Class: Cardiotonic Agents
VA Class: CV050
CAS Number: 20830-75-5
Brands: Digitek, Lanoxicaps, Lanoxin

Introduction

Digoxin is a cardiac glycoside with positive inotropic effects.b

Uses for Digoxin

Used for digitalization and maintenance therapy.a

Used IV for rapid digitalization in emergency situations.a

Used principally in the prophylactic management and treatment of CHF and to control the ventricular rate in supraventricular tachyarrhythmias (e.g., atrial fibrillation or flutter).a 397

Digoxin is the only remaining cardiac glycoside in the US, primarily because it can be administered by various routes, it has an intermediate duration of action, and its pharmacokinetics in patients with or without renal insufficiency have been extensively studied.a

CHF

Used in conjunction with ACE inhibitors, diuretics, and/or β-adrenergic blocking agents in the management of symptomatic CHF associated with left ventricular systolic dysfunction.395

Therapy may be initiated in the early development of heart failure in patients who have started but not yet responded symptomatically to an ACE inhibitor or a β-adrenergic blocking agent;395 alternatively, digoxin may be withheld until the patient’s symptomatic response to the ACE inhibitor or β-blocker has been defined395 and then used only in those patients who remain symptomatic while receiving an ACE inhibitor or β-adrenergic blocking agent.395

In CHF patients receiving digoxin without an ACE inhibitor or β-blocker, digoxin should not be withdrawn, but appropriate therapy with an ACE inhibitor and/or a β-blocker should be initiated.395

Alleviates symptoms and improves clinical status.395 Beneficial effects are additive with those of ACE inhibitors and/or diuretics.384 388 389 390 391

Increases cardiac output resulting in diuresis and symptomatic relief of right-sided heart failure caused by systemic venous congestion (e.g., peripheral edema) and of left-sided heart failure caused by pulmonary congestion (e.g., dyspnea, orthopnea, and paroxysmal nocturnal dyspnea).a

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Increases left ventricular ejection fraction and improves symptoms of heart failure (as evidenced by exercise capacity, heart failure-related hospitalizations and emergency care), while having no apparent effect on overall mortality.379 384 386 387 390 391 392

Generally, most effective in the management of low-output failure secondary to hypertension, coronary artery or atherosclerotic heart disease, primary myocardial disease, nonobstructive cardiomyopathies, and valvular heart disease.a

Not recommended for patients with asymptomatic left ventricular systolic dysfunction (NYHA heart failure functional class I) since only treatment to prevent progression of heart failure is indicated in these patients and digoxin has not been shown to have a demonstrable effect on such progression.395

Worsens outflow obstruction as a result of its inotropic effects in patients with idiopathic hypertrophic subaortic stenosis.a

Patients with certain disorders involving heart failure associated with preserved left ventricular ejection fraction (e.g., restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, acute cor pulmonale) may be particularly susceptible to digoxin toxicity.379 385

Atrial Fibrillation and Flutter

Management depends on the clinical situation and the patient’s condition and ventricular rate.a

Other antiarrhythmics (e.g., β-adrenergic blocking agents, diltiazem, magnesium) are first-line therapy for atrial fibrillation and a rapid ventricular response.397

Because conversion of atrial fibrillation to normal sinus rhythm may be associated with embolism, adequate anticoagulation is recommended before administration of digoxin when atrial fibrillation is of >48 hours’ duration.396 397

Atrial arrhythmias associated with hypermetabolic states are particularly resistant to digoxin treatment, and care must to taken to avoid toxicity.a

In patients with atrial arrhythmias and hypothyroidism, the requirement for digoxin is reduced.a

Sinus Tachycardia

Used to slow the heart rate when sinus tachycardia is caused by CHF.a

Ventricular or atrial premature complexes caused by CHF may remit when failure is treated with digoxin, but the drug should not be used to treat premature complexes without heart failure.a

Generally ineffective and not indicated for sinus tachycardia without heart failure, such as that caused by fever, anemia, blood loss, or hyperthyroidism.a

Paroxysmal Supraventricular Tachycardias

Used for prevention and treatment of paroxysmal supraventricular tachycardias (PSVTs) such as paroxysmal atrial tachycardia, paroxysmal AV junctional rhythm, or paroxysmal atrial fibrillation/flutter.a

Treatments of choice for paroxysmal atrial tachycardia include measures to increase vagal tone (such as carotid sinus massage, Valsalva maneuver, and/or gagging) or administration of adenosine.a 397

May be useful in the prophylactic management and treatment of regular supraventricular (reciprocating) tachycardia associated with Wolff-Parkinson-White (W-P-W) syndrome, but generally not alone since it may enhance conduction via the accessory pathway and, in the presence of atrial fibrillation or flutter, result in extremely rapid ventricular rates and even ventricular fibrillation.a 397

Generally not used in the treatment of tachyarrhythmias, especially atrial fibrillation or flutter, when anomalous AV conduction is present.a 397

MI

Use in acute MI is controversial.386 387 388 389 390

Mild left ventricular dysfunction after acute MI usually is treated with modest diuresis and afterload and preload reduction (e.g., with parenteral nitroglycerin); institution of ACE inhibitor therapy also may be appropriate.386

Equivocal results with digoxin in terms of mortality, and concern about increased mortality associated with long-term milrinone therapy has prompted reexamination of digoxin use.386 387

Can be used selectively during acute MI recovery, but generally reserved for supraventricular arrhythmias and for systolic left ventricular heart failure that is refractory to first-line agents.386

Effective for persistent supraventricular tachyarrhythmias in acute MI.a

Rapid digitalization can slow a rapid ventricular response and improve left ventricular function in supraventricular tachyarrhythmias, especially atrial fibrillation.386

May be particularly useful for slowing a rapid ventricular response in coexisting left ventricular dysfunction.386

Cardiogenic Shock

Value in the treatment of cardiogenic shock has not been established, but occasionally used, especially when pulmonary edema is present.a

Used to improve left ventricular function in cardiogenic shock and atrial fibrillation or flutter with rapid ventricular rate.a

Angina Pectoris

May be useful, especially in conjunction with a β-adrenergic blocking agent, in the treatment of angina pectoris when cardiomegaly and CHF are present.a

Not beneficial alone in the treatment of angina pectoris without cardiomegaly and CHF.a

Arrhythmia and CHF Prophylaxis during Stress in Heart Disease without Failure

Has been used prophylactically to prevent arrhythmias and CHF in heart disease without failure during certain stressful situations (e.g., surgery, severe illness, pregnancy).

Obesity

Do not use alone or in combination with other drugs as an anorexiant for the treatment of obesity, since anorexia caused by digoxin is a symptom of toxicity, and potentially fatal arrhythmias may occur.380

Digoxin Dosage and Administration

General

  • Low therapeutic index; therefore, cautious dosage determination is essential.b

  • Usual dosages are averages that may require considerable modification as determined by individual requirements and response; the general condition, cardiovascular status, and renal function of the patient; lean (i.e., ideal body) weight and age of the patient; concomitant disease states, drugs, or other factors likely to alter the pharmacokinetics or pharmacodynamics of digoxin; and plasma digoxin concentrations.b 398 399 400 401 402 403

Switching Dosage Forms

  • Consider differences in the bioavailability of IV, oral, and IM preparations when patients are switched from one route of administration to another.b 398 399 400 401 402 403

  • When switching from oral (tablets or elixir) or IM to IV therapy, must reduce digoxin dosage by about 20–25%.b

  • When switching from tablets, elixir, or IM therapy to liquid-filled capsules, must reduce digoxin dosage by about 20%.b 398 399 400 401 402 403

  • Liquid-filled capsules are 90–100% absorbed; therefore, dosage with the capsules is equivalent to IV dosage.b 399

Considerations for ECG Monitoring and Dosage Reduction

  • Perform ECG monitoring of cardiac function during therapy, especially during IV therapy or when given orally for prolonged periods or to patients with increased risk of adverse reactions (e.g., those with severe heart or renal disease).b

  • Reduce dosage in hypokalemia, hypothyroidism, extensive myocardial damage, or conduction disorders, and in geriatric patients, especially those with CAD.b

  • Carefully individualize dosage during concomitant quinidine therapy, since clearance and volume of distribution of digoxin may be decreased.b

Administration

Oral Administration

Usually administer orally as a single daily dose.b

Divided daily dosing generally recommended in infants and young children (<10 years of age).b c 398 399 401 402 403

Divided daily dosing generally recommended for liquid-filled capsules for:

  • Infants and children <10 years of age.b 399

  • Patients requiring a daily dose of ≥300 mcg.b 399

  • Patients with a history of cardiac glycoside toxicity or those considered likely to become toxic.b 399

  • Patients in whom compliance is not a problem; when compliance is considered a problem, once daily dosing may be appropriate.b 399

IV Injection

Used when oral therapy is not feasible or when rapid therapeutic effect is necessary; oral therapy should replace IV administration as soon as possibleb 398 399 400 401 402 403

Possibility of inadvertent overdosage when a tuberculin syringe is used to measure very small doses; exercise caution.b 400 401

Do not flush the syringe with the parenteral solution following IV administration.b 400 401

Do not mix with other drugs in the same container nor administer simultaneously in the same IV line.b 400 401

Inject IV cautiously in hypertensive patients because IV administration can increase blood pressure transiently.a

Dilution

Inject IV either undiluted over ≥5 minutes or diluted with ≥4-fold volume of sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection and give over ≥5 minutes; use of <4-fold volume of diluent may result in precipitation of digoxin.b 400 401

Use diluted IV solutions of digoxin immediately.b 400 401

Rate of Administration

Slow IV infusion is preferred to rapid (i.e., bolus) IV administration.400 401 Rapid IV infusion may cause systemic and coronary arteriolar constriction, which may be clinically undesirable; exercise caution.400 401

Administer over ≥5 minutes.400 401

IM Injection

Rarely justified because of frequent severe local irritation and pain, and unpredictable and/or slow onset relative to IV injection;b 400 401 IV injection is preferred to IM injection.400 401 IM injection offers no advantages unless other routes of administration are contraindicated.400 401

Inject deep into the muscle, followed by massage of the injection site; inject ≤2 mL at any one site.b 400 401

Replace IM with oral administration as soon as possible.b

Dosage

Dosage guidelines provided are based upon average patient response and substantial patient variation can be expected.398 399 400 401 402 403 Ultimate dosage selection must be based upon clinical assessment of the patient.398 399 400 401 402 403

Pediatric Patients

Titrate dosage carefully in neonates, especially premature infants, because renal clearance of digoxin is reduced.b 398 399 401 402 403

Infants and young children (up to 10 years of age) generally require proportionally larger doses than children older than 10 years of age and adults when calculated on the basis of lean or ideal body weight or body surface area.b 398 399 401 402 403

Children >10 years of age require adult dosages in proportion to the child’s body weight.398 399 401 402 403

Liquid-filled capsules may not be the formulation of choice in infants and young children (<10 years of age) where dosage adjustment is frequent and outside of the fixed dosages provided by the capsules.399

CHF

Digitalization may be accomplished by one of two approaches (i.e., rapid digitalization or slow digitalization) that vary in dosage and frequency of administration, but achieve the same total amount of digoxin accumulated in the body.398 401 402

Rapid digitalization (if considered medically appropriate): Administer a loading dose based upon projected peak digoxin body stores.401 402 Daily maintenance dose (calculated as a percentage of the loading dose) will follow loading dose.401 402

Peak body digoxin stores of 8–12 mcg/kg generally provide therapeutic effect with minimum risk of toxicity in most patients with CHF, normal sinus rhythm, and normal renal function.b 401 402

Slow digitalization: Initiate therapy with an appropriate daily maintenance dose, which allows digoxin body stores to accumulate slowly.b 401 402 Steady-state serum digoxin concentrations will be achieved in about 5 half-lives of the drug for the individual patient; depending on the patient’s renal function, this may take 1–3 weeks.b 401 402

Digitalizing (i.e., Loading) and Maintenance Dosages

Total digitalizing (i.e., loading) doses and maintenance dosages in pediatric patients (depending on the dosage form administered) are given in the tables that follow,b 398 399 401 402 403 and should provide therapeutic effect with minimum risk of toxicity in most patients with CHF, normal sinus rhythm, and normal renal function.398 399 401 402 403

Administer the loading dose in divided doses, with about 50% of the total dose given as the first (i.e., initial) dose; additional fractions (generally 25%) are administered at 4- to 8-hour intervals IV or 6- to 8-hour intervals orally or IM, with careful assessment of the patient’s clinical response before each additional dose is administered.b 401 402 If the patient’s clinical response requires a change from the calculated loading dose, then calculation of the maintenance dose is based upon the amount (i.e., total loading dose) actually administered.401 402

Oral

Divided daily dosing is generally recommended in infants and young children (<10 years of age).b c 398 403

Table 1. Usual Pediatric Maintenance Dosages for Digoxin Tablets (normal renal function, based on lean body weight)b398403

Age

Oral Maintenance Dosage (mcg/kg daily)

2–5 years of age

10–15

5–10 years of age

7–10

>10 years of age

3–5

IV digitalizing doses are 80% of oral digitalizing doses of digoxin tablets or elixir.401 402

Divided daily dosing is generally recommended in infants and young children (<10 years of age).b c 402

Estimated or actual digitalizing dose that provides desired clinical response.b 402

Table 2. Usual Pediatric Digitalizing and Maintenance Dosages for Digoxin Elixir (normal renal function, based on lean body weight)b402

Age

Oral Digitalizing (Loading) Dose (mcg/kg)

Oral Maintenance Dosage (mcg/kg daily)

Premature neonates

20–30

20–30% of oral loading dose

Full-term neonates

25–35

25–35% of oral loading dose

1–24 months

35–60

25–35% of oral loading dose

2–5 years of age

30–40

25–35% of oral loading dose

5–10 years of age

20–35

25–35% of oral loading dose

>10 years of age

10–15

25–35% of oral loading dose

IV digitalizing doses are the same as oral digitalizing doses of liquid-filled capsules.399

Divided daily dosing is generally recommended in infants and young children (<10 years of age).b c 399

Estimated or actual digitalizing dose that provides desired clinical response.b 399

Table 3. Usual Pediatric Digitalizing and Maintenance Dosages for Digoxin Liquid-Filled Capsules (normal renal function, based on lean body weight)b399

Age

Oral Digitalizing (Loading) Dose (mcg/kg)

Oral Maintenance Dosage (mcg/kg daily)

2–5 years of age

25–35

25–35% of oral or IV loading dose

5–10 years of age

15–30

25–35% of oral or IV loading dose

>10 years of age

 8–12

25–35% of oral or IV loading dose

IV

IV digitalizing doses are 80% of oral digitalizing doses of digoxin tablets or elixir.401 402

Divided daily dosing is generally recommended in infants and young children (<10 years of age).b c 401

Estimated or actual digitalizing dose that provides desired clinical response.b 401

Table 4. Usual Pediatric Digitalizing and Maintenance Dosages for IV Digoxin (normal renal function, based on lean body weight)b401

Age

IV Digitalizing (Loading) Dose (mcg/kg)

IV Maintenance Dosage (mcg/kg daily)

Premature neonates

15–25

20–30% of IV loading dose

Full-term neonates

20–30

25–35% of IV loading dose

1–24 months

30–50

25–35% of IV loading dose

2–5 years of age

25–35

25–35% of IV loading dose

5–10 years of age

15–30

25–35% of IV loading dose

>10 years of age

 8–12

25–35% of IV loading dose

Atrial Fibrillation

Peak digoxin body stores exceeding the 8–12 mcg/kg required for most patients with CHF and normal sinus rhythm have been used for control of ventricular rate in patients with atrial fibrillation.b 401 402 In the treatment of chronic atrial fibrillation, titrate dosage to the minimum dosage that achieves the desired ventricular rate control without causing undesirable adverse effects.401 402 Appropriate target resting or exercising rates have not been established.401 402

Adults

CHF

Digitalization may be accomplished by one of two approaches (i.e., rapid digitalization or slow digitalization) that vary in dosage and frequency of administration, but achieve the same total amount of digoxin accumulated in the body.398 399 400 403

Rapid digitalization (if considered medically appropriate): Administer a loading dose based upon projected peak digoxin body stores.398 399 400 403 Daily maintenance dose (calculated as a percentage of the loading dose) will follow loading dose.398 399 400 403 Peak digoxin body stores of 8–12 mcg/kg generally provide therapeutic effect with minimum risk of toxicity in most patients with CHF, normal sinus rhythm, and normal renal function.b 398 399 400 403

Slow digitalization: Initiate therapy with an appropriate daily maintenance dose, which allows digoxin body stores to accumulate slowly.b 398 399 400 403 Steady-state serum digoxin concentrations will be achieved in about 5 half-lives of the drug for the individual patient; depending on the patient’s renal function, this may take 1–3 weeks.b 398 399 400 403

Loading Dose (for rapid digitalization)

Administer the loading dose in divided doses, with about 50% of the total dose given as the first (i.e., initial) dose; additional fractions (generally 25%) are administered at 6- to 8-hour intervals orally, IM, or IV, with careful assessment of the patient’s clinical response before each additional dose is administered.b 398 399 400 403 If the patient’s clinical response requires a change from the calculated loading dose, then calculation of the maintenance dose is based upon the amount (i.e., total loading dose) actually administered.398 399 400 403

Oral

Usually, a single initial dose of 500–750 mcg (0.5–0.75 mg) of digoxin tablets398 403 or 400–600 mcg (0.4–0.6 mg) of digoxin liquid-filled capsules399 produces a detectable effect in 0.5–2 hours that becomes maximal in 2–6 hours.398 399 403

Cautiously administer additional doses of 125–375 mcg (0.125–0.375 mg) of digoxin tablets or 100–300 mcg (0.1–0.3 mg) of digoxin liquid-filled capsules at 6- to 8-hour intervals until clinical evidence of an adequate response is achieved.398 399 403

Usual amount (i.e., total loading dose) of digoxin tablets or liquid-filled capsules that a 70-kg patient requires to achieve 8–12 mcg/kg peak body stores is 750–1250 mcg (0.75–1.25 mg) or 600–1000 mcg (0.6–1 mg), respectively.398 399 403

IV

Usually, a single initial dose of 400–600 mcg (0.4–0.6 mg) IV produces a detectable effect in 5–30 minutes that becomes maximal in 1–4 hours.400

Cautiously administer additional doses of 100–300 mcg (0.1–0.3 mg) IV at 6- to 8-hour intervals until clinical evidence of an adequate response is achieved.400

Usual amount (i.e., total loading dose) of digoxin IV that a 70-kg patient requires to achieve 8–12 mcg/kg peak body stores is 600–1000 mcg (0.6–1 mg).400

Maintenance Dosage

Daily maintenance dosage is a replacement of daily digoxin loss from the body and can be estimated by multiplying the daily percentage loss by the peak body stores (i.e., loading dose).b 398 399 400 403

About 30% of total digoxin in the body is eliminated daily in patients with normal renal function; anuric patients eliminate approximately 14% of the total digoxin stores daily.b The % of digoxin eliminated from the body daily can be estimated by the following equation:b 398 399 400 403

daily % loss = 14 + [creatinine clearance (in mL/min) / 5]

Use this method with caution, since Clcr does not accurately measure renal or total body clearance of digoxin.b

Oral

Tablets: Usually, 125–500 mcg (0.125–0.5 mg) once daily; titrate according to the patient’s age, lean body weight, and renal function.398 399 403 Generally, initiate at 250 mcg (0.25 mg) once daily in patients <70 years of age with normal renal function; may increase dosage every 2 weeks according to clinical response.398 399 403

Capsules (liquid-filled): Usually, 150–350 mcg (0.15–0.35 mg) daily in patients with Clcr of ≥50 mL/minute.399

IV

Usually, 125–350 mcg (0.125–0.35 mg) once daily in patients with Clcr of ≥50 mL/minute.400

Atrial Fibrillation

Peak digoxin body stores exceeding the 8–12 mcg/kg required for most patients with CHF and normal sinus rhythm have been used for control of ventricular rate in patients with atrial fibrillation.b 398 399 400 403

In the treatment of chronic atrial fibrillation, titrate dosage to the minimum dosage that achieves the desired ventricular rate control without causing undesirable adverse effects.398 399 400 403 Appropriate target resting or exercising rates have not been established.398 399 400 403

Special Populations

Hepatic Impairment

No dosage adjustment is necessary in liver disease if renal function is normal.b

Renal Impairment

Loading doses (based upon projected peak digoxin body stores) in patients with renal insufficiency (particularly those with Clcr <10 mL/minute) should be conservative (i.e., based upon peak digoxin body stores of 6–10 mcg/kg) because of altered digoxin distribution and elimination.b 398 399 400 401 402 403

Pediatric Patients: Cautiously adjust dosage based on clinical response.398 399 401 402 403

Adults: For maintenance dosage, generally initiate at 125 mcg once daily orally (digoxin tablets) in patients with impaired renal function or at 62.5 mcg once daily orally (digoxin tablets) in patients with marked renal impairment; may increase dosage every 2 weeks according to clinical response.398 399 400 403

Geriatric Patients

Reduce dosage, especially in those with CAD.b

Advanced age may be an indicator of decreased renal function even in patients with normal Scr (i.e., <1.5 mg/dL).398 399 400 401 402 403 (See Renal Impairment under Dosage and Administration.)

Geriatric Patients ≥70 years of age: For maintenance dosage, generally initiate at 125 mcg once daily orally (digoxin tablets).398 399 400 403

Cautions for Digoxin

Contraindications

  • Ventricular fibrillation379 380 c

  • Known hypersensitivity to digoxin or other digitalis preparations379 380 c

Warnings/Precautions

Warnings

Sinus Node Disease and AV Block

Administer with caution in patients with incomplete AV block, especially in those with Adams-Stokes attacks, since digoxin may induce advanced or complete AV block.380 395

If digoxin is used, a pacemaker should be inserted.c

May be used in patients with severe bradycardia or complete, stable AV block who have CHF, if the block has not been induced by cardiac glycosides.a

Accessory AV pathway (Wolff-Parkinson-White Syndrome) and Anomalous AV Conduction

Generally, should not be used alone in the management of W-P-W syndrome since it may enhance conduction via the accessory pathway and, in the presence of atrial fibrillation or flutter, result in extremely rapid ventricular rates and even ventricular fibrillation.a

Generally, not used in the treatment of tachyarrhythmias, especially atrial fibrillation or flutter, in patients with anomalous AV conduction unless it has been shown that digoxin will not result in an increased ventricular rate via an effect on anomalous AV pathway conduction.a

Patients with Preserved Left Ventricular Systolic Function

Certain disorders involving heart failure associated with preserved left ventricular ejection fraction (e.g., restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, acute cor pulmonale) may be associated with particular susceptibility to digoxin toxicity.379 385

Idiopathic Hypertrophic Subaortic Stenosis

Worsening of outflow obstruction as a result of the inotropic effects of digoxin in idiopathic hypertrophic subaortic stenosis.a

Major Toxicities

Pathogenesis

Widespread use and the very narrow margin between effective therapeutic and toxic dosages contribute to the high incidence of toxicity and the relatively high associated mortality rate.250 251 257 258 259 260 270 295

Toxic effects are mainly GI, CNS, biochemical, and cardiac in origin.46 107 257 261 262 263 264 265 266

Minimum toxic and lethal doses are not well established.258 267

Infants and children appear to be more tolerant to therapeutic and toxic actions;51 258 267 270 277 278 283 285 children without underlying cardiac problems usually can tolerate an acute dose of several mg of digoxin without potentially life-threatening cardiac toxicity.267

Serum digoxin concentrations are useful in confirming the diagnosis of intoxication; however, clinical diagnosis and management should not be based on serum concentrations alone but should always be interpreted in the overall clinical context with all other relevant information.232 257 265 270 274 277 395

At least 6–10 hours usually are necessary for digoxin to equilibrate between plasma and tissue; plasma specimens drawn prior to this time may show glycoside concentrations greater than those present after equilibration.248 275 295 360 361

Use in conjunction with diuretics is a frequent cause of chronic toxicity.270 277

Failure to individualize dosage is another contributing factor in many cases of toxicity.258 266 272

Manifestations

Overdosage is manifested by a wide variety of signs and symptoms that are difficult to distinguish from effects associated with cardiac disease (e.g., adverse GI effects, arrhythmias).12 262 263 266 270 273 274 275 276 278

Before additional doses are administered, attempts should be made to determine whether the manifestations are digoxin induced.262 263 266 276 277

If intoxication cannot be excluded, withhold digoxin therapy temporarily, if clinical situation permits.380

Extracardiac Effects

Extracardiac manifestations of intoxication are similar in both acute and chronic intoxication.261 274

GI effects and, to a lesser extent, CNS and visual disturbances may be more pronounced following acute overdosage.261 274

Acute toxicity may cause hyperkalemia, whereas chronic toxicity may be associated with hypokalemia or normokalemia.261 274

Pediatric patients: Drowsiness52 258 269 and vomiting51 269 are most prominent extracardiac effects;281 life-threatening cardiac arrhythmias have developed suddenly without evidence of any extracardiac signs of intoxication.269 282

GI Effects

Anorexia,46 260 262 263 265 nausea,46 260 262 263 265 267 and vomiting46 260 262 263 265 267 are common early signs of toxicity and may precede or follow evidence of cardiotoxicity.50 262 263 277 380

Large doses may produce emesis by direct GI irritation.258 270 Episodes of nausea and vomiting may start and stop abruptly.270

Nervous System Effects

Headache,38 46 48 66 261 262 265 266 267 268 270 fatigue,46 48 66 261 266 270 276 malaise,46 48 261 266 270 276 drowsiness,38 46 48 52 125 261 265 266 269 270 and generalized muscle weakness38 46 48 262 266 267 269 270 are common.a

Neuropsychiatric disturbances are especially likely to develop in geriatric patients with atherosclerotic disease270 and are easily overlooked in chronic digoxin therapy.48 289

Disorientation,38 48 107 264 265 267 270 confusion,38 47 48 66 265 266 276 277 depression,38 48 266 memory impairment,40 48 264 amnesia,38 48 aphasia,38 48 270 bad dreams,46 266 289 delirium,38 40 46 48 66 107 261 266 268 270 276 289 delusions,38 48 264 276 illusions,48 264 and hallucinations.38 40 46 47 48 264 265 276 362

Ocular Effects

Visual disturbances induced by toxic doses probably result from a direct effect on the retina38 75 290 363 (cones are affected more than rods).75 363

Color vision is commonly affected74 363 and objects may appear yellow or green or, less commonly, brown, red, blue, or white.38 270

Visual disorders generally are reversible after digoxin withdrawal.38 46 74 105

Effects on Potassium

Hypokalemic or normokalemic with chronic toxicity.261 274

Severe intoxication may cause hyperkalemia.77 97 139 261 274

Cardiovascular Effects

Most well defined and dangerous toxic actions.270 274

Cardiac signs of toxicity may occur with or without other signs of toxicity46 50 and often precede other toxic effects.50

Arrhythmias associated with intoxication may result in worsening of CHF.47 50 270 295

It often is difficult to distinguish toxic cardiac effects caused by an underlying heart disease or digoxin.38 54 262 263 266 270 275 276

If the possibility of toxicity cannot be excluded, digoxin should be withdrawn temporarily, if possible, and the clinical response monitored.12 258 262 263 277 289

Chronic toxicity commonly presents with ventricular arrhythmias, such as VPCs or ventricular tachycardia.139 261 274 284 291

AV conduction disturbances are frequent in chronic toxicity.261 274 284 291

Pediatric patients with healthy hearts often present with sinus bradycardia and conduction disturbances; ventricular arrhythmias also occur but are less common than in adults.51 52 222 269 297

In neonates, premonitory signs of toxicity may include sinus bradycardia, SA arrest, or prolongation of the PR interval.51 52 222 269 297

First-degree AV block is common25 38 50 53 54 and generally indicates a therapeutic rather than a toxic effect;25 53 106 AV block may progressively increase in patients with toxicity.258 262 263

Electrolyte imbalances, especially hypokalemia,23 52 53 54 66 225 258 262 263 270 380 and, to a lesser extent, hypomagnesemia23 66 224 270 380 or hypercalcemia,23 53 66 270 380 may predispose to the cardiotoxic effects.23 24 270 379 380

Periodically assess serum electrolytes.380

Conditions causing hypokalemia increase the risk of cardiotoxicity.23 24 270

Treatment

Discontinue digoxin immediately if signs of toxicity appear;12 258 262 263 277 289 in many patients further treatment of intoxication is unnecessary,54 96 262 263 particularly if toxic effects are mild and appear after the peak effect of the drug has occurred.50 51 262 263

Consult specialized references for details on cardiac glycoside toxicity treatment.a

Measures to Enhance Cardiac Glycoside Elimination and to Manage Hyperkalemia

Digoxin immune Fab is a specific antidote that binds to digoxin (preventing and reversing pharmacologic and toxic effects and enhancing elimination) and can be used in the treatment of potentially life-threatening, acute or chronic, digoxin toxicity.232 235 236 248 249 280

In cases of potentially life-threatening cardiotoxicity or hyperkalemia, digoxin immune Fab should be administered if available.248 276

Massive digoxin overdosage may cause hyperkalemia,77 97 139 261 274 which can be refractory to conventional therapy.12 24 97 139 232 235 257 269

Prognosis appears to correlate with serum potassium concentration (i.e., the greater the serum potassium concentration, the worse the prognosis) in patients treated by conventional symptomatic and supportive measures that do not include digoxin immune Fab.97 232 236 247 258 261 265 294

Severe hyperkalemia refractory to standard measures is an indication for digoxin immune Fab.248 267

If digoxin immune Fab is not readily available, emergency measures for the treatment of hyperkalemia should include IV administration of glucose and insulin,261 267 269 291 sodium bicarbonate,267 269 peritoneal dialysis or hemodialysis,257 261 269 274 291 and/or use of exchange resins.269 274

Avoid use of calcium infusions in the treatment of hyperkalemia because calcium may worsen cardiac irregularities.261

Other measures that can enhance digoxin elimination include multiple-dose oral activated charcoal227 228 229 250 251 252 265 276 277 289 and oral anion-exchange resins.24 59 94 229 230 231 261 265 274 289 291 298 299

General Precautions

Because the likelihood of digoxin-induced cardiac arrhythmias is increased,379 380 use with caution in patients with:

  • severe pulmonary disease

  • hypoxia

  • myxedema

  • acute myocardial infarction

  • severe heart failure

  • acute myocarditis (including rheumatic carditis)

  • an otherwise damaged myocardium

Acute MI and CHF

Use in acute MI may result in an undesirable increase in oxygen demand and associated ischemia.379

Extreme caution in patients with acute glomerulonephritis and CHF; if digoxin is necessary, total daily dosage must be reduced and given in divided doses with constant ECG monitoring;380 treat these patients concomitantly with diuretics and hypotensive agents and the glycoside should be discontinued as soon as possible.380

Pericarditis

Used with caution in chronic constrictive pericarditis because of possible unfavorable response.a

Idiopathic Hypertrophic Subaortic Stenosis

Use with extreme caution, if at all, because increased obstruction to left ventricular outflow may result.379 380

Rheumatic Carditis

Dosage should be low initially and increased gradually until a beneficial effect is obtained or, if improvement does not occur, the drug should be discontinued.a

Hypertension

Give IV with caution in hypertensive patients, since IV administration may increase blood pressure transiently.a

Atrial Fibrillation or Flutter

Digoxin may reduce, but does not abolish, the dangers of increased ventricular rates produced by disopyramide, procainamide, and quinidine.a

Arrhythmias and Tachycardia

Do not use for the treatment of multifocal atrial tachycardia.379

Use with caution in patients with increased carotid sinus sensitivity, since digoxin causes increased vagal tone.a

Carotid sinus massage can cause ventricular fibrillation in patients receiving digoxin.a

Caution in frequent VPCs or ventricular tachycardia, especially if these arrhythmias are not caused by heart failure.a

Withhold digoxin 1–2 days before elective cardioversion in atrial fibrillation and start with initial shocks of 25–50 watt-seconds and increase by 100 watt-second increments until normal sinus rhythm or 400 watt-seconds is reached since digoxin predisposes to postcardioversion arrhythmias.379

Elective cardioversion should be postponed in patients with manifestations of digoxin toxicity.379

After cardioversion, subsequent digoxin dosage adjustment is necessary to avoid provoking ventricular arrhythmias.379

Specific Populations

Pregnancy

Category C.c

Lactation

Use caution when administering to nursing women.c

Pediatric Use

Neonates exhibit considerable variability in their tolerance to digoxin.c Pharmacologic effects in nursing infants is unlikely despite presence in breast milk.c

Premature and immature infants are particularly susceptible, and dosage must be reduced and individualized according to maturity.c

Adverse effect profile differs in infants and children, particularly regarding initial signs of toxicity.c Cardiac arrhythmias, including sinus bradycardia, usually occur earliest and most frequently.c In children, any arrhythmia can occur.c

Any arrhythmia or alteration in cardiac conduction in a child should be considered a sign of toxicity.c

Geriatric Use

Most experience is in geriatric patients, and response and adverse effects do not appear to differ from those in younger patients; however, use with caution because of increased toxicity risk secondary to decreased renal function in the elderly.c

Monitor renal function.c

Toxic neuropsychiatric effects may be particularly likely relative to younger adults, particularly in presence of atherosclerosis.48 270 289

Increased risk of estrogen-like effects (e.g., gynecomastia).a

Common Adverse Effects

In addition to toxic effects (See Major Toxicities under Warnings/Precautions), other adverse effects may occur.a

Estrogen-like effects may occur with chronic administration of digoxin, especially in geriatric men and women whose endogenous concentrations of sex hormones are low.a

Unilateral and bilateral gynecomastia and enlargement of the mammary glands in women after chronic therapy; reversible when the drug is withdrawn.a

Vaginal cornification in postmenopausal women and may result in the incorrect diagnosis of endometrial carcinoma.a

Interactions for Digoxin

Drugs and Radiation Affecting GI Absorption

A number of drugs are capable of binding cardiac glycosides and/or inhibiting the absorption of the glycosides from the GI tract, which may result in low plasma concentrations of the glycoside.a

GI absorption of oral digoxin tablets may be reduced substantially in patients receiving radiation therapy,300 certain antineoplastic agents,376 or various combination chemotherapy regimens,301 possibly as a result of temporary damage to intestinal mucosa caused by the radiation or cytotoxic agents.300 301 309 Use of digoxin oral elixir300 or liquid-filled capsules301 may minimize the potential interaction.300 301

Drugs that alter GI transit time and/or motility of the GI tract (e.g., antimuscarinics, diphenoxylate) may alter the rate of digoxin absorption. Concurrent use of antimuscarinics and slow-dissolving digoxin tablets may result in increased digoxin concentrations. This interaction can be avoided by using digoxin oral solution or tablets that dissolve rapidly (e.g., Lanoxin). Patients receiving an antimuscarinic and digoxin should be closely observed for signs of digitalis toxicity.

Specific Drugs or Laboratory Tests

Drug or Laboratory Test

Interaction

Comments

Amiodarone

Increased serum digoxin concentrations and toxicity.a

Magnitude of the increase may be much greater in children.a

Need for continued cardiac glycoside therapy should be reassessed when initiating amiodarone, and digoxin discontinued if appropriate; if concomitant therapy is necessary, reduce digoxin by 50% when amiodarone therapy is begun.a

Monitor serum digoxin concentrations carefully and reduce digoxin dosage as necessary; observe closely for signs of cardiac glycoside toxicity.

Monitor thyroid function carefully, since amiodarone-induced changes in thyroid function may increase or decrease serum digoxin concentrations or alter sensitivity to the therapeutic and toxic effects of the cardiac glycoside.a

Aminosalicylic Acid

Reduce GI absorption of digoxin (resulting in low plasma digoxin concentrations), especially when administered at the same time as digoxin

Should be spaced as far apart as possiblea

Antiarrhythmic Agents

Quinidine, procainamide, disopyramide, phenytoin, propranolol, and lidocaine may have negative inotropic effects with larger than usual doses, especially in patients with cardiac glycoside toxicity (propranolol has negative inotropic effects with usual doses).a

Such combined therapy may be useful in controlling atrial fibrillation, but digoxin dosage in patients receiving such therapy should be carefully individualized given the considerable interaction variability.379 380

β-Adrenergic blocking agents

Concomitant use of digoxin and β-adrenergic blocking agents can have additive negative effects on AV conduction, which can result in complete heart block.379 380

Antacids (i.e., aluminum hydroxide, magnesium hydroxide, magnesium trisilicate)

Reduce GI absorption of digoxin (resulting in low plasma digoxin concentrations), especially when administered at the same time as digoxin

Should be spaced as far apart as possiblea

Anti-infectives

In patients who form substantial amounts of reduced metabolites, alteration of enteric bacterial flora by some anti-infective agents (e.g., oral erythromycin or tetracycline hydrochloride) may result in increased bioavailability of active drug and up to a twofold increase in serum digoxin concentrations.254

The clinical importance of this interaction remains to be determined, but be alert to possible need for digoxin dosage adjustment.254 256

Calcium-channel blocking agents

Concomitant use can have additive negative effects on AV conduction.379 380 381 382 (See Diltiazem.)

Calcium salts

Inotropic and toxic effects of digoxin and calcium are synergistic and arrhythmias may occur if used concomitantly (particularly when calcium is given IV).379

IV administration of calcium should be avoided in patients receiving digoxin; if necessary, calcium should be given slowly in small amounts.a

Captopril

Serum digoxin concentrations may increase by about 15–30% when captopril and digoxin are used concomitantly for CHF.366 367 368

Captopril has been administered concomitantly with digoxin in patients with congestive heart failure without unusual adverse effects366 367 or apparent increased risk of cardiac glycoside toxicity.366 367 368 Captopril-induced increases in serum potassium may offset the potential toxic effects of increased serum digoxin concentrations.366 368

Reduction in digoxin dosage does not appear to be necessary when captopril is initiated;366 however, serum digoxin concentrations should be monitored and the patient observed for signs of glycoside toxicity when the drugs are used concomitantly.366 368

Cholestyramine and colestipol

May bind digoxin in the GI tract and impair its absorption (resulting in low plasma digoxin concentrations), particularly if the glycoside and bile acid sequestrant are administered simultaneously or close together.a

Orally, digoxin should be given at least 1.5–2 hours before cholestyramine or colestipol.a

Diltiazem

Conflicting reports on whether diltiazem substantially affects the pharmacokinetics of digoxin when the drugs are administered concomitantly.313 314 315 316 317 318 319 320 321 In some studies, diltiazem reportedly increased average steady-state serum digoxin concentrations by about 20–50%,313 315 316 317 possibly by decreasing the renal and nonrenal clearance of the glycoside, but not in others.313 314 315 317 318 319 320 321

Concomitant use can have negative effects on AV conduction, which can result in complete heart block.379 380

Despite conflicting reports, serum digoxin concentrations should be carefully monitored and the patient observed closely for signs of digoxin toxicity when diltiazem and digoxin are administered concomitantly.313 315 317 318 322

Although such combined therapy may be useful in controlling atrial fibrillation, digoxin dosage should be carefully individualized when such therapy is used because of the considerable variability of these interactions.379 380

Electrolyte balance, drugs affecting

Electrolyte disturbances produced by diuretics (primarily hypokalemia but also hypomagnesemia and, with the thiazides, hypercalcemia) predispose to digoxin toxicity, including fatal cardiac arrhythmias.

Other drugs that deplete body potassium (e.g., amphotericin B, corticosteroids, corticotropin, edetate disodium, laxatives, sodium polystyrene sulfonate) or that reduce extracellular potassium (e.g., glucagon, large doses of dextrose, dextrose-insulin infusions) also may predispose digitalized patients to toxicity.

Periodic electrolyte determinations must be performed during concomitant therapy and corrective measures undertaken if warranted.a

Flecainide

Plasma digoxin concentrations may be increased when used concomitantly.304 305 306 307 308

Flecainide-induced increases in plasma digoxin concentration generally appear to be of a small magnitude and are unlikely to be clinically important in most cases; however, patients with AV nodal dysfunction,306 plasma digoxin concentrations in the upper end of the therapeutic range, and/or high plasma flecainide concentrations may be at increased risk of digoxin toxicity.305 306

Patients receiving flecainide and digoxin should be monitored for signs of digoxin toxicity.305 306

Indomethacin

May prolong elimination half-life and increase serum concentrations of digoxin372 373 374

Monitor serum digoxin concentrations carefully.372

Itraconazole

Concomitant use of digoxin and itraconazole may result in increased serum digoxin concentrations;263 377 378 digoxin toxicity may occur.263 377 378

Monitor serum digoxin concentrations carefully, observe for clinical signs and symptoms of digoxin toxicity,377 378 and decrease digoxin dosage as necessary.377 378

Metoclopramide

Reduce GI absorption of digoxin (resulting in low plasma digoxin concentrations), especially when administered at the same time as digoxin

Should be spaced as far apart as possible.

Neomycin

Oral neomycin may cause malabsorption of digoxin, resulting in low plasma digoxin concentrations.a

Nifedipine

Most evidence indicates that nifedipine does not substantially affect the pharmacokinetics of digoxin,303 324 325 326 327 but some data suggest increased serum digoxin concentrations.328 329

Isolated reports of increased serum digoxin concentrations during concomitant use warrant monitoring of serum digoxin concentrations and toxicity when nifedipine therapy is initiated or discontinued or dosage of nifedipine is adjusted in patients receiving digoxin.303 328 330

Propafenone

Concomitant use may result in increased serum digoxin concentrations.a

Monitor for possible toxicity.a

Quinidine

Concomitant use produces increased plasma digoxin concentrations.303 308 311 312

Although variability exists in the magnitude of the increase, plasma digoxin concentrations usually increase twofold to threefold when quinidine therapy is initiated in patients digitalized with digoxin.303 308 311

When quinidine therapy is initiated in a patient receiving digoxin, serum digoxin concentrations should be carefully monitored and the digoxin dosage reduced as needed; the patient should be observed closely for signs of toxicity.302 303 308

Reduce digoxin dosage by one-half when quinidine therapy is initiated;302 303 308 additional dosage adjustments are likely.303 308

If severe toxicity occurs or if digoxin dosage adjustment is difficult, an alternative antiarrhythmic drug should be used instead of quinidine (e.g., procainamide).303

If digoxin therapy is initiated in a patient receiving quinidine, lower than usual dosages of digoxin may be sufficient to produce desired plasma concentrations.302 303 308

If quinidine is discontinued in a patient stabilized on therapy with both drugs, the patient should be observed for signs of decreased response to digoxin and dosage of the cardiac glycoside adjusted as necessary.302 303 308

Quinine

Possible interaction similar to that reported with quinidine could occur with concomitant digoxin and quinine (or another cinchona alkaloid)a

Rauwolfia alkaloids

Concomitant use may predispose to the development of cardiac arrhythmias.a

Consider possible interaction in patients prone to arrhythmias; large parenteral doses of reserpine should be avoided

Succinylcholine

Potentiates effects of digoxin on conduction and ventricular irritability.

Cardiac arrhythmias have occurred; succinylcholine should be administered with caution in digitalized patients.

Sulfasalazine

Reduce GI absorption of digoxin (resulting in low plasma digoxin concentrations), especially when administered at the same time as digoxin

Should be spaced as far apart as possible.

Sympathomimetics (ephedrine, epinephrine, isoproterenol)

Sympathomimetics should be used with caution in digitalized patients, since the risk of arrhythmias may be increased.

Test, exercise testing

Digoxin may cause false-positive ST-T changes during exercise testing.a

Verapamil

Oral verapamil may increase serum digoxin concentrations by 50–75% during the first week of verapamil therapy; may be more pronounced in patients with underlying hepatic disease (e.g., cirrhosis).a

When verapamil is administered, dosage of digoxin should generally be reduced and the patient monitored closely for clinical response and cardiac glycoside toxicity.a

Combined therapy with the drugs (e.g., for control of ventricular rate in patients with atrial fibrillation and/or flutter) usually is well tolerated if digoxin dosage is properly adjusted.a

Whenever toxicity is suspected, digoxin dosage should be further reduced and/or temporarily withheld.a

If verapamil is discontinued in a patient stabilized on digoxin, monitor closely and increase digoxin dosage as necessary to avoid underdigitalization.

Digoxin Pharmacokinetics

Absorption

Bioavailability

Mainly from the small intestine, presumably by a passive, nonsaturable process.b

Tablet or elixir: Approximately 60–85% of the dose is usually absorbed.b

Liquid-filled capsules: Approximately 90–100% absorbed.b

IM: About 80% is absorbed.b

Onset

Undigitalized patients, Oral: 0.5–2 hours;b 398 399 402 403 maximal effect: 2–6 hours.398 399 402 403

Undigitalized patients, IV: 5–30 minutes;b 399 400 402 402 403 maximal effect: 1–4 hours.399 400 403

Undigitalized patients, IM: 30 minutes;b maximal effect: 4–6 hours.b

Duration

3–4 days after drug withdrawal in digitalized patients.b

Food

Delayed gastric emptying or the presence of food in the GI tract may slow the rate but not the extent of absorption of oral digoxin.b

Plasma Concentrations

Determine plasma concentrations by obtaining blood samples at least 6–8 hours after the daily dose and preferably just prior to the next scheduled daily dose.b 398 399 400 401 402 403

Therapeutic plasma concentrations in adults are generally 0.5–2 ng/mL.b 398 399 400 401 402 403

In adults, toxicity is usually, but not always, associated with steady-state plasma digoxin concentrations >2 ng/mL.b 398 399 400 401 402 403

In some patients with atrial fibrillation, slowing of ventricular rate may require steady-state plasma concentrations of 2–4 ng/mL.b

Neonates and infants appear to tolerate slightly higher plasma concentrations,b 398 399 401 402 403 but plasma concentrations >2 ng/mL are associated with little, if any, additional therapeutic benefit.b Steady-state plasma concentrations of 1.1–1.7 ng/mL generally are associated with adequate therapeutic effects in neonates and infants.b

Interpret plasma concentrations in the overall clinical context; thus, do not use an isolated plasma concentration measurement alone as the basis for adjusting dosage.398 399 400 401 402 403

Distribution

Extent

Widely distributed in body tissues; highest concentrations in the heart, kidneys, intestine, stomach, liver, and skeletal muscle.b

In the myocardium, digoxin is found in the sarcolemma-T system bound to a receptor.b

Plasma Protein Binding

About 20–30%b

Special Populations

Crosses the placenta.b

Distributes into breast milk.b

Elimination

Metabolism

Usually, only small amounts are metabolized, but the extent of metabolism is variable and may be substantial in some patients.b

Some presumably occurs in the liver, but digoxin also apparently is metabolized by bacteria within the lumen of the large intestine following oral administration and possibly after biliary elimination following parenteral administration.b

Elimination Route

Mainly in urine, principally as unchanged drug.b

Small amounts of metabolites and unchanged drug also are excreted in bile and feces.b

Half-life

34–44 hours in normal renal function.b

Special Populations

Renal impairment: Fecal excretion may be increased.b

Renal failure and hypothyroidism: Terminal elimination half-life is prolonged.b

Acute digoxin overdosage and hyperthyroidism: Terminal elimination half-life is decreased.b

Stability

Storage

Protect from light at 15–25°C.b

Parenteral

Injection

Compatible with most commercially available IV infusion fluids.b

Before IV administration, digoxin injection may be diluted with ≥4-fold volume of sterile water for injection, 5% dextrose injection, or 0.9% sodium chloride injection; use of <4-fold volume of diluent may result in precipitation of digoxin.b 400 401

Diluted solutions of digoxin should be used immediately.b 400 401

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.45% with potassium chloride 20 mEq

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.45 or 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Bretylium tosylate

Cimetidine HCl

Furosemide

Lidocaine HCl

Ranitidine HCl

Verapamil HCl

Incompatible

Dobutamine HCl

Y-Site CompatibilityHID

Compatible

Bivalirudin

Ciprofloxacin

Dexmedetomidine HCl

Diltiazem HCl

Famotidine

Fenoldopam mesylate

Heparin sodium with hydrocortisone sodium succinate

Hetastarch in lactated electrolyte injection (Hextend)

Inamrinone lactate

Linezolid

Meperidine HCl

Meropenem

Midazolam HCl

Milrinone lactate

Morphine sulfate

Potassium chloride

Remifentanil HCl

Tacrolimus

Vitamin B complex with C

Incompatible

Amiodarone HCl

Amphotericin B cholesteryl sulfate complex

Fluconazole

Foscarnet sodium

Lansoprazole

Propofol

Variable

Insulin, regular (Humulin R)

Actions

  • Digoxin is a cardiac glycoside.b

  • Exact mechanism of action has not been fully elucidated.a

  • The main pharmacologic property is its ability to increase the force and velocity of myocardial systolic contraction (positive inotropic action) by a direct action on the myocardium both in patients with nonfailing hearts and in those with failing hearts.a

  • Inhibits the activity of sodium-potassium-activated adenosine triphosphatase (Na+-K+-ATPase), an enzyme required for active transport of sodium across myocardial cell membranes.a

  • Hypothesized that digoxin acts in heart failure principally by attenuating the activation of the neurohormonal system, rather than by a positive inotropic action.395

  • Toxic doses cause efflux of potassium from the myocardium and concurrent influx of sodium.a

  • Toxicity results in part from loss of intracellular potassium associated with inhibition of Na+-K+-ATPase.a

  • With therapeutic doses, augmentation of calcium influx to the contractile proteins with resultant enhancement of excitation-contraction coupling is involved in the positive inotropic action of cardiac glycosides; the role of Na+-K+-ATPase in this effect is controversial.a

  • CHF: Causes reflex reduction in peripheral resistance by increasing myocardial contractility; this compensates for the direct vasoconstrictor action and, therefore, total peripheral resistance usually is reduced.a

  • CHF: Increased myocardial contractility and cardiac output reflexly reduce sympathetic tone, thus slowing increased heart rate and causing diuresis in edematous patients.a

  • CHF: Increased myocardial contractility is accompanied by increased myocardial oxygen consumption.a

  • CHF: Reduced ventricular end-diastolic pressure and increased myocardial contractility produce a net decrease or no change in myocardial oxygen consumption.a No decrease in coronary blood flow, and in patients with heart failure the restoration of efficient heart action may improve coronary circulation.a

  • Decreases conduction velocity through the atrioventricular (AV) node and prolongs the effective refractory period (ERP) of the AV node by increasing vagal activity, by a direct effect on the AV node, and by a sympatholytic effect.a

  • With therapeutic doses, may cause prolongation of the PR interval, shortening of the QT interval, and ST segment depression, but these ECG effects are not a quantitative measure of the degree of digitalization.a

  • Toxic doses increase the automaticity (increased spontaneous diastolic depolarization) of all areas of the heart except the SA node.b

  • Anorexia, nausea, and vomiting are probably mediated by chemoreceptors located in the area postrema of the medulla.b

Advice to Patients

  • Importance of explaining common signs and symptoms of toxicity and to contact a clinician if they occur.b (See Major Toxicities under Warnings/Precautions.)

  • Importance of warning patient to immediately contact a clinician if color vision is affected or objects appear yellow or green or, less commonly, brown, red, blue, or white;38 270 halos or borders on objects (often are white and appear on dark objects) are also signs of toxicity and reason for consulting a clinician.74 270

  • Advise patients, particularly geriatric patients, of the importance of obtaining laboratory tests (e.g., periodic renal function and electrolyte determinations) as recommended by their clinician.c

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Digoxin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

50 mcg

Lanoxicaps

GlaxoSmithKline

100 mcg

Lanoxicaps

GlaxoSmithKline

200 mcg

Lanoxicaps

GlaxoSmithKline

Elixir

50 mcg/mL*

Digoxin Elixir

Lanoxin Elixir Pediatric

GlaxoSmithKline

Tablets

125 mcg*

Digitek

Bertek, UDL

Digoxin Tablets

Lanoxin (scored)

GlaxoSmithKline

250 mcg*

Digoxin Tablets

Lanoxin (scored)

GlaxoSmithKline

Parenteral

Injection

100 mcg/mL*

Digoxin Injection Pediatric

Lanoxin Injection Pediatric

GlaxoSmithKline

250 mcg/mL*

Digoxin Injection

Lanoxin

GlaxoSmithKline

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Digoxin 0.05MG/ML Solution (ROXANE): 60/$39.99 or 180/$100.97

Digoxin 0.125MG Tablets (LANNETT): 30/$19.26 or 90/$30.79

Digoxin 0.25MG Tablets (LANNETT): 30/$16.99 or 90/$25.97

Lanoxin 0.125MG Tablets (GLAXO SMITH KLINE): 30/$21.99 or 60/$32.97

Lanoxin 0.25MG Tablets (GLAXO SMITH KLINE): 30/$20.87 or 60/$30.14

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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322. Hansten PD. Diltiazem and digoxin. Drug Interact Newsl. 1984; 4:33-4.

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