Digoxin: uses, appearance and warnings

Digoxin is a cardiac glycoside indicated for: Treatment of mild to moderate heart failure in adults. ( 1.1 ) Increasing myocardial contractility in pediatric patients with heart failure. ( 1.2 ) Control of resting ventricular rate in patients with chronic atrial fibrillation in adults. ( 1.3 ) 1.1 Heart Failure in Adults Digoxin is indicated for the treatment of mild to moderate heart failure in adults. Digoxin increases left ventricular ejection fraction and improves heart failure symptoms as evidenced by improved exercise capacity and decreased heart failure-related hospitalizations and emergency care, while having no effect on mortality. Where possible, digoxin should be used in combination with a diuretic and an angiotensin-converting enzyme (ACE) inhibitor. 1.2 Heart Failure in Pediatric Patients Digoxin increases myocardial contractility in pediatric patients with heart failure. 1.3 Atrial Fibrillation in Adults Digoxin is indicated for the control of ventricular response rate in adult patients with chronic atrial fibrillation.

125 mcg tablets are yellow, round, scored tablets imprinted with “JSP-544”. 250 mcg tablets are white, round, scored tablets imprinted with “JSP-545”. Scored Tablets 125 and 250 mcg

Digoxin Tablets, USP, 125 mcg (0.125 mg), Scored I.D. Imprint JSP-544 (yellow): Bottles of 100 (NDC 82685-201-01) and 1000 (NDC 82685-201-10). Digoxin Tablets, USP, 250 mcg (0.250 mg), Scored I.D. Imprint JSP-545 (white): Bottles of 100 (NDC 82685-202-01) and 1000 (NDC 82685-202-10). Store at controlled room temperature 15° - 25°C (59°F - 77°F) in a dry place and protect from light. Keep out of reach of children. Dispense in a tight, light-resistant container as defined in the USP.

Digoxin is contraindicated in patients with: Ventricular fibrillation [see Warnings and Precautions (5.1)] Known hypersensitivity to digoxin (reactions seen include unexplained rash, swelling of the mouth, lips or throat or a difficulty in breathing). A hypersensitivity reaction to other digitalis preparations usually constitutes a contraindication to digoxin. Ventricular fibrillation. ( 4 ) Known hypersensitivity to digoxin or other forms of digitalis. ( 4 )

Risk of rapid ventricular response leading to ventricular fibrillation in patients with AV accessory pathway. ( 5.1 ) Risk of advanced or complete heart block in patients with sinus node disease and AV block. ( 5.2 ) Digoxin toxicity: Indicated by nausea, vomiting, visual disturbances, and cardiac arrhythmias. Advanced age, low body weight, impaired renal function and electrolyte abnormalities predispose to toxicity. ( 5.3 ) Risk of ventricular arrhythmias during electrical cardioversion. ( 5.4 ) Not recommended in patients with acute myocardial infarction. ( 5.5 ) Avoid digoxin in patients with myocarditis. ( 5.6 ) 5.1 Ventricular Fibrillation in Patients With Accessory AV Pathway (Wolff-Parkinson- White Syndrome) Patients with Wolff-Parkinson-White syndrome who develop atrial fibrillation are at high risk of ventricular fibrillation. Treatment of these patients with digoxin leads to greater slowing of conduction in the atrioventricular node than in accessory pathways, and the risks of rapid ventricular response leading to ventricular fibrillation are thereby increased. 5.2 Sinus Bradycardia and Sino-atrial Block Digoxin may cause severe sinus bradycardia or sinoatrial block particularly in patients with pre-existing sinus node disease and may cause advanced or complete heart block in patients with pre-existing incomplete AV block. Consider insertion of a pacemaker before treatment with digoxin. 5.3 Digoxin Toxicity Signs and symptoms of digoxin toxicity include anorexia, nausea, vomiting, visual changes and cardiac arrhythmias [first-degree, second-degree (Wenckebach), or third-degree heart block (including asystole); atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular fibrillation]. Toxicity is usually associated with digoxin levels greater than 2 ng/ml although symptoms may also occur at lower levels. Low body weight, advanced age or impaired renal function, hypokalemia, hypercalcemia, or hypomagnesemia may predispose to digoxin toxicity. Obtain serum digoxin levels in patients with signs or symptoms of digoxin therapy and interrupt or adjust dose if necessary [see Adverse Reactions (6) and Overdosage (10) ] . Assess serum electrolytes and renal function periodically. The earliest and most frequent manifestation of digoxin toxicity in infants and children is the appearance of cardiac arrhythmias, including sinus bradycardia. In children, the use of digoxin may produce any arrhythmia. The most common are conduction disturbances or supraventricular tachyarrhythmias, such as atrial tachycardia (with or without block) and junctional (nodal) tachycardia. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmias or alteration in cardiac conduction that develops in a child taking digoxin should initially be assumed to be a consequence of digoxin intoxication. Given that adult patients with heart failure have some symptoms in common with digoxin toxicity, it may be difficult to distinguish digoxin toxicity from heart failure. Misidentification of their etiology might lead the clinician to continue or increase digoxin dosing, when dosing should actually be suspended. When the etiology of these signs and symptoms is not clear, measure serum digoxin levels. 5.4 Risk of Ventricular Arrhythmias During Electrical Cardioversion It may be desirable to reduce the dose of or discontinue digoxin for 1 to 2 days prior to electrical cardioversion of atrial fibrillation to avoid the induction of ventricular arrhythmias, but physicians must consider the consequences of increasing the ventricular response if digoxin is decreased or withdrawn. If digitalis toxicity is suspected, elective cardioversion should be delayed. If it is not prudent to delay cardioversion, the lowest possible energy level should be selected to avoid provoking ventricular arrhythmias. 5.5 Risk of Ischemia in Patients With Acute Myocardial Infarction Digoxin is not recommended in patients with acute myocardial infarction because digoxin may increase myocardial oxygen demand and lead to ischemia. 5.6 Vasoconstriction In Patients With Myocarditis Digoxin can precipitate vasoconstriction and may promote production of pro-inflammatory cytokines; therefore, avoid use in patients with myocarditis. 5.7 Decreased Cardiac Output in Patients With Preserved Left Ventricular Systolic Function Patients with heart failure associated with preserved left ventricular ejection fraction may experience decreased cardiac output with use of digoxin. Such disorders include restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Patients with idiopathic hypertrophic subaortic stenosis may have worsening of the outflow obstruction due to the inotropic effects of digoxin. Patients with amyloid heart disease may be more susceptible to digoxin toxicity at therapeutic levels because of an increased binding of digoxin to extracellular amyloid fibrils. Digoxin should generally be avoided in these patients, although it has been used for ventricular rate control in the subgroup of patients with atrial fibrillation. 5.8 Reduced Efficacy in Patients With Hypocalcemia Hypocalcemia can nullify the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal. These interactions are related to the fact that digoxin affects contractility and excitability of the heart in a manner similar to that of calcium. 5.9 Altered Response in Thyroid Disorders and Hypermetabolic States Hypothyroidism may reduce the requirements for digoxin. …

The following adverse reactions are included in more detail in the Warnings and Precautions section of the label: Cardiac arrhythmias [see Warnings and Precautions (5.1 , 5.2 )] Digoxin Toxicity [see Warnings and Precautions (5.3) ] The overall incidence of adverse reactions with digoxin has been reported as 5-20%, with 15-20% 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Oliva Therapeutics at 1-877-200-6088 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

Digoxin has a narrow therapeutic index, increased monitoring of serum digoxin concentrations and for potential signs and symptoms of clinical toxicity is necessary when initiating, adjusting, or discontinuing drugs that may interact with digoxin. Prescribers should consult the prescribing information of any drug which is co-prescribed with digoxin for potential drug interaction information. PGP Inducers/Inhibitors: Drugs that induce or inhibit PGP have the potential to alter digoxin pharmacokinetics. ( 7.1 ) The potential for drug-drug interactions must be considered prior to and during drug therapy. See full prescribing information. ( 7.2 , 7.3 , 12.3 ) 7.1 P-Glycoprotein (PGP) Inducers/Inhibitors Digoxin is a substrate of P-glycoprotein, at the level of intestinal absorption, renal tubular section and biliary–intestinal secretion. …