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Digoxin: Drug information

Digoxin: Drug information
(For additional information see "Digoxin: Patient drug information" and see "Digoxin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Digitek [DSC];
  • Digox [DSC];
  • Lanoxin;
  • Lanoxin Pediatric
Brand Names: Canada
  • JAMP-Digoxin;
  • Lanoxin [DSC];
  • PMS-Digoxin
Pharmacologic Category
  • Antiarrhythmic Agent, Miscellaneous;
  • Cardiac Glycoside
Dosing: Adult

Dosage guidance:

Safety: Toxicity may occur even at therapeutic concentrations in some settings (eg, hypokalemia). Periodically monitor digoxin concentrations as appropriate for the condition being treated, especially if kidney impairment occurs.

Dosing: When changing from oral (tablets or liquid) to IV therapy, reduce dosage by 20% to 25%.

Atrial fibrillation/flutter, rate control

Atrial fibrillation/flutter, rate control (alternative agent): Note: Some experts reserve digoxin for patients whose rate has not adequately been controlled with other agents or interventions (Ref). Additionally, digoxin is not effective for rate control during high-adrenergic states (eg, exercise); a beta-blocker is preferred. Do not use in patients with preexcitation associated with an accessory pathway, as this can lead to ventricular arrhythmias (Ref).

Total digitalizing dose (TDD):

Note: May initiate with a loading dose followed by maintenance dosing if rapid titration is desired or initiate with maintenance dosing without a loading dose.

Oral/IV: 0.25 to 0.5 mg once; repeat doses of 0.25 mg every 6 hours to a maximum of 1.5 mg over 24 hours (Ref).

or

Oral/IV: 8 to 12 mcg/kg (use lean body weight; not to exceed 0.75 to 1.5 mg over 24 hours); administer by giving 50% of TDD once, then administer the remaining 50% as 2 doses of 25% of TDD at 4- to 8-hour intervals; round doses to standard amounts (Ref). For example, TDD of 12 mcg/kg in an 80 kg patient by lean body weight = 960 mcg. Administer 0.5 mg once, then 0.25 mg every 6 hours for 2 doses.

Maintenance dose: Oral: 0.125 to 0.25 mg once daily (Ref).

Fetal supraventricular tachyarrhythmia, sustained

Fetal supraventricular tachyarrhythmia, sustained (maternal administration for transplacental transfer to the fetus) (off-label use): Note: These patients should be managed by a highly experienced fetal arrhythmia team. Due to decreased placental transfer, maternal administration of digoxin may be less effective when fetal hydrops is present (Ref). The lowest effective dose should be used to avoid maternal adverse events (Ref). Prior to use, evaluate appropriateness of therapy to the mother (eg, maternal electrolytes, kidney function, ECG).

Maternal dose:

Loading dose (may be given oral or IV):

IV: 1.2 to 1.5 mg over 24 hours given in divided doses every 8 hours; follow with oral maintenance regimen (Ref). Some experts do not recommend IV administration (Ref).

Oral: 1 to 2 mg given over 24 to 48 hours in divided doses (eg, 0.5 mg followed by 0.25 mg, then 0.25 mg over the first 18 to 24 hours with subsequent additional doses as needed to achieve target levels); follow with an oral maintenance regimen (Ref).

Maintenance dose: Oral: 0.375 mg to 0.75 mg per day given in divided doses every 8 to 12 hours. Adjust dose to maintain a target maternal blood level between 0.7 and 2 ng/mL (Ref). Some experts recommend dividing into 3 times daily dosing to ensure adequate drug levels (Ref).

Heart failure with reduced ejection fraction

Heart failure with reduced ejection fraction: Note: Reserve for use in patients with persistent New York Heart Association functional class III or IV symptoms despite optimal guideline-directed medical therapy (Ref).

Maintenance dose (loading dose not recommended): Oral: 0.125 to 0.25 mg once daily; target a serum digoxin concentration of 0.5 to <0.9 ng/mL; higher daily doses are rarely necessary. If patient is >70 years of age, has impaired kidney function, or has a low lean body mass, low doses (eg, 0.125 mg daily or every other day) should be used initially (Ref). A dosing nomogram is also available based on lean body weight and CrCl (Ref).

Supraventricular tachycardia, rate control

Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia), rate control (alternative agent) (off-label use):

Total digitalizing dose:

Oral: Initial: 0.5 mg loading dose, with additional 0.125 to 0.25 mg doses administered at 6- to 8-hour intervals until evidence of adequate effect (maximum total dose over 24 hours: 8 to 12 mcg/kg [use lean body weight], not to exceed 0.75 to 1.5 mg) (Ref).

IV: Initial: 0.25 to 0.5 mg loading dose, with additional 0.25 mg doses administered at 6- to 8-hour intervals until evidence of adequate effect (maximum total dose over 24 hours: 8 to 12 mcg/kg [use lean body weight], not to exceed 0.75 to 1.5 mg) (Ref).

Maintenance dose: Oral: 0.125 to 0.25 mg once daily (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Periodically monitor digoxin concentrations as appropriate for the condition being treated. Toxicity may occur even at therapeutic concentrations in some settings (eg, hypokalemia).

Altered kidney function:

Atrial fibrillation/flutter, supraventricular tachycardia:

IV, Oral:

Loading dose: Note: Use with caution and only when rapid ventricular rate control is necessary.

CrCl >15 mL/minute: No dosage adjustment necessary.

CrCl ≤15 mL/minute: Administer 50% of usual dose (Ref).

Maintenance dose (Ref):

Note: Patients with low lean body weight may require lower doses. Doses of 0.0625 mg once daily may be given as 0.125 mg every other day.

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 45 to <60 mL/minute: 0.0625 to 0.125 mg once daily.

CrCl 30 to <45 mL/minute: 0.0625 mg once daily.

CrCl <30 mL/minute: 0.0625 mg every 48 hours or consider alternative agent.

Heart failure:

Oral:

Digoxin Dosing Suggestions When Used for Heart Failurea,b

Ideal body weight (kg)

CrCl (mL/minute)

Digoxin dose

aDerived from a contemporary digoxin dosing nomogram using CrCl and ideal body weight or height for determining the initial maintenance dose in patients with heart failure to achieve a target digoxin concentration of 0.7 ng/mL (Bauman 2006, DiDomenico 2014).

bNo loading dose necessary.

cMay administer as 0.125 mg every other day.

45 to 50

>60

0.125 mg once daily

15 to 60

0.0625 mg once dailyc

>50 to 60

>110

0.25 mg once daily

>45 to 110

0.125 mg once daily

15 to 45

0.0625 mg once dailyc

>60 to 70

>110

0.25 mg once daily

>35 to 110

0.125 mg once daily

15 to 35

0.0625 mg once dailyc

>70 to 80

>80 to 110

0.25 mg once daily

>20 to 80

0.125 mg once daily

15 to 20

0.0625 mg once dailyc

>80

>70

0.25 mg once daily

15 to 70

0.125 mg once daily

Hemodialysis, intermittent (thrice weekly): Not dialyzable (Ref):

Note: Avoid use if possible; use in end-stage kidney disease is associated with increased mortality (Ref).

Atrial fibrillation/flutter, supraventricular tachycardia:

Loading dose: Oral, IV: Use with caution and only when rapid ventricular rate control is necessary. Reduce to 50% of usual dose (Ref).

Maintenance dose: Oral, IV: 0.0625 mg every 48 hours or 3 times/week may be considered (Ref).

Heart failure: Maintenance dose: Oral: 0.0625 mg every 48 hours or 3 times/week may be considered (Ref).

Peritoneal dialysis: Not dialyzable (Ref):

Note: Avoid use if possible (Ref).

Atrial fibrillation/flutter, supraventricular tachycardia:

Loading dose: Oral, IV: Use with caution and only when rapid rate control is necessary. Reduce to 50% of usual dose (Ref).

Maintenance dose: Oral, IV: 0.0625 mg every 48 hours may be considered (Ref).

Heart failure: Maintenance dose: Oral: 0.0625 mg every 48 hours may be considered (Ref).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response, serum drug concentrations, and adverse reactions (eg, arrhythmias) due to drug accumulation is important.

Note: Avoid use if possible (Ref).

Atrial fibrillation/flutter, supraventricular tachycardia:

Loading dose: Oral, IV: Reduce to 50% of usual dose (Ref). Use with caution and only when rapid rate control is necessary.

Maintenance dose: Oral, IV: 0.0625 to 0.125 mg every 48 hours may be considered (Ref).

Heart failure: Maintenance dose: Oral: 0.0625 to 0.125 mg every 48 hours may be considered (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Close monitoring of response, serum drug concentrations, and adverse reactions (eg, arrhythmias) due to drug accumulation is important.

Note: Avoid use if possible (Ref).

Atrial fibrillation/flutter, supraventricular tachycardia:

Loading dose: Oral, IV: Reduce to 50% of usual dose (Ref). Use with caution and only when rapid rate control is necessary.

Maintenance dose: Oral, IV: 0.0625 to 0.125 mg every 48 hours may be considered (Ref).

Heart failure: Maintenance dose: Oral: 0.0625 mg every 48 hours may be considered (Ref).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Older Adult

Dose is based on assessment of lean body mass and kidney function. Elderly patients with low lean body mass may experience higher digoxin concentrations due to reduced volume of distribution (Ref). Decrease dose in patients with decreased kidney function (see Dosing: Altered Kidney Function).

Atrial fibrillation: Avoid as first-line therapy; if used, do not exceed 0.125 mg/day in patients ≥65 years (Ref).

Heart failure with reduced ejection fraction: If patient is >70 years of age, low doses (eg, 0.125 mg daily or every other day) should be used (Ref). Avoid as first-line therapy; if used, do not exceed 0.125 mg/day in patients ≥65 years of age. Use caution when discontinuing due to potential for clinical worsening (Ref).

Dosing: Pediatric

(For additional information see "Digoxin: Pediatric drug information")

Dosage guidance:

Dosing: Dosage must be individualized due to substantial individual variation and must take into account renal function. Doses should be based on lean body weight. When changing from oral solution to IV therapy, dosage should be reduced by 20% to 25%.

Heart failure

Heart failure: Injection, Oral: Infants, Children, and Adolescents: The dosage tables below list dosage recommendations for normal renal function and are based upon average patient response; lower doses are needed for patients with renal impairment.

Digitalizing dose, initial regimen (optional): Total digitalizing dose should be divided (see below); digitalizing dose (loading dose) may not be necessary; consider use if rapid titration is desired. To avoid toxicity, consider doses at lower end of the recommended range; dosage should be individualized based on patient response (eg, clinical response, serum drug levels).

Dosage Recommendations for Digitalizing DoseA (Optional)

Age

Total Digitalizing Dose

Administer in 3 divided dosesB

(mcg/kg)

Oral Solution

Tablets

IVC

ABased on lean body weight and normal renal function for age.

B Do not give full total digitalizing dose (TDD) at once. Give one-half of the TDD for the initial dose, then give one-quarter of the TDD for each of 2 subsequent doses at 6- to 8-hour intervals; prior to additional doses, clinical response should be fully evaluated (eg, ECG).

CMay also be administered by IM; however, not recommended.

1 to 24 months

35 to 60

30 to 50

2 to 5 years

30 to 45

25 to 35

5 to 10 years

20 to 35

20 to 45

15 to 30

>10 years

10 to 15

10 to 15

8 to 12

Maintenance Dosage Recommendations for DigoxinA,B

Age

Daily Maintenance Dose

If ≤10 years, administer in equal divided doses twice daily

If >10 years, administer once daily

(mcg/kg/day)

Oral Solution

Tablets

IVC,D

ADosing reflects clinical practice and in some cases, varies from manufacturer labeling (Bakir 1994; Bendayan 1983; Latifi 2000; Park 1986).

BBased on lean body weight and normal renal function for age. Decrease maintenance dose in patients with decreased renal function.

CMay also be administered by IM; however, not recommended.

DDaily maintenance IV dose is typically 20% to 30% of total digitalizing IV dose in pediatric patients ≤24 months and 25% to 35% in older pediatric patients.

1 to 24 months

10 to 15

9 to 15

2 to 5 years

8 to 10

6 to 9

5 to 10 years

5 to 10

6 to 12

4 to 8

>10 years

2.5 to 5

2.5 to 5

2 to 3

Tachyarrhythmias, treatment

Tachyarrhythmias, treatment: Limited data available (Ref): Injection, Oral: Infants, Children, and Adolescents:

Initial (digitalizing dose):

IV: 10 to 12 mcg/kg/dose every 8 hours for 3 doses

Oral: 13 to 17 mcg/kg/dose every 8 hours for 3 doses

Maintenance: Oral: 8 to 10 mcg/kg/day divided once or twice daily (Escudero 2012); use twice daily dosing in infants and young children (Ref)

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: Oral, IV:

Digitalizing (loading) dose: There are no dosage adjustments provided in the manufacturer's labeling for digitalizing dose; however, 50% to 70% of a digoxin dose is excreted unchanged in the urine. The following adjustments have been recommended in adults with end-stage renal disease (ESRD): Reduce usual dose by 50% (Ref).

Maintenance dose:

Manufacturer's labeling: Dosage reductions and close monitoring recommended; see product labeling for CrCl-specific dosage recommendation

Alternate dosing: The following adjustments have been recommended (Ref):

GFR >50 mL/minute/1.73 m2: No dosage adjustment necessary

GFR: 30 to 50 mL/minute/1.73 m2: Administer 75% of normal dose at normal intervals

GFR: 10 to 29 mL/minute/1.73 m2: Administer 50% of normal dose at normal intervals or administer normal dose every 36 hours

GFR: <10 mL/minute/1.73 m2: Administer 25% of normal dose at normal intervals or administer normal dose every 48 hours

Intermittent hemodialysis: Nondialyzable (0% to 5%). Administer 25% of normal dose at normal intervals or administer normal dose every 48 hours

Peritoneal dialysis (PD): Administer 25% of normal dose at normal intervals or administer normal dose every 48 hours

Continuous renal replacement therapy (CRRT): Administer 75% of normal dose at normal intervals; titrate to desired effect; monitor serum concentrations

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions (Significant): Considerations
Digoxin toxicity

Digoxin toxicity in adult and pediatric patients is typically associated with levels >2 ng/mL; however, due to its narrow therapeutic window, digoxin toxicity is possible at therapeutic levels (Ref). Digoxin serum concentrations obtained <6 hours after ingestion may appear falsely elevated (Ref). Symptoms of digoxin toxicity may include nausea, vomiting, visual disturbances (“halos,” yellow or blurred vision), lethargy, and/or life-threatening arrhythmias. Arrhythmias may include paroxysmal atrial tachycardia, atrioventricular (AV) block (all types; first degree atrioventricular block, second degree atrioventricular block, complete atrioventricular block [Mobitz type II more unlikely]), and ventricular premature contractions. In severe cases, arrythmias may include ventricular tachycardia (bidirectional) or ventricular fibrillation. Children are more likely to experience cardiac arrhythmia as a sign of excessive dosing; CNS and GI symptoms are not frequently observed. Conduction disturbances or tachyarrhythmia (atrial tachycardia with or without block) and junctional tachycardia are most common. Sinus bradycardia may be a sign of digoxin toxicity, especially in infants. Ventricular tachyarrhythmias are less common. Cardiac arrhythmias are the primary cause of death associated with digoxin toxicity and may present without any additional symptoms. Digoxin toxicity is reversible upon discontinuation or administration of digoxin immune fab (Ref).

Mechanism: Serum concentration-related; related to the pharmacologic action. Increased intracellular calcium and increased activation of the parasympathetic nervous system due to significant inhibition of the Na+/K+ ATPase pump and AV nodal blockade, respectively, lead to increased automaticity and decreased conduction (Ref).

Onset: Varied; serum concentration-related; acute and chronic toxicity may occur (Ref).

Risk factors :

• Digoxin concentration >2 ng/mL (Ref)

• Older adults (Ref)

• Chronic obstructive pulmonary disease (Ref)

• Hypothyroidism (Ref)

• Kidney impairment (Ref)

• Electrolyte disturbances (eg, hypercalcemia, hypokalemia, hypomagnesemia) (Ref)

• Dehydration/over-diuresis (Ref)

• Amyloidosis (Ref)

• Concurrent use of interacting medications that increase digoxin concentration (eg, amiodarone, dronedarone, erythromycin, itraconazole, lapatinib, propafenone, quinidine, ranolazine, ritonavir, verapamil) (Ref)

• Low body weight

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Accelerated atrioventricular junctional rhythm, asystole, atrial tachycardia (Tisdale 2020) atrioventricular dissociation, complete atrioventricular block (Mahdyoon 1990; Tisdale 2020), depression of ST segment on ECG, first degree atrioventricular block (Mahdyoon 1990; Tisdale 2020), prolongation P-R interval on ECG, second degree atrioventricular block (Mahdyoon 1990; Tisdale 2020), ventricular fibrillation (Ma 2001; Tisdale 2020), ventricular premature contractions (Ma 2001), ventricular tachycardia (Ma 2001; Tisdale 2020)

Dermatologic: Skin rash (bullous, erythematous, maculopapular [most common], papular, scarlatiniform, vesicular) (Martin 1994)

Endocrine & metabolic: Gynecomastia

Gastrointestinal: Abdominal pain, anorexia, diarrhea, intestinal necrosis (hemorrhagic), mesenteric ischemia, nausea (Limon 2016), vomiting (Limon 2016)

Hematologic & oncologic: Thrombocytopenia (Pirovino 1981)

Nervous system: Altered mental status, anxiety, apathy, confusion, delirium, depression, dizziness, hallucination, headache, lethargy (Pincus 2016)

Neuromuscular & skeletal: Asthenia

Ophthalmic: Blurred vision, visual disturbances (blurred or yellow vision) (Limon 2016), xanthopsia

Contraindications

Hypersensitivity to digoxin, other forms of digitalis, or any component of the formulation; ventricular fibrillation

Warnings/Precautions

Concerns related to adverse effects:

• Extravasation: IV administration: Vesicant; ensure proper needle or catheter placement prior to and during administration; avoid extravasation.

Disease-related concerns:

• Accessory bypass tract (eg, Wolff-Parkinson-White [WPW] syndrome): During an episode of atrial fibrillation or flutter in patients with an accessory bypass tract or pre-excitation syndrome, use has been associated with increased anterograde conduction down the accessory pathway leading to ventricular fibrillation; avoid use in such patients (ACLS [Neumar 2010]; AHA/ACC/HRS [January 2014]).

• Acute coronary syndrome: Use with caution in patients with an acute MI; may increase myocardial oxygen demand and lead to ischemia. During an acute coronary syndrome, digoxin administered IV may be used to slow a rapid ventricular response and improve left ventricular (LV) function in the acute treatment of atrial fibrillation associated with severe LV function and heart failure or hemodynamic instability (AHA/ACC/HRS [January 2014]).

• Atrial fibrillation: When used for rate control in patients with atrial fibrillation, monitor serum concentrations closely; may be associated with an increased risk of mortality especially when serum concentrations are not properly controlled (Vamos 2015).

• Beri beri heart disease: Patients with beri beri heart disease may fail to adequately respond to digoxin therapy; treat underlying thiamine deficiency concomitantly.

• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy. Hypercalcemia may increase the risk of digoxin toxicity and hypocalcemia can nullify the effects of digoxin; maintain normocalcemia.

• Heart failure with reduced ejection fraction: Digoxin should be considered for use only in heart failure (HF) with reduced ejection fraction (HFrEF) when symptoms remain despite guideline-directed medical therapy. It may also be considered in patients with both HF and atrial fibrillation; however, beta blockers may offer better ventricular rate control than digoxin (AHA/ACC/HFSA [Heidenreich 2022]). Withdrawal of digoxin in clinically stable patients with HF may lead to recurrence of HF symptoms (Packer 1993). Monitor serum concentrations closely; may be associated with an increased risk of mortality especially when serum concentrations are not properly controlled (Vamos 2015).

• Hypermetabolic states: Atrial arrhythmias associated with hypermetabolic (eg, hyperthyroidism) or hyperdynamic (hypoxia, arteriovenous shunt) states are very difficult to treat; treat underlying condition first. If digoxin is used, ensure digoxin toxicity does not occur.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Outflow obstruction may worsen due to the positive inotropic effects of digoxin; avoid use unless used to control ventricular response with atrial fibrillation. Digoxin is potentially harmful in the treatment of dyspnea in patients with HCM in the absence of atrial fibrillation (AHA/ACC [Ommen 2020]).

• Kidney impairment: Use with caution in patients with kidney impairment; dosage adjustment needed.

• Myocarditis: In a murine model of viral myocarditis, digoxin in high doses was shown to be detrimental (Matsumori 1999). If used in humans, therefore, digoxin should be used with caution and only at low doses (Frishman 2007). The manufacturer recommends avoiding the use of digoxin in patients with myocarditis.

• Preserved left ventricular function: Decreased cardiac output may occur in patients with preserved left ventricular systolic function, including restrictive or hypertrophic cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale; in general, the manufacturer recommends to avoid use unless used to control ventricular response with atrial fibrillation.

• Sinus node disease and atrioventricular (AV) block: Because digoxin slows sinoatrial and AV conduction, the drug commonly prolongs the PR interval. Digoxin may cause severe sinus bradycardia or sinoatrial block particularly in patients with preexisting sinus node disease. Avoid use in patients with second- or third-degree heart block (except in patients with a functioning artificial pacemaker); incomplete AV block (eg, Stokes-Adams attacks) may progress to complete block with digoxin administration. In such patients, if treatment with digoxin is necessary, consider the insertion of a pacemaker before treatment.

• Thyroid disease: Use with caution in patients with hypothyroidism, higher digoxin concentrations may result due to significant reduction in digoxin clearance (Burk 2010). In patients with hyperthyroidism, lower digoxin concentrations may result due to an increase in renal clearance of digoxin. No significant differences in absorption were seen in either thyroid condition compared with those with normal thyroid function (Burk 2010). Note: New-onset atrial fibrillation or exacerbation of ventricular arrhythmias should prompt evaluation of thyroid status.

Special populations:

• Infants: Newborn infants display considerable variability to their tolerance to digoxin; premature and immature infants are particularly sensitive to the effects of digoxin.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Elective electrical cardioversion: It is not necessary to routinely reduce or hold digoxin therapy prior to elective electrical cardioversion for atrial fibrillation; however, exclusion of digoxin toxicity (eg, clinical and ECG signs) is necessary prior to cardioversion. If signs of digoxin excess exist, withhold digoxin and delay cardioversion until toxicity subsides (AHA/ACC/HRS [January 2014]).

Warnings: Additional Pediatric Considerations

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Lanoxin: 0.25 mg/mL (2 mL) [contains alcohol, usp, propylene glycol]

Lanoxin Pediatric: 0.1 mg/mL (1 mL) [contains alcohol, usp, propylene glycol]

Generic: 0.25 mg/mL (2 mL)

Solution, Oral:

Generic: 0.05 mg/mL (60 mL)

Tablet, Oral:

Digitek: 125 mcg [DSC] [scored; contains quinoline (d&c yellow #10) aluminum lake]

Digitek: 250 mcg [DSC] [scored]

Digox: 125 mcg [DSC] [scored; contains quinoline (d&c yellow #10) aluminum lake]

Digox: 250 mcg [DSC] [scored]

Lanoxin: 62.5 mcg [contains corn starch, fd&c yellow #6 (sunset yellow)]

Lanoxin: 125 mcg [scored; contains fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]

Lanoxin: 250 mcg [DSC]

Lanoxin: 250 mcg [scored]

Generic: 62.5 mcg, 125 mcg, 250 mcg

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Digoxin Injection)

0.25 mg/mL (per mL): $3.30 - $3.74

Solution (Digoxin Oral)

0.05 mg/mL (per mL): $2.48 - $2.84

Solution (Lanoxin Injection)

0.25 mg/mL (per mL): $75.82

Solution (Lanoxin Pediatric Injection)

0.1 mg/mL (per mL): $151.63

Tablets (Digoxin Oral)

62.5 mcg (per each): $13.82 - $15.55

125 mcg (per each): $0.45 - $4.56

250 mcg (per each): $0.45 - $4.56

Tablets (Lanoxin Oral)

62.5 mcg (per each): $19.86

125 mcg (per each): $19.86

250 mcg (per each): $19.86

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection:

Lanoxin: 0.25 mg/mL ([DSC]) [contains alcohol, usp]

Generic: 0.25 mg/mL (2 mL)

Solution, Oral:

Generic: 0.05 mg/mL (115 mL)

Tablet, Oral:

Generic: 62.5 mcg, 125 mcg, 250 mcg, 0.0625 mg, 0.125 mg

Administration: Adult

IM: IV route preferred. If IM injection necessary, administer by deep injection followed by massage at the injection site. Inject no more than 2 mL per injection site. May cause intense pain.

IV: May be administered undiluted or diluted. Inject slowly over ≥5 minutes.

When used for the management of fetal tachycardia (off-label use), IV or oral doses are administered to the mother for transplacental transfer to the fetus (Ref).

Vesicant; ensure proper needle or catheter placement prior to and during administration; avoid extravasation.

Extravasation management: If extravasation occurs, stop IV administration immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

Administration: Pediatric

Neonatal, Infants, Children, and Adolescents:

Oral: Administer consistently with relationship to meals; avoid concurrent administration (ie, administer digoxin 1 hour before or 2 hours after) with meals high in fiber or pectin and with drugs that decrease oral absorption of digoxin.

Oral solution: Only the calibrated manufacturer-provided dropper or a calibrated oral syringe should be used to measure the dose. For doses <0.2 mL the manufacturer-provided dropper is not accurate and should not be used; use a calibrated oral syringe.

Parenteral:

IV: May be slowly administered IV over ≥5 minutes (usually 5 to 10 minutes); avoid rapid IV infusion since this may result in systemic and coronary arteriolar vasoconstriction.

Vesicant; ensure proper needle or catheter placement prior to and during administration; avoid extravasation. If extravasation occurs, stop IV administration immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity.

IM: Not usually recommended due to local irritation, pain, and tissue damage; if necessary, administer by deep injection followed by massage at the injection site. May cause intense pain.

FETAL: IM: Administer into FETAL buttock or thigh under direct ultrasound guidance.

Use: Labeled Indications

Atrial fibrillation or atrial flutter, rate control: Control of ventricular response rate in adults with chronic atrial fibrillation.

Heart failure with reduced ejection fraction (HFrEF): Treatment of mild to moderate (or stage C as recommended by the ACCF/AHA) heart failure in adults; to increase myocardial contractility in pediatric patients with heart failure

Use: Off-Label: Adult

Fetal supraventricular tachyarrhythmia, sustained (maternal administration for transplacental transfer to the fetus); Supraventricular tachycardia (eg, atrioventricular nodal reentrant tachycardia), rate control

Medication Safety Issues
Sound-alike/look-alike issues:

Digoxin may be confused with Desoxyn, doxepin

Lanoxin may be confused with Lasix, levothyroxine, Levoxyl, Levsinex, Lomotil, Mefoxin, naloxone, Xanax

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Older Adult: High-Risk Medication:

Beers Criteria: Digoxin is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older as first-line therapy for atrial fibrillation (due to safer and more effective alternatives for rate control) or as first-line therapy for heart failure (due to conflicting and low quality evidence for benefits and harms, evidence that other agents decrease hospitalizations and mortality, and lack of additional benefit when higher doses are used despite the increased risk of toxicity). Exercise caution when discontinuing therapy in patients with heart failure with reduced ejection fraction due to limited evidence suggesting worse outcomes following discontinuation. If used, avoid doses greater than 0.125 mg/day due to decreased renal clearance of digoxin which may result in increased risk of toxic effects; further dose reductions may be warranted in patients with Stage 4 or 5 chronic kidney disease (Beers Criteria [AGS 2023]).

International issues:

Lanoxin [US, Canada, and multiple international markets] may be confused with Limoxin brand name for ambroxol [Indonesia] and amoxicillin [Mexico]

Metabolism/Transport Effects

Substrate of CYP3A4 (minor), P-glycoprotein/ABCB1 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May decrease the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Acarbose: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Adenosine: Digoxin may enhance the adverse/toxic effect of Adenosine. Risk C: Monitor therapy

Aminoglycosides: May decrease the serum concentration of Cardiac Glycosides. This effect has only been demonstrated with oral aminoglycoside administration. Risk C: Monitor therapy

Amiodarone: May increase the serum concentration of Cardiac Glycosides. Management: Reduce the dose of cardiac glycosides by 30% to 50% or reduce the frequency of administration when initiating concomitant amiodarone therapy. Monitor for increased serum concentrations and toxic effects of cardiac glycosides. Risk D: Consider therapy modification

Amphotericin B: May enhance the adverse/toxic effect of Cardiac Glycosides. Risk C: Monitor therapy

Anagliptin: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Antithyroid Agents: May increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Asciminib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Asunaprevir: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Atorvastatin: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Barnidipine: May enhance the adverse/toxic effect of Digoxin. Risk C: Monitor therapy

Benidipine: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Berotralstat: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Cardiac Glycosides. Risk C: Monitor therapy

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Risk C: Monitor therapy

Bretylium: May enhance the adverse/toxic effect of Cardiac Glycosides. Management: Bretylium should only be used in digitalis-treated patients when other antiarrhythmic options are ineffective and when arrhythmia is not suspected to be related to digitalis toxicity. Bretylium is contraindicated in digitalis-induced arrhythmias. Risk D: Consider therapy modification

Brimonidine (Topical): May enhance the bradycardic effect of Digoxin. Risk C: Monitor therapy

BuPROPion: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Calcium Channel Blockers (Nondihydropyridine): May enhance the AV-blocking effect of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Calcium Polystyrene Sulfonate: May enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, the risk for increased digoxin toxicity may occur if hypokalemia is present. Risk C: Monitor therapy

Calcium Salts: May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Canagliflozin: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Carvedilol: Digoxin may enhance the bradycardic effect of Carvedilol. Carvedilol may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Risk D: Consider therapy modification

Cobicistat: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Colchicine: Digoxin may enhance the adverse/toxic effect of Colchicine. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

CycloSPORINE (Systemic): May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Diacerein: May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Disulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination

Dronedarone: Digoxin may enhance the AV-blocking effect of Dronedarone. Digoxin may also enhance the other electrophysiologic effects of Dronedarone. Dronedarone may increase the serum concentration of Digoxin. Management: Avoid concurrent use of digoxin when possible. If concurrent use is necessary, reduce digoxin dose by 50%, monitor digoxin concentration closely, and increase monitoring for both clinical response to therapy and the occurrence of adverse effects. Risk D: Consider therapy modification

Edrophonium: May enhance the AV-blocking effect of Cardiac Glycosides. Risk C: Monitor therapy

Elacestrant: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Enasidenib: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

EPHEDrine (Nasal): Cardiac Glycosides may enhance the arrhythmogenic effect of EPHEDrine (Nasal). Risk C: Monitor therapy

EPHEDrine (Systemic): May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Epoprostenol: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: If coadministration with these narrow therapeutic index/sensitive P-gp substrates is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of these P-gp substrates. Risk D: Consider therapy modification

Etrasimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Etravirine: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Fexinidazole: Bradycardia-Causing Agents may enhance the arrhythmogenic effect of Fexinidazole. Risk X: Avoid combination

Fingolimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Fingolimod. Management: Consult with the prescriber of any bradycardia-causing agent to see if the agent could be switched to an agent that does not cause bradycardia prior to initiating fingolimod. If combined, perform continuous ECG monitoring after the first fingolimod dose. Risk D: Consider therapy modification

Flecainide: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Flibanserin: May increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with flibanserin. Reduce digoxin concentrations by either reducing the digoxin dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

FLUoxetine: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Futibatinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Gilteritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Glycopyrrolate (Systemic): May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Hydroxychloroquine: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Ibrutinib: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Istradefylline: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Itraconazole: May increase the serum concentration of Cardiac Glycosides. Management: Measure cardiac glycoside serum concentrations before initiating treatment with itraconazole. Reduce cardiac glycoside concentrations by either reducing the dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Risk C: Monitor therapy

Kaolin: May decrease the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Risk C: Monitor therapy

Lapatinib: May increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with lapatinib. Reduce digoxin concentrations by either reducing the digoxin dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Lenacapavir: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Lenalidomide: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Levosulpiride: May enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, levosulpiride may diminish symptoms of cardiac glycoside-related toxicity. Risk C: Monitor therapy

Licorice: May enhance the adverse/toxic effect of Cardiac Glycosides. Risk C: Monitor therapy

Lonafarnib: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of loop diuretics. Risk C: Monitor therapy

Lumacaftor and Ivacaftor: May decrease the serum concentration of Digoxin. Lumacaftor and Ivacaftor may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Macrolide Antibiotics: May increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Maribavir: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Metaraminol: May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, a disulfiram-like reaction may occur and CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination

Metoclopramide: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid combination

Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Milnacipran: May enhance the adverse/toxic effect of Digoxin. The risk of postural hypotension and tachycardia may be increased. Risk X: Avoid combination

Mirabegron: May increase the serum concentration of Digoxin. Management: Consider initiating the lowest dose of digoxin in patients beginning treatment with a combination of digoxin and mirabegron. Monitor digoxin concentrations and adjust the digoxin dose as needed. Risk D: Consider therapy modification

Mitapivat: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Nefazodone: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Neuromuscular-Blocking Agents: May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

NIFEdipine: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Nirmatrelvir and Ritonavir: May increase the serum concentration of Digoxin. Management: Reduce the digoxin dose by approximately 30% to 50%, or reduce the dosing frequency, when these agents are combined. Monitor digoxin levels closely and adjust digoxin dose as needed. Risk D: Consider therapy modification

Nitrendipine: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Octreotide: May enhance the bradycardic effect of Digoxin. Octreotide may increase the serum concentration of Digoxin. Risk C: Monitor therapy

Ornidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination

Ornidazole: May enhance the adverse/toxic effect of Products Containing Propylene Glycol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination

Ozanimod: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Pacritinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Parathyroid Hormone: May enhance the adverse/toxic effect of Cardiac Glycosides. More specifically, Parathyroid Hormone-related hypercalcemia may predispose to digitalis toxicity. Risk C: Monitor therapy

Paricalcitol: May enhance the adverse/toxic effect of Digoxin. Risk C: Monitor therapy

Pectin: May decrease the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

PenicillAMINE: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification

Polyethylene Glycol 3350: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Polyethylene Glycol 4000: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: May decrease the absorption of Digoxin. Management: Give oral digoxin at least 2 hours before or at least 6 hours after polyethylene glycol-electrolyte solutions that contain magnesium sulfate (Suflave brand). Other products without magnesium do not require dose separation. Risk D: Consider therapy modification

Ponesimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Ponesimod. Management: Avoid coadministration of ponesimod with drugs that may cause bradycardia when possible. If combined, monitor heart rate closely and consider obtaining a cardiology consult. Do not initiate ponesimod in patients on beta-blockers if HR is less than 55 bpm. Risk D: Consider therapy modification

Posaconazole: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Pretomanid: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Propafenone: May increase the serum concentration of Cardiac Glycosides. Management: Measure cardiac glycoside serum concentrations before initiating treatment with propafenone. Reduce cardiac glycoside concentrations by either reducing the dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Propantheline: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

QuiNIDine: May increase the serum concentration of Cardiac Glycosides. Management: Measure cardiac glycoside serum concentrations before initiating treatment with quinidine. Reduce cardiac glycoside concentrations by either reducing the dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Quinidine (Non-Therapeutic): May increase the serum concentration of Cardiac Glycosides. Management: Measure cardiac glycoside serum concentrations before initiating treatment with quinidine. Reduce cardiac glycoside concentrations by either reducing the dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Ranolazine: May increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with ranolazine. Reduce digoxin concentrations by either reducing the digoxin dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Reserpine: May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Ritonavir: May increase the serum concentration of Digoxin. Management: Reduce the digoxin dose by approximately 30% to 50%, or reduce the dosing frequency, when these agents are combined. Monitor digoxin levels closely and adjust digoxin dose as needed. Risk D: Consider therapy modification

Roxithromycin: May increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Sarecycline: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination

Secnidazole: Products Containing Propylene Glycol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination

Senna: May enhance the adverse/toxic effect of Digoxin. Risk C: Monitor therapy

Simvastatin: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. If combined, consider obtaining a cardiology consult regarding patient monitoring. Risk D: Consider therapy modification

Sotorasib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management: Consider avoiding use of sotorasib and narrow therapeutic index/sensitive P-gp substrates. If combined use is unavoidable, monitor for increased toxicities of the substrate and consider a decrease in the substrate dosage. Risk D: Consider therapy modification

Sparsentan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Spironolactone: May increase the serum concentration of Digoxin. Spironolactone (and/or its metabolites) may also interfere with the assays used to determine Digoxin concentrations, falsely increasing or decreasing Digoxin concentrations. Risk C: Monitor therapy

St John's Wort: May decrease the serum concentration of Digoxin. Risk C: Monitor therapy

Sucralfate: May decrease the serum concentration of Digoxin. Specifically, sucralfate may decrease the absorption of digoxin. Management: Administer digoxin at least 2 hours before sucralfate. Concomitant administration should be avoided. Monitor for decreased digoxin levels/effects with initiation of sucralfate therapy. Risk D: Consider therapy modification

Taurursodiol: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid combination

Telmisartan: May increase the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Thiazide and Thiazide-Like Diuretics: May enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Risk C: Monitor therapy

Thyroid Products: May decrease the serum concentration of Cardiac Glycosides. Specifically, returning to a euthyroid state from a hypothyroid state may decrease the serum concentration of cardiac glycosides. Risk C: Monitor therapy

Ticagrelor: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Risk C: Monitor therapy

Tolvaptan: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

TraMADol: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Trimethoprim: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Valbenazine: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Vandetanib: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Vemurafenib: May increase the serum concentration of Digoxin. Management: Avoid coadministration of vemurafenib and digoxin when possible. If combined, measure digoxin levels and reduce digoxin concentrations by either reducing the digoxin dose by 30% to 50% or by modifying the dosing frequency. Risk D: Consider therapy modification

Venetoclax: May increase the serum concentration of Digoxin. Management: Avoid concomitant use of venetoclax and digoxin if possible. If combined, administer digoxin at least 6 hours before venetoclax to minimize the potential for an interaction. Risk D: Consider therapy modification

Vibegron: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Vilazodone: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Vitamin D Analogs: May enhance the arrhythmogenic effect of Cardiac Glycosides. Risk C: Monitor therapy

Zanubrutinib: May increase the serum concentration of Digoxin. Risk C: Monitor therapy

Food Interactions

Digoxin peak serum concentrations may be decreased if taken with food. Meals containing increased fiber (bran) or foods high in pectin may decrease oral absorption of digoxin.

Pregnancy Considerations

Digoxin crosses the placenta.

Available guidelines note experience with digoxin in pregnancy is extensive (ESG [Regitz-Zagrosek 2018]). Based on available data, an increased risk of adverse pregnancy outcomes has not been observed. However, untreated maternal heart failure and atrial fibrillation may increase the risk of preterm birth and low birth weight, respectively. The manufacturer recommends monitoring neonates for signs and symptoms of digoxin toxicity following in utero exposure.

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of digoxin may be altered. Close monitoring of maternal serum digoxin is recommended (Hebert 2008; Luxford 1983; Martin-Suarez 2017); dose adjustments may be required during pregnancy and postpartum.

Heart failure and atrial fibrillation may worsen during pregnancy. Digoxin is recommended as a first-line agent for the chronic treatment of highly symptomatic supraventricular tachycardia (SVT) in pregnancy; the lowest effective dose is recommended (ACC/AHA/HRS [Page 2015]). Digoxin may be considered for long-term rate control of maternal atrial tachycardia or atrial fibrillation when preferred agents fail (ESG [Regitz-Zagrosek 2018]). Monitor for an increased risk of maternal arrhythmias during labor and delivery.

Digoxin may be considered for the in utero management of fetal SVT or atrial flutter with hydrops or ventricular dysfunction. Digoxin may also be considered for SVT without hydrops or ventricular dysfunction if heart rate is ≥200 bpm, atrial flutter, or other rare tachycardias with an average heart rate of ≥200 bpm (AHA [Donofrio 2014]).

Breastfeeding Considerations

Digoxin is present in breast milk.

The manufacturer reports the relative infant dose (RID) of digoxin to be 1% to 7% of a weight-adjusted maternal dose or ~ 0.2% to 4% of a neonatal maintenance dose.

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

The RID of digoxin was calculated by the manufacturer using milk concentrations of 0.4 to 1 ng/mL, providing an estimated daily infant dose via breast milk of 0.03 to 0.16 mcg/kg/day. This milk concentration was obtained following maternal administration of digoxin 0.25 mg once daily to 13 lactating women. Higher milk concentrations (<12 ng/mL) were obtained following an IV bolus dose of 500 mcg to 1 breastfeeding woman; however, digoxin levels rapidly decreased to ~1 ng/mL ~2 hours after the injection. This study found milk concentrations declined in parallel to maternal serum concentrations following either oral or IV dosing (Reinhardt 1982). Digoxin can be detected in the serum of breastfed infants (Finley 1979).

The amount of digoxin available to the infant via breast milk is not likely to be clinically significant. The World Health Organization considers digoxin to be compatible with breastfeeding (WHO 2002).

Dietary Considerations

Maintain adequate amounts of potassium in diet to decrease risk of hypokalemia (hypokalemia may increase risk of digoxin toxicity).

Monitoring Parameters

Heart rate and rhythm should be monitored along with periodic ECGs to assess desired effects and signs of toxicity; baseline and periodic serum creatinine. Periodically monitor serum potassium, magnesium, and calcium especially if on medications where these electrolyte disturbances can occur (eg, diuretics), or if patient has a history of hypokalemia or hypomagnesemia. Observe patients for noncardiac signs of toxicity, confusion, and depression.

When to draw serum digoxin concentrations: Digoxin serum concentrations are monitored because digoxin possesses a narrow therapeutic serum range; the therapeutic endpoint is difficult to quantify and digoxin toxicity may be life-threatening. Digoxin serum concentrations should be drawn at least 6 to 8 hours after last dose, regardless of route of administration (optimally 12 to 24 hours after a dose). Note: Serum digoxin concentrations may decrease in response to exercise due to increased skeletal muscle uptake; a period of rest (eg, ~2 hours) after exercise may be necessary prior to drawing serum digoxin concentrations.

Initiation of therapy:

If a loading dose is given: Digoxin serum concentration may be drawn within 12 to 24 hours after the initial loading dose administration. Concentrations drawn this early may confirm the relationship of digoxin plasma concentrations and response but are of little value in determining maintenance doses.

If a loading dose is not given: Digoxin serum concentration should be obtained after 3 to 5 days of therapy.

Maintenance therapy:

Trough concentrations should be followed just prior to the next dose or at a minimum of 6 to 8 hours after last dose.

Digoxin serum concentrations should be obtained within 5 to 7 days (approximate time to steady-state) after any dosage changes. Continue to obtain digoxin serum concentrations 7 to 14 days after any change in maintenance dose. Note: In patients with end-stage kidney disease, it may take 15 to 20 days to reach steady-state.

Patients who are receiving electrolyte-depleting medications such as diuretics, serum potassium, magnesium, and calcium should be monitored closely.

Digoxin serum concentrations should be obtained whenever any of the following conditions occur:

Questionable patient compliance or to evaluate clinical deterioration following an initial good response

Changing kidney function

Suspected digoxin toxicity

Initiation or discontinuation of therapy with drugs (eg, amiodarone, quinidine, verapamil) which potentially interact with digoxin.

Any disease changes (eg, thyroid disease)

Reference Range

Digoxin therapeutic serum concentrations:

Heart failure: 0.5 to 0.9 ng/mL (SI: 0.6 to 1.2 nmol/L) (AHA/ACC/HFSA [Heidenreich 2022]).

Toxic: Risk (including mortality) increases with serum concentrations >1.2 ng/mL (SI: >1.5 nmol/L), but toxicity can occur at any time and may occur at lower levels in the setting of hypokalemia, hypomagnesemia, or hypothyroidism (AHA/ACC/HFSA [Heidenreich 2022]).

Atrial fibrillation: 0.8 to 2 ng/mL (SI: 1 to 2.6 nmol/L); <0.5 ng/mL (SI: <0.6 nmol/L) probably indicates underdigitalization unless there are special circumstances. A serum concentration ≥1.2 ng/mL (SI: ≥1.5 nmol/L) may be associated with increased all-cause mortality in patients with atrial fibrillation (regardless of heart failure) (Lopes 2018).

Digoxin-like immunoreactive substance (DLIS) may cross-react with digoxin immunoassay. DLIS has been found in patients with kidney and liver disease, heart failure, neonates, and pregnant women (third trimester).

Mechanism of Action

Heart failure: Inhibition of the sodium/potassium ATPase pump in myocardial cells results in a transient increase of intracellular sodium, which in turn promotes calcium influx via the sodium-calcium exchange pump leading to increased contractility. May improve baroreflex sensitivity (Gheorghiade 1991).

Supraventricular arrhythmias: Direct suppression of the AV node conduction to increase effective refractory period and decrease conduction velocity - positive inotropic effect, enhanced vagal tone, and decreased ventricular rate to fast atrial arrhythmias. Atrial fibrillation may decrease sensitivity and increase tolerance to higher serum digoxin concentrations.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Heart rate control: Oral: 1 to 2 hours; IV: 5 to 60 minutes.

Peak effect: Heart rate control: Oral: 2 to 8 hours; IV: 1 to 6 hours; Note: In patients with atrial fibrillation, median time to ventricular rate control in one study was 6 hours (range: 3 to 15 hours) (Siu 2009).

Duration: Adults: 3 to 4 days.

Absorption: By passive nonsaturable diffusion in the upper small intestine; food may delay, but does not affect extent of absorption.

Distribution:

Normal kidney function: 6 to 7 L/kg.

Vd: Extensive to peripheral tissues, with a distinct distribution phase which lasts 6 to 8 hours; concentrates in heart, liver, kidney, skeletal muscle, and intestines. Heart/serum concentration is 70:1. Pharmacologic effects are delayed and do not correlate well with serum concentrations during distribution phase.

Hyperthyroidism: Increased Vd.

Hyperkalemia, hyponatremia: Decreased digoxin distribution to heart and muscle.

Hypokalemia: Increased digoxin distribution to heart and muscles.

Concomitant quinidine therapy: Decreased Vd.

Chronic kidney failure: 4 to 6 L/kg.

Decreased sodium/potassium ATPase activity - decreased tissue binding.

Neonates, full-term: 7.5 to 10 L/kg.

Children: 16 L/kg.

Adults: 7 L/kg, decreased with kidney disease.

Protein binding: ~25%; in uremic patients, digoxin is displaced from plasma protein binding sites.

Metabolism: Via sequential sugar hydrolysis in the stomach or by reduction of lactone ring by intestinal bacteria (in ~10% of population, gut bacteria may metabolize up to 40% of digoxin dose); once absorbed, only ~16% is metabolized to 3-beta-digoxigenin, 3-keto-digoxigenin, and glucuronide and sulfate conjugates; metabolites may contribute to therapeutic and toxic effects of digoxin; metabolism is reduced with decompensated HF.

Bioavailability: Oral (formulation dependent): Elixir: 70% to 85%; Tablet: 60% to 80%.

Half-life elimination (age, renal and cardiac function dependent):

Neonates: Premature: 61 to 170 hours; Full-term: 35 to 45 hours.

Infants: 18 to 25 hours.

Children: 18 to 36 hours.

Adults: 36 to 48 hours.

Adults, anephric: 3.5 to 5 days.

Half-life elimination: Parent drug: 38 hours; Metabolites: Digoxigenin: 4 hours; Monodigitoxoside: 3 to 12 hours.

Time to peak, serum: Oral: 1 to 3 hours.

Excretion: Urine (50% to 70% as unchanged drug).

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Clearance correlates with CrCl. Half-life is 3.5 to 5 days in anuric patients.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Lanicor | Lanoxin | Lanoxin pg | Toloxin;
  • (AR) Argentina: Cardiogoxin | Digocard-g | Digoxina | Lanicor | Lanoxin (igoxina);
  • (AT) Austria: Lanicor | Novodigal;
  • (AU) Australia: Lanoxin | Sigmaxin;
  • (BD) Bangladesh: Agoxin | Centoxin | Lanoxin;
  • (BE) Belgium: Digoxine nativelle | Lanoxin | Lanoxin Digoxine;
  • (BG) Bulgaria: Dilacor | Novodigal;
  • (BR) Brazil: Beldigox | Cardcor | Cardionil | Cimecard | Digitax | Digixina | Digobal | Digox | Digoxan | Digoxen | Digoxil | Digoxina | Furp digoxina | Lanoxin | Neo digoxin | Valoxin;
  • (CH) Switzerland: Digoxin juvise | Digoxin mepha | Digoxin streuli | Digoxine labatec | Lanoxin;
  • (CL) Chile: Digoxina;
  • (CN) China: Ke li;
  • (CO) Colombia: Digicor | Digoxina;
  • (CZ) Czech Republic: Digoxin nativelle | Digoxin orion | Lanicor;
  • (DE) Germany: Digacin | Digoxin digoregen | Digoxin Goedecke | Dilanacin | Lanicor | Lenoxin;
  • (DO) Dominican Republic: Digoxina | Digoxina Inmenol | Lanicor | Lanigoxina | Lanoxin;
  • (EC) Ecuador: Digoxina | Lanicor;
  • (EE) Estonia: Digoxin ns | Lanicor | Lanoxin;
  • (EG) Egypt: Cardixin | Lanoxin digoxin | Lanoxin pg;
  • (ES) Spain: Digoxina boehringer | Digoxina kern pharma | Lanacordin;
  • (FI) Finland: Cardigoxin | Cedoxin | Digoxin medipolar | Digoxin orion | Digoxin star | Lanadix | Lanoxin | Medigoxin medica;
  • (FR) France: Digoxine Dci | Digoxine nativelle | Hemigoxine | Hemigoxine nativelle | Lanoxin;
  • (GB) United Kingdom: Digamex | Digoxin almus | Digoxin boots | Digoxin cox | Digoxin dc | Digoxin kent | Lanoxin | Nativelle digoxin;
  • (GR) Greece: Digoxine | Lanoxin;
  • (HK) Hong Kong: Lanoxin;
  • (HR) Croatia: Lanicor;
  • (HU) Hungary: Digoxin sopharma | Digoxina kern pharma | Huma-digoxin;
  • (ID) Indonesia: Fargoxin | Lanoxin;
  • (IE) Ireland: Lanoxin;
  • (IL) Israel: Digoxin Zori | Lanoxin | Lanoxin pg;
  • (IN) India: Cardin | Cardioxin | Caxin | Digitran | Digon | Dixin | Lanoxin | Sangoxin;
  • (IT) Italy: Cardioreg | Lanicor | Lanoxin;
  • (JO) Jordan: Lanoxin | Lanoxin pg;
  • (JP) Japan: Digohan | Digosin | Digoxin Alfresa | Digoxin hd | Digoxin Novartis | Digoxin taiyo | Halfdigoxin | Halfdigoxin KY | Lanoxin;
  • (KE) Kenya: Digomet | Lanoxin;
  • (KR) Korea, Republic of: Digosin | Lanoxin;
  • (KW) Kuwait: Lanoxin;
  • (LB) Lebanon: Lanoxin digoxin | Lanoxin pg;
  • (LT) Lithuania: Digoxin bm | Digoxin bp | Digoxin leciva | Digoxine | Dilacor | Dixin | Lanicor | Lanoxin;
  • (LU) Luxembourg: Lanoxin Digoxine;
  • (LV) Latvia: Dilacor | Lanicor | Lanoxin;
  • (MA) Morocco: Digoxine nativelle;
  • (MX) Mexico: Digoxina | Gonet | Lanoxin | Lanoxin digoxina | Mapluxin | Valvulan | Vidaxil;
  • (MY) Malaysia: Lanoxin | Lanoxin pg;
  • (NL) Netherlands: Digoxine | Digoxine eureco pharma | Digoxine gf | Lanoxin | Lanoxin injectie;
  • (NO) Norway: Digoxin dak | Digoxin nycomed | Digoxin orifarm | Digoxin tak | Lanoxin;
  • (NZ) New Zealand: Digoxin sandoz | Lanoxin;
  • (PE) Peru: Digoxina;
  • (PH) Philippines: Digox | Dixin | Inoxin | Lanoxin | Ligoxin;
  • (PK) Pakistan: Digitek | Digox | Lanoxin;
  • (PL) Poland: Digoxin bm | Digoxin sopharma;
  • (PR) Puerto Rico: Digitek | Lanoxin;
  • (PT) Portugal: Digoxina | Lanoxin | Lanoxin MD;
  • (PY) Paraguay: Digoxil | Digoxina fapasa | Digoxina indufar | Digoxina l.ch. | Lanoxin | Metoxal;
  • (QA) Qatar: Lanoxin | Lanoxin PG;
  • (RO) Romania: Digoxin leciva | Digoxin zentiva;
  • (RU) Russian Federation: Digoxin nycomed | Dilacor | Lanicor | Lanoxin;
  • (SA) Saudi Arabia: Lanicor | Lanoxin | Toloxin;
  • (SE) Sweden: Digoxin astrazeneca | Digoxin Biophausia | Lanoxin;
  • (SG) Singapore: Lanoxin | Lanoxin Pg Paediatric/Geriatric;
  • (SI) Slovenia: Digoxina kern pharma | Lanicor;
  • (SK) Slovakia: Digoxin leciva;
  • (TH) Thailand: Digoxin sandoz | Grexin | Lanoxin | Lanoxin pg | Toloxin;
  • (TN) Tunisia: Digoxine | Digoxine nativelle | Digoxine nihfi;
  • (TR) Turkey: Digoxin assos | Digoxin nativelle;
  • (TW) Taiwan: Digosin | Lanoxin;
  • (UA) Ukraine: Lanicor;
  • (UG) Uganda: Dix;
  • (UY) Uruguay: Digoxil | Digoxina | Lanicor | Lanoxin;
  • (VE) Venezuela, Bolivarian Republic of: Digoxina | Lanicor;
  • (ZA) South Africa: Lanoxin | Purgoxin;
  • (ZM) Zambia: Digox | Kaydigo | Lanoxin;
  • (ZW) Zimbabwe: Lanoxin
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