Digoxin with St John's Wort Interaction Details
Brand Names Associated with Digoxin
- Cardoxin®
- Digitek®
- Digoxin
- Lanoxicaps®
- Lanoxin®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Jan 08, 2024
Interaction Effect
Reduced digoxin efficacy
Interaction Summary
St. John's Wort may induce P-gp (ABCB1)-mediated efflux transport of digoxin. In a systematic review of studies, concomitant use resulted in a decrease in digoxin AUC of 18% to 27% with St. Johns wort products containing hyperforin dosages of 7.5 to 54 mg/day. Measure digoxin concentrations prior to initiation of concurrent use. Increase the digoxin dose (by approximately 20% to 40% for oral), if necessary, and continue monitoring digoxin plasma concentration levels .
Severity
Major
Onset
Delayed
Evidence
Established
How To Manage Interaction
St. John's Wort may induce P-gp (ABCB1)-mediated efflux transport of digoxin. Measure digoxin concentrations prior to initiation of concurrent use. Increase the digoxin dose (by approximately 20% to 40% for oral), if necessary, and continue monitoring digoxin plasma concentration levels .
Mechanism Of Interaction
Induction of P-glycoprotein drug transporter
Literature Reports
A) 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 .
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(R)) 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(R), 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 .
C) St. John's Wort significantly increased P-glycoprotein 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-glycoprotein 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-glycoprotein 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-glycoprotein expression occurred in subjects receiving placebo. P-glycoprotein expression returned to baseline 16 days after discontinuing St. John's Wort. Efflux of the known P-glycoprotein substrate rhodamine was significantly increased with St. John's Wort; no change in efflux occurred with placebo. Ritonavir (5 micromoles), known to reverse P-glycoprotein 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% .
Digoxin Overview
-
Digoxin is used to treat heart failure and abnormal heart rhythms (arrhythmias). It helps the heart work better and it helps control your heart rate.
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Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.