What Should You Not Mix with Digoxin? A Guide to Interactions

October 9, 2025 •

4 min read

The overall incidence of adverse reactions with digoxin is reported to be between 5% and 20% [1.6.1]. Understanding what you should not mix with digoxin is critical, as its narrow therapeutic index means many substances can lead to dangerous interactions [1.3.1].

Quick Summary

Digoxin is a heart medication with a narrow safety margin. Many common prescription drugs, OTC products, herbal supplements, and even certain foods can alter its effects, leading to toxicity or reduced effectiveness.

Key Points

Diuretics and Electrolytes: Diuretics can lower potassium levels, which dramatically increases the risk of digoxin toxicity [1.3.2, 1.5.2].
Heart Medications: Other heart drugs like amiodarone and verapamil can significantly raise digoxin levels, often requiring a dose reduction [1.7.4].
Herbal Supplements: St. John's Wort can make digoxin less effective, while licorice root increases toxicity risk [1.2.2, 1.4.1].
OTC Medications: Antacids and NSAIDs like ibuprofen can interfere with digoxin; antacids should be taken at a different time [1.9.3, 1.9.4].
Dietary Fiber: High-fiber meals can reduce the amount of digoxin your body absorbs, so timing is important [1.2.3, 1.4.2].
Toxicity Symptoms: Be aware of toxicity signs like nausea, confusion, and vision changes (e.g., yellow halos) [1.5.4, 1.5.6].
Consult Professionals: Always consult a doctor or pharmacist before starting or stopping any new medication or supplement while taking digoxin [1.7.3].

Digoxin is a cardiac glycoside medication used to treat conditions like heart failure and certain irregular heartbeats (arrhythmias) such as atrial fibrillation [1.5.1]. It works by increasing the force of heart muscle contractions and slowing conduction through the atrioventricular (AV) node [1.5.1]. However, digoxin has a narrow therapeutic index, meaning the difference between a therapeutic dose and a toxic dose is very small [1.5.5]. Because of this, it is crucial to be aware of the numerous substances that can interact with it.

Recognizing Digoxin Toxicity

Before exploring specific interactions, it's important to recognize the signs of digoxin toxicity. Symptoms are often non-specific and can be mistaken for other conditions [1.5.5]. They can include:

Gastrointestinal Issues: Nausea, vomiting, loss of appetite, and diarrhea are among the most common early symptoms [1.5.2, 1.5.6].
Neurological Symptoms: Confusion, headache, fatigue, weakness, and delirium can occur, especially in older adults [1.5.4, 1.5.6].
Visual Disturbances: Patients may experience blurred vision, blind spots, or changes in color perception, such as seeing yellow or green halos around objects (xanthopsia) [1.5.4, 1.5.6].
Cardiac Effects: Any type of heart arrhythmia can occur, from a slow heart rate (bradycardia) to more dangerous ventricular arrhythmias [1.5.1].

Electrolyte imbalances, particularly low potassium (hypokalemia), low magnesium (hypomagnesemia), and high calcium (hypercalcemia), significantly increase the risk of toxicity [1.5.2, 1.5.3].

Prescription Medications to Use with Caution

Many prescription drugs can alter digoxin levels in the body, either by affecting its absorption, distribution, metabolism, or excretion. Always inform your healthcare provider of all medications you are taking.

Diuretics (Water Pills)

Diuretics are often prescribed alongside digoxin for heart failure. However, certain types, particularly loop diuretics (like furosemide) and thiazide diuretics, can cause the body to lose potassium and magnesium [1.3.2]. Low levels of these electrolytes increase the heart's sensitivity to digoxin, raising the risk of toxicity even at normal drug levels [1.5.2].

Heart Rhythm and Blood Pressure Medications

Several other cardiovascular drugs interact with digoxin:

Amiodarone, Quinidine, Verapamil, Diltiazem: These antiarrhythmic and calcium channel blocker medications can significantly increase digoxin levels in the blood, often requiring a reduction in the digoxin dose by 30-50% [1.3.2, 1.7.4, 1.7.5].
Beta-Blockers: Drugs like carvedilol and metoprolol also slow the heart rate. When combined with digoxin, they can cause an excessively slow heart rate (bradycardia) [1.3.2].
ACE Inhibitors and ARBs: Medications like captopril and telmisartan can increase digoxin levels [1.3.2].

Antibiotics

Certain antibiotics can increase digoxin absorption. Macrolides like clarithromycin and erythromycin can alter gut bacteria that normally break down a portion of the digoxin dose, leading to higher-than-expected blood levels [1.2.5, 1.3.5].

Over-the-Counter (OTC) Products and Supplements

Interactions are not limited to prescription drugs. Common OTC products and herbal supplements can also pose a risk.

Herbal Supplements

St. John's Wort: This supplement, often used for depression, can decrease the effectiveness of digoxin by increasing its elimination from the body [1.2.2, 1.4.5]. If you are taking both, stopping St. John's wort suddenly could cause digoxin levels to rise dangerously [1.4.1].
Licorice Root: Real licorice (containing glycyrrhizin) can lower potassium levels, increasing the risk of digoxin toxicity [1.2.2, 1.2.3].
Other Herbs: Senna, hawthorn, sarsaparilla, and Siberian ginseng may also interfere with digoxin's action or levels [1.2.2, 1.2.3].

OTC Medications

Antacids: Antacids containing aluminum or magnesium can decrease the absorption of digoxin. It's recommended to separate the administration of digoxin and antacids by at least two hours [1.9.3, 1.9.4].
NSAIDs (Non-Steroidal Anti-Inflammatory Drugs): Regular use of NSAIDs like ibuprofen and naproxen may increase digoxin levels in the body [1.2.5, 1.9.4]. For pain relief, acetaminophen (Tylenol) is generally considered a safer option for patients with heart conditions, though you should always consult your provider [1.8.4].

Foods and Diet

Dietary choices can also influence how digoxin works.

High-Fiber Foods: Meals rich in fiber, such as those containing wheat bran or psyllium, can decrease the absorption of digoxin from the digestive tract [1.2.3, 1.4.2]. To avoid this, take digoxin at least one hour before or two hours after eating a high-fiber meal [1.2.3, 1.2.6].
Black Licorice: As with the supplement, black licorice candy containing glycyrrhizin can lead to potassium loss and increase the risk of an irregular heartbeat with digoxin [1.2.3, 1.2.6].


Substance Class	Examples	Potential Interaction with Digoxin	Management Recommendation
Diuretics	Furosemide, Hydrochlorothiazide	Lowers potassium, increasing toxicity risk [1.3.2, 1.5.2]	Monitor electrolyte levels closely [1.5.2].
Antiarrhythmics	Amiodarone, Quinidine	Significantly increases digoxin levels [1.3.1, 1.7.4]	Reduce digoxin dose; monitor levels [1.7.4].
Macrolide Antibiotics	Clarithromycin, Erythromycin	Increases digoxin absorption and levels [1.2.5]	Monitor for signs of toxicity [1.7.4].
Herbal Supplements	St. John's Wort	Decreases digoxin levels and effectiveness [1.2.2]	Avoid combination; consult provider before stopping St. John's wort [1.4.1].
Antacids	Aluminum/magnesium hydroxide	Decreases digoxin absorption [1.9.4]	Separate doses by at least 2 hours [1.9.3].
High-Fiber Foods	Wheat bran, psyllium	Decreases digoxin absorption [1.4.2]	Take digoxin 1-2 hours apart from fiber [1.2.3].

Conclusion

Managing treatment with digoxin requires constant vigilance from both patients and healthcare providers [1.7.3]. Due to its narrow therapeutic window, even minor changes in diet, supplements, or other medications can have significant consequences. Always maintain an updated list of all medications and supplements you take and review it regularly with your doctor and pharmacist. Never start or stop any new medication, including OTC products and herbal remedies, without first consulting your healthcare provider to ensure it is safe to combine with digoxin. For more information from an authoritative source, consider visiting MedlinePlus [1.9.2].

Frequently Asked Questions

Acetaminophen (Tylenol) is generally considered a safer option for pain relief for people with heart conditions compared to NSAIDs like ibuprofen or naproxen, which may interact with digoxin [1.8.4, 1.9.4]. Always consult your healthcare provider first.

Yes, but you must separate the doses. Antacids containing aluminum or magnesium can reduce digoxin absorption. Take the antacid at least two hours before or two hours after your digoxin dose [1.9.3, 1.9.4].

You should avoid eating high-fiber foods at the same time as your digoxin dose, as fiber can reduce its absorption [1.4.2]. Also, avoid real black licorice, which can deplete potassium and increase toxicity risk [1.2.3, 1.2.6].

Early signs of digoxin toxicity often include gastrointestinal issues like loss of appetite, nausea, and vomiting, as well as fatigue and confusion [1.5.2, 1.5.6]. Visual disturbances, like seeing yellow halos, are also a characteristic sign [1.5.4].

Yes, St. John's Wort can significantly decrease the blood levels of digoxin, making it less effective. You should avoid this combination [1.2.2, 1.4.5].

Many diuretics cause the body to lose potassium and magnesium. Low levels of these electrolytes make the heart more sensitive to digoxin's effects, which can lead to toxicity even if the digoxin level in the blood is normal [1.3.2, 1.5.2].

You should avoid or limit alcohol, as it may increase drowsiness and potentially decrease the amount of digoxin in your bloodstream, which could affect heart function [1.2.3].