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Digoxin Drug Interactions

Worst Pills, Best Pills Newsletter article March, 2010

Digoxin (DIGITEK, LANOXI­CAPS, LANOXIN), used to treat heart failure and heart arrhyth­mias, can interact with several dozen other drugs, with results ranging from no effect from digoxin to digoxin tox­icity. With more than 12 million pre­scriptions filled in 2008 for digoxin, the drug is very widely used and thus the possibility of interactions (espe­cially in older people who use more prescription drugs) is very high.

While it is very useful, digoxin has what is called a “narrow...

Digoxin (DIGITEK, LANOXI­CAPS, LANOXIN), used to treat heart failure and heart arrhyth­mias, can interact with several dozen other drugs, with results ranging from no effect from digoxin to digoxin tox­icity. With more than 12 million pre­scriptions filled in 2008 for digoxin, the drug is very widely used and thus the possibility of interactions (espe­cially in older people who use more prescription drugs) is very high.

While it is very useful, digoxin has what is called a “narrow therapeutic window.” This means that the blood levels of digoxin must be precise for the drug to work as intended. A mod­erate increase in the digoxin blood level sometimes causes serious toxic­ity, while a moderate decrease may substantially reduce its therapeutic ef­fectiveness. Its dosage must therefore be fine-tuned for the drug to be both effective and safe.

A recently published article found that people using digoxin and the antibiotic azithromycin (ZITHRO­MAX) were 15 times more likely to be hospitalized for digoxin toxic­ity than those using digoxin with a different antibiotic. Patients using digoxin were 3.7 times more likely to be hospitalized if they were also using erythromycin (EES, ERYTHROCIN, E-MYCIN) or clarithromycin (BI­AXIN) than patients using another antibiotic.

The body treats digoxin as a foreign chemical and tries to reduce expo­sure to it by blocking what it can and eliminating the rest as quickly as possible. The body accomplishes this with P-glycoprotein (PGP), a substance that exists naturally in the body. PGP reduces the intestine’s ab­sorption of digoxin and increases the elimination of digoxin by the kidneys.

Some drugs can block PGP’s effects. When taken with digoxin, these drugs can actually increase the rate of digoxin absorption and reduce digoxin elimination, thus increasing the risk of digoxin toxicity. Table 1 lists 24 drugs that block PGP’s effects.

On the other hand, some drugs can increase PGP’s effects, and taking these drugs with digoxin can lower blood levels of digoxin, potentially reducing the desired effects of the digoxin. Table 2 lists 11 drugs and one dietary supplement that increase PGP’s effects.

Low potassium blood levels increase risk of toxicity

The risk of digoxin toxicity is increased if potassium levels in the blood fall below normal. This prob­lem has been known for many years, and most prescribers are careful to make sure people on digoxin do not become potassium-depleted.

However, diuretics (sometimes called “water pills”) are often given with digoxin, and these drugs can cause potassium depletion. Your prescriber may recommend periodic measurements of your blood potas­sium levels if you are taking digoxin.

Patients can prevent potassium depletion by eating potassium-rich foods such as fresh and dried fruits and vegetables, fresh and canned juices, and fresh meats.

Signs of digoxin toxicity

When digoxin levels get too high, patients may develop gastrointestinal symptoms such as loss of appetite, nausea and vomiting. Patients also may experience visual problems (green or yellow tinting, blurred vi­sion, halos) and neurological symp­toms (agitation, confusion, lethargy).

Irregular heartbeat (heart arrhyth­mia) may occur — especially with severe digoxin toxicity — and this can be dangerous.

What You Can Do

Because digoxin toxicity can be severe or even life-threatening, it is important to take steps to reduce the risk. A reduced digoxin effect also can be problematic, because it may result in a worsening of your heart failure or heart arrhythmia.

Patients who are taking digoxin should not take any of the drugs in Table 1 or 2 without consulting with the prescriber who is monitor­ing the digoxin therapy.

In some circumstances, patients may need to use the drugs listed in the tables with digoxin. For example, patients often take blood pressure medications verapamil (CALAN, CALAN SR, COVERA-HS, ISOP­TIN, ISOPTIN SR, VERELAN) or diltiazem (CARDIZEM, CARD­IZEM CD, DILACOR XR, TIAZ­AC) with digoxin. But in such cases, the prescribing physician may want to monitor the patient’s progress more closely, especially in the weeks following addition of the interacting drug, and consider changing the dose of either digoxin or the other drugs.

Patients taking digoxin should not add any new drugs (prescription, nonprescription or herbal) without checking with their physician and/or pharmacist to make sure the drugs do not interact with digoxin.

Patients who are already taking one or more of the drugs in Table 1 or 2 and who start digoxin at a normal dose should be aware that the digoxin level may be higher or lower than expected.

Table 1. Drugs That May Reduce PGP Activity and Increase Digoxin Blood Levels

 

Generic Name

BRAND NAME

amiodarone

CORDARONE; PACERONE****

azithromycin

ZITHROMAX**

bepridil

VASCOR

clarithromycin

BIAXIN**

conivaptan

VAPRISOL

cyclosporine

NEORAL; SANDIMMUNE

diltiazem

CARDIZEM CD; CARDIZEM; DILACOR XR; TIAZAC**

erythromycin

EES, ERYTHROCIN

indinavir

CRIXIVAN

itraconazole

SPORANOX*

ketoconazole

NIZORAL

lapatinib

TYKERB

nelfinavir

VIRACEPT

nicardipine

CARDENE

posaconazole

NOXAFIL

propafenone

RYTHMOL

quinidine

DURAQUIN, QUINAGLUTE DURA-TABS, QUINIDEX**

ranolazine

RANEXA***

ritonavir

NORVIR

saquinavir

INVIRASE

tacrolimus

PROGRAF, PROTOPIC

tamoxifen

NOLVADEX**

telithromycin

KETEK*

verapamil

CALAN, CALAN SR, COVERA-HS, ISOPTIN, ISOPTIN SR, VERELAN

* Do Not Use on WorstPills.org
** Limited Use on WorstPills.org
*** Do Not Use Until 2014 on WorstPills.org
****Last Choice on WorstPills.org

Table 2. Drugs That May Increase PGP Activity and Decrease Digoxin Blood Levels

 

Generic Name

BRAND NAME

carbamazepine

CARBATROL; TEGRETOL

efavirenz

SUSTIVA

nafcillin

NALLPEN; UNIPEN

nevirapine

VIRAMUNE

oxcarbazepine

TRILEPTAL

phenobarbital

LUMINAL; SOLOFTON**

phenytoin

DILANTIN

primidone

MYSOLINE

rifabutin

MYCOBUTIN

rifampin

RIFADIN; RIMACTANE

rifapentine

PRIFTIN

St. John’s wort*

*Do Not Use on WorstPills.org
** Limited Use on WorstPills.org