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Digoxin: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Feb 15, 2021.

1. How it works

  • Digoxin may be used to treat heart failure or atrial fibrillation.
  • Digoxin works by inhibiting an enzyme (called Na-K ATPase) responsible for the exchange of sodium for other electrolytes in cells. This, in turn, increases the amount of calcium that enters the heart, affecting the electrical system of the heart and ultimately the way the heart beats.
  • Digoxin belongs to the class of medicines known as digitalis glycosides (may also be called cardiac glycosides). It may also be called a Group V antiarrhythmic or an inotropic agent.

2. Upsides

  • May be used in the treatment of mild-to-moderate heart failure. It improves left ventricular ejection fraction (which is the amount of blood pumped out of the heart with each beat) and improves symptoms of heart failure (such as exercise capacity) and reduces the number of hospitalizations. Current use for heart failure is limited because of the lack of demonstrated survival benefits.
  • May also be used in the treatment of persistent atrial fibrillation (AF) to control the ventricular response rate (how fast the ventricles in the heartbeat).
  • Available in an injectable form for people requiring needing rapid digitalization or who cannot swallow oral tablets; however, intravenous injection is preferred because an intramuscular injection can be extremely painful.
  • Has positive inotropic (strengthens the heartbeat) effects and antiarrhythmic effects.
  • Serum digoxin concentrations can help guide dosing; however, these should be interpreted within the overall clinical context and an isolated measurement alone should not be used to base dosing on. Obtain blood samples at least 6 to 8 hours after the daily dose and preferably just before the next scheduled dose.
  • Available as oral tablets, oral solution, or IV.
  • Can be administered once daily; however, divided dosing is recommended in infants and young children aged less than 10 years. Titrate the dosage carefully in neonates, especially premature infants because the renal clearance of digoxin is decreased.
  • May be administered with or without a loading dose.
  • No dosage adjustment is needed in liver disease.
  • Digoxin Immune Fab may be used to treat potentially life-threatening cardiotoxicity or hyperkalemia. Activated charcoal can also enhance digoxin elimination. Avoid use of calcium infusions for the treatment of hyperkalemia because the calcium may worsen cardiac irregularities.
  • Generic digoxin is available.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • A headache, weakness, dizziness, anxiety, abdominal pain, nausea, and vomiting. Estrogen-like effects can occur with long-term administration especially in older men and women whose endogenous concentrations of sex hormones are low. May cause gynecomastia (breast enlargement in males) and the enlargement of breasts in women.
  • There is a fine line between toxic levels of digoxin and therapeutic levels. Factors such as body weight, age, kidney function, interacting medications, and potassium intake can all upset the balance, so ongoing monitoring of digoxin and electrolyte levels is required. Cautious dosage determination is essential, and lean body weight should be used when determining dosage calculations.
  • Signs of toxicity include nausea, vomiting, visual disturbances, arrhythmia, and weight loss. Discontinue digoxin immediately if signs of toxicity appear. Place patient on a cardiac monitor and address any contributing factors such as electrolyte and thyroid abnormalities and contributing drugs.
  • The dosage of digoxin requires adjusting in people with kidney disease. Lower dosages are recommended for the management of heart failure in seniors over the age of 70 years.
  • Digoxin is not suitable for some people with certain types of arrhythmia (such as ventricular fibrillation or WPW syndrome and pre-excited atrial fibrillation) and with some other types of cardiac disease, such as myocarditis or substantial sinus or AV block unless a pacemaker is present. Less effective for high-output heart failure. People with heart failure associated with preserved left ventricular ejection fraction may experience a decreased cardiac output with digoxin.
  • Digoxin interacts with several drugs, including antibiotics, atorvastatin, other heart medications, and indomethacin. See here for a full list of interactions.
  • Regular monitoring of digoxin levels is necessary. However, a dosage adjustment should never be based on an isolated measurement of serum digoxin concentration as these can be falsely elevated by digoxin-like substances. Regular monitoring of potassium levels and kidney function is also necessary. Administer potassium supplementation in patients with hypokalemia to keep the concentration at between 4 and 5.5 mEq/L.
  • Taking digoxin does not appear to increase or decrease a person's risk of death.
  • Effects may be better when used in combination with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor.
  • There is an increased risk of ventricular arrhythmias developing in patients taking digoxin during electrical cardioversion. Reduce dosage or withhold therapy for 1 to 2 days before elective cardioversion. Postpone in those with digoxin toxicity.
  • When switching from IV digoxin to oral digoxin and vice-versa, the differences in bioavailability between the preparations need to be considered. Reduce the dosage by about 20% to 25% when switching from oral tablets or solution to IV. • Not recommended in patients with acute myocardial infarction (heart attack).
  • Has been administered to pregnant women when there is a risk the underlying cardiac abnormalities may increase the risk of adverse pregnancy outcomes. Distributed into breast milk; however, the quantities present are unlikely to be clinically important.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Digoxin is one of the oldest and most controversial heart medications. In heart failure, it is usually only used alongside standard medications. In atrial fibrillation, there is still much debate about its benefits and risks. Dosing may be difficult because many individual factors influence blood levels of digoxin, and there is a fine line between taking too much or too little.

5. Tips

  • May be taken with or without food.
  • If taking digoxin liquid, carefully measure the dose using the calibrated dropper provided (do not use a normal household teaspoon because there is no guarantee you are getting the correct dose).
  • Take as directed by your doctor. Do not increase or decrease the dosage without his or her advice.
  • Your doctor may advise you to record your heart rate and blood pressure daily while taking digoxin.
  • Some doctors may initiate digoxin dosing with a loading dose (a higher than normal dose) followed by a smaller, regular maintenance dose. Others may just choose to start with a regular maintenance dose - this means it will take a few days to reach effective blood levels. Any further dosage increases should happen at two weekly intervals to allow time for digoxin to reach peak levels.
  • Digoxin may need to be temporarily stopped or reduced before electrical cardioversion. Your doctor will advise you about this.
  • Your doctor needs to monitor your blood levels of digoxin regularly, and also your kidney function and potassium levels. Although there is an ideal range for digoxin levels in the blood (0.5-2 ng/mL), doctors should interpret your levels based on your response to the drug.
  • Talk to your doctor or pharmacist before taking any other medication with digoxin, including medicine brought over-the-counter, because several medicines, including herbal medicines and supplements, can interact with digoxin.
  • Seek immediate medical advice if you experience nausea or vomiting, persistent diarrhea, confusion, weakness, or visual disturbances (including blurred vision, green-yellow color disturbances, halo effect) because these may be a sign that your digoxin levels are too high.
  • In infants, symptoms of high digoxin levels may differ from adults and include weight loss, failure to thrive, abdominal pain, and behavioral disturbances.

6. Response and effectiveness

  • Although some effects of digoxin may be noticed soon after taking, it can take up to 7-14 days or longer after drug initiation or a dosage change for the full effects to be seen. Allow approximately 2 weeks between dosage changes to allow time for serum concentrations to stabilize.
  • Digoxin levels of less than 0.5 ng/mL have been associated with reduced efficacy, while levels above 2 ng/mL have been associated with toxicity without increased benefit. However, digoxin levels should always be interpreted taking into account what effects the drug is having and any symptoms of toxicity.
  • Although digoxin has historically been used extensively for the treatment of heart failure it is not currently considered a first-line agent for this indication because of a lack of survival benefit, potential for serious adverse effects, and the availability of other medications, such as ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors, or beta-blockers) that have been shown to reduce morbidity and mortality.

7. Interactions

Medicines that interact with digoxin may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with digoxin. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with digoxin include:

  • acarbose
  • ACE inhibitors
  • albuterol
  • alprazolam
  • aspirin
  • antacids containing magnesium, calcium, or aluminum
  • antiarrhythmics such as amiodarone, verapamil, procainamide, or flecainide
  • antibiotics, such as erythromycin, clarithromycin, gentamicin, neomycin, tobramycin, or trimethoprim
  • anticonvulsants, such as phenytoin
  • atorvastatin
  • beta-blockers such as atenolol, betaxolol, or metoprolol
  • bupropion
  • calcium salts
  • cholesterol-lowering medications, such as atorvastatin, cholestyramine or colestipol
  • cyclosporine
  • grapefruit juice
  • heart medications, such as angiotensin II receptor antagonists, or captopril
  • HIV medications such as ritonavir
  • loop diuretics, such as furosemide and potassium-sparing diuretics such as spironolactone
  • metformin
  • metoclopramide
  • nefazodone
  • NSAIDs such as diclofenac or ibuprofen
  • proton pump inhibitors such as esomeprazole, omeprazole, and pantoprazole, and other heartburn medications such as famotidine
  • some herbal supplements (eg, Lily of the Valley, St. John's Wort)
  • trimethoprim
  • Vitamin D analogs.

Digoxin is a substrate of the P-glycoprotein (P-gp) transporter) and may interact with other drugs that induce or inhibit P-gp, such as amiodarone, protease inhibitors, or rifampicin.

Use digoxin cautiously with other medicines that can depress sinus or AV nodal function, that inhibit renal function, or that alter gastrointestinal transit time.

Note that this list is not all-inclusive and includes only common medications that may interact with digoxin. You should refer to the prescribing information for digoxin for a complete list of interactions.

References

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use digoxin only for the indication prescribed.

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

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