[10][11] The most common indications for digoxin are atrial fibrillation and atrial flutter with rapid ventricular response,[12][13] especially in older or less active patients,[14] though beta blockers and/or calcium channel blockers may be preferred in some patients, such as younger more active ones, or those without heart failure or hemodynamic instability.

Since the introduction of other drugs with better outcomes and fewer adverse effects, it is generally now only used where heart failure is associated with atrial fibrillation and or a rapid ventricular rate.

[25] The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity).

Gynaecomastia (enlargement of breast tissue) is mentioned in many textbooks as a side effect, thought to be due to the estrogen-like steroid moiety of the digoxin molecule,[26] but when systematically sought, the evidence for this is equivocal as of 2005[update].

This is because co-administration of Digoxin with drugs such as thiazides and loop diuretics which can cause hypokalemia, low serum levels of potassium in the blood.

If arrhythmias prove troublesome, or malignant hyperkalemia occurs (inexorably rising potassium level due to paralysis of the cell membrane-bound, ATPase-dependent Na/K pumps), the specific antidote is antidigoxin (antibody fragments against digoxin, trade names Digibind and Digifab).

Digoxin's primary mechanism of action involves inhibition of the sodium potassium adenosine triphosphatase (Na+/K+ ATPase), mainly in the myocardium.

[citation needed] The inhibition of the sodium pump may also improve baroreceptor sensitivity in heart failure and may explain some of the neurohormonal effects of digoxin.

Vagus nerve stimulation slows down conduction at the AV node by increasing the refractory period of cardiac myocytes.

While IV therapy may be better tolerated (less nausea), digoxin has a very long distribution half-life into the cardiac tissue, which will delay its onset of action by a number of hours.

[36] This recommendation is based on post hoc analysis of prospective trials, suggesting higher levels may be associated with increased mortality rates.

[39] Digoxin appears to be a peripherally selective drug due to limited brain uptake caused by binding to P-glycoprotein.

[42] These effects have been studied through comparisons of North Americans and Southern Indians, in which a reduced digoxin metabolite profile correlates with E. lenta abundance.

[43] Further studies have also revealed an increase in digoxin toxicity when used alongside erythromycin or tetracycline, the researches attributed this to the decrease in the E. lenta population.

[45] William Withering is credited with the first published description of the systematic use of Digitalis derivatives in his 1785 book An Account of the Foxglove and some of its Medical Uses With Practical Remarks on Dropsy and Other Diseases.

[51] On April 25, 2008, the U.S. Food and Drug Administration (FDA) issued a press release[52] alerting the public to a Class I recall of Digitek, a brand of digoxin produced by Mylan.

[54] On March 31, 2009, the FDA announced another generic digoxin pill recall by posting this company press release on the agency's web site: "Caraco Pharmaceutical Laboratories, Ltd.

A March 31 press release from Caraco, a generic pharmaceutical company, stated: [All] tablets of Caraco brand Digoxin, USP, 0.125 mg, and Digoxin, USP, 0.25 mg, distributed prior to March 31, 2009, which are not expired and are within the expiration date of September, 2011, are being voluntarily recalled to the consumer level.

[citation needed]A 2008 study suggested digoxin has beneficial effects not only for the heart, but also in reducing the risk of certain kinds of cancer.

[55] However, comments on this study suggested that digoxin is not effective at reducing cancer risk at therapeutic concentrations of the drug,[56] so the results need further investigation.

[57] Digoxin preparations are marketed under the brand names Cardigox; Cardiogoxin; Cardioxin; Cardoxin; Coragoxine; Digacin; Digicor; Digitek; Digomal; Digon; Digosin; Digoxine Navtivelle; Digoxina-Sandoz; Digoxin-Sandoz; Digoxin-Zori; Dilanacin; Eudigox; Fargoxin; Grexin; Lanacordin; Lanacrist; Lanicor; Lanikor; Lanorale; Lanoxicaps; Lanoxin; Lanoxin PG; Lenoxicaps; Lenoxin; Lifusin; Mapluxin; Natigoxin; Novodigal; Purgoxin; Sigmaxin; Sigmaxin-PG; Toloxin.

Digoxin has the ability to bind oestrogen receptors, and therefore it has been proposed that it might increase the risk of oestrogen-sensitive breast and uterine cancers.

[62] A large Danish study found a complicated picture, with slightly increased risk of breast cancer amongst women taking digoxin, but better prognostic features.