What happens when you take digoxin with licorice?
Digoxin is a narrow-therapeutic-index cardiac glycoside used to slow heart rate in atrial fibrillation and provide modest inotropic support in heart failure. Its sensitivity to potassium is well established: when serum potassium drops, digoxin binds more tightly to the cardiac Na+/K+ ATPase, and toxic effects can occur even at otherwise therapeutic blood levels.
Licorice (Glycyrrhiza glabra) contains the active compound glycyrrhizin, which is metabolized to glycyrrhetinic acid. Glycyrrhetinic acid inhibits an enzyme in the kidney called 11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2). When that enzyme is blocked, endogenous cortisol can spuriously activate the mineralocorticoid receptor. The clinical result is a state called apparent mineralocorticoid excess or pseudoaldosteronism: sodium and water retention, elevated blood pressure, and, critically, urinary potassium loss leading to hypokalemia.
The hypokalemia, not a direct pharmacokinetic interaction with digoxin, is what makes this combination dangerous. Falling potassium increases digoxin's affinity for its target and amplifies its electrophysiologic effects. Cases of digoxin toxicity have been reported in patients whose only change in regimen was the addition of licorice candy, herbal tea, or chewing tobacco containing licorice flavoring.
Why is this important?
Digoxin toxicity is potentially lethal. Early symptoms include nausea, vomiting, abdominal pain, fatigue, visual disturbances (classically yellow-green halos around lights), and confusion. Cardiac manifestations include atrial tachycardia with block, ventricular bigeminy, AV block, ventricular tachycardia, and ventricular fibrillation. Treatment requires hospital admission, electrolyte correction, and sometimes digoxin-specific antibody fragments (DigiFab) for severe poisoning.
The risk is amplified in elderly patients, in those with kidney impairment (which slows digoxin clearance), in patients also taking diuretics (which further lower potassium), and in heart failure patients on aggressive diuresis. A single licorice exposure rarely causes toxicity, but daily consumption of black licorice candy or licorice tea over weeks routinely produces clinically significant hypokalemia.
This interaction is not theoretical. It is documented in case reports and explicitly flagged by drug interaction databases including Drugs.com, IBM Micromedex, and Lexicomp. The FDA and other regulatory agencies have specifically warned about licorice-induced hypokalemia, including a 2017 FDA consumer update advising that more than 2 ounces of black licorice a day for two weeks could cause arrhythmia in adults over 40.
What should you do?
Avoid sources of glycyrrhizin while taking digoxin. That includes black licorice candy (red licorice does not contain real licorice extract), licorice-flavored herbal teas, licorice root capsules, certain throat lozenges, and traditional Chinese medicine preparations such as gan cao. Deglycyrrhizinated licorice (DGL), used for heartburn, has had the glycyrrhizin removed and is generally safe with digoxin, but read labels carefully because some products labeled DGL still contain residual glycyrrhizin.
If you have been consuming licorice and are on digoxin, tell your prescriber. They can check serum potassium, magnesium, and digoxin levels and look for ECG changes. Do not stop digoxin without guidance. If you develop nausea, vomiting, palpitations, visual changes, or unusual fatigue, seek urgent evaluation.
Which specific products are affected?
Glycyrrhizin-containing products include black licorice candy (Twizzlers Black Licorice, Panda licorice, Australian black licorice), licorice root extract supplements, herbal blends marketed for adrenal support or low blood pressure, traditional Chinese formulas containing gan cao, anise- and licorice-flavored liqueurs (in some cases), and certain throat and cough lozenges.
Digoxin products affected include Lanoxin tablets, Digox tablets, generic digoxin tablets, and pediatric oral solution. The interaction depends on the resulting hypokalemia, not the formulation, so all digoxin products are equally at risk. Other digitalis-like medications (digitoxin, where available) face the same concern.
The bottom line
Licorice and digoxin is a high-severity interaction driven by glycyrrhizin-induced hypokalemia, which sensitizes the heart to digoxin and can precipitate toxic arrhythmias. Patients on digoxin should avoid black licorice candy, licorice root supplements, and any product containing glycyrrhizin. Deglycyrrhizinated licorice (DGL) is generally safe but read labels. Disclose all licorice exposure to your prescriber so potassium and digoxin levels can be checked.