Digoxin 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 recordDigoxin
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
Altered digoxin exposure and an increased risk of digoxin toxicity
Interaction Deep Dive
Concomitant use of digoxin and St. John's Wort (P-gp inhibitor and P-gp inducer) may alter digoxin exposure1243. Measure digoxin exposure prior to initiation of concurrent use. Increase the digoxin dose (by approximately 20% to 40% for oral), if necessary, and continue monitoring digoxin exposure 12. Also, continue monitoring digoxin exposure and monitor potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing St. John's Wort 12.
Why it happens (mechanism)
Induction of P-gp-mediated efflux transport of digoxin; inhibition of P-gp-mediated efflux transport of digoxin
Literature reports
3 reports — tap to read
a) St. John's Wort may induce P-gp (ABCB1)-mediated efflux transport of digoxin. In a systematic review of studies of pharmacokinetic interactions involving St John's Wort, concomitant use with digoxin in 6 studies resulted in no change in digoxin AUC with products containing hyperforin dosages of 0.04 to 5.3 mg/day, and a decrease in digoxin AUC of 18% to 27% with hyperforin dosages of 7.5 to 54 mg/day 5.
b) The effect on digoxin levels was dependent on dose and formulation of St. John's Wort in a randomized, double-blinded, placebo-controlled, parallel group study of 55 volunteers. After digoxin reached steady-state, St. John's Wort was added for 14 days. St. John's Wort formulations and dosages used were as follows: St. John's Wort extract 900 mg (Jarsin®) daily; encapsulated powder 0.5 grams, 1 gram, 2 grams, or 4 grams; 2 cups of tea each with 1.6 grams St. John's Wort; or 1.2 grams encapsulated fatty oil formulation. Digoxin 24-hour AUC was reduced by 27.1% with 4 grams encapsulated powder, 24.6% with Jarsin®), and 17.6% with 2 grams encapsulated powder. Digoxin trough levels in these groups were reduced by 18%, 18%, and 13%, respectively. Encapsulated powder 0.5 grams and 1 gram, tea, and fatty oil formulations did not significantly alter digoxin AUC and trough levels 6.
c) St. John's Wort significantly increased P-gp expression and associated drug efflux in a randomized, single-blind, placebo-controlled trial of 22 healthy subjects (13 female, 9 male). Subjects received St. John's Wort (Good n' Natural, standardized to 0.15% hypericin) 600 mg (n=15) or placebo (n=7) 3 times daily for 16 days. P-gp expression in peripheral blood mononuclear cells increased a significant 4.2-fold with St. John's Wort after 16 days (29.5 median fluorescence intensity (MFI, a measure of P-gp expression) versus 7 MFI). Individual variability occurred with a range of 1.09 to 9.06 MFI after St. John's Wort. No change in P-gp expression occurred in subjects receiving placebo. P-gp expression returned to baseline 16 days after discontinuing St. John's Wort. Efflux of the known P-gp substrate rhodamine was significantly increased with St. John's Wort; no change in efflux occurred with placebo. Ritonavir (5 micromoles), known to reverse P-gp drug efflux, was significantly less effective in reducing rhodamine efflux in subjects treated with St. John's Wort (75.4 vs 23.9). Three subjects receiving St. John's Wort withdrew from the study, one experienced adverse effects (nausea, dry mouth), and two needed potentially interacting medications. Analyses of 2 capsules from 3 batches of St. John's Wort with high performance liquid chromatography verified the hypericin content to be 0.15%, 0.14%, and 0.15% 7.
Common questions
Can I take Digoxin and St John's Wort together?
Altered digoxin exposure and an increased risk of digoxin toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Digoxin 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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Digoxin 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 (7)
- Product Information: LANOXIN(R) oral tablets, digoxin oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2019. DailyMed
- Product Information: DIGOXIN oral tablets, digoxin oral tablets. Aurobindo Pharma USA, Inc. (per Dailymed), East Windsor, NJ, May. DailyMed
- Product Information: DIGOXIN intravenous injection, digoxin intravenous injection. Hikma Pharmaceuticals USA Inc. (per Dailymed), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: LANOXIN® intravenous, intramuscular injection, digoxin intravenous, intramuscular injection. Covis Pharma (per FDA), King of Prussia, PA, 2025. DailyMed
- 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 2019; 71(1):129-138.
- Uehleke B, Mueller SC, Uehleke B, et al: Interaction of St. John's Wort with digoxin the relation to dosage and formulation (abstract). Phytomedicine 2000; 7(SII):20.
- Hennessy M, Kelleher D, Spiers JP, et al: St. John's Wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002; 53(1):75-82. DOI
Keep reading about St John's Wort
Keep reading about Digoxin
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