Potentially Dangerous Digoxin Drug Interactions

Digoxin (LANOXIN), which is approved by the Food and Drug Administration (FDA) to treat heart failure and to control heart rate in patients with atrial fibrillation (a common abnormal heart rhythm characterized by an irregular and often rapid heartbeat),[1] can interact with several dozen other drugs. These interactions can result in either digoxin toxicity or decreased digoxin effectiveness, depending on the other drug being used concomitantly.

Digoxin was initially approved by the FDA in 1954. Once one of the most commonly prescribed heart medications, use of digoxin has declined significantly in recent years.[2] Nevertheless, with more than 5 million prescriptions filled in 2015, digoxin remains one of the top 200 most commonly prescribed drugs in the U.S., and the possibility of frequent dangerous interactions between digoxin and other drugs (especially in older people who use more prescription drugs) is still very high.

Although it is useful for some patients, digoxin has a “narrow therapeutic window.” This means that the blood levels of digoxin must be precisely maintained within a narrow range for the drug to work as intended. A moderate increase in the digoxin blood level above this range sometimes causes serious toxicity, while a moderate decrease may substantially reduce its desired therapeutic effect. The drug’s dosage must therefore be fine-tuned for it to be effective and safe. For these reasons, patients using digoxin need to have periodic blood tests to monitor levels of the drug.

Drugs that increase digoxin levels

Table 1 below lists 40 drugs that, when taken concomitantly with digoxin, can increase digoxin blood levels.[3] Most of these drugs increase digoxin levels by blocking the effect of P-glycoprotein (PGP),[4] a substance that exists naturally in the intestines, kidneys and other organs.[5] PGP in the intestines and kidneys normally removes digoxin from the body by excreting it into the stool and urine, respectively, thereby lowering blood levels of the drug.[6] When taken with digoxin, drugs that inhibit PGP activity reduce the elimination of digoxin by the intestines and kidneys, thus increasing the risk of digoxin toxicity.

Table 1: Drugs That Increase Digoxin Blood Levels

*Designated as Limited Use
**Designated as Do Not Use
***Combination drug that contains other active ingredients not listed
†Designated Do Not Use except for malaria
††Designated Do Not Use except for panic attacks

The drugs in Table 1 are divided into three groups based on the extent to which they affect digoxin levels. They include certain commonly used drugs for treating bacterial, fungal or viral infections (such as clarithromycin [BIAXIN]); high blood pressure (such as carvedilol [COREG]); abnormal heart rhythms (such as quinidine [generic only]); heartburn (such as lansoprazole [PREVACID]); type 2 diabetes (such as metformin [FORTAMET, GLUCOPHAGE]); high cholesterol (such as atorvastatin [CADUET, LIPITOR]); and pain or fever (such as ibuprofen [ADVIL]).

The most common symptoms of digoxin toxicity are loss of appetite, nausea, vomiting and fatigue.[7] Patients also may experience visual problems (green or yellow tinting, blurred vision and halos) and neurological symptoms (headache, weakness, dizziness, confusion, anxiety, depression, delirium and hallucinations). A wide range of dangerous, even lifethreatening, abnormal heart rhythms may occur — especially with severe digoxin toxicity.

Drugs that decrease digoxin levels

Table 2 below lists 10 drugs and one dietary supplement (St John’s Wort) that can decrease digoxin levels. Some of these drugs decrease digoxin blood levels by increasing PGP activity in the intestines and kidneys.[8] Others interfere with the absorption of digoxin from the gut. Taking either type of drug with digoxin can reduce or prevent the desired effects of the digoxin.

The drugs that can lower digoxin levels include certain drugs for diabetes (such as miglitol [GLYSET]), high cholesterol (such as cholestyramine [PREVALITE]), seizures (such as phenytoin [DILANTIN]) and infections (such as rifampin [RIFADIN]).

Table 2: Drugs That Decrease Digoxin Blood Levels

*Designated as Limited Use
**Designated as Do Not Use
***Combination drug that contains other active ingredients not listed

Low potassium blood levels also increase risk of toxicity

The risk of digoxin toxicity is increased when potassium levels in the blood fall below normal. Importantly, some diuretics, sometimes called “water pills” (for example, hydrochlorothiazide [MICROZIDE] and furosemide [LASIX]), often are given with digoxin, and these drugs can cause potassium depletion. Therefore, patients taking these diuretics along with digoxin need periodic measurements of blood potassium levels. Patients can prevent potassium depletion by eating potassium-rich foods such as fresh and dried fruits, fresh and dried vegetables, fresh and canned juices and fresh meats.

What You Can Do

These types of potentially dangerous drug interactions reinforce the importance of bringing all of the prescription and nonprescription drugs that you take each time you visit any doctor. Because many drugs, including others not listed in this article, may affect the levels of digoxin, find out from your doctor whether any other prescribed drugs will interact with your digoxin treatment.

If you are taking digoxin and begin or end treatment with a drug that can either increase or decrease digoxin blood levels, speak with your doctor about whether you will need to adjust your digoxin dosage or whether there is an alternative drug that will not interact with digoxin. Your doctor likely will need to measure your blood digoxin level following any adjustment in your digoxin dose.

References

[1] Concordia Pharmaceuticals. Label: digoxin tablet (LANOXIN). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020405s14lbl.pdf. Accessed September 4, 2018.

[2] ClinCalc. Digoxin: Drug usage statistics, United States, 2005-2015. http://clincalc.com/DrugStats/Drugs/Digoxin. Accessed September 4, 2018.

[3] Concordia Pharmaceuticals. Label: digoxin tablet (LANOXIN). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020405s14lbl.pdf. Accessed September 4, 2018.

[4] Levine M, O’Connor A. Digitalis (cardiac glycoside) poisoning. UpToDate. June 13, 2018.

[5] Ledwitch KV, Roberts AG. Cardiovascular ion channel inhibitor drug-drug interactions with P-glycoprotein. AAPS J. 2017;19(2):409-420.

[6] Levine M, O’Connor A. Digitalis (cardiac glycoside) poisoning. UpToDate. June 13, 2018.

[7] Concordia Pharmaceuticals. Label: digoxin tablet (LANOXIN). August 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020405s14lbl.pdf. Accessed September 4, 2018.

[8] Levine M, O’Connor A. Digitalis (cardiac glycoside) poisoning. UpToDate. June 13, 2018.