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. The half-life is about 36 hours for patients with normal renal function, digoxin is given once daily, usually in 125 μg or 250 μg doses.Digoxin elimination is mainly by renal excretion and involves P-glycoprotein, which leads to significant clinical interactions with P-glycoprotein inhibitor drugs. Examples commonly used in patients with heart problems include spironolactone, verapamil and amiodarone. In patients with decreased kidney function the half-life is considerably longer, along with decrease in Vd (volume of distribution), calling for a reduction in dose or a switch to a different glycoside, such as digitoxin (not available in the United States), which has a much longer elimination half-life of around seven days and is eliminated by the liver.Effective plasma levels vary depending on the medical indication. For congestive heart failure, levels between 0.5 and 1.0 ng/mL are recommended. This recommendation is based on post hoc analysis of prospective trials, suggesting higher levels may be associated with increased mortality rates. For heart rate control (atrial fibrillation), plasma levels are less defined and are generally titrated to a goal heart rate. Typically, digoxin levels are considered therapeutic for heart rate control between 0.5 and 2.0 ng/mL (or 0.6 and 2.6 nmol/L). In suspected toxicity or ineffectiveness, digoxin levels should be monitored. Plasma potassium levels also need to be closely controlled (see side effects, below).
The English physician William Withering is credited with the first published description of the 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. Its effects were first explained by Arthur Robertson Cushny. The name is derived from that of digitoxin, which explains its pronunciation. In 1930, Digoxin was first isolated by Dr. Sydney Smith from the foxglove plant, Digitalis lanata. Initially, the digoxin was purified by dissolving the dried plant material in acetone and boiling the solution in chloroform. The solution was then reacted with acetic acid and small amount of ferric chloride and sulfuric acid (Keller reaction). Digoxin was distinguishable from other glucosides by the olive-green colored solution produced from this reaction, completely free of red. Society and culture
Charles Cullen admitted in 2003 to killing as many as 40 hospital patients with overdoses of heart medication—usually digoxin—at hospitals in New Jersey and Pennsylvania over his 19-year career as a nurse. On March 10, 2006, he was sentenced to 18 consecutive life sentences and is not eligible for parole.On April 25, 2008, the U.S. Federal Drug Administration (FDA) issued a press release alerting the public to a Class I recall of Digitek, a brand of digoxin produced by Mylan. Some tablets had been released at double thickness and therefore double strength, causing some patients to experience digoxin toxicity.