St. John's Wort + Warfarin Sodium
Warfarin Sodium brand names: Coumadin, Panwarfin, Sofarin.
Warfarin Sodium falls into 5 drug categories that St. John's Wort can interact with; the most serious is rated major. St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.
Read the full interaction reportSt. John's Wort and Warfarin Sodium
These two interact in 5 distinct ways. Each one is explained separately below.
Why Are There 5 Interactions?
St. John's Wort interacts with whole categories of medication. Warfarin Sodium falls into 5 of those categories, so it can interact with St. John's Wort in 5 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Major).
CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES
1 of 5Why this applies to Warfarin Sodium
Warfarin Sodium falls under CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES — the group St. John's Wort interacts with.
St. John's wort induces CYP3A4 enzymes and increases metabolism of CYP3A4 substrates. Clinically significant interactions have been reported with St. John's wort products containing hyperforin 1 mg or more.
Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports..
Here's the short version: St. John's wort revs up a liver enzyme (CYP3A4) that helps clear warfarin from your body. When that enzyme speeds up, warfarin gets broken down faster and its levels drop. For a blood thinner, that's a real problem. Less warfarin means your blood may clot more easily again, which raises the risk of the very thing it's meant to prevent, like a stroke or a clot in your leg or lungs.
Warfarin is a narrow-therapeutic-index drug, so even small shifts can throw off your INR (the blood test that guides your dose). And if someone later stops the herb, warfarin can swing back up and bleeding risk climbs. Please don't start or stop either one on your own. Talk with your pharmacist or doctor first so they can monitor you safely.
- Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
- Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St. John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003;290:1500-4.. PubMed
- Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.. PubMed
- Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
- Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004;32:512-8. PubMed
- Smith M, Lin KM, and Zheng YP. PIII-89 an open trial of nifedipine-herb interactions: Nifedipine with St. John's wort, ginseng or ginkgo biloba. Clin Pharm Ther 2001;69:P86.
- Kawaguchi, A., Ohmori, M., Tsuruoka, S., Nishiki, K., Harada, K., Miyamori, I., Yano, R., Nakamura, T., Masada, M., and Fujimura, A. Drug interaction between St John's Wort and quazepam. Br.J.Clin Pharmacol. 2004;58(4):403-410. PubMed
- Dresser, G. K., Schwarz, U. I., Wilkinson, G. R., and Kim, R. B. Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects. Clin Pharmacol Ther 2003;73(1):41-50. PubMed
- Patel, J., Buddha, B., Dey, S., Pal, D., and Mitra, A. K. In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am.J.Ther. 2004;11(4):262-277. PubMed
- Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
- Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ. Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol. 2018.
- Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
- Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
- Gümüs KS, Teegelbekkers A, Sauter M, et al. Effect of Tacrolimus Formulation (Prolonged-Release vs Immediate-Release) on Its Susceptibility to Drug-Drug Interactions with St. John's Wort. Clin Pharmacol Drug Dev 2024. PubMed
WARFARIN (Coumadin)
2 of 5Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers. This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4. St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin. In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption.
Well-controlled human studies have demonstrated the likely existence of this interaction.
Here's the practical takeaway: St. John's wort tends to make warfarin work less well. The herb revs up liver enzymes (CYP1A2 and CYP3A4) that clear warfarin out of your body faster, and it may even bind to some of the warfarin in your gut so less gets absorbed. The result is a lower INR, meaning your blood may clot more easily than your doctor intends.
Why this matters: warfarin is a narrow-margin drug, so even small shifts can be a big deal. With less protection, you could be at higher risk for the very clots warfarin is meant to prevent, like a stroke or a clot in the leg or lung. Please don't start or stop either one on your own. Talk with your pharmacist or doctor first so they can check your INR and adjust safely.
- Yue QY, Bergquist C, Gerden B. Safety of St. John's wort (Hypericum perforatum). Lancet 2000;355:576-7. PubMed
- Groning R, Breitkreutz J, Muller RS. Physico-chemical interactions between extracts of Hypericum perforatum L. and drugs. Eur J Pharm Biopharm 2003;56:231-6.. PubMed
- Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57:592-9. PubMed
- Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES
3 of 5Warfarin Sodium also falls under CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES.
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces CYP2C19 and increases metabolism of mephenytoin (Mesantoin). In patients with wild-type 2C19 (2C19*1/*1) metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism. Theoretically, St. John's wort might increase metabolism of other CYP2C19 substrates.
Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
Here's the practical takeaway for warfarin. St. John's wort tends to speed up several liver enzymes that clear medications, and warfarin is one of those drugs. When the herb revs up that breakdown, your body can clear warfarin faster, which often means thinner protection against clots. In real life that can show up as a dropping INR and a higher risk of the very clots warfarin is meant to prevent.
Because warfarin is a narrow therapeutic index drug, even small shifts matter a lot, and St. John's wort is famous for being unpredictable here. Please don't start, stop, or change either one on your own. Talk with your pharmacist or doctor first, since they may want to check your INR more closely.
- Wang LS, Zhu B, Abd El-Aty A, et al. The influence of St. John's wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol 2004;44:577-81. PubMed
CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES
4 of 5Warfarin Sodium also falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES.
Clinical and in vitro research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4.
Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
Here's the practical worry with this pair. St. John's wort tends to speed up some of the liver enzymes that break down warfarin (it nudges CYP1A2, and even more so other pathways your body uses to clear warfarin). When those enzymes work faster, your warfarin can get cleared too quickly, so its blood-thinning effect may weaken. In real terms, that could let your blood clot more easily, raising the risk of the very things warfarin is meant to prevent, like a stroke, a clot in the leg, or a clot in the lung.
Warfarin is a narrow-therapeutic-index drug, meaning small shifts can throw off your INR and matter a lot. Please don't start or stop anything on your own. Talk with your pharmacist or doctor first so they can guide you and check your INR.
- Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
- Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
- Van Strater, A. C. and Bogers, J. P. Interaction of St John's wort (Hypericum perforatum) with clozapine. Int.Clin.Psychopharmacol. 2012;27(2):121-124. PubMed
- Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES
5 of 5Warfarin Sodium also falls under CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES.
There is contradictory research about the effect of St. John's wort on CYP2C9. Some in vitro research shows that St. John's wort induces CYP2C9, but to a lesser extent than CYP3A4. St. John's wort also induces metabolism of the S-warfarin isomer, which is a CYP2C9 substrate. Other research shows that St. John's wort 300 mg three times daily for 21 days does not significantly affect the pharmacokinetics of a single 400 mg dose of ibuprofen, which is also a CYP2C9 substrate. Until more is known, use St. John's wort cautiously in patients who are taking CYP2C9 substrates.
Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
Here's the practical concern with mixing St. John's wort and warfarin. This herb can speed up the liver enzymes (including CYP2C9) that break warfarin down. When warfarin gets cleared faster, your blood level of the drug drops, and so does its blood-thinning power. In real terms, that can let a clot form, which is exactly what you're trying to prevent with conditions like atrial fibrillation, a mechanical heart valve, or a prior clot.
Warfarin is a tricky, narrow-margin drug, so even a modest shift can pull your INR out of range. The evidence here is moderate and a little mixed, but warfarin is one drug where I'd never gamble. Please don't start or stop anything on your own. Talk with your pharmacist or doctor first so your INR can be watched closely.
- Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
- Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
- Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004;32:512-8. PubMed
- Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57:592-9. PubMed
- Bell EC, Ravis WR, Lloyd KB, Stokes TJ. Effects of St. John's wort supplementation on ibuprofen pharmacokinetics. Ann Pharmacother 2007;41:229-34. PubMed
What These Ratings Mean
Every interaction above is graded three ways — here’s the key to each label.
Clinically significant. Avoid the combination, or use only under close professional supervision.
Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.
Generally not serious. Be aware of it and mention it to your pharmacist.
- LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
- ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
- PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
- UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
- AHigh-quality meta-analysis (quantitative systematic review).
- BCase-control study.
- CConsensus.
- DAnecdotal evidence.
These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.
St. John's Wort Also Interacts With Other Medications
St. John's Wort has 754 major, 388 moderate known drug interactions in our database — the Warfarin Sodium one above is among them. If you take anything else, check it against the full list below.
Check Another of Your Medications Against St. John's Wort
We haven’t checked that one against St. John's Wort yet — ask our pharmacists directly.
Covers the 2,830 medications we’ve checked against St. John's Wort. Pick one to open its full report.
Questions About St. John's Wort or Warfarin Sodium
These are real questions from readers, answered by the pharmacists at HelloPharmacist — written by a person, not generated from a database. Each one covers St. John's Wort or Warfarin Sodium, not necessarily both, but if one is close to what you were about to ask it will usually go further than a database entry can:
- Is St. John's Wort Safe To Take With Diovan (Valsartan)? ›
- Does Ginger Water Interfere With Amoxicillin-Clavulanate? ›
- How Can You Switch From Zoloft To St. John's Wort? ›
- Can You Take Nattokinase With a 40 mg Statin? ›
Not quite your question? Ask our pharmacists directly — it is free, there is no account required, and answers usually come back within 24 hours.
See Every Supplement That Interacts With Warfarin Sodium
This page covers St. John's Wort only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Warfarin Sodium page lists 361 supplements it has a documented interaction with, worst first, each one explained.
The most serious there right now: Activated Charcoal (major), Alfalfa (major), American Ginseng (major), Beer (major) and Cannabis (major).
Taking St. John's Wort as Part of a Dietary Supplement Product? Check It for Interactions
We hold 1,159 real supplement products containing St. John's Wort, each one broken down to its full ingredient list — and combination products often carry several ingredients besides St. John's Wort. Your product may carry other ingredients that interact with Warfarin Sodium too, on top of St. John's Wort — and those would not show on this page. Find your product and we’ll check every ingredient on its label:
Where St. John's Wort and Warfarin Sodium Sit Against Everything Else
Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.
#157 of 1,452 supplements looked up here in the last 7 days
#23 of 2,830 medications looked up here in the last 7 days
Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.
About St. John's Wort
What is St. John's Wort?
- Mild to moderate depression
- Anxiety and stress
- Sleep problems
- Menopausal symptoms
- Wound healing (topical)
St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with prescription medicines and is not safe for everyone, so always talk to your pharmacist or doctor before taking it.
About Warfarin
What Is Warfarin Used For?
Brand names: Coumadin, Panwarfin, Sofarin
Warfarin sodium tablets and Jantoven tablets are both used to prevent and treat venous thrombosis (blood clots in the veins) and pulmonary embolism (a clot in the lungs). They are also used to prevent clot-related complications in people with atrial fibrillation (an irregular heart rhythm) or who have had a heart valve replaced.
In people who have had a heart attack, warfarin is used to reduce the risk of death, another heart attack, stroke, or other clotting events. It does not dissolve an existing clot, but it helps prevent the clot from growing and stops new dangerous clots from forming.
Other Drugs & St. John's Wort
Browse every other medication we’ve checked against St. John's Wort — both the ones with a known interaction and the ones without. Select any drug for the full detail.
No drugs match “”.
754 interactions
- Diltiazem ›
- Nifedipine ›
- Hydrocortisone ›
- Pancrelipase (prescription Drug) ›
- Doxycycline ›
- Erythromycin ›
- Estradiol ›
- Minocycline ›
- Tetracycline ›
- Lidocaine ›
- Ranitidine ›
- Norethindrone ›
- Testosterone ›
- Verapamil ›
- Levonorgestrel ›
- Prednisone ›
- Quinidine ›
- Cyclosporine ›
- Dexamethasone ›
- Triazolam ›
- Zopiclone ›
- Colchicine ›
- Fentanyl ›
- Oxybutynin ›
- Oxycodone ›
- Phenytoin ›
- Prednisolone ›
- Tacrolimus ›
- Temazepam ›
- Triamcinolone ›
- Apomorphine ›
- Budesonide ›
- Carbamazepine ›
- Clindamycin ›
- Dextromethorphan ›
- Doxorubicin ›
- Fluticasone ›
- Miconazole ›
- Morphine Sulfate ›
- Buprenorphine ›
- Conjugated Estrogens ›
- Diazepam ›
- Everolimus ›
- Ivabradine ›
- Ivermectin ›
- Medroxyprogesterone ›
- Medroxyprogesterone Acetate ›
- Rifampin ›
- Testosterone Undecanoate ›
- Aripiprazole ›
- Betamethasone ›
- Caffeine (otc Drug) ›
- Ciclesonide ›
- Cimetidine ›
- Clonazepam ›
- Cyclobenzaprine ›
- Dapsone ›
- Digoxin ›
- Doxycycline Hyclate ›
- Erythromycin Ethylsuccinate ›
Showing 60 of 754 major interactions — see all 754 on the St. John's Wort page.
388 interactions
- Diclofenac Sodium ›
- Theophylline ›
- Ibuprofen ›
- Diphenhydramine ›
- Methylphenidate ›
- Naproxen ›
- Propranolol ›
- Hydrochlorothiazide ›
- Glyburide ›
- Bupropion ›
- Ciprofloxacin ›
- Flurbiprofen ›
- Isotretinoin ›
- Orphenadrine ›
- Diclofenac Potassium ›
- Formoterol ›
- Indomethacin ›
- Phenylephrine ›
- Procainamide ›
- Tazarotene ›
- Trimipramine ›
- Acetaminophen ›
- Etodolac ›
- Griseofulvin ›
- Ketoprofen ›
- Lofepramine ›
- Meloxicam ›
- Nortriptyline ›
- Ofloxacin ›
- Selegiline ›
- Sumatriptan Succinate ›
- Topiramate ›
- Tretinoin ›
- Trichlormethiazide ›
- Azithromycin ›
- Bendamustine ›
- Bendroflumethiazide ›
- Desipramine ›
- Doxepin ›
- Duloxetine ›
- Fluphenazine ›
- Interferon Alfa-2b ›
- Interferon Beta-1b ›
- Levofloxacin ›
- Lisinopril ›
- Metoclopramide ›
- Metolazone ›
- Paroxetine ›
- Riluzole ›
- Sulfasalazine ›
- Valproic Acid ›
- Vortioxetine ›
- Acetazolamide ›
- Aminolevulinic Acid Hydrochloride ›
- Asenapine ›
- Brompheniramine ›
- Captopril ›
- Carisoprodol ›
- Carvedilol ›
- Celecoxib ›
Showing 60 of 388 moderate interactions — see all 388 on the St. John's Wort page.
No interaction 1,687 drugs checked — show the list
We also checked St. John's Wort against these medications and found no known interaction in our sources. Open any page to confirm.
- Levothyroxine ›
- Metoprolol ›
- Aspirin ›
- Docusate ›
- Hydroxyurea ›
- Valacyclovir ›
- Tirzepatide ›
- Semaglutide ›
- Metformin ›
- Amoxicillin ›
- Acyclovir ›
- Methotrexate ›
- Amphetamine ›
- Pregabalin ›
- Lamotrigine ›
- Gabapentin ›
- Bisoprolol ›
- Levothyroxine, Liothyronine ›
- Candesartan Cilexetil ›
- Cephalexin ›
- Cyclopentolate ›
- Acetaminophen, Dextromethorphan, Doxylamine ›
- Roxithromycin ›
- Mannitol ›
- Levetiracetam ›
- Pegunigalsidase Alfa-iwxj ›
- Ezetimibe ›
- Levothyroxine Sodium ›
- Daptomycin ›
- Amoxicillin, Clavulanate Potassium ›
- Mitomycin ›
- Spironolactone ›
- Hexobarbitone ›
- Thyroid Hormone ›
- Carbidopa, Levodopa ›
- Factor 7a ›
- Levodopa ›
- Minoxidil ›
- Cefaclor ›
- Hethylphenidate Hcl ›
- Lenvatinib ›
- Azelaic Acid ›
- Codeine Sulfate ›
- Hydroxychloroquine ›
- Tenecteplase ›
- Vancomycin ›
- Dirithromycin ›
- Triptorelin ›
- Pizotifen ›
- Acetylsalicylic Acid ›
- Bentoquatam ›
- Pentobarbitone ›
- Ribavirin Aerosol ›
- Dextrothyroxine ›
- Tocainide ›
- Rocuronium ›
- Telmisartan ›
- Mitomycin C ›
- Lomustine ›
- Flecainide ›
Showing the 60 most looked-up of 1,687 medications checked with no known interaction — see the full St. John's Wort list.
Sources & How We Checked
Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference for vitamins, herbs and supplements — the basis for our interaction data.
- MedlinePlus, U.S. National Library of Medicine — NIH consumer drug information, used for the medication overviews.
- NIH Dietary Supplement Label Database (DSLD) — Official supplement product labels.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.
Parts of this content are provided by the Therapeutic Research Center, LLC.
DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.
© 2021 Therapeutic Research Center, LLC
Taking St. John's Wort and Warfarin Sodium Together: Common Questions
Can you take St. John's Wort with Warfarin Sodium?
Why are there 5 interactions listed for St. John's Wort and Warfarin Sodium?
How serious is the St. John's Wort and Warfarin Sodium interaction?
Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy
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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.