Side effect of digoxin

Contents

Studies have shown that several classes of drugs are best to treat heart failure.

Heart failure patients may need multiple medications. Each one treats a different symptom or contributing factor and comes with its own instructions and rules.

You and your caregivers should work with your healthcare team to understand the medications and when, how often and in what dosage to take them.

It’s important to discuss all of the drugs you take with your doctor (or other healthcare providers) and understand their desired effects and possible side effects. Your doctor and your pharmacist are your best sources of information. Don’t hesitate to ask them questions about your medicines.

It’s critical that people with heart failure take their medications exactly as directed by their healthcare provider, to optimize the benefits. The use of these drugs has saved lives, prolonged life and improved the heart’s function.

The following list gives you a quick look at many typical medications to treat heart failure at different stages. Your prescription may have a different name from the ones listed here. Brand names commonly available in the United States are shown in parentheses after the generic name for each drug.

*Some of the major types of commonly prescribed heart failure medications are summarized in this section. For your information and reference, we have included generic names as well as major trade names to help you identify what you may be taking; however, the AHA is not recommending or endorsing any specific products. If your prescription medication isn’t on this list, remember that your healthcare provider and pharmacist are your best sources of information. It’s important to discuss all of the drugs you take with your doctor and understand their desired effects and possible side effects. Never stop taking a medication and never change your dose or frequency without first consulting your doctor.

Angiotensin-Converting Enzyme (ACE) Inhibitors

Commonly prescribed include:

Angiotensin II Receptor Blockers (or Inhibitors)

(Also known as ARBs or Angiotensin-2 Receptor Antagonists)

Commonly prescribed include:

  • Candesartan (Atacand)
  • Losartan (Cozaar)
  • Valsartan (Diovan)

Angiotensin-Receptor Neprilysin Inhibitors (ARNIs)

ARNIs are a new drug combination of a neprilysin inhibitor and an ARB.

  • Sacubitril/valsartan

If Channel Blocker (or inhibitor)

This drug class reduces the heart rate, similar to another class of drugs called beta blockers.

  • Ivabradine (Corlanor)

Beta Blockers (Also known as Beta-Adrenergic Blocking Agents)

Commonly prescribed include:

  • Bisoprolol (Zebeta)
  • Metoprolol succinate (Toprol XL)
  • Carvedilol (Coreg)
  • Carvedilol CR (Coreg CR)Toprol XL

Aldosterone Antagonists

Commonly prescribed include:

  • Spironolactone (Aldactone)
  • Eplerenone (Inspra)

Hydralazine and isosorbide dinitrate (specifically benefits African-Americans with heart failure)

Commonly prescribed:

  • Hydralazine and isosorbide dinitrate (combination drug) – (Bidil)

Diuretics (Also known as water pills)

Commonly prescribed include:

  • Furosemide (Lasix)
  • Bumetanide (Bumex)
  • Torsemide (Demadex)
  • Chlorothiazide (Diuril)
  • Amiloride (Midamor Chlorthalidone (Hygroton)
  • Hydrochlorothiazide or HCTZ (Esidrix, Hydrodiuril)
  • Indapamide (Lozol)
  • Metolazone (Zaroxolyn)
  • Triamterene (Dyrenium)

What this type of medication does:

  • Causes the body to rid itself of excess fluids and sodium through urination.
  • Helps to relieve the heart’s workload.
  • Decreases the buildup of fluid in the lungs and other parts of the body, such as the ankles and legs. Different diuretics remove fluid at varied rates and through different methods.

Other medications that might be prescribed

Your doctor may also prescribe other less commonly used drugs depending on your additional health problems. These drugs include:

  • Anticoagulants (*blood thinners) These drugs may be prescribed if you are a heart failure patient with atrial fibrillation or have another problem with your heart. Anticoagulants are not used to treat heart failure without the presence of atrial fibrillation.
  • Cholesterol-lowering drugs (statins) Your doctor may prescribe this class of medication if you have high cholesterol or have had a heart attack. This class of drugs is not used to treat heart failure, but other conditions as indicated.
  • Digoxin Some heart failure patients might be prescribed this drug if the doctor feels it’s warranted.

Additional medication information:

Find further descriptions of how these medications also affect cardiovascular diseases other than heart failure.

Lanoxin Tablets

CLINICAL PHARMACOLOGY

Mechanism of Action

All of digoxin’s actions are mediated through its effects on Na-K ATPase. This enzyme, the “sodium pump,” is responsible for maintaining the intracellular milieu throughout the body by moving sodium ions out of and potassium ions into cells. By inhibiting Na-K ATPase, digoxin

  • causes increased availability of intracellular calcium in the myocardium and conduction system, with consequent increased inotropy, increased automaticity, and reduced conduction velocity
  • indirectly causes parasympathetic stimulation of the autonomic nervous system, with consequent effects on the sino-atrial (SA) and atrioventricular (AV) nodes
  • reduces catecholamine reuptake at nerve terminals, rendering blood vessels more sensitive to endogenous or exogenous catecholamines
  • increases baroreceptor sensitization, with consequent increased carotid sinus nerve activity and enhanced sympathetic withdrawal for any given increment in mean arterial pressure
  • increases (at higher concentrations) sympathetic outflow from the central nervous system (CNS) to both cardiac and peripheral sympathetic nerves
  • allows (at higher concentrations) progressive efflux of intracellular potassium, with consequent increase in serum potassium levels.

The cardiologic consequences of these direct and indirect effects are an increase in the force and velocity of myocardial systolic contraction (positive inotropic action), a slowing of the heart rate (negative chronotropic effect), decreased conduction velocity through the AV node, and a decrease in the degree of activation of the sympathetic nervous system and renin-angiotensin system (neurohormonal deactivating effect).

Pharmacodynamics

The times to onset of pharmacologic effect and to peak effect of preparations of LANOXIN are shown in Table 7.

Table 7: Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations of LANOXIN

Product Time to Onset of Effecta Time to Peak Effecta
LANOXIN Tablets 0.5 -2 hours 2 -6 hours
LANOXIN Injection/IV 5 -30 minutes b 1 -4 hours
aDocumented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes.
bDepending upon rate of infusion.

Hemodynamic Effects

Short-and long-term therapy with the drug increase cardiac output and lowers pulmonary artery pressure, pulmonary capillary wedge pressure, and systemic vascular resistance in patients with heart failure. These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions.

ECG Changes

The use of therapeutic doses of LANOXIN may cause prolongation of the PR interval and depression of the ST segment on the electrocardiogram. LANOXIN may produce false positive ST-T changes on the electrocardiogram during exercise testing. These electrophysiologic effects are not indicative of toxicity. LANOXIN does not significantly reduce heart rate during exercise.

Pharmacokinetics

Absorption

Following oral administration, peak serum concentrations of digoxin occur at 1 to 3 hours. Absorption of digoxin from LANOXIN Tablets has been demonstrated to be 60% to 80% complete compared to an identical intravenous dose of digoxin (absolute bioavailability). When LANOXIN Tablets are taken after meals, the rate of absorption is slowed, but the total amount of digoxin absorbed is usually unchanged. When taken with meals high in bran fiber, however, the amount absorbed from an oral dose may be reduced. Comparisons of the systemic availability and equivalent doses for oral preparations of LANOXIN are shown in Dosage and Administration (2.6).

Digoxin is a substrate for P-glycoprotein. As an efflux protein on the apical membrane of enterocytes, P-glycoprotein may limit the absorption of digoxin.

In some patients, orally administered digoxin is converted to inactive reduction products (e.g., dihydrodigoxin) by colonic bacteria in the gut. Data suggest that 1 in 10 patients treated with digoxin tablets, colonic bacteria will degrade 40% or more of the ingested dose. As a result, certain antibiotics may increase the absorption of digoxin in such patients. Although inactivation of these bacteria by antibiotics is rapid, the serum digoxin concentration will rise at a rate consistent with the elimination half-life of digoxin. Serum digoxin concentration relates to the extent of bacterial inactivation, and may be as much as doubled in some cases .

Patients with malabsorption syndromes (e.g., short bowel syndrome, celiac sprue, jejunoileal bypass) may have a reduced ability to absorb orally administered digoxin.

Distribution

Following drug administration, a 6-to 8-hour tissue distribution phase is observed. This is followed by a much more gradual decline in the serum concentration of the drug, which is dependent on the elimination of digoxin from the body. The peak height and slope of the early portion (absorption/distribution phases) of the serum concentration-time curve are dependent upon the route of administration and the absorption characteristics of the formulation. Clinical evidence indicates that the early high serum concentrations do not reflect the concentration of digoxin at its site of action, but that with chronic use, the steady-state post-distribution serum concentrations are in equilibrium with tissue concentrations and correlate with pharmacologic effects. In individual patients, these post-distribution serum concentrations may be useful in evaluating therapeutic and toxic effects .

Digoxin is concentrated in tissues and therefore has a large apparent volume of distribution (approximately 475 to 500L). Digoxin crosses both the blood-brain barrier and the placenta. At delivery, the serum digoxin concentration in the newborn is similar to the serum concentration in the mother. Approximately 25% of digoxin in the plasma is bound to protein. Serum digoxin concentrations are not significantly altered by large changes in fat tissue weight, so that its distribution space correlates best with lean (i.e., ideal) body weight, not total body weight.

Metabolism

Only a small percentage (13%) of a dose of digoxin is metabolized in healthy volunteers. The urinary metabolites, which include dihydrodigoxin, digoxigenin bisdigitoxoside, and their glucuronide and sulfate conjugates, are polar in nature and are postulated to be formed via hydrolysis, oxidation, and conjugation. The metabolism of digoxin is not dependent upon the cytochrome P-450 system, and digoxin is not known to induce or inhibit the cytochrome P-450 system.

Excretion

Elimination of digoxin follows first-order kinetics (that is, the quantity of digoxin eliminated at any time is proportional to the total body content). Following intravenous administration to healthy volunteers, 50% to 70% of a digoxin dose is excreted unchanged in the urine. Renal excretion of digoxin is proportional to creatinine clearance and is largely independent of urine flow. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5 to 2 days. The half-life in anuric patients is prolonged to 3.5 to 5 days. Digoxin is not effectively removed from the body by dialysis, exchange transfusion, or during cardiopulmonary bypass because most of the drug is bound to extravascular tissues.

Special Populations

Geriatrics: Because of age-related declines in renal function, elderly patients would be expected to eliminate digoxin more slowly than younger subjects. Elderly patients may also exhibit a lower volume of distribution of digoxin due to age-related loss of lean muscle mass. Thus, the dosage of digoxin should be carefully selected and monitored in elderly patients .

Gender: In a study of 184 patients, the clearance of digoxin was 12% lower in females than in male patients. This difference is not likely to be clinically important.

Hepatic Impairment: Because only a small percentage (approximately 13%) of a dose of digoxin undergoes metabolism, hepatic impairment would not be expected to significantly alter the pharmacokinetics of digoxin. In a small study, plasma digoxin concentration profiles in patients with acute hepatitis generally fell within the range of profiles in a group of healthy subjects. No dosage adjustments are recommended for patients with hepatic impairment; however, serum digoxin concentrations should be used as appropriate to help guide dosing in these patients.

Renal Impairment: Since the clearance of digoxin correlates with creatinine clearance, patients with renal impairment generally demonstrate prolonged digoxin elimination half-lives and greater exposures to digoxin. Therefore, digoxin must be carefully titrated in these patients based on clinical response, and based on monitoring of serum digoxin concentrations, as appropriate.

Race: The impact of race differences on digoxin pharmacokinetics has not been formally studied. Because digoxin is primarily eliminated as unchanged drug via the kidney and because there are no important differences in creatinine clearance among races, pharmacokinetic differences due to race are not expected.

Drug-drug Interactions

Based on literature reports no significant changes in digoxin exposure were reported when digoxin was co-administered with the following drugs:

alfuzosin, aliskiren, amlodipine, aprepitant, argatroban, aspirin, atorvastatin, benazepril, bisoprolol, black cohosh, bosentan, candesartan, citalopram, clopidogrel, colesevelam, dipyridamole, disopyramide, donepezil, doxazosin, dutasteride, echinacea, enalapril, eprosartan, ertapenem, escitalopram, esmolol, ezetimibe, famciclovir, felodipine, finasteride, flecainide, fluvastatin, fondaparinux, galantamine, gemifloxacin, grapefruit juice, irbesartan, isradipine, ketorlac, levetiracetam, levofloxacin, lisinopril, losartan, lovastatin, meloxicam, mexilitine, midazolam, milk thistle, moexipril, montelukast, moxifloxacin, mycophenolate, nateglinide, nesiritide, nicardipine, nisoldipine, olmesartan, orlistat, pantoprazole, paroxetine,perindopril, pioglitazone, pravastatin, prazosin, procainamide, quinapril, raloxifene, ramipril, repaglinide, rivastigmine, rofecoxib, ropinirole, rosiglitazone, rosuvastatin, sertraline, sevelamer, simvastatin, sirolimus, solifenacin, tamsulosin, tegaserod, terbinafine, tiagabine, ticlopidine, tigecycline, topiramate, torsemide, tramadol, trandolapril, triamterene, trospium, trovafloxacin, valacyclovir, valsartan, varenicline, voriconazole, zaleplon, zolpidem

Clinical Studies

Chronic Heart Failure

Two 12-week, double-blind, placebo-controlled studies enrolled 178 (RADIANCE trial) and 88 (PROVED trial) patients with NYHA class II or III heart failure previously treated with digoxin, a diuretic, and an ACE inhibitor (RADIANCE only) and randomized them to placebo or treatment with LANOXIN. Both trials demonstrated better preservation of exercise capacity in patients randomized to LANOXIN. Continued treatment with LANOXIN reduced the risk of developing worsening heart failure, as evidenced by heart failure-related hospitalizations and emergency care and the need for concomitant heart failure therapy.

Dig Trial of LANOXIN in Patients with Heart Failure

The Digitalis Investigation Group (DIG) main trial was a 37-week, multicenter, randomized, double-blind mortality study comparing digoxin to placebo in 6800 adult patients with heart failure and left ventricular ejection fraction ≤ 0.45. At randomization, 67% were NYHA class I or II, 71% had heart failure of ischemic etiology, 44% had been receiving digoxin, and most were receiving a concomitant ACE inhibitor (94%) and diuretics (82%). As in the smaller trials described above, patients who had been receiving open-label digoxin were withdrawn from this treatment before randomization. Randomization to digoxin was again associated with a significant reduction in the incidence of hospitalization, whether scored as number of hospitalizations for heart failure (relative risk 75%), risk of having at least one such hospitalization during the trial (RR 72%), or number of hospitalizations for any cause (RR 94%). On the other hand, randomization to digoxin had no apparent effect on mortality (RR 99%, with confidence limits of 91 to 107%).

Chronic Atrial Fibrillation

Digoxin has also been studied as a means of controlling the ventricular response to chronic atrial fibrillation in adults. Digoxin reduced the resting heart rate, but not the heart rate during exercise.

In 3 different randomized, double-blind trials that included a total of 315 adult patients, digoxin was compared to placebo for the conversion of recent-onset atrial fibrillation to sinus rhythm. Conversion was equally likely, and equally rapid, in the digoxin and placebo groups. In a randomized 120-patient trial comparing digoxin, sotalol, and amiodarone, patients randomized to digoxin had the lowest incidence of conversion to sinus rhythm, and the least satisfactory rate control when conversion did not occur.

In at least one study, digoxin was studied as a means of delaying reversion to atrial fibrillation in adult patients with frequent recurrence of this arrhythmia. This was a randomized, double-blind, 43-patient crossover study. Digoxin increased the mean time between symptomatic recurrent episodes by 54%, but had no effect on the frequency of fibrillatory episodes seen during continuous electrocardiographic monitoring.

Digoxin: A Medicine for Heart Problems

What is digoxin?

Digoxin is a medicine used to treat certain heart problems such as heart failure. Heart failure results when the heart can’t pump blood well enough to supply the body’s needs. If you have heart failure, digoxin can improve your heart’s ability to pump blood. This will often improve symptoms such as shortness of breath.

Digoxin can also help people who have a rapid or irregular heartbeat. This can be caused by a heart problem called atrial fibrillation. Digoxin helps by slowing down and controlling the heart rate.

Digoxin comes in tablet, capsule, and liquid form. It works with minerals in the cells of the heart to reduce strain and keep the heart beating normally.

Path to improved health

How should I take my digoxin?

It’s very important to take your digoxin exactly as your doctor tells you. Digoxin is usually taken once a day. You should try to take it at the same time every day. If you miss a dose, you can take it if less than 12 hours have passed since your normal dosage time. If more than 12 hours have passed, skip that dose altogether. You don’t want to double up on digoxin doses.

It may take several weeks to several months for digoxin to start working. Don’t be surprised if you don’t feel better right away. Keep taking your digoxin, even after you are feeling better. Don’t suddenly stop taking your digoxin. This could make your heart problems worse. Call your doctor if you have any problems taking the medicine.

Do any foods or other medicines affect how digoxin works?

Some medicines and foods can decrease the amount of digoxin your body absorbs. These include:

  • Antacids that contain aluminum or magnesium.
  • Some cholesterol-lowering medicines (cholestyramine and colestipol).
  • Certain medicines that treat gastrointestinal issues, such metoclopramide or sulfasalazine.
  • Some antidiarrheal medicines that contain kaolin and pectin.
  • Bulk laxatives (such as psyllium, Metamucil or Citrucel).
  • High-fiber foods (such as bran muffins) or nutritional supplements (such as Ensure).

Don’t take these medicines or eat high-fiber foods too close to the time you take your digoxin. It could mean that you’ll have too little digoxin in your bloodstream to help your heart. It is better to take digoxin on an empty stomach. Check with your doctor before taking any of the medicines listed above. If your doctor says it’s okay to take these medicines, wait 2 hours between a dose of digoxin and a dose of these medicines.

Digoxin interacts with many other medicines, too. You should always tell your doctor and your pharmacist about all the medicines you are taking. This includes any over-the-counter medicines, natural remedies, and herbal medicines. Always talk to your doctor before you take any new medicines.

How will my doctor know if I am getting the right amount of digoxin?

The digoxin dose needed to treat heart conditions is different for different people. Your doctor may do a blood test to make sure you have the right amount of digoxin in your body. This blood test has to be done at least 6 hours after your last dose of digoxin. Tell your doctor when you normally take your digoxin. Your doctor may want you to wait to take your dose. Or he or she may want to schedule your appointment so that you will have your blood drawn at the right time.

Things to consider

Most people can take digoxin without experiencing many side effects. However, you could have side effects, especially if you get too much digoxin. These side effects include:

  • nausea
  • vomiting
  • diarrhea
  • stomach pain
  • loss of appetite
  • tiredness or weakness
  • slow heartbeat
  • palpitations
  • irregular heartbeat
  • drowsiness
  • confusion
  • fainting
  • vision changes (blurred or yellow).

It is important to pay attention to these side effects. Too much digoxin is dangerous. You should call your doctor right away if you experience any of these symptoms.

There are also symptoms when you are not getting enough digoxin. You should discuss your condition and symptoms with you doctor. If you have heart failure, the following symptoms may mean that you are not getting enough digoxin:

  • More shortness of breath than usual.
  • A decrease in your ability to climb stairs or walk.
  • Waking up short of breath at night.
  • Shortness of breath when you lie flat or sleep on more pillows than usual.
  • More frequent trips to the bathroom during the night.
  • Increased ankle swelling or feeling that your shoes are suddenly too tight.

If you have atrial fibrillation, the following symptoms may mean that you are not getting enough digoxin:

  • Rapid pulse (more than 100 beats per minute).
  • Palpitations, or a feeling that your heart is racing.
  • Change in your heart rate.
  • Dizziness.
  • Fainting or blackouts.

If you develop any of these symptoms, call your doctor right away. Your doctor will decide how to adjust medication and/or manage symptoms as needed.

Questions to ask your doctor

  • Is digoxin the right medicine for me?
  • How should I take this medicine?
  • What are possible side effects?
  • What are symptoms I need to watch out for?
  • What should I do if I miss a dose?
  • How long will I need to take digoxin?

Resources

U.S. National Library of Medicine, Digoxin

Digoxin, Oral Tablet

Digoxin oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with digoxin are listed below.

Heart failure drug

Taking digoxin with ivabradine, a heart failure drug, can increase your risk of side effects. These side effects include bradycardia (a slowed heart rhythm). If you need to take these drugs together, your doctor may monitor you closely.

Heart rhythm drugs

Taking digoxin with certain heart rhythm drugs may increase the levels of digoxin in your body and increase your risk of side effects, including heart problems. If you need to take these drugs with digoxin, your doctor may monitor you closely.

Examples of these drugs include:

  • amiodarone
  • quinidine
  • dofetilide
  • dronedarone
  • propafenone
  • sotalol

HIV medications

Taking digoxin with certain HIV drugs can increase the level of digoxin in your body. This could cause increased side effects. If you need to take these drugs with digoxin, your doctor may lower your dose of digoxin before you start taking these medications.

Examples of these drugs include:

  • ritonavir
  • saquinavir
  • lopinavir/ritonavir

Blood pressure drugs

Taking digoxin with certain blood pressure medications can increase the level of digoxin in your body. If you need to take these drugs with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with these drugs.

Examples of these drugs include:

  • captopril
  • carvedilol
  • diltiazem
  • verapamil
  • nifedipine
  • spironolactone
  • telmisartan

Antibiotics

Taking digoxin with certain antibiotics can increase digoxin levels in your body. If you need to take these drugs with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with these drugs.

Examples of these drugs include:

  • azithromycin
  • clarithromycin
  • erythromycin
  • gentamicin
  • trimethoprim
  • tetracycline

Immune-suppressing drug

Taking digoxin with cyclosporine can increase digoxin levels in your body. If you need to take cyclosporine with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with cyclosporine.

Cholesterol-lowering drug

Taking digoxin with atorvastatin can increase digoxin levels in your body. If you need to take atorvastatin with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with atorvastatin.

Antifungal drugs

Taking digoxin with certain antifungal drugs can increase digoxin levels in your body. If you need to take these drugs with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with these drugs.

Examples of these drugs include:

  • itraconazole
  • ketoconazole

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Taking digoxin with NSAIDs can increase digoxin levels in your body. If you need to take these drugs with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with NSAIDs.

Examples of NSAIDs include:

  • indomethacin
  • ibuprofen
  • diclofenac

Antidepressant

Taking digoxin with nefazodone can increase digoxin levels in your body. If you need to take this drug with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with nefazodone.

Antimalarial drug

Taking digoxin with quinine can increase digoxin levels in your body. If you need to take this drug with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with quinine.

Chest pain drug

Taking digoxin with ranolazine can increase digoxin levels in your body. If you need to take this drug with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with ranolazine.

Stimulant drugs

Taking digoxin with drugs called stimulants can lead to an irregular heart rhythm. Examples of these drugs include:

  • epinephrine
  • norepinephrine
  • phenylephrine

Neuromuscular blocker

Taking digoxin with succinylcholine can lead to an irregular heart rhythm.

Drugs used to treat low sodium levels

Taking digoxin with certain drugs used to increase sodium levels in your blood may increase digoxin levels in your body. If you need to take these drugs with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with these drugs.

These medications are:

  • tolvaptan
  • conivaptan

Cancer drug

Taking digoxin with lapatinib can increase digoxin levels in your body. If you need to take this drug with digoxin, your doctor may need to adjust your digoxin dosage.

Proton pump inhibitors

Taking digoxin with proton pump inhibitors (PPIs) can increase the levels of digoxin in your body. If you need to take these drugs with digoxin, your doctor may need to adjust your digoxin dosage.

Examples of PPIs include:

  • rabeprazole
  • esomeprazole
  • lansoprazole
  • omeprazole

Antiplatelet drug

Taking digoxin with ticagrelor can increase digoxin levels in your body. If you need to take this drug with digoxin, your doctor may need to adjust your digoxin dosage.

Overactive bladder drug

Taking digoxin with mirabegron can increase digoxin levels in your body. If you need to take this drug with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with mirabegron.

Propantheline

Taking digoxin with propantheline can increase digoxin levels in your body. If you need to take this drug with digoxin, your doctor will likely reduce your digoxin dosage first. They may also monitor your digoxin levels during your treatment with propantheline.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

GENERIC NAME: DIGITALIS MEDICINE – ORAL (didge-ih-TAL-iss)

BRAND NAME(S): Crystodigin

Medication Uses | How To Use | Side Effects | Precautions | Drug Interactions | Overdose | Notes | Missed Dose | Storage | Medical Alert

USES: Digitalis medication works directly on the heart muscle to strengthen and regulate the heartbeat. It is used to treat certain heart conditions.

HOW TO USE: Take this medication exactly as prescribed. Try to take it at the same time(s) each day. May be taken with food or milk to avoid stomach irritation. Do not stop taking this medication without consulting your doctor. Some conditions may become worse when the drug is suddenly stopped.

SIDE EFFECTS: Diarrhea, loss of appetite, drowsiness, headache, muscle weakness, and fatigue may occur as your body adjusts to the medication. Inform your doctor if you develop: confusion, visual disturbances (blurred vision or yellow/green halos around objects), fast/slow/irregular heartbeat, skin rash, breast enlargement, severe stomach upset. If you notice other effects not listed above, contact your doctor or pharmacist.

PRECAUTIONS: Tell your doctor if you have a history of: liver or kidney disease, lung disease, thyroid problems, rheumatic fever. Food high in fiber may decrease the absorption of digoxin. Be sure to take digoxin a few hours before or after eating something high in fiber (such as bran). Difficulty breathing and swelling in your lower legs and ankles may be signs that your dose is too low. If normal activity causes shortness of breath or if you awaken frequently during the night due to shortness of breath, tell your doctor. Do not change your dose without consulting your doctor. Before having surgery, including dental surgery, tell the doctor that you take digoxin. This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor. Digoxin is excreted into breast milk. Though, to date, no problems have been noted in nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Tell your doctor of all prescription and nonprescription medication you may use, especially: amphotericin, diuretics (“water pills”), corticosteroids (e.g., prednisone), amiodarone, acarbose, neomycin, quinidine, cyclosporine, verapamil, quinine, thyroid medication, propafenone, sucralfate, erythromycin-like drugs, rifampin, bepridil, penicillamine, drugs used for cancer, tetracycline, dextrothyroxine, St John’s wort. Cholestyramine, colestipol or psyllium (Metamucil) should be taken at least 2 hours after digoxin to prevent interference. If you are taking aminosalicylic acid (PAS), antacids, kaolin-pectin, milk of magnesia or sulfasalazine, take it as far apart as possible from digoxin. Do not start or stop any medicine without doctor or pharmacist approval.

Heart failure drug digoxin linked to premature death

“A heart drug taken by 250,000 Britons can actually hasten death,” the Mail Online warns today. An analysis of previous research on digoxin, used to treat heart failure and heart rhythm abnormalities, suggests that it can raise the risk of premature death.

The analysis pooled the results of 19 different studies investigating whether digoxin – used in the treatment of heart failure and atrial fibrillation – increases the risk of death from any cause.

Overall, the review found that people taking digoxin had a 21% higher risk of death from any cause compared to people not taking the drug.

The risk increase was slightly higher for people taking digoxin for atrial fibrillation (29%) than for heart failure (14%).

Though an effective drug, digoxin has long been known to have potentially serious adverse effects and always needs to be used with care. However, in this analysis, it is difficult to know how much of the higher risk of death is due solely to digoxin, and how much is due to health differences between the people who were and were not taking the drug. People who were prescribed digoxin may have had more severe health problems and these may have increased their mortality risk.

If you are taking digoxin and you have any concerns, or any new or worsening symptoms, do not stop taking your medication, but contact your health professional as soon as possible.

Where did the story come from?

The study was carried out by researchers from Goethe University in Germany. No sources of funding are reported, though one of the authors declares receiving consulting fees from various pharmacological companies.

The study was published in the peer-reviewed medical journal European Heart Journal.

Unsurprisingly, the UK media was vigorous in highlighting the potential dangers of digoxin. However, they did take the responsible step of advising readers not to stop taking digoxin without first consulting their GP.

The Express’ headline of “Popular heart pill raises death risk by a third” was a little misleading. This figure actually refers to the risk in people with atrial fibrillation (29%). The overall figure, for atrial fibrillation and congestive heart failure combined, was slightly lower, at just over a fifth (21%).

What kind of research was this?

This was a systematic review that searched for all relevant studies looking at the link between digoxin use and mortality risk. They pooled the results in a meta-analysis.

Digoxin is a heart drug that increases the strength of each heartbeat. It also controls the rate that electrical impulses signalling the heart muscle to contract are transmitted through the heart chambers. For this reason, it can be used in the control of fast and irregular heartbeats such as atrial fibrillation, and is also sometimes used in the treatment of heart failure.

However, digoxin has side effects. It takes a long time for the drug to be broken down by the body, so it can sometimes have toxic effects, particularly at high blood concentrations. Side effects often centre upon heart function, so it can sometimes be difficult to distinguish between what are direct side effects of the drug and what is due to the worsening clinical condition.

Various studies are said to have caused uncertainty over the side effects of digoxin, with some suggesting it could increase mortality risk. The researchers therefore aimed to carry out a systematic review to pool the evidence on the safety of the drug, particularly looking at mortality effects.

What did the research involve?

The researchers searched two literature databases (Medline and Cochrane) up to November 2014 to identify English language publications looking at the effect of digoxin on all-cause mortality (death from any cause) in people taking the drug for heart failure or atrial fibrillation.

There were 19 studies included, nine of which included people with atrial fibrillation, seven of people with heart failure, and three studies that included a combination of the two. These studies included a total of 235,047 people with atrial fibrillation and 91,379 with heart failure. Study duration ranged from less than one year to 4.7 years (average 2.5 years). Only one of the studies was a randomised controlled trial, the rest were observational studies. All studies were assessed to be of high quality.

Results were pooled and took into account the differences between study results, due to their different study design (heterogeneity).

What were the basic results?

In a pooled analysis of all 19 studies, people taking digoxin had a 21% increased risk of all-cause mortality compared with people not taking this drug (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.07 to 1.38). When separately analysed by condition, people with atrial fibrillation had a slightly higher risk of all-cause mortality (HR 1.29, 95% CI 1.21 to 1.39) compared to people taking the drug for heart failure (HR 1.14, 95% CI 1.06 to 1.22).

How did the researchers interpret the results?

The researchers conclude: “The present systematic review and meta-analysis of all available data sources suggests that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF.”

Conclusion

This is a valuable systematic review that has searched the global literature to investigate the link between digoxin use and death from any cause in people with atrial fibrillation or heart failure.

Overall, it found that people taking the drug had increased risk of death from any cause. People who were taking the drug for atrial fibrillation had a slightly higher risk than those taking it for heart failure.

These are important findings in terms of trying to quantify the size of the increased risk. However, there are points to consider:

  • The researchers report how the individual studies had adjusted their results for potential confounders that could be influencing the results. However, the factors adjusted for are likely to have differed between studies, and we do not know how completely they will have taken into account all of the differences in characteristics between people who were and weren’t taking digoxin. This means it’s still not clear how much of the increase in mortality risk is due directly to digoxin, and how much could be due to the health differences between the people studied.
  • As the researchers also noted, the studies provided limited information on how mortality risk was associated with a particular therapeutic dose of digoxin, or with blood concentration levels. As such, it is difficult to know of a particular “toxic dose” when it comes to increased overall mortality risk.
  • This study has also only focused on all-cause mortality. It has not investigated the underlying reasons for death. Therefore, the review cannot inform us on the reasons why digoxin could be increasing mortality risk (for example, by causing adverse effects on the way the heart functions).

Digoxin is already recognised by the medical profession to be a drug with potential serious adverse effects, and one that needs careful monitoring. This review again highlights the delicate balance there may be between its beneficial therapeutic effects upon conditions such as atrial fibrillation and heart failure, and its possible risks.

It is reported that the Medicines & Healthcare Products Regulatory Agency (the government body that regulates medicines and medical devices in the UK) is now looking at the evidence provided by this new analysis.

People taking digoxin should discuss with the doctor in charge of their care if they have any concerns, or any new or worsening symptoms. These could include lethargy or fatigue, feeling lightheaded or dizzy, or sickness.

However, it is important not to suddenly stop taking digoxin without having an alternative treatment plan, as there could be serious risk from the untreated heart problem.

Analysis by Bazian
Edited by NHS Website

Links to the headlines

Irregular heartbeat drug taken by 250,000 Britons ‘can raise risk of death’

Mail Online, 5 May 2015

Popular heart pill raises death risk by a third

Daily Express, 5 May 2015

Links to the science

Vamos M, Erath JW, Hohnloser SH.

Digoxin-associated mortality: a systematic review and meta-analysis of the literature

European Heart Journal. Published online May 4 2015

Digoxin Side Effects

Medically reviewed by Drugs.com. Last updated on Jan 7, 2019.

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For the Consumer

Applies to digoxin: oral solution, oral tablet

Along with its needed effects, digoxin may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking digoxin:

More common

  • Dizziness
  • fainting
  • fast, pounding, or irregular heartbeat or pulse
  • slow heartbeat

Rare

  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • bloody vomit
  • pinpoint red spots on the skin
  • rash with flat lesions or small raised lesions on the skin
  • severe stomach pain
  • unusual bleeding or bruising

Incidence not known

  • Chest pain or discomfort
  • nausea
  • shortness of breath
  • sweating
  • swelling of the feet and lower legs
  • troubled breathing
  • unusual tiredness or weakness

Some side effects of digoxin may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

  • Agitation or combativeness
  • anxiety
  • confusion
  • depression
  • diarrhea
  • expressed fear of impending death
  • hallucinations
  • rash
  • vomiting

Incidence not known

  • Blurred or loss of vision
  • disturbed color perception
  • double vision
  • halos around lights
  • headache
  • lack of feeling or emotion
  • loss of appetite
  • night blindness
  • overbright appearance of lights
  • swelling of the breasts or breast soreness in both females and males
  • tunnel vision
  • weakness
  • weight loss

For Healthcare Professionals

Applies to digoxin: compounding powder, injectable solution, oral capsule, oral elixir, oral tablet

General

Overall incidence of adverse reactions with this drug has been reported to be 5% to 20%, with 15% to 20% of adverse events considered serious. Cardiac toxicity accounts for about one-half, gastrointestinal disturbances for about one-fourth, and CNS and other toxicity for about one-fourth of these adverse events.

Cardiovascular

Common (1% to 10%): Arrhythmia, conduction disturbances, bigeminy, trigeminy, PR prolongation, sinus bradycardia

Postmarketing reports: Supraventricular tachyarrhythmia, atrial tachycardia, nodal tachycardia, ventricular arrhythmia, ventricular premature contraction, ST segment depression, atrioventricular block, ventricular fibrillation

Gastrointestinal

Common (1% to 10%): Nausea, vomiting, diarrhea, lower stomach pain

Frequency not reported: Intestinal ischemia, intestinal hemorrhagic necrosis

Nervous system

Common (1% to 10%): Central nervous system (CNS) disturbances, dizziness, drowsiness, headache

Other

Common (1% to 10%): Central nervous system (CNS) disturbances, dizziness, drowsiness, headache

Dermatologic

Common (1% to 10%): Skin rashes of urticarial or scarlatiniform character

Frequency not reported: Maculopapular rash

Metabolic

Common (1% to 10%): Anorexia or loss of appetite

Ocular

Common (1% to 10%): Blurred vision or visual disturbances

Psychiatric

Uncommon (0.1% to 1%): Depression

Frequency not reported: Apathy, confusion, anxiety, delirium, hallucination

Postmarketing reports: Psychosis

Hematologic

Frequency not reported: Thrombocytopenia

1. “Product Information. Lanoxin (digoxin).” Glaxo Wellcome, Research Triangle Park, NC.

2. Cerner Multum, Inc. “UK Summary of Product Characteristics.” O 0

3. Cerner Multum, Inc. “Australian Product Information.” O 0

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.

Medical Disclaimer

More about digoxin

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  • Drug class: group V antiarrhythmics
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Other brands: Lanoxin, Digox, Digitek, Lanoxicaps

Professional resources

  • Digoxin (AHFS Monograph)
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Related treatment guides

  • Atrial Fibrillation
  • Heart Failure

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