Digoxin
Digoxin (Lanoxin)
Digoxin
(dih- JOX-in)
Pregnancy Category: A Lanoxicaps Lanoxin Novo-Digoxin (Rx)

Classification: Cardiac glycoside

Action/Kinetics: Digoxin increases the force and velocity of myocardial contraction (positive inotropic effect) by increasing the refractory period of the AV node and increasing total peripheral resistance. This effect is due to inhibition of sodium/potassium-ATPase in the sarcolemmal membrane, which alters excitation-contraction coupling. Inhibiting sodium, potassium-ATPase results in an increase of calcium influx and an increased release of free calcium ions within the myocardial cells, which then potentiate the contractility of cardiac muscle fibers. Digoxin also decreases the rate of conduction and increase the refractory period of the AV node due to an increase in parasympathetic tone and a decrease in sympathetic tone. Clinical effects are not seen until steady-state plasma levels are reached. The initial dose of digoxin is larger (loading dose) and is traditionally referred to as the digitalizing dose; subsequent doses are referred to as maintenance doses. Onset: PO, 0.5-2 hr; time to peak effect: 2-6 hr. Duration: Over 24 hr. Onset, IV: 5-30 min; time to peak effect: 1-4 hr. Duration: 6 days. t 1/2: 30-40 hr. Therapeutic serum level: 0.5-2.0 ng/mL. From 20% to 25% is protein bound. Serum levels above 2.5 ng/mL indicate toxicity. Fifty percent to 70% is excreted unchanged by the kidneys. Bioavailability depends on the dosage form: tablets (60%-80%), capsules (90%-100%), and elixir (70%-85%). Thus, changing dosage forms may require dosage adjustments.

Uses: CHF, including that due to venous congestion, edema, dyspnea, orthopnea, and cardiac arrhythmia. May be drug of choice for CHF because of rapid onset, relatively short duration, and ability to be administered PO or IV.
Control of rapid ventricular contraction rate in clients with atrial fibrillation or flutter. Slow HR in sinus tachycardia due to CHF. Supraventricular tachycardia. Prophylaxis and treatment of recurrent paroxysmal atrial tachycardia with paroxysmal AV junctional rhythm. Cardiogenic shock (value not established).

Contraindications: Ventricular fibrillation or tachycardia (unless congestive failure supervenes after protracted episode not due to digitalis), in presence of digitalis toxicity, hypersensitivity to cardiac glycosides, beriberi heart disease, certain cases of hypersensitive carotid sinus syndrome.

Special Concerns: Use with caution in clients with ischemic heart disease, acute myocarditis, hypertrophic subaortic stenosis, hypoxic or myxedemic states, Adams-Stokes or carotid sinus syndromes, cardiac amyloidosis, or cyanotic heart and lung disease, including emphysema and partial heart block. Those with carditis associated with rheumatic fever or viral myocarditis are especially sensitive to digoxin-induced disturbances in rhythm. Electric pacemakers may sensitize the myocardium to cardiac glycosides. Also use with caution and at reduced dosage in elderly, debilitated clients, pregnant women and nursing mothers, and newborn, term, or premature infants who have immature renal and hepatic function and in reduced renal and/or hepatic function.
The half-life of cardiac glycosides is prolonged in the elderly; anticipate smaller drug doses. Be especially alert to cardiac arrhythmias in children. This sign of toxicity occurs more frequently in children than in adults.

Side Effects: Cardiac glycosides are extremely toxic and have caused death even in clients who have received the drugs for long periods of time. There is a narrow margin of safety between an effective therapeutic dose and a toxic dose. Overdosage caused by the cumulative effects of the drug is a constant danger in therapy with cardiac glycosides. Digoxin toxicity is characterized by a wide variety of symptoms, which are hard to differentiate from those of the cardiac disease itself.
One of the most serious side effects of digitalis-type drugs is hypokalemia (lowering of serum potassium levels). This may lead to cardiac arrhythmias, muscle weakness, hypotension, and respiratory distress. Other agents causing hypokalemia reinforce this effect and increase the chance of digitalis toxicity. Such reactions may occur in clients who have been on digitalis maintenance for a long time.  CV: Changes in the rate, rhythm, and irritability of the heart and the mechanism of the heartbeat. Extrasystoles, bigeminal pulse, coupled rhythm, ectopic beat, and other forms of arrhythmias have been noted. Death most often results from ventricular fibrillation. Cardiac glycosides should be discontinued in adults when pulse rate falls below 60 beats/min. All cardiac changes are best detected by the ECG, which is also most useful in clients suffering from intoxication. Acute hemorrhage. GI: Anorexia, N&V;, excessive salivation, epigastric distress, abdominal pain, diarrhea, bowel necrosis. Clients on digitalis therapy may experience two vomiting stages. The first is an early sign of toxicity and is a direct effect of digitalis on the GI tract. Late vomiting indicates stimulation of the vomiting center of the brain, which occurs after the heart muscle has been saturated with digitalis. CNS: Headaches, fatigue, lassitude, irritability, malaise, muscle weakness, insomnia, stupor. Psychotomimetic effects (especially in elderly or arteriosclerotic clients or neonates) including disorientation, confusion, depression, aphasia, delirium, hallucinations, and, rarely, convulsions. Neuromuscular: Neurologic pain involving the lower third of the face and lumbar areas, paresthesia. Visual disturbances: Blurred vision, flickering dots, white halos, borders around dark objects, diplopia, amblyopia, color perception changes. Hypersensitivity (5-7 days after starting therapy): Skin reactions (urticaria, fever, pruritus, facial and angioneurotic edema). Other: Chest pain, coldness of extremities.

Laboratory Test Alterations: May PT. Alters tests for 17-ketosteroids and 17-hydroxycorticosteroids.

Overdose Management: The relationship of digoxin levels to symptoms of toxicity varies significantly from client to client; thus, it is not possible to identify digoxin levels that would define toxicity accurately. Symptoms (Toxicity): GI: Anorexia, N&V;, diarrhea, abdominal discomfort, or pain. CNS: Blurred, yellow, or green vision and halo effect; headache, weakness, drowsiness, mental depression, apathy, restlessness, disorientation, confusion, seizures EEG abnormalities, delirium, hallucinations, neuralgia, psychosis. CV: Ventricular tachycardia, unifocal or multiform PVCs (especially in bigeminal or trigeminal patterns), paroxysmal and nonparoxysmal nodal rhythms, AV dissociation, accelerated junctional rhythm, excessive slowing of the pulse, AV block (may proceed to complete block) atrial fibrillation, ventricular fibrillation (most common cause of death). Children: Visual disturbances, headache, weakness, apathy, and psychosis occur but may be difficult to recognize. CV: Conduction disturbances, supraventricular tachyarrhythmias (e.g., AV block), atrial tachycardia with or without block, nodal tachycardia, unifocal or multiform ventricular premature contractions, ventricular tachycardia, sinus bradycardia (especially in infants). Treatment in Adults: Discontinue drug and admit to the intensive care area for continuous monitoring of ECG. If serum potassium is below normal, potassium chloride should be administered in divided PO doses totaling 3-6 g (40-80 mEq). Potassium should not be used when severe or complete heart block is due to digitalis and not related to tachycardia. Atropine: A dose of 0.01 mg/kg IV to treat severe sinus bradycardia or slow ventricular rate due to secondary AV block. Cholestyramine, colestipol, activated charcoal: To bind digitalis in the intestine, thus preventing enterohepatic recirculation. Digoxin immune FAB: See drug entry. Given in approximate equimolar quantities as digoxin, it reverses S&S; of toxicity, often with improvement seen within 30 min. Lidocaine: A dose of 1 mg/kg given over 5 min followed by an infusion of 15-50 mcg/kg/min to maintain normal cardiac rhythm. Phenytoin: For atrial or ventricular arrhythmias unresponsive to potassium, can give a dose of 0.5 mg/kg at a rate not exceeding 50 mg/min (given at 1-2 hr intervals). The maximum dose should not exceed 10 mg/kg/day. Countershock: A direct-current countershock can be used only as a last resort. If required, therapy should be initiated at low voltage levels.
Treatment in Children: Give potassium in divided doses totaling 1-1.5 mEq/kg (if correction of arrhythmia is urgent, a dose of 0.5 mEq/kg/hr can be used) with careful monitoring of the ECG. The potassium IV solution should be dilute to avoid local irritation although IV fluid overload must be avoided. Digoxin immune FAB may also be used.

Drug Interactions: The following drugs increase serum digoxin levels, leading to possible toxicity: Aminoglycosides, amiodarone, anticholinergics, benzodiazepines, captopril, diltiazem, erythromycin, esmolol, flecainide, hydroxychloroquine, ibuprofen, indomethacin, nifedipine, quinidine, quinine, tetracyclines, tolbutamide, verapamil. Albuterol / Digoxin binding to skeletal muscle Aloe / Potential for digoxin effect R/T aloe-induced hypokalemia Amiloride / Digoxin inotropic effects Aminoglycosides / Digoxin effect R/T GI tract absorption Aminosalicylic acid / Digoxin effect R/T GI tract absorption Amphotericin B / K depletion caused by digoxin; risk of digitalis toxicity Antacids / Digoxin effect of R/T GI tract absorption Beta blockers / Complete heart block possible Buckthorn bark/berry / Potential for digoxin effect R/T to buckthorn-induced hypokalemia Calcium preparations / Cardiac arrhythmias following parenteral calcium Cascara sagrada bark / Potential for digoxin effect R/T to cascara-induced hypokalemia Chlorthalidone / K and Mg loss with chance of digitalis toxicity Cholestyramine / Binds digoxin in the intestine and its absorption Colestipol / Binds digoxin in the intestine and its absorption Disopyramide / May alter effect of digoxin Ephedra / Chance of cardiac arrhythmias Ephedrine / Chance of cardiac arrhythmias Epinephrine / Chance of cardiac arrhythmias Ethacrynic acid / K and Mg loss with chance of digitalis toxicity Fluoxetine / Possible Serum digoxin levels Furosemide / K and Mg loss with chance of digoxin toxicity German chamomile flower / Potential for digoxin effect R/T to chamomile-induced hypokalemia Ginseng / Digoxin levels Glucose infusions / Large infusions of glucose may cause in serum potassium and chance of digoxin toxicity Hawthorn / Potentiation of digoxin effect Hypoglycemic drugs / Effect of digitalis glycosides due to breakdown by liver Iceland moss / Potential for digoxin effect R/T to iceland moss-induced hypokalemia Indian snakeroot / Risk of bradycardia Ivy leaf / Potential for digoxin effect R/T to ivy leaf-induced hypokalemia Licorice / Potential for digoxin effect R/T to licorice-induced hypokalemia Marshmallow root / Potential for digoxin effect R/T to marshmallow root-induced hypokalemia Methimazole / Chance of toxic effects of digitalis Metoclopramide / Digoxin effect R/T GI tracat absorption Muscle relaxants, nondepolarizing / Risk of cardiac arrhythmias Penicillamine / Serum digoxin levels. Propranolol / Potentiates digitalis-induced bradycardia Rhubarb root / Potential for digoxin effect R/T to rhubarb root-induced hypokalemia St. John's wort / Digoxin plasma levels R/T renal excretion Sarsaparilla root / Potential for absorption of digoxin Senna pod/leaf / Potential for digoxin effect R/T to senna-induced hypokalemia Spironolactone / Either or toxic effects of digoxin Succinylcholine / Chance of cardiac arrhythmias Sulfasalazine / Digoxin effect of R/T GI tract absorption Sympathomimetics / Chance of cardiac arrhythmias Thiazides / K and Mg loss with chance of digoxin toxicity Thioamines / Effect and toxicity of digoxin Thyroid / Digoxin effect Triamterene / Digoxin effects

How Supplied: Capsule: 0.05 mg, 0.1 mg, 0.2 mg; Elixir: 0.05 mg/mL; Injection: 0.1 mg/mL, 0.25 mg/mL; Tablet: 0.125 mg, 0.25 mg

Dosage
?Capsules Digitalization: Rapid.
Adults: 0.4-0.6 mg initially followed by 0.1-0.3 mg q 6-8 hr until desired effect achieved.
Digitalization: Slow.
Adults: A total of 0.05-0.35 mg/day divided in two doses for a period of 7-22 days to reach steady-state serum levels. Pediatric. Digitalizing dosage is divided into three or more doses with the initial dose being about one-half the total dose; doses are given q 4-8 hr. Children, 10 years and older: 0.008-0.012 mg/kg. 5-10 years: 0.015-0.03 mg/kg. 2-5 years: 0.025-0.035 mg/kg. 1 month-2 years: 0.03-0.05 mg/kg. Neonates, full-term: 0.02-0.03 mg/kg. Neonates, premature: 0.015-0.025 mg/kg.
Maintenance.
Adults: 0.05-0.35 mg once or twice daily. Premature neonates: 20%-30% of total digitalizing dose divided and given in two to three daily doses. Neonates to 10 years: 25%-35% of the total digitalizing dose divided and given in two to three daily doses.
?Elixir, Tablets Digitalization: Rapid.
Adults: A total of 0.75-1.25 mg divided into two or more doses each given at 6-8-hr intervals.
Digitalization: Slow.
Adults: 0.125-0.5 mg/day for 7 days. Pediatric. (Digitalizing dose is divided into two or more doses and given at 6-8-hr intervals.) Children, 10 years and older, rapid or slow: Same as adult dose. 5-10 years: 0.02-0.035 mg/kg. 2-5 years: 0.03-0.05 mg/kg. 1 month-2 years: 0.035-0.06 mg/kg. Premature and newborn infants to 1 month: 0.02-0.035 mg/kg.
Maintenance.
Adults: 0.125-0.5 mg/day. Pediatric: One-fifth to one-third the total digitalizing dose daily. NOTE: An alternate regimen (referred to as the ``small-dose'' method) is 0.017 mg/kg/day. This dose causes less toxicity.
?IV Digitalization.
Adults: Same as tablets. Maintenance: 0.125-0.5 mg/day in divided doses or as a single dose. Pediatric: Same as tablets.