to Barrett's esophagus), Zollinger-Ellison syndrome, and H. pylori eradication regimens (which depend on PPI to maintain gastric pH high enough for antibiotics to work).
If omeprazole exposure drops by 30-50%, the acid-suppressing effect can become inadequate. Breakthrough symptoms return, esophagitis may not heal, and H. pylori eradication rates drop. For someone on omeprazole for a serious ulcer or as part of triple therapy, this is not a trivial loss of efficacy.
The broader problem with St. John's wort is that it does not interact with just omeprazole. It induces CYP3A4 and P-glycoprotein, which together metabolize an estimated 50% of marketed drugs. The list of clinically significant interactions includes: SSRIs and SNRIs (additive serotonergic effect, risk of serotonin syndrome), warfarin (reduced INR, thrombosis risk), oral contraceptives (contraceptive failure with breakthrough bleeding and unintended pregnancy), immunosuppressants like cyclosporine and tacrolimus (transplant rejection), antiretrovirals like indinavir (loss of HIV control), digoxin, statins, calcium channel blockers, benzodiazepines, and many chemotherapeutics. The FDA has issued specific warnings on multiple drug labels because of St. John's wort interactions.
What should you do?
- Do not combine. If omeprazole is medically necessary, avoid St. John's wort. The interaction is well-documented and clinically meaningful.
- Disclose all supplements to your doctor and pharmacist. St. John's wort is widely used for low mood, anxiety, and sleep. Many patients do not consider it a "real" medication and fail to mention it. Always include it in your medication list.
- For mood concerns, talk to your clinician. Mild to moderate depression has multiple evidence-based options that do not interact with omeprazole the way St. John's wort does (though SSRI choice on PPIs has its own considerations). Therapy and structured behavioral approaches are also effective.
- If you have been on both, do not stop omeprazole abruptly. Rebound acid hypersecretion can occur. Stop St. John's wort, recognize that enzyme induction takes about 2 weeks to wash out, and discuss with your doctor whether your PPI dose needs adjustment during that window.
- H. pylori eradication is high stakes. If you are on a triple- or quadruple-therapy regimen including omeprazole, do not take St. John's wort during the 10-14 day treatment. Eradication failure makes resistant H. pylori more likely.
- Check other medications. If you take St. John's wort, you also need to check for interactions with everything else you take. Warfarin, oral contraceptives, and immunosuppressants are especially high-risk.
Which specific products are affected?
St. John's wort is sold under many brand names and as generic Hypericum perforatum extract. Strengths range from 300-450 mg of extract standardized to 0.3% hypericin or 3-5% hyperforin. Brands include Kira, Nature's Way St. John's Wort, Nature's Bounty, Solgar, NOW, and many others. Tea preparations also induce enzymes, though less reliably. The interaction is driven primarily by hyperforin content, so high-hyperforin extracts (3-5%) cause stronger induction than low-hyperforin extracts. However, all standard extracts induce enough to clinically affect omeprazole.
On the omeprazole side, the interaction applies to all formulations: Prilosec OTC, Prilosec prescription, omeprazole/sodium bicarbonate (Zegerid), and generic omeprazole capsules and tablets. The interaction extends to other PPIs metabolized by CYP2C19 and CYP3A4: esomeprazole (Nexium), pantoprazole (Protonix), lansoprazole (Prevacid), and rabeprazole (AcipHex). Pantoprazole and rabeprazole are less CYP2C19-dependent so the interaction may be slightly smaller, but still clinically present.
The bottom line
St. John's wort potently induces CYP3A4 and CYP2C19, which together metabolize omeprazole. The result is significantly lower omeprazole plasma concentrations and reduced acid suppression, which can compromise treatment of GERD, peptic ulcers, and H. pylori eradication. Avoid this combination. If you have been taking both, stop St. John's wort and talk to your doctor; PPI dose may need adjustment until enzyme induction washes out over about 2 weeks. Remember that St. John's wort has many other clinically significant interactions including SSRIs (serotonin syndrome), warfarin, oral contraceptives, and immunosuppressants. Always disclose herbal products to your prescriber and pharmacist.