Digoxin: Drug information

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Contributor Disclosures

For additional information see "Digoxin: Patient drug information" and "Digoxin:
Pediatric drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US
Digitek [DSC]; Digox [DSC]; Lanoxin; Lanoxin Pediatric

Brand Names: Canada

AURO-Digoxin; JAMP-Digoxin; 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: Reserve

digoxin for patients whose rate has not adequately been controlled with other
agents or interventions. 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: 0.0625 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:

Total digitalizing dose:

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

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

CrCl ≤15 mL/minute: IV, Oral: 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: Oral: No dosage adjustment necessary.

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

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

CrCl <30 mL/minute: Oral: 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) Oral digoxin dose

>60 0.125 mg once daily

45 to 50
15 to 60 0.0625 mg once dailyc

>110 0.25 mg once daily

>50 to 60 >45 to 110 0.125 mg once daily

15 to 45 0.0625 mg once dailyc

>110 0.25 mg once daily

>60 to 70 >35 to 110 0.125 mg once daily

15 to 35 0.0625 mg once dailyc

>80 to 110 0.25 mg once daily

>70 to 80 >20 to 80 0.125 mg once daily

15 to 20 0.0625 mg once dailyc

>70 0.25 mg once daily

>80
15 to 70 0.125 mg once daily
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.
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:

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

Maintenance dose: Oral: 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:

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

Maintenance dose: Oral: 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:

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

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

Maintenance dose: Oral: 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: Liver 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. The dose equivalents when changing between dosage forms
(oral solution, tablets, IV/injection) is 125 mcg oral solution = 125 mcg tablets =
100 mcg IV/injection.

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)

Total Digitalizing Dose

Administer in 3 divided dosesB
Age
(mcg/kg)

Oral Solution Tablets IVC

 Total Digitalizing Dose
Administer in 3 divided dosesB
Age (mcg/kg)

Oral Solution Tablets IVC

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
A Based 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).
C May also be administered by IM; however, not recommended.

Maintenance Dosage Recommendations for DigoxinA,B

Daily Maintenance Dose

If ≤10 years, administer in equal divided doses twice daily
Age If >10 years, administer once daily
(mcg/kg/day)

Oral Solution Tablets IVC,D

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

A Dosing reflects clinical practice and in some cases, varies from manufacturer labeling (Bakir 1994;
Bendayan 1983; Latifi 2000; Park 1986).
B Based on lean body weight and normal renal function for age. Decrease maintenance dose in patients
with decreased renal function.
C May also be administered by IM; however, not recommended.
D Daily 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 (Lanoxin injection prescribing information 2012).

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.

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 an IV
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: Liver 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 (Ref) atrioventricular dissociation, complete atrioventricular block
(Ref), depression of ST segment on ECG, first degree atrioventricular block
(Ref), prolongation P-R interval on ECG, second degree atrioventricular block
(Ref), ventricular fibrillation (Ref), ventricular premature contractions (Ref),
ventricular tachycardia (Ref)

Dermatologic: Skin rash (bullous, erythematous, maculopapular [most

common], papular, scarlatiniform, vesicular) (Ref)

Endocrine & metabolic: Gynecomastia

Gastrointestinal: Abdominal pain, anorexia, diarrhea, intestinal necrosis

(hemorrhagic), mesenteric ischemia, nausea(Ref), vomiting (Ref)

Hematologic & oncologic: Thrombocytopenia (Ref)

Nervous system: Altered mental status, anxiety, apathy, confusion, delirium,

depression, dizziness, hallucination, headache, lethargy (Ref)

Neuromuscular & skeletal: Asthenia

Ophthalmic: Blurred vision, visual disturbances (blurred or yellow vision) (Ref),

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]; ACC/AHA [Joglar
2024]).

• 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
2024]).

• 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).

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] [contains quinoline (d&c yellow #10) aluminum lake]

Digitek: 250 mcg [DSC] [scored]

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

Digox: 250 mcg [DSC]

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 [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): $85.94

Solution (Lanoxin Pediatric Injection)

0.1 mg/mL (per mL): $171.87

Tablets (Digoxin Oral)

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

125 mcg (per each): $0.45 - $2.30

 250 mcg (per each): $0.45 - $2.30

Tablets (Lanoxin Oral)

62.5 mcg (per each): $21.78

125 mcg (per each): $21.78

250 mcg (per each): $21.78

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
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assumes no liability with respect to accuracy of price or price range data published in
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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:

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 [DSC], 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 <0.1
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 (Ref).

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 (Ref).

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 (IV
and oral formulations) and also drug class (antiarrhythmics, IV; inotropic
medications, IV) among its list of drugs/classes which have a heightened risk of
causing significant patient harm when used in error (High-Alert Medications in
Acute Care and Long-Term Care Settings).
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]).

Digoxin is identified in the Screening Tool of Older Person's Prescriptions

(STOPP) criteria as a potentially inappropriate medication in older adults (≥65
years of age) as first-line therapy for long-term (>3 months) treatment in atrial
fibrillation. In addition, some disease states of concern include renal
impairment, heart failure, bradycardia, heart block, or history of QTc
prolongation (O’Mahony 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 (Major); Note: Assignment of
Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions
(For additional information: Launch drug interactions program)
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 drug interactions program by clicking on the
“Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May decrease serum concentrations of Cardiac

Glycosides. Risk C: Monitor

Acarbose: May decrease serum concentrations of Digoxin. Risk C: Monitor

Acrivastine: May increase adverse/toxic effects of Cardiac Glycosides. Risk C:

Monitor
Adenosine: Digoxin may increase adverse/toxic effects of Adenosine. Risk C:
Monitor
Aminoglycosides: May decrease serum concentrations of Cardiac Glycosides. This
effect has only been demonstrated with oral aminoglycoside administration. Risk
C: Monitor
Amiodarone: May increase serum concentrations 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 increase adverse/toxic effects of Cardiac Glycosides. Risk C:

Monitor

Anagliptin: May increase serum concentrations of Digoxin. Risk C: Monitor

Antithyroid Agents: May increase serum concentrations of Cardiac Glycosides. Risk

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

Atorvastatin: May increase serum concentrations of Cardiac Glycosides. Risk C:

Monitor
Barnidipine: May increase adverse/toxic effects of Digoxin. Risk C: Monitor

Benidipine: May increase serum concentrations of Digoxin. Risk C: Monitor

Berotralstat: May increase serum concentrations of P-glycoprotein/ABCB1

Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

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

Monitor
Bradycardia-Causing Agents: May increase bradycardic effects of Bradycardia-
Causing Agents. Risk C: Monitor

Bretylium: May increase adverse/toxic effects 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 (Ophthalmic): May increase bradycardic effects of Digoxin. Risk C:

Monitor

Brimonidine (Topical): May increase bradycardic effects of Digoxin. Risk C: Monitor

BuPROPion: May decrease serum concentrations of Digoxin. Risk C: Monitor

Calcium Channel Blockers (Nondihydropyridine): May increase AV-blocking effects

of Cardiac Glycosides. Calcium Channel Blockers (Nondihydropyridine) may
increase serum concentrations of Cardiac Glycosides. Risk C: Monitor

Calcium Polystyrene Sulfonate: May increase adverse/toxic effects of Cardiac

Glycosides. Specifically, the risk for increased digoxin toxicity may occur if
hypokalemia is present. Risk C: Monitor

Calcium Salts: May increase arrhythmogenic effects of Cardiac Glycosides. Risk C:

Monitor
Canagliflozin: May increase serum concentrations of Digoxin. Risk C: Monitor

Carvedilol: Digoxin may increase bradycardic effects of Carvedilol. Carvedilol may

increase serum concentrations of Digoxin. Risk C: Monitor
Ceritinib: Bradycardia-Causing Agents may increase bradycardic effects 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

Certoparin: Cardiac Glycosides may decrease therapeutic effects of Certoparin.

Risk C: Monitor
Charcoal, Activated: May decrease serum concentrations of Cardiac Glycosides.
Management: Separating administration of these agents by at least 2 hours
appears may lessen this interaction but may not avoid it entirely, particularly with
repeated ingestion of activated charcoal. Risk D: Consider Therapy Modification

Cobicistat: May increase serum concentrations of Digoxin. Risk C: Monitor

Colchicine: Digoxin may increase adverse/toxic effects of Colchicine. Risk C:

Monitor
Conivaptan: May increase serum concentrations of Digoxin. Risk C: Monitor

Corticosteroids (Systemic): May increase adverse/toxic effects of Cardiac

Glycosides. Risk C: Monitor

CycloSPORINE (Systemic): May increase serum concentrations of Digoxin. Risk C:

Monitor
Diacerein: May increase arrhythmogenic effects of Cardiac Glycosides. Risk C:
Monitor

Disulfiram: May increase adverse/toxic effects of Products Containing Ethanol.

Management: Do not use disulfiram with dosage forms that contain ethanol. Risk
X: Avoid
Dronedarone: Digoxin may increase AV-blocking effects of Dronedarone. Digoxin
may also enhance the other electrophysiologic effects of Dronedarone.
Dronedarone may increase serum concentrations 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
Elacestrant: May increase serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Elobixibat: May increase serum concentrations of Digoxin. Risk C: Monitor

Enasidenib: May increase serum concentrations of Digoxin. Risk C: Monitor

Enzalutamide: May increase serum concentrations of Digoxin. Management:

Measure digoxin serum concentrations before initiating treatment with
enzalutamide. Reduce digoxin concentrations by reducing the digoxin dose by
15% to 30% or by modifying the dosing frequency. Be aware enzalutamide may
interfere with some digoxin assays Risk D: Consider Therapy Modification

EPHEDrine (Nasal): Cardiac Glycosides may increase arrhythmogenic effects of

EPHEDrine (Nasal). Risk C: Monitor

EPHEDrine (Systemic): May increase arrhythmogenic effects of Cardiac Glycosides.

Risk C: Monitor
EPINEPHrine (Systemic): May increase arrhythmogenic effects of Cardiac
Glycosides. Risk C: Monitor

Epoprostenol: May increase serum concentrations of Digoxin. Risk C: Monitor

Erdafitinib: May increase serum concentrations 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 increase bradycardic effects of Bradycardia-Causing Agents. Risk

C: Monitor
Etravirine: May increase serum concentrations of Digoxin. Risk C: Monitor

Felodipine: May increase serum concentrations of Cardiac Glycosides. Risk C:

Monitor
Fexinidazole: Bradycardia-Causing Agents may increase arrhythmogenic effects of
Fexinidazole. Risk X: Avoid
Fingolimod: Bradycardia-Causing Agents may increase bradycardic effects 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 serum concentrations of Cardiac Glycosides. Risk C:

Monitor

Flibanserin: May increase serum concentrations 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 serum concentrations of Digoxin. Risk C: Monitor

Gentamicin (Systemic): May increase serum concentrations of Cardiac Glycosides.

Risk C: Monitor

Gepotidacin: May increase serum concentrations of Digoxin. Risk C: Monitor

Gilteritinib: May increase serum concentrations of P-glycoprotein/ABCB1

Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Glycopyrrolate (Systemic): May increase serum concentrations of Digoxin. Risk C:

Monitor

Gossypol: May increase adverse/toxic effects of Cardiac Glycosides. Risk C: Monitor

Hydroxychloroquine: May increase serum concentrations of Digoxin. Risk C:

Monitor
Ibrutinib: May increase serum concentrations of Digoxin. Risk C: Monitor

Istradefylline: May increase serum concentrations of Digoxin. Risk C: Monitor

Itraconazole: May increase serum concentrations 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 increase bradycardic effects of
Ivabradine. Risk C: Monitor

Kaolin: May decrease serum concentrations of Cardiac Glycosides. Risk C: Monitor

Ketoconazole (Systemic): May increase serum concentrations of Digoxin. Risk C:

Monitor

Lacosamide: Bradycardia-Causing Agents may increase AV-blocking effects of

Lacosamide. Risk C: Monitor

Landiolol: Bradycardia-Causing Agents may increase bradycardic effects of

Landiolol. Risk X: Avoid

Lapatinib: May increase serum concentrations 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 serum concentrations of P-glycoprotein/ABCB1

Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid

Lenacapavir: May increase serum concentrations of Digoxin. Risk C: Monitor

Lenalidomide: May increase serum concentrations of Digoxin. Risk C: Monitor

Levacetylleucine: May increase serum concentrations of P-glycoprotein/ABCB1

Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Levosulpiride: May increase adverse/toxic effects of Cardiac Glycosides.

Specifically, levosulpiride may diminish symptoms of cardiac glycoside-related
toxicity. Risk C: Monitor

Licorice: May increase adverse/toxic effects of Cardiac Glycosides. Risk C: Monitor

Lithium: May increase adverse/toxic effects of Cardiac Glycosides. Risk C: Monitor

Lonafarnib: May increase serum concentrations of P-glycoprotein/ABCB1

Substrates (High risk with Inhibitors). Risk C: Monitor
Loop Diuretics: May increase adverse/toxic effects of Cardiac Glycosides.
Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and
hypomagnesemic effect of loop diuretics. Risk C: Monitor

Lumacaftor and Ivacaftor: May decrease serum concentrations of Digoxin.

Lumacaftor and Ivacaftor may increase serum concentrations of Digoxin. Risk C:
Monitor
Macrolide Antibiotics: May increase serum concentrations of Cardiac Glycosides.
Risk C: Monitor
Maribavir: May increase serum concentrations of Digoxin. Risk C: Monitor

Metaraminol: May increase arrhythmogenic effects of Cardiac Glycosides. Risk C:

Monitor

Methotrimeprazine: May increase CNS depressant effects of Products Containing

Ethanol. Management: Avoid products containing alcohol in patients treated with
methotrimeprazine. Risk X: Avoid

Metoclopramide: May decrease serum concentrations of Cardiac Glycosides. Risk

C: Monitor
Midodrine: May increase bradycardic effects of Bradycardia-Causing Agents. Risk
C: Monitor
Midostaurin: May increase serum concentrations of Digoxin. Risk C: Monitor

Milnacipran: May increase adverse/toxic effects of Digoxin. The risk of postural

hypotension and tachycardia may be increased. Risk X: Avoid

Mirabegron: May increase serum concentrations 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 serum concentrations of P-glycoprotein/ABCB1 Substrates

(Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Multivitamins/Fluoride (with ADE): May increase arrhythmogenic effects of Cardiac

Glycosides. Risk C: Monitor
Multivitamins/Minerals (with ADEK, Folate, Iron): May increase arrhythmogenic
effects of Cardiac Glycosides. Risk C: Monitor

Multivitamins/Minerals (with AE, No Iron): May increase arrhythmogenic effects of

Cardiac Glycosides. Risk C: Monitor

Nefazodone: May increase serum concentrations of Digoxin. Risk C: Monitor

Neuromuscular-Blocking Agents: May increase arrhythmogenic effects of Cardiac

Glycosides. Risk C: Monitor

NIFEdipine (Systemic): May increase serum concentrations of Cardiac Glycosides.

Risk C: Monitor
NIFEdipine (Topical): May increase serum concentrations of Digoxin. Risk C:
Monitor

Nirmatrelvir and Ritonavir: May increase serum concentrations 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 serum concentrations of Digoxin. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents (Topical): May increase serum

concentrations of Digoxin. Risk C: Monitor

Nonsteroidal Anti-Inflammatory Agents: May increase serum concentrations of

Cardiac Glycosides. Risk C: Monitor

Octreotide: May increase bradycardic effects of Digoxin. Octreotide may increase

serum concentrations of Digoxin. Risk C: Monitor

Ozanimod: May increase bradycardic effects of Bradycardia-Causing Agents. Risk

C: Monitor

P-glycoprotein/ABCB1 Inducers: May decrease serum concentrations of Digoxin.

Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentrations 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

Pacritinib: May increase serum concentrations of Digoxin. Risk C: Monitor

Parathyroid Hormone Products: May increase arrhythmogenic effects of Cardiac

Glycosides. Risk C: Monitor

Paricalcitol: May increase adverse/toxic effects of Digoxin. Risk C: Monitor

Pectin: May decrease serum concentrations of Cardiac Glycosides. Risk C: Monitor

PenicillAMINE: May decrease serum concentrations of Digoxin. Risk C: Monitor

Polyethylene Glycol 3350: May decrease serum concentrations of Digoxin. Risk C:

Monitor
Polyethylene Glycol 4000: May decrease serum concentrations of Digoxin. Risk C:
Monitor
Polyethylene Glycol-Electrolyte Solution: May decrease 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 increase bradycardic effects 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

Potassium Phosphate: Digoxin may increase hyperkalemic effects of Potassium

Phosphate. Management: Avoid coadministration of potassium phosphate and
digoxin due to the risk of severe and potentially fatal hyperkalemia. If
coadministration is required, monitor serum potassium concentrations closely.
Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor
Primaquine: May increase serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Propafenone: May increase serum concentrations 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 serum concentrations of Digoxin. Risk C: Monitor

Quinidine (Non-Therapeutic): May increase serum concentrations 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: May increase serum concentrations 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 serum concentrations 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
Remibrutinib: May increase serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Reproterol: May increase adverse/toxic effects of Cardiac Glycosides. Risk C:

Monitor
Reserpine: May increase arrhythmogenic effects of Cardiac Glycosides. Risk C:
Monitor
Rilzabrutinib: May increase serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Ritonavir: May increase serum concentrations 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 serum concentrations of Cardiac Glycosides. Risk C:

Monitor
Sarecycline: May increase serum concentrations of Digoxin. Risk C: Monitor

Secnidazole: Products Containing Ethanol may increase adverse/toxic effects of

Secnidazole. Risk X: Avoid

Senna: May increase adverse/toxic effects of Digoxin. Risk C: Monitor

Simvastatin: May increase serum concentrations of Digoxin. Risk C: Monitor

Siponimod: Bradycardia-Causing Agents may increase bradycardic effects 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 serum concentrations 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 serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid

Spironolactone: May increase serum concentrations of Cardiac Glycosides.

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
Sucralfate: May decrease serum concentrations 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 serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk X: Avoid

Telmisartan: May increase serum concentrations of Cardiac Glycosides. Risk C:

Monitor
Tetracycline (Systemic): May increase serum concentrations of Cardiac Glycosides.
Risk C: Monitor

Thiazide and Thiazide-Like Diuretics: May increase adverse/toxic effects of Cardiac

Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the
hypokalemic and hypomagnesemic effect of thiazide diuretics. Risk C: Monitor

Thyroid Products: May decrease serum concentrations of Cardiac Glycosides.

Specifically, returning to a euthyroid state from a hypothyroid state may decrease
the serum concentration of cardiac glycosides. Risk C: Monitor

Ticagrelor: May increase serum concentrations of Digoxin. Risk C: Monitor

Tolvaptan: May increase serum concentrations of Digoxin. Risk C: Monitor

TraMADol: May increase serum concentrations of Digoxin. Risk C: Monitor

Trimethoprim: May increase serum concentrations of Digoxin. Risk C: Monitor

Valbenazine: May increase serum concentrations of Digoxin. Risk C: Monitor

Vandetanib: May increase serum concentrations of Digoxin. Risk C: Monitor

Vemurafenib: May increase serum concentrations 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 serum concentrations of P-glycoprotein/ABCB1
Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Management:
Avoid concomitant use of venetoclax and oral p-glycoprotein (P-gp) substrates if
possible. If combined use is unavoidable, administer the P-gp substrate at least 6
hours before venetoclax to minimize the potential for an interaction. Risk D:
Consider Therapy Modification
Vibegron: May increase serum concentrations of Digoxin. Risk C: Monitor

Vilazodone: May increase serum concentrations of Digoxin. Risk C: Monitor

Vimseltinib: May increase serum concentrations of P-glycoprotein/ABCB1

Substrates (High risk with Inhibitors). Management: Avoid concomitant use of
vimseltinib and P-gp substrates when possible. If combined, administer
vimseltinib at least 4 hours before the P-gp substrate. Risk D: Consider Therapy
Modification
Vitamin D Analogs: May increase arrhythmogenic effects of Cardiac Glycosides.
Risk C: Monitor

Xanomeline: May increase serum concentrations of P-glycoprotein/ABCB1

Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor

Zanubrutinib: May increase serum concentrations of Digoxin. Risk C: Monitor

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.

Data related to the presence of digoxin in breast milk are available from multiple
studies (Chan 1978; Finley 1979; Levy 1977; Loughnan 1978; Reinhardt 1982).

• Product labeling summarizes data from 2 studies that included 13 lactating

patients following maternal use of digoxin 0.25 mg once daily. Using breast
milk concentrations of 0.4 to 1 ng/mL, the estimated infant dose of digoxin via
breast milk is reported to be 0.03 to 0.16 mcg/kg/day, providing a relative
infant dose (RID) of 1% to 7% compared to the weight-adjusted maternal dose,
or 0.2% to 4% compared to the neonatal maintenance dose. (In general,
 breastfeeding is considered acceptable when the RID of a medication is <10%
[Anderson 2016; Ito 2000]).

• Digoxin concentrations were evaluated following maternal use of oral digoxin

0.75 mg daily throughout pregnancy and following delivery. Digoxin
concentrations 7 days postpartum were 1.9 ng/mL (breast milk), 2.1 ng/mL
(maternal serum), and 0.2 ng/mL (infant serum). Time of sampling following
the maternal dose was not stated (Finley 1979).

• Higher breast milk concentrations were obtained following an IV bolus dose

of digoxin 500 mcg to 1 lactating 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).

According to the manufacturer, 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

Find brand name(s) by country (for United States and Canada see separate Brand
Names sections)

Enter a Country or Country Code

International Brand Names by Country

For country code abbreviations ( show table)

(AE) United Arab Emirates: Lanicor | Lanoxin | Lanoxin pg | Toloxin; (AR) Argentina:
Cardiogoxin | Digoxina | Digoxina biol | Lanicor | Lanoxin (igoxina); (AT) Austria:
Lanicor; (AU) Australia: Lanoxin | Sigmaxin; (BD) Bangladesh: Agoxin | Centoxin |
Lanoxin; (BE) Belgium: Digoxine nativelle | Lanoxin | Lanoxin Digoxine; (BG) Bulgaria:
Dilacor; (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; (CR) Costa Rica: Digoxina kern pharma; (CZ) Czech
Republic: Digoxin leciva | 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 | Digoxina teofarma | 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; (GT) Guatemala: Valvulan; (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; (PA) Panama: Digoxil | Digoxina |
Digoxina kern pharma; (PE) Peru: Digoxina; (PH) Philippines: Digosaph | 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 [Link]. | 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 | Digoxin evolan | Lanoxin; (SG) Singapore:
Lanoxin | Lanoxin Pg Paediatric/Geriatric; (SI) Slovenia: Digoxina kern pharma |
Lanicor; (SK) Slovakia: Digoxin leciva; (SR) Suriname: Lanoxin; (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 | Lanoxin; (VE) Venezuela, Bolivarian Republic of: Digoxina | Lanicor; (VN) Viet
Nam: Digoxinequaly; (ZA) South Africa: Lanoxin | Purgoxin; (ZM) Zambia: Digox |
Kaydigo | Lanoxin; (ZW) Zimbabwe: Lanoxin

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