Fondaparinux and St John's Wort: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
St John's Wort
No brand names on recordFondaparinux
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.
What happens
Reduced anticoagulants exposure and reduced efficacy of anticoagulants
Interaction Deep Dive
In an open-label, randomized, crossover study, the coadministration of St John's Wort with warfarin significantly reduced warfarin bioavailability, causing clinically meaningful reductions in the INR1. Several case reports have shown decreases in INR when patients stabilized on warfarin added St. John's Wort 2. In healthy volunteers, St. John's Wort significantly decreased the AUC of phenprocoumon, an anticoagulant similar to warfarin 3.
Why it happens (mechanism)
Induction of CYP3A4-mediated metabolism by St. John's Wort; induction of CYP1A2-mediated metabolism by St. John's Wort; induction of CYP2C9-mediated metabolism by St. John's Wort
Literature reports
4 reports — tap to read
a) The coadministration of St John's Wort with warfarin significantly reduced warfarin bioavailability, causing clinically meaningful reductions in the International Normalized Ratio (INR). In an open-label, randomized, 3-way cross-over study, healthy subjects (n=12) received a single oral dose of racemic warfarin 25 milligrams (mg) with or without pretreatment using either Panax ginseng (2 capsules given 3 times daily for 1 week) or St John's Wort (1 tablet 3 times daily for 2 weeks, per customary recommended dosing). Each treatment period was separated by a washout period, minimum of 2 weeks duration. Dosing of St John's Wort continued for 1 week after administration of the warfarin dose. Serial blood pharmacokinetic and INR analysis occurred from 48 hours pre-warfarin dose to 168 hours after administration of warfarin. Significant changes were not observed in warfarin pharmacokinetics with coadministration of Panax ginseng with warfarin. However, when compared with warfarin alone, the concomitant administration of St John's Wort and warfarin significantly reduced mean ratios of the area under the concentration-time curve for both R- and S-warfarin enantiomers (AUC, 0-inf; by approximately 23% and 27% , respectively; p less than 0.05), and similarly reduced plasma half lives for the R-warfarin and S-warfarin enantiomer (by 21%, both enantiomers, p less than 0.05). The mean ratio for apparent total clearance was increased for both R- and S-warfarin (by 23% and 29%, respectively; p less than 0.05). The mean ratio of the AUC (0-168) for warfarin-mediated INR with versus without St John's Wort was 0.79 1.
b) Seven case reports have shown an approximate 50% decrease in the International Normalized Ratio (INR) when patients stabilized on warfarin began taking St. John's Wort. None of the patients experienced thromboembolic complications. After St. John's Wort was discontinued or the warfarin dose increased, the INR returned to the target range. Induction of CYP2C9 was suggested as a mechanism for the decreased effect of warfarin 2.
c) In a randomized, single blind, placebo-controlled cross-over study of 10 healthy volunteers, St. John's Wort 900 mg/day for 11 days significantly decreased the AUC of free phenprocoumon after a single 12 mg dose (p=0.007). Hypothesized causes of the interaction were forced elimination, induction of CYP450 enzymes, or inhibition of absorption 3.
d) The mechanism of the interaction is not fully understood. St. John's Wort induced CYP3A4 in humans 45; and had no effect on CYP1A2 or CYP2C9 in humans 6, though induction of CYP1A2 was hypothesized to be the reason for the significant decrease in theophylline levels observed in one case report and supported by an in vitro study 7. CYP3A4 and CYP1A2 metabolizes R-warfarin, and CYP2C9 metabolizes S-warfarin. Alteration of S-warfarin primarily affects warfarin efficacy, with R-warfarin metabolism of less importance 8.
Common questions
Can I take Fondaparinux and St John's Wort together?
Reduced anticoagulants exposure and reduced efficacy of anticoagulants Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fondaparinux 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 "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Fondaparinux 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 (8)
- 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 Cliin Pharmacol 2004; 57(5):592-599. PubMed
- Yue QY, Bergquist C, & Gerden B: Safety of St. John's Wort. Lancet 2000; 355:576-577.
- Maurer A, Johne A, Bauer S, et al: Interaction of St. John's wort extract with phenprocoumon (abstract). Eur J Clin Pharmacol 1999; 55:A22.
- Moore LB, Goodwin B, Jones SA, et al: St. John's Wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proc Natl Adac Sci U S A 2000; 97(13):7500-7502. PubMed
- Ruschitzka F, Meier P, Turina M, et al: Acute heart transplant rejection due to St. John's Wort (letter). Lancet 2000; 355(9203):548-549.
- Wang Z, Gorski JC, Hamman MA, et al: The effects of St. John's Wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 2001; 70(4):317-326.
- Nebel A, Schneider BJ, Baker RK, et al: Potential metabolic interaction between St. John's Wort and theophylline. Ann Pharmacotherapy 1999; 33:502. PubMed
- Kaminsky LS & Zhang ZY: Human P450 metabolism of warfarin. Pharmacol Ther 1997; 73(1):67-74. PubMed
Keep reading about St John's Wort
Keep reading about Fondaparinux
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