Lanoxin

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Lanoxin

Classes

Plain Cardiac Glycosides

Administration
Oral Administration

All dosage forms: May be administered without regard to meals.

Oral Solid Formulations

Tablets: May be crushed and administered with food or fluids.

Oral Liquid Formulations

Pediatric elixir: Administer using a calibrated measuring device.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Administer intramuscularly (IM) or intravenously (IV). The IV route is preferred due to more rapid therapeutic effect and less pain.
Oral therapy should replace parenteral therapy as soon as possible.

Intravenous Administration

May be given undiluted or each 1 mL may be diluted in 4 mL of sterile water for injection, 0.9% Sodium Chloride for injection, or 5% Dextrose for injection. Diluent volumes less than 4 mL will cause precipitation. Use diluted solutions immediately.
Inject over at least 5 minutes. Rapid injection may cause systemic and coronary arteriolar constriction.
If tuberculin syringes are used to measure very small doses, do not flush the syringe with the parenteral solution after its contents are expelled into an indwelling vascular catheter to avoid over administration of digoxin.

Intramuscular Administration

IM injection of digoxin causes considerable pain at the injection site and is generally not recommended unless other routes cannot be used.
In adults, do not administer more than 500 mcg at any one IM injection site. In pediatric patients, do not administer more than 200 mcg at any one injection site.
If IM administration must be used, inject deep into the muscle. Aspirate prior to injection to avoid injection into a blood vessel. Massage area after administration.

Adverse Reactions
Severe

visual impairment / Early / 3.3-3.3
cardiac arrest / Early / 0.8-0.8
bradycardia / Rapid / Incidence not known
atrial fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
atrial tachycardia / Early / Incidence not known
AV block / Early / Incidence not known
hyperkalemia / Delayed / Incidence not known
ventricular fibrillation / Early / Incidence not known
bowel necrosis / Delayed / Incidence not known
bowel ischemia / Delayed / Incidence not known

Moderate

sinus tachycardia / Rapid / 1.6-1.6
palpitations / Early / 0.8-0.8
premature ventricular contractions (PVCs) / Early / 0.8-0.8
ST-T wave changes / Rapid / Incidence not known
hypokalemia / Delayed / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
PR prolongation / Rapid / Incidence not known
confusion / Early / Incidence not known
delirium / Early / Incidence not known
hallucinations / Early / Incidence not known
depression / Delayed / Incidence not known
xanthopsia / Delayed / Incidence not known
blurred vision / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known

Mild

dizziness / Early / 4.9-4.9
nausea / Early / 3.3-3.3
diarrhea / Early / 3.3-3.3
anxiety / Delayed / 3.3-3.3
headache / Early / 3.3-3.3
vomiting / Early / 1.6-1.6
rash / Early / 1.6-1.6
anorexia / Delayed / 0.8-0.8
premature atrial contractions (PACs) / Early / Incidence not known
weakness / Early / Incidence not known
abdominal pain / Early / Incidence not known
maculopapular rash / Early / Incidence not known
gynecomastia / Delayed / Incidence not known

Common Brand Names

Digitek, Lanoxin, Lanoxin Pediatric

Dea Class

Rx

Description

Oral and parenteral cardiac glycoside
Used for CHF and treatment/prophylaxis of supraventricular tachyarrhythmias
Use in patients with WPW increases the risk of rapid ventricular response

Dosage And Indications
For the treatment of chronic atrial fibrillation to control resting ventricular rate. Intravenous or Intramuscular dosage Adults

2.4 to 3.6 mcg/kg/dose IV or IM once daily. May consider a loading dose of 4 to 6 mcg/kg/dose IV or IM as a single dose, then 2 to 3 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 8 to 12 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Older Adults

2.4 to 3.6 mcg/kg/dose IV or IM once daily. May consider a loading dose of 4 to 6 mcg/kg/dose IV or IM as a single dose, then 2 to 3 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 8 to 12 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Oral dosage (tablets) Adults

3.4 to 5.1 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet.

Older Adults

3.4 to 5.1 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Oral dosage (liquid) Adults

3 to 4.5 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Older Adults

3 to 4.5 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Oral dosage (conversion from intravenous digoxin) Adults

62.5 mcg/dose PO for 50 mcg/dose IV, 125 mcg/dose PO for 100 mcg/dose IV, 250 mcg/dose PO for 200 mcg/dose IV, and 500 mcg/dose PO for 400 mcg/dose IV.

Older Adults

62.5 mcg/dose PO for 50 mcg/dose IV, 125 mcg/dose PO for 100 mcg/dose IV, 250 mcg/dose PO for 200 mcg/dose IV, and 500 mcg/dose PO for 400 mcg/dose IV. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Children and Adolescents 11 to 17 years

62.5 mcg/dose PO for 50 mcg/dose IV, 125 mcg/dose PO for 100 mcg/dose IV, 250 mcg/dose PO for 200 mcg/dose IV, and 500 mcg/dose PO for 400 mcg/dose IV.

For the treatment of heart failure. Intravenous or Intramuscular dosage Adults

2.4 to 3.6 mcg/kg/dose IV or IM once daily. May consider a loading dose of 4 to 6 mcg/kg/dose IV or IM as a single dose, then 2 to 3 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 8 to 12 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Older Adults

2.4 to 3.6 mcg/kg/dose IV or IM once daily. May consider a loading dose of 4 to 6 mcg/kg/dose IV or IM as a single dose, then 2 to 3 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 8 to 12 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Children and Adolescents 11 to 17 years

2.4 to 3.6 mcg/kg/dose IV or IM once daily. May consider a loading dose of 4 to 6 mcg/kg/dose IV or IM as a single dose, then 2 to 3 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 8 to 12 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Children 5 to 10 years

2.3 to 4.5 mcg/kg/dose IV or IM twice daily. May consider a loading dose of 7.5 to 15 mcg/kg/dose IV or IM as a single dose, then 3.75 to 7.5 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 15 to 30 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Children 2 to 4 years

3.8 to 5.3 mcg/kg/dose IV or IM twice daily. May consider a loading dose of 12.5 to 17.5 mcg/kg/dose IV or IM as a single dose, then 6.25 to 8.75 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 25 to 35 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Infants and Children 1 year

4.5 to 7.5 mcg/kg/dose IV or IM twice daily. May consider a loading dose of 15 to 25 mcg/kg/dose IV or IM as a single dose, then 7.5 to 12.5 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 30 to 50 mcg/kg IV or IM. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Term Neonates

3 to 4.5 mcg/kg/dose IV or IM twice daily. May consider a loading dose of 10 to 15 mcg/kg/dose IV or IM as a single dose, then 5 to 7.5 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 20 to 30 mcg/kg IV or IM. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Premature Neonates

1.9 to 3.1 mcg/kg/dose IV or IM twice daily. May consider a loading dose of 7.5 to 12.5 mcg/kg/dose IV or IM as a single dose, then 3.75 to 6.25 mcg/kg/dose IV or IM every 6 to 8 hours for 2 doses for a total loading dose of 15 to 25 mcg/kg IV or IM. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. IV administration is preferred.

Oral dosage (tablets) Adults

3.4 to 5.1 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet.

Older Adults

3.4 to 5.1 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Children and Adolescents 11 to 17 years

3.4 to 5.1 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet.

Children 5 to 10 years

3.2 to 6.4 mcg/kg/dose PO twice daily. May consider a loading dose of 10 to 22.5 mcg/kg/dose PO as a single dose, then 5 to 11.25 mcg/kg/dose PO every 6 to 8 hours for 2 doses for a total loading dose of 20 to 45 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Round dose to the nearest whole/half tablet.

Oral dosage (solution) Adults

3 to 4.5 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Older Adults

3 to 4.5 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Children and Adolescents 11 to 17 years

3 to 4.5 mcg/kg/dose PO once daily. May consider a loading dose of 5 to 7.5 mcg/kg/dose PO as a single dose, then 2.5 to 3.75 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 10 to 15 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Children 5 to 10 years

2.8 to 5.6 mcg/kg/dose PO twice daily. May consider a loading dose of 10 to 17.5 mcg/kg/dose PO as a single dose, then 5 to 8.75 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 20 to 35 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Children 2 to 4 years

4.7 to 6.6 mcg/kg/dose PO twice daily. May consider a loading dose of 15 to 22.5 mcg/kg/dose PO as a single dose, then 7.5 to 11.25 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 30 to 45 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Infants and Children 1 year

5.6 to 9.4 mcg/kg/dose PO twice daily. May consider a loading dose of 17.5 to 30 mcg/kg/dose PO as a single dose, then 8.75 to 15 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 35 to 60 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Term Neonates

3.8 to 5.6 mcg/kg/dose PO twice daily. May consider a loading dose of 12.5 to 17.5 mcg/kg/dose PO as a single dose, then 6.25 to 8.75 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 25 to 35 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Premature Neonates

2.3 to 3.9 mcg/kg/dose PO twice daily. May consider a loading dose of 10 to 15 mcg/kg/dose PO as a single dose, then 5 to 7.5 mcg/kg/dose PO every 4 to 8 hours for 2 doses for a total loading dose of 20 to 30 mcg/kg PO. Base dose on lean body weight. Adjust dose based on toxicity, efficacy, and serum digoxin concentrations.

Oral dosage (conversion from intravenous digoxin) Adults

62.5 mcg/dose PO for 50 mcg/dose IV, 125 mcg/dose PO for 100 mcg/dose IV, 250 mcg/dose PO for 200 mcg/dose IV, and 500 mcg/dose PO for 400 mcg/dose IV.

Older Adults

62.5 mcg/dose PO for 50 mcg/dose IV, 125 mcg/dose PO for 100 mcg/dose IV, 250 mcg/dose PO for 200 mcg/dose IV, and 500 mcg/dose PO for 400 mcg/dose IV. Digoxin is considered a potentially inappropriate medication (PIM) in geriatric adults and should be avoided as first-line therapy. If use is necessary, limit dose to 125 mcg/day due to lack of additional benefit and increased risk of toxicity.

Children and Adolescents 11 to 17 years

62.5 mcg/dose PO for 50 mcg/dose IV, 125 mcg/dose PO for 100 mcg/dose IV, 250 mcg/dose PO for 200 mcg/dose IV, and 500 mcg/dose PO for 400 mcg/dose IV.

For the treatment of fetal supraventricular arrhythmias†, including atrial ectopic tachycardia†, atrial flutter†, multifocal atrial tachycardia†, and supraventricular tachycardia†. Intravenous dosage Adults

1,200 to 1,500 mcg IV loading dose, with the total dose divided every 8 hours, followed by oral maintenance therapy. Guidelines recommend transplacental digoxin as first or second-line therapy for atrial ectopic tachycardia, atrial flutter, multifocal atrial tachycardia, as well as supraventricular tachycardia (SVT) with hydrops or ventricular dysfunction or SVT 200 beats per minute or more without hydrops or ventricular dysfunction.

Oral dosage Adults

375 to 750 mcg/day PO divided every 8 to 12 hours, after an initial IV loading dose. Guidelines recommend transplacental digoxin as first or second-line therapy for atrial ectopic tachycardia, atrial flutter, multifocal atrial tachycardia, as well as supraventricular tachycardia (SVT) with hydrops or ventricular dysfunction or SVT 200 beats per minute or more without hydrops or ventricular dysfunction.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

No specific dosage adjustments are recommended for patients with hepatic impairment. However, patients with combined renal and hepatic impairment may have reduced digoxin clearance and potential for drug accumulation; monitor serum digoxin concentrations and therapeutic response closely in such patients.

Renal Impairment

Loading dose
Administer 50% of usual load in patients with end-stage renal disease (ESRD). Specific pediatric recommendations are not available.
 
Maintenance dose
Adult
GFR more than 50 mL/minute: No dosage adjustment necessary.
GFR 10 to 50 mL/minute: Administer 25% to 75% of usual dose every 36 hours.
GFR less than 10 mL/minute: Administer 10% to 25% of usual dose every 48 hours.
 
Pediatric
GFR more than 50 mL/minute/1.73 m2: No dosage adjustment necessary.
GFR 30 to 50 mL/minute/1.73 m2: Administer 75% of usual dose at usual intervals.
GFR 10 to 29 mL/minute/1.73 m2: Administer 50% of usual dose at usual intervals, or usual dose every 36 hours.
GFR less than 10 mL/minute/1.73 m2: Administer 25% of usual dose at usual intervals, or usual dose every 48 hours.
 
FDA-approved labeling recommends the following daily maintenance dose requirements for heart failure based on corrected CrCl (mL/minute per 70 kg or mL/minute/1.73m2) and lean body weight (LBW). Higher doses may be required for treating arrhythmias than for treating heart failure.
 
Intravenous dosage: Adults, Adolescents, and Children older than 10 years
CrCl 100 mL/minute/1.73m2 or more:
LBW 40 to 49 kg: 136 mcg IV once daily.
LBW 50 to 59 kg: 170 mcg IV once daily.
LBW 60 to 69 kg: 204 mcg IV once daily.
LBW 70 to 79 kg: 238 mcg IV once daily.
LBW 80 to 89 kg: 272 mcg IV once daily.
LBW 90 to 99 kg: 306 mcg IV once daily.
LBW 100 kg or more: 340 mcg IV once daily.
 
CrCl 90 to 99 mL/minute/1.73m2:
LBW 40 to 49 kg: 128 mcg IV once daily.
LBW 50 to 59 kg: 160 mcg IV once daily.
LBW 60 to 69 kg: 192 mcg IV once daily.
LBW 70 to 79 kg: 224 mcg IV once daily.
LBW 80 to 89 kg: 256 mcg IV once daily.
LBW 90 to 99 kg: 288 mcg IV once daily.
LBW 100 kg or more: 320 mcg IV once daily.
 
CrCl 80 to 89 mL/minute/1.73m2:
LBW 40 to 49 kg: 120 mcg IV once daily.
LBW 50 to 59 kg: 150 mcg IV once daily.
LBW 60 to 69 kg: 180 mcg IV once daily.
LBW 70 to 79 kg: 210 mcg IV once daily.
LBW 80 to 89 kg: 240 mcg IV once daily.
LBW 90 to 99 kg: 270 mcg IV once daily.
LBW 100 kg or more: 300 mcg IV once daily.
 
CrCl 70 to 79 mL/minute/1.73m2:
LBW 40 to 49 kg: 112 mcg IV once daily.
LBW 50 to 59 kg: 140 mcg IV once daily.
LBW 60 to 69 kg: 168 mcg IV once daily.
LBW 70 to 79 kg: 196 mcg IV once daily.
LBW 80 to 89 kg: 224 mcg IV once daily.
LBW 90 to 99 kg: 252 mcg IV once daily.
LBW 100 kg or more: 280 mcg IV once daily.
 
CrCl 60 to 69 mL/minute/1.73m2:
LBW 40 to 49 kg: 104 mcg IV once daily.
LBW 50 to 59 kg: 130 mcg IV once daily.
LBW 60 to 69 kg: 156 mcg IV once daily.
LBW 70 to 79 kg: 182 mcg IV once daily.
LBW 80 to 89 kg: 208 mcg IV once daily.
LBW 90 to 99 kg: 234 mcg IV once daily.
LBW 100 kg or more: 260 mcg IV once daily.
 
CrCl 50 to 59 mL/minute/1.73m2:
LBW 40 to 49 kg: 96 mcg IV once daily.
LBW 50 to 59 kg: 120 mcg IV once daily.
LBW 60 to 69 kg: 144 mcg IV once daily.
LBW 70 to 79 kg: 168 mcg IV once daily.
LBW 80 to 89 kg: 192 mcg IV once daily.
LBW 90 to 99 kg: 216 mcg IV once daily.
LBW 100 kg or more: 240 mcg IV once daily.
 
CrCl 40 to 49 mL/minute/1.73m2:
LBW 40 to 49 kg: 88 mcg IV once daily.
LBW 50 to 59 kg: 110 mcg IV once daily.
LBW 60 to 69 kg: 132 mcg IV once daily.
LBW 70 to 79 kg: 154 mcg IV once daily.
LBW 80 to 89 kg: 176 mcg IV once daily.
LBW 90 to 99 kg: 198 mcg IV once daily.
LBW 100 kg or more: 220 mcg IV once daily.
 
CrCl 30 to 39 mL/minute/1.73m2:
LBW 40 to 49 kg: 80 mcg IV once daily.
LBW 50 to 59 kg: 100 mcg IV once daily.
LBW 60 to 69 kg: 120 mcg IV once daily.
LBW 70 to 79 kg: 140 mcg IV once daily.
LBW 80 to 89 kg: 160 mcg IV once daily.
LBW 90 to 99 kg: 180 mcg IV once daily.
LBW 100 kg or more: 200 mcg IV once daily.
 
CrCl 20 to 29 mL/minute/1.73m2:
LBW 40 to 49 kg: 72 mcg IV once daily.
LBW 50 to 59 kg: 90 mcg IV once daily.
LBW 60 to 69 kg: 108 mcg IV once daily.
LBW 70 to 79 kg: 126 mcg IV once daily.
LBW 80 to 89 kg: 144 mcg IV once daily.
LBW 90 to 99 kg: 162 mcg IV once daily.
LBW 100 kg or more: 180 mcg IV once daily.
 
CrCl 10 to 19 mL/minute/1.73m2:
LBW 40 to 49 kg: 64 mcg IV once daily.
LBW 50 to 59 kg: 80 mcg IV once daily.
LBW 60 to 69 kg: 96 mcg IV once daily.
LBW 70 to 79 kg: 112 mcg IV once daily.
LBW 80 to 89 kg: 128 mcg IV once daily.
LBW 90 to 99 kg: 144 mcg IV once daily.
LBW 100 kg or more: 160 mcg IV once daily.
 
Intravenous dosage: Infants and Children 10 years and younger
CrCl 100 mL/minute/1.73m2 or more:
LBW 5 to 9 kg: 17 mcg IV twice daily.
LBW 10 to 19 kg: 34 mcg IV twice daily.
LBW 20 to 29 kg: 68 mcg IV twice daily.
LBW 30 to 39 kg: 102 mcg IV twice daily.
LBW 40 to 49 kg: 136 mcg IV twice daily.
LBW 50 to 59 kg: 170 mcg IV twice daily.
LBW 60 to 69 kg: 204 mcg IV twice daily.
 
CrCl 90 to 99 mL/minute/1.73m2:
LBW 5 to 9 kg: 16 mcg IV twice daily.
LBW 10 to 19 kg: 32 mcg IV twice daily.
LBW 20 to 29 kg: 64 mcg IV twice daily.
LBW 30 to 39 kg: 96 mcg IV twice daily.
LBW 40 to 49 kg: 128 mcg IV twice daily.
LBW 50 to 59 kg: 160 mcg IV twice daily.
LBW 60 to 69 kg: 192 mcg IV twice daily.
 
CrCl 80 to 89 mL/minute/1.73m2:
LBW 5 to 9 kg: 15 mcg IV twice daily.
LBW 10 to 19 kg: 30 mcg IV twice daily.
LBW 20 to 29 kg: 60 mcg IV twice daily.
LBW 30 to 39 kg: 90 mcg IV twice daily.
LBW 40 to 49 kg: 120 mcg IV twice daily.
LBW 50 to 59 kg: 150 mcg IV twice daily.
LBW 60 to 69 kg: 180 mcg IV twice daily.
 
CrCl 70 to 79 mL/minute/1.73m2:
LBW 5 to 9 kg: 14 mcg IV twice daily.
LBW 10 to 19 kg: 28 mcg IV twice daily.
LBW 20 to 29 kg: 56 mcg IV twice daily.
LBW 30 to 39 kg: 84 mcg IV twice daily.
LBW 40 to 49 kg: 112 mcg IV twice daily.
LBW 50 to 59 kg: 140 mcg IV twice daily.
LBW 60 to 69 kg: 168 mcg IV twice daily.
 
CrCl 60 to 69 mL/minute/1.73m2:
LBW 5 to 9 kg: 13 mcg IV twice daily.
LBW 10 to 19 kg: 26 mcg IV twice daily.
LBW 20 to 29 kg: 52 mcg IV twice daily.
LBW 30 to 39 kg: 78 mcg IV twice daily.
LBW 40 to 49 kg: 104 mcg IV twice daily.
LBW 50 to 59 kg: 130 mcg IV twice daily.
LBW 60 to 69 kg: 156 mcg IV twice daily.
 
CrCl 50 to 59 mL/minute/1.73m2:
LBW 5 to 9 kg: 12 mcg IV twice daily.
LBW 10 to 19 kg: 24 mcg IV twice daily.
LBW 20 to 29 kg: 48 mcg IV twice daily.
LBW 30 to 39 kg: 72 mcg IV twice daily.
LBW 40 to 49 kg: 96 mcg IV twice daily.
LBW 50 to 59 kg: 120 mcg IV twice daily.
LBW 60 to 69 kg: 144 mcg IV twice daily.
 
CrCl 40 to 49 mL/minute/1.73m2:
LBW 5 to 9 kg: 11 mcg IV twice daily.
LBW 10 to 19 kg: 22 mcg IV twice daily.
LBW 20 to 29 kg: 44 mcg IV twice daily.
LBW 30 to 39 kg: 66 mcg IV twice daily.
LBW 40 to 49 kg: 88 mcg IV twice daily.
LBW 50 to 59 kg: 110 mcg IV twice daily.
LBW 60 to 69 kg: 132 mcg IV twice daily.
 
CrCl 30 to 39 mL/minute/1.73m2:
LBW 5 to 9 kg: 10 mcg IV twice daily.
LBW 10 to 19 kg: 20 mcg IV twice daily.
LBW 20 to 29 kg: 40 mcg IV twice daily.
LBW 30 to 39 kg: 60 mcg IV twice daily.
LBW 40 to 49 kg: 80 mcg IV twice daily.
LBW 50 to 59 kg: 100 mcg IV twice daily.
LBW 60 to 69 kg: 120 mcg IV twice daily.
 
CrCl 20 to 29 mL/minute/1.73m2:
LBW 5 to 9 kg: 9 mcg IV twice daily.
LBW 10 to 19 kg: 18 mcg IV twice daily.
LBW 20 to 29 kg: 36 mcg IV twice daily.
LBW 30 to 39 kg: 54 mcg IV twice daily.
LBW 40 to 49 kg: 72 mcg IV twice daily.
LBW 50 to 59 kg: 90 mcg IV twice daily.
LBW 60 to 69 kg: 108 mcg IV twice daily.
 
CrCl 10 to 19 mL/minute/1.73m2:
LBW 5 to 9 kg: 8 mcg IV twice daily.
LBW 10 to 19 kg: 16 mcg IV twice daily.
LBW 20 to 29 kg: 32 mcg IV twice daily.
LBW 30 to 39 kg: 48 mcg IV twice daily.
LBW 40 to 49 kg: 64 mcg IV twice daily.
LBW 50 to 59 kg: 80 mcg IV twice daily.
LBW 60 to 69 kg: 96 mcg IV twice daily.
 
Oral dosage (tablets): Adults, Adolescents, and Children older than 10 years
CrCl 100 mL/minute/1.73m2 or more:
LBW 40 to 49 kg: 187.5 mcg PO once daily.
LBW 50 to 59 kg: 250 mcg PO once daily.
LBW 60 to 79 kg: 312.5 mcg PO once daily.
LBW 80 to 89 kg: 375 mcg PO once daily.
LBW 90 to 99 kg: 437.5 mcg PO once daily.
LBW 100 kg or more: 500 mcg PO once daily.
 
CrCl 90 to 99 mL/minute/1.73m2:
LBW 40 to 49 kg: 187.5 mcg PO once daily.
LBW 50 to 69 kg: 250 mcg PO once daily.
LBW 70 to 79 kg: 312.5 mcg PO once daily.
LBW 80 to 89 kg: 375 mcg PO once daily.
LBW 90 kg or more: 437.5 mcg PO once daily.
 
CrCl 80 to 89 mL/minute/1.73m2:
LBW 40 to 59 kg: 187.5 mcg PO once daily.
LBW 60 to 69 kg: 250 mcg PO once daily.
LBW 70 to 89 kg: 312.5 mcg PO once daily.
LBW 90 to 99 kg: 375 mcg PO once daily.
LBW 100 kg or more: 437.5 mcg PO once daily.
 
CrCl 70 to 79 mL/minute/1.73m2:
LBW 40 to 59 kg: 187.5 mcg PO once daily.
LBW 60 to 79 kg: 250 mcg PO once daily.
LBW 80 to 89 kg: 312.5 mcg PO once daily.
LBW 90 kg or more: 375 mcg PO once daily.
 
CrCl 60 to 69 mL/minute/1.73m2:
LBW 40 to 49 kg: 125 mcg PO once daily.
LBW 50 to 59 kg: 187.5 mcg PO once daily.
LBW 60 to 79 kg: 250 mcg PO once daily.
LBW 80 to 99 kg: 312.5 mcg PO once daily.
LBW 100 kg or more: 375 mcg PO once daily.
 
CrCl 40 to 59 mL/minute/1.73m2:
LBW 40 to 49 kg: 125 mcg PO once daily.
LBW 50 to 69 kg: 187.5 mcg PO once daily.
LBW 70 to 89 kg: 250 mcg PO once daily.
LBW 90 kg or more: 312.5 mcg PO once daily.
 
CrCl 30 to 39 mL/minute/1.73m2:
LBW 40 to 59 kg: 125 mcg PO once daily.
LBW 60 to 79 kg: 187.5 mcg PO once daily.
LBW 80 to 99 kg: 250 mcg PO once daily.
LBW 100 kg or more: 312.5 mcg PO once daily.
 
CrCl 20 to 29 mL/minute/1.73m2:
LBW 40 to 69 kg: 125 mcg PO once daily.
LBW 70 to 89 kg: 187.5 mcg PO once daily.
LBW 90 kg or more: 250 mcg PO once daily.
 
CrCl less than 20 mL/minute/1.73m2:
LBW 40 to 49 kg: 62.5 mcg PO once daily.
LBW 50 to 69 kg: 125 mcg PO once daily.
LBW 70 to 99 kg: 187.5 mcg PO once daily.
LBW 100 kg or more: 250 mcg PO once daily.
 
Oral dosage (tablets): Children 10 years and younger
NOTE: Doses are rounded to the nearest whole/half tablet
CrCl 100 mL/minute/1.73m2 or more:
LBW 20 to 29 kg: 62.5 mcg PO twice daily.
LBW 30 to 39 kg: 125 mcg PO twice daily.
LBW 40 to 49 kg: 187.5 mcg PO twice daily.
LBW 50 to 59 kg: 250 mcg PO twice daily.
LBW 60 to 69 kg: 312.5 mcg PO twice daily.
 
CrCl 90 to 99 mL/minute/1.73m2:
LBW 20 to 29 kg: 62.5 mcg PO twice daily.
LBW 30 to 39 kg: 125 mcg PO twice daily.
LBW 40 to 49 kg: 187.5 mcg PO twice daily.
LBW 50 to 69 kg: 250 mcg PO twice daily.
 
CrCl 80 to 89 mL/minute/1.73m2:
LBW 20 to 29 kg: 62.5 mcg PO twice daily.
LBW 30 to 39 kg: 125 mcg PO twice daily.
LBW 40 to 59 kg: 187.5 mcg PO twice daily.
LBW 60 to 69 kg: 250 mcg PO twice daily.
 
CrCl 70 to 79 mL/minute/1.73m2:
LBW 20 to 29 kg: 62.5 mcg PO twice daily.
LBW 30 to 39 kg: 125 mcg PO twice daily.
LBW 40 to 59 kg: 187.5 mcg PO twice daily.
LBW 60 to 69 kg: 250 mcg PO twice daily.
 
CrCl 60 to 69 mL/minute/1.73m2:
LBW 20 to 29 kg: 62.5 mcg PO twice daily.
LBW 30 to 49 kg: 125 mcg PO twice daily.
LBW 50 to 59 kg: 187.5 mcg PO twice daily.
LBW 60 to 69 kg: 250 mcg PO twice daily.
 
CrCl 50 to 59 mL/minute/1.73m2:
LBW 20 to 29 kg: 62.5 mcg PO twice daily.
LBW 30 to 49 kg: 125 mcg PO twice daily.
LBW 50 to 69 kg: 187.5 mcg PO twice daily.
 
CrCl 40 to 49 mL/minute/1.73m2:
LBW 20 to 39 kg: 62.5 mcg PO twice daily.
LBW 40 to 49 kg: 125 mcg PO twice daily.
LBW 50 to 69 kg: 187.5 mcg PO twice daily.
 
CrCl 30 to 39 mL/minute/1.73m2:
LBW 20 to 39 kg: 62.5 mcg PO twice daily.
LBW 40 to 59 kg: 125 mcg PO twice daily.
LBW 60 to 69 kg: 187.5 mcg PO twice daily.
 
CrCl 20 to 29 mL/minute/1.73m2:
LBW 20 to 39 kg: 62.5 mcg PO twice daily.
LBW 40 to 69 kg: 125 mcg PO twice daily.
 
CrCl less than 20 mL/minute/1.73m2:
LBW 30 to 49 kg: 62.5 mcg PO twice daily.
LBW 50 to 69 kg: 125 mcg PO twice daily.
 
Oral dosage (liquid): Adults, Adolescents, and Children older than 10 years
CrCl 100 mL/minute/1.73m2 or more:
LBW 40 to 49 kg: 170 mcg PO once daily.
LBW 50 to 59 kg: 213 mcg PO once daily.
LBW 60 to 69 kg: 255 mcg PO once daily.
LBW 70 to 79 kg: 298 mcg PO once daily.
LBW 80 to 89 kg: 340 mcg PO once daily.
LBW 90 to 99 kg: 383 mcg PO once daily.
LBW 100 kg or more: 425 mcg PO once daily.
 
CrCl 90 to 99 mL/minute/1.73m2:
LBW 40 to 49 kg: 160 mcg PO once daily.
LBW 50 to 59 kg: 200 mcg PO once daily.
LBW 60 to 69 kg: 240 mcg PO once daily.
LBW 70 to 79 kg: 280 mcg PO once daily.
LBW 80 to 89 kg: 320 mcg PO once daily.
LBW 90 to 99 kg: 360 mcg PO once daily.
LBW 100 kg or more: 400 mcg PO once daily.
 
CrCl 80 to 89 mL/minute/1.73m2:
LBW 40 to 49 kg: 150 mcg PO once daily.
LBW 50 to 59 kg: 188 mcg PO once daily.
LBW 60 to 69 kg: 225 mcg PO once daily.
LBW 70 to 79 kg: 263 mcg PO once daily.
LBW 80 to 89 kg: 300 mcg PO once daily.
LBW 90 to 99 kg: 338 mcg PO once daily.
LBW 100 kg or more: 375 mcg PO once daily.
 
CrCl 70 to 79 mL/minute/1.73m2:
LBW 40 to 49 kg: 140 mcg PO once daily.
LBW 50 to 59 kg: 175 mcg PO once daily.
LBW 60 to 69 kg: 210 mcg PO once daily.
LBW 70 to 79 kg: 245 mcg PO once daily.
LBW 80 to 89 kg: 280 mcg PO once daily.
LBW 90 to 99 kg: 315 mcg PO once daily.
LBW 100 kg or more: 350 mcg PO once daily.
 
CrCl 60 to 69 mL/minute/1.73m2:
LBW 40 to 49 kg: 130 mcg PO once daily.
LBW 50 to 59 kg: 163 mcg PO once daily.
LBW 60 to 69 kg: 195 mcg PO once daily.
LBW 70 to 79 kg: 228 mcg PO once daily.
LBW 80 to 89 kg: 260 mcg PO once daily.
LBW 90 to 99 kg: 293 mcg PO once daily.
LBW 100 kg or more: 325 mcg PO once daily.
 
CrCl 50 to 59 mL/minute/1.73m2:
LBW 40 to 49 kg: 120 mcg PO once daily.
LBW 50 to 59 kg: 150 mcg PO once daily.
LBW 60 to 69 kg: 180 mcg PO once daily.
LBW 70 to 79 kg: 210 mcg PO once daily.
LBW 80 to 89 kg: 240 mcg PO once daily.
LBW 90 to 99 kg: 270 mcg PO once daily.
LBW 100 kg or more: 300 mcg PO once daily.
 
CrCl 40 to 49 mL/minute/1.73m2:
LBW 40 to 49 kg: 110 mcg PO once daily
LBW 50 to 59 kg: 138 mcg PO once daily.
LBW 60 to 69 kg: 165 mcg PO once daily.
LBW 70 to 79 kg: 193 mcg PO once daily.
LBW 80 to 89 kg: 220 mcg PO once daily.
LBW 90 to 99 kg: 248 mcg PO once daily.
LBW 100 kg or more: 275 mcg PO once daily.
 
CrCl 30 to 39 mL/minute/1.73m2:
LBW 40 to 49 kg: 100 mcg PO once daily.
LBW 50 to 59 kg: 125 mcg PO once daily.
LBW 60 to 69 kg: 150 mcg PO once daily.
LBW 70 to 79 kg: 175 mcg PO once daily.
LBW 80 to 89 kg: 200 mcg PO once daily.
LBW 90 to 99 kg: 225 mcg PO once daily.
LBW 100 kg or more: 250 mcg PO once daily.
 
CrCl 20 to 29 mL/minute/1.73m2:
LBW 40 to 49 kg: 90 mcg PO once daily.
LBW 50 to 59 kg: 113 mcg PO once daily.
LBW 60 to 69 kg: 135 mcg PO once daily.
LBW 70 to 79 kg: 158 mcg PO once daily.
LBW 80 to 89 kg: 180 mcg PO once daily.
LBW 90 to 99 kg: 203 mcg PO once daily.
LBW 100 kg or more: 225 mcg PO once daily.
 
CrCl less than 20 mL/minute/1.73m2:
LBW 40 to 49 kg: 80 mcg PO once daily.
LBW 50 to 59 kg: 100 mcg PO once daily.
LBW 60 to 69 kg: 120 mcg PO once daily.
LBW 70 to 79 kg: 140 mcg PO once daily.
LBW 80 to 89 kg: 160 mcg PO once daily.
LBW 90 to 99 kg: 180 mcg PO once daily.
LBW 100 kg or more: 200 mcg PO once daily.
 
Oral dosage (liquid): Infants and Children 10 years and younger
CrCl 100 mL/minute/1.73m2 or more:
LBW 5 to 9 kg: 21 mcg PO twice daily.
LBW 10 to 19 kg: 43 mcg PO twice daily.
LBW 20 to 29 kg: 85 mcg PO twice daily.
LBW 30 to 39 kg: 128 mcg PO twice daily.
LBW 40 to 49 kg: 170 mcg PO twice daily.
LBW 50 to 59 kg: 213 mcg PO twice daily.
LBW 60 to 69 kg: 255 mcg PO twice daily.
 
CrCl 90 to 99 mL/minute/1.73m2:
LBW 5 to 9 kg: 20 mcg PO twice daily.
LBW 10 to 19 kg: 40 mcg PO twice daily.
LBW 20 to 29 kg: 80 mcg PO twice daily.
LBW 30 to 39 kg: 120 mcg PO twice daily.
LBW 40 to 49 kg: 160 mcg PO twice daily.
LBW 50 to 59 kg: 200 mcg PO twice daily.
LBW 60 to 69 kg: 240 mcg PO twice daily.
 
CrCl 80 to 89 mL/minute/1.73m2:
LBW 5 to 9 kg: 19 mcg PO twice daily.
LBW 10 to 19 kg: 38 mcg PO twice daily.
LBW 20 to 29 kg: 75 mcg PO twice daily.
LBW 30 to 39 kg: 113 mcg PO twice daily.
LBW 40 to 49 kg: 150 mcg PO twice daily.
LBW 50 to 59 kg: 188 mcg PO twice daily.
LBW 60 to 69 kg: 225 mcg PO twice daily.
 
CrCl 70 to 79 mL/minute/1.73m2:
LBW 5 to 9 kg: 18 mcg PO twice daily.
LBW 10 to 19 kg: 35 mcg PO twice daily.
LBW 20 to 29 kg: 70 mcg PO twice daily.
LBW 30 to 39 kg: 105 mcg PO twice daily.
LBW 40 to 49 kg: 140 mcg PO twice daily.
LBW 50 to 59 kg: 175 mcg PO twice daily.
LBW 60 to 69 kg: 210 mcg PO twice daily.
 
CrCl 60 to 69 mL/minute/1.73m2:
LBW 5 to 9 kg: 16 mcg PO twice daily.
LBW 10 to 19 kg: 33 mcg PO twice daily.
LBW 20 to 29 kg: 65 mcg PO twice daily.
LBW 30 to 39 kg: 98 mcg PO twice daily.
LBW 40 to 49 kg: 130 mcg PO twice daily.
LBW 50 to 59 kg: 163 mcg PO twice daily.
LBW 60 to 69 kg: 195 mcg PO twice daily.
 
CrCl 50 to 59 mL/minute/1.73m2:
LBW 5 to 9 kg: 15 mcg PO twice daily.
LBW 10 to 19 kg: 30 mcg PO twice daily.
LBW 20 to 29 kg: 60 mcg PO twice daily.
LBW 30 to 39 kg: 90 mcg PO twice daily.
LBW 40 to 49 kg: 120 mcg PO twice daily.
LBW 50 to 59 kg: 150 mcg PO twice daily.
LBW 60 to 69 kg: 180 mcg PO twice daily.
 
CrCl 40 to 49 mL/minute/1.73m2:
LBW 5 to 9 kg: 14 mcg PO twice daily.
LBW 10 to 19 kg: 28 mcg PO twice daily.
LBW 20 to 29 kg: 55 mcg PO twice daily.
LBW 30 to 39 kg: 83 mcg PO twice daily.
LBW 40 to 49 kg: 110 mcg PO twice daily.
LBW 50 to 59 kg: 138 mcg PO twice daily.
LBW 60 to 69 kg: 165 mcg PO twice daily.
 
CrCl 30 to 39 mL/minute/1.73m2:
LBW 5 to 9 kg: 13 mcg PO twice daily.
LBW 10 to 19 kg: 25 mcg PO twice daily.
LBW 20 to 29 kg: 50 mcg PO twice daily.
LBW 30 to 39 kg: 75 mcg PO twice daily.
LBW 40 to 49 kg: 100 mcg PO twice daily.
LBW 50 to 59 kg: 125 mcg PO twice daily.
LBW 60 to 69 kg: 150 mcg PO twice daily.
 
CrCl 20 to 29 mL/minute/1.73m2:
LBW 5 to 9 kg: 11 mcg PO twice daily.
LBW 10 to 19 kg: 23 mcg PO twice daily.
LBW 20 to 29 kg: 45 mcg PO twice daily.
LBW 30 to 39 kg: 68 mcg PO twice daily.
LBW 40 to 49 kg: 90 mcg PO twice daily.
LBW 50 to 59 kg: 113 mcg PO twice daily.
LBW 60 to 69 kg: 135 mcg PO twice daily.
 
CrCl less than 20 mL/minute/1.73m2:
LBW 5 to 9 kg: 10 mcg PO twice daily.
LBW 10 to 19 kg: 20 mcg PO twice daily.
LBW 20 to 29 kg: 40 mcg PO twice daily.
LBW 30 to 39 kg: 60 mcg PO twice daily.
LBW 40 to 49 kg: 80 mcg PO twice daily.
LBW 50 to 59 kg: 100 mcg PO twice daily.
LBW 60 to 69 kg: 120 mcg PO twice daily.
 
Intermittent hemodialysis
Adult
Supplemental dose not required.
Pediatric
Administer 25% of usual dose at usual intervals, or usual dose every 48 hours. Digoxin is not effectively removed by dialysis because of its large extravascular volume of distribution.
 
Peritoneal dialysis
Adult
Supplemental dose not required.
Pediatric
Administer 25% of usual dose at usual intervals, or usual dose every 48 hours.
 
Continuous renal replacement therapy
Adult
Administer 25% to 75% of usual dose every 36 hours; monitor serum concentrations.
Pediatric
Administer 75% of usual dose at usual intervals; monitor serum concentrations and titrate to effect.

Drug Interactions

Abrocitinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing abrocitinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and abrocitinib is a P-gp inhibitor.
Acarbose: (Moderate) Acarbose, an alpha-glucosidase inhibitor, has been found to decrease the mean bioavailability (AUC) of digoxin by 16% (90% confidence interval: range 8-23%), decrease the mean Cmax of digoxin by 26% (90% confidence interval: range 16-34%), and decrease the mean trough concentration of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). Miglitol, also an alpha-glucosidase inhibitor, may impair the oral absorption of digoxin and lead to subtherapeutic serum digoxin concentrations in some patients. In healthy volunteers, coadministration of miglitol 50 mg or 100 mg with digoxin reduced the average plasma concentrations of digoxin by 19% and 28%, respectively. However, in diabetic patients under treatment with digoxin, plasma digoxin concentrations were not altered when coadministered with miglitol. The mechanism of the interaction is not well understood. The manufacturer of digoxin recommends measuring digoxin concentrations prior to initiating acarbose or miglitol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20-40% as necessary. Some experts have recommended that these agents be administered 6 hours after an oral digoxin dose to ensure time for adequate digoxin absorption.
Acebutolol: (Moderate) Because the pharmacologic effects of acebutolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Acetaminophen; Ibuprofen: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Adagrasib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing adagrasib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and adagrasib is a P-gp inhibitor. Concomitant use of adagrasib 600 mg twice daily is predicted to increase digoxin overall exposure by 1.5-fold.
Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as digoxin, may decrease adefovir elimination by competing for common renal tubular transport systems; therefore increasing serum concentrations of either adefovir and/or digoxin may occur. Coadministration of these drugs has not been studied, but caution is warranted.
Adenosine: (Moderate) Use adenosine with caution in the presence of digoxin due to the potential for additive or synergistic depressant effects on the sinoatrial and atrioventricular nodes. Concomitant use has rarely been associated with ventricular fibrillation.
Albuterol: (Moderate) Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol or levalbuterol and digoxin on a chronic basis is unclear. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of albuterol or levalbuterol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Albuterol; Budesonide: (Moderate) Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol or levalbuterol and digoxin on a chronic basis is unclear. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of albuterol or levalbuterol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Aldesleukin, IL-2: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients.
Alemtuzumab: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Alkylating agents: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Alogliptin; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Alogliptin; Pioglitazone: (Moderate) Concentrations of digoxin may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of digoxin was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with digoxin 0.2 mg twice daily (loading dose) then 0.25 mg daily (maintenance dose, 7 days) resulted in a 15% and 17% increase in digoxin AUC and Cmax, respectively. Carefully monitor serum digoxin concentrations; observe patients carefully for signs of digoxin toxicity.
Alpha-glucosidase Inhibitors: (Moderate) Acarbose, an alpha-glucosidase inhibitor, has been found to decrease the mean bioavailability (AUC) of digoxin by 16% (90% confidence interval: range 8-23%), decrease the mean Cmax of digoxin by 26% (90% confidence interval: range 16-34%), and decrease the mean trough concentration of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). Miglitol, also an alpha-glucosidase inhibitor, may impair the oral absorption of digoxin and lead to subtherapeutic serum digoxin concentrations in some patients. In healthy volunteers, coadministration of miglitol 50 mg or 100 mg with digoxin reduced the average plasma concentrations of digoxin by 19% and 28%, respectively. However, in diabetic patients under treatment with digoxin, plasma digoxin concentrations were not altered when coadministered with miglitol. The mechanism of the interaction is not well understood. The manufacturer of digoxin recommends measuring digoxin concentrations prior to initiating acarbose or miglitol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20-40% as necessary. Some experts have recommended that these agents be administered 6 hours after an oral digoxin dose to ensure time for adequate digoxin absorption.
Alprazolam: (Moderate) Monitor serum digoxin concentrations during concomitant alprazolam use. Alprazolam may increase digoxin concentrations by increasing digoxin plasma protein binding and/or affecting the renal tubules resulting in decreased digoxin clearance.
Altretamine: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Aluminum Hydroxide: (Moderate) Monitor digoxin concentrations as appropriate and watch for decreased digoxin efficacy if coadministration with antacids is necessary. The dose of digoxin may need to be adjusted. Antacids may decrease the absorption of digoxin.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Monitor digoxin concentrations as appropriate and watch for decreased digoxin efficacy if coadministration with antacids is necessary. The dose of digoxin may need to be adjusted. Antacids may decrease the absorption of digoxin.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Monitor digoxin concentrations as appropriate and watch for decreased digoxin efficacy if coadministration with antacids is necessary. The dose of digoxin may need to be adjusted. Antacids may decrease the absorption of digoxin.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Monitor digoxin concentrations as appropriate and watch for decreased digoxin efficacy if coadministration with antacids is necessary. The dose of digoxin may need to be adjusted. Antacids may decrease the absorption of digoxin.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Monitor digoxin concentrations as appropriate and watch for decreased digoxin efficacy if coadministration with antacids is necessary. The dose of digoxin may need to be adjusted. Antacids may decrease the absorption of digoxin.
Amiloride: (Moderate) Amiloride can alter the response to digoxin therapy if administered concomitantly. Typically, digoxin concentrations are slightly elevated by amiloride, and a reduced responsiveness to the positive inotropic effects of digoxin therapy has been noted in patients receiving both agents simultaneously. Patients receiving these two drugs concurrently should be monitored for altered responses to digoxin therapy.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Amiloride can alter the response to digoxin therapy if administered concomitantly. Typically, digoxin concentrations are slightly elevated by amiloride, and a reduced responsiveness to the positive inotropic effects of digoxin therapy has been noted in patients receiving both agents simultaneously. Patients receiving these two drugs concurrently should be monitored for altered responses to digoxin therapy.
Amiodarone: (Major) Amiodarone increases orally administered digoxin serum concentration by 70% when given concomitantly. When amiodarone is coadministered with intravenous (IV) digoxin, the serum concentration of digoxin is increased by 17%. Measure serum digoxin concentrations before initiating amiodarone. According to the manufacturer of amiodarone, the digoxin dose should be reduced by 50% upon initiation of amiodarone. The manufacturer of digoxin recommends measuring the serum digoxin concentration before initiating amiodarone and reducing the serum digoxin concentration by reducing the oral dose by approximately 30 to 50%, decreasing the IV digoxin dose by 15 to 30%, or modifying the dosing frequency and continue monitoring. The mechanism of the increase in digoxin serum concentration is thought to result from inhibition of gastrointestinal P-glycoprotein (increased oral bioavailability) and/or a decrease in digoxin renal or nonrenal clearance. Because of the depressant effects of digoxin on the sinus and AV node, concurrent use can potentiate amiodarone's electrophysiologic and hemodynamic effects resulting in bradycardia, sinus arrest, and AV block. Furthermore, amiodarone may induce changes in thyroid function and alter sensitivity to cardiac glycosides, and thyroid function should be monitored closely in patients receiving both drugs simultaneously. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Close monitoring of serum digoxin concentrations and heart rate is essential to avoid enhanced toxicity.
Amlodipine; Atorvastatin: (Major) Measure serum digoxin concentrations before initiating atorvastatin. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Coadministration of digoxin and atorvastatin increases the serum concentration and AUC of digoxin by 22% and 15%, respectively. Digoxin and atorvastatin are both substrates for P-glycoprotein (P-gp).
Amlodipine; Benazepril: (Moderate) Coadministration of digoxin and captopril increases the serum concentration and AUC of digoxin by 58% and 39%, respectively. However, captopril and digoxin are administered together in patients with congestive heart failure. Measure serum digoxin concentrations before initiating captopril. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Amlodipine; Celecoxib: (Moderate) Monitor digoxin concentrations before and during concomitant use of celecoxib and reduce the digoxin dose if necessary. Elevated digoxin concentrations and prolonged digoxin half-life have been observed when celecoxib has been coadministered with digoxin.
Amlodipine; Olmesartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Amlodipine; Valsartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Amobarbital: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Amoxicillin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin has been reported to increase the digoxin AUC by 70% when digoxin is administered orally. No significant changes in digoxin exposure were reported when digoxin was administered intravenously (IV). Originally, this interaction was thought to be due to inhibition of intestinal flora, which leads to decreased intestinal metabolism of digoxin to inactive digoxin reduction products (DRPs). While this may occur, only 5% of a digoxin dose is subject to metabolism by gut flora and this mechanism does not account for the large increases in digoxin levels that occur with the coadministration of clarithromycin. A more important factor is clarithromycin inhibition of P-glycoprotein (P-gp), an energy-dependent drug efflux pump. Digoxin is a P-gp substrate. Inhibition of this protein in the intestinal cell wall leads to increased oral absorption and decreased renal and non-renal clearance of digoxin. Measure serum digoxin concentrations before initiating clarithromycin. Reduce digoxin concentrations by decreasing the oral digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring. No dosage adjustment is required when digoxin is administered IV. (Moderate) Omeprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Omeprazole increases the AUC of digoxin by about 10%. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Amoxicillin; Clavulanic Acid: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Amphotericin B lipid complex (ABLC): (Moderate) Amphotericin B-induced hypokalemia can potentiate the cardiac toxicity of cardiac glycosides (e.g., digoxin). If used concomitantly, closely monitor serum electrolytes and cardiac function.
Amphotericin B liposomal (LAmB): (Moderate) Amphotericin B-induced hypokalemia can potentiate the cardiac toxicity of cardiac glycosides (e.g., digoxin). If used concomitantly, closely monitor serum electrolytes and cardiac function.
Amphotericin B: (Moderate) Amphotericin B-induced hypokalemia can potentiate the cardiac toxicity of cardiac glycosides (e.g., digoxin). If used concomitantly, closely monitor serum electrolytes and cardiac function.
Ampicillin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Ampicillin; Sulbactam: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Antacids: (Moderate) Monitor digoxin concentrations as appropriate and watch for decreased digoxin efficacy if coadministration with antacids is necessary. The dose of digoxin may need to be adjusted. Antacids may decrease the absorption of digoxin.
Antimetabolites: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Antithyroid agents: (Minor) Serum concentrations of digoxin can increase as hyperthyroidism is corrected. In patients receiving antithyroid therapy, the dosage of digoxin may need to be reduced as the patient becomes euthyroid.
Apalutamide: (Moderate) Increase monitoring of serum digoxin concentrations when starting, adjusting, or discontinuing apalutamide. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and apalutamide is a weak P-gp inducer. Drugs that induce P-gp have the potential to alter digoxin pharmacokinetics.
Apraclonidine: (Minor) No specific drug interactions were identified with systemic agents and apraclonidine during clinical trials. It is theoretically possible that additive blood pressure reductions could occur when apraclonidine is combined with cardiac glycosides.
Arsenic Trioxide: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Aspirin, ASA; Omeprazole: (Moderate) Omeprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Omeprazole increases the AUC of digoxin by about 10%. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Atazanavir: (Moderate) Atazanavir can prolong the PR interval and pharmacodynamic interactions between atazanavir and drugs that also prolong the PR interval, such as digoxin, cannot be ruled out; caution is advised when these drugs are used together; monitor the patient for appropriate clinical responses.
Atazanavir; Cobicistat: (Moderate) Atazanavir can prolong the PR interval and pharmacodynamic interactions between atazanavir and drugs that also prolong the PR interval, such as digoxin, cannot be ruled out; caution is advised when these drugs are used together; monitor the patient for appropriate clinical responses. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of digoxin with cobicistat. Digoxin is a substrate for P-gp; cobicistat is an inhibitor of this drug transporter. Concurrent use may result in elevated digoxin plasma concentration.
Atenolol: (Moderate) Because the pharmacologic effects of atenolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Atenolol; Chlorthalidone: (Moderate) Because the pharmacologic effects of atenolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Atorvastatin: (Major) Measure serum digoxin concentrations before initiating atorvastatin. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Coadministration of digoxin and atorvastatin increases the serum concentration and AUC of digoxin by 22% and 15%, respectively. Digoxin and atorvastatin are both substrates for P-glycoprotein (P-gp).
Atorvastatin; Ezetimibe: (Major) Measure serum digoxin concentrations before initiating atorvastatin. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Coadministration of digoxin and atorvastatin increases the serum concentration and AUC of digoxin by 22% and 15%, respectively. Digoxin and atorvastatin are both substrates for P-glycoprotein (P-gp).
Atropine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Atropine; Difenoxin: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Azilsartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Azilsartan; Chlorthalidone: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Azithromycin: (Moderate) Monitor digoxin concentrations before and during concomitant use of azithromycin and reduce the digoxin dose if necessary. Elevated digoxin concentrations have been observed when azithromycin has been coadministered with digoxin.
Bacillus Calmette-Guerin Vaccine, BCG: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Barbiturates: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Benazepril: (Moderate) Coadministration of digoxin and captopril increases the serum concentration and AUC of digoxin by 58% and 39%, respectively. However, captopril and digoxin are administered together in patients with congestive heart failure. Measure serum digoxin concentrations before initiating captopril. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of digoxin and captopril increases the serum concentration and AUC of digoxin by 58% and 39%, respectively. However, captopril and digoxin are administered together in patients with congestive heart failure. Measure serum digoxin concentrations before initiating captopril. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Benztropine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Berotralstat: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing berotralstat. Concurrent use may increase digoxin exposure. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and berotralstat is a P-gp inhibitor.
Betaxolol: (Moderate) Because the pharmacologic effects of betaxolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Bexarotene: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
Bisoprolol: (Moderate) Concomitant use of digoxin and beta-blockers can increase the risk of bradycardia. Both digoxin and beta-blockers slow AV node conduction and additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant use of digoxin and beta-blockers can increase the risk of bradycardia. Both digoxin and beta-blockers slow AV node conduction and additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Bleomycin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Blinatumomab: (Moderate) No drug interaction studies have been performed with blinatumomab. The drug may cause a transient release of cytokines leading to an inhibition of CYP450 enzymes. The interaction risk with CYP450 substrates is likely the highest during the first 9 days of the first cycle and the first 2 days of the second cycle. Monitor patients receiving concurrent CYP450 substrates that have a narrow therapeutic index (NTI) such as digoxin. In addition, Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients.
Bortezomib: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Bretylium: (Major) Avoid simultaneous initiation of bretylium and digoxin. Bretylium is contraindicated in digitalis-induced arrhythmias. In a digitalized patient, use bretylium only if the arrhythmia does not appear to be digitalis-induced and other antiarrhythmic agents are not effective. The initial release of norepinephrine cause by bretylium may aggravate digitalis toxicity.
Brigatinib: (Moderate) Monitor digoxin levels and watch for an increase in digoxin-related adverse reactions if coadministration with brigatinib is necessary. Digoxin is a substrate of P-glycoprotein (P-gp). Brigatinib inhibits P-gp in vitro and may have the potential to increase concentrations of P-gp substrates.
Brimonidine: (Minor) Alpha-agonists as a class, may reduce heart rate and blood pressure. Although ophthalmic brimonidine administration generally does not have clinically significant effects on pulse and blood pressure, it should be used with caution with cardiac glycosides.
Brimonidine; Brinzolamide: (Minor) Alpha-agonists as a class, may reduce heart rate and blood pressure. Although ophthalmic brimonidine administration generally does not have clinically significant effects on pulse and blood pressure, it should be used with caution with cardiac glycosides.
Brimonidine; Timolol: (Moderate) Monitor heart rate during concomitant digoxin and timolol use due to increased risk for bradycardia. Both digoxin and timolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block. (Minor) Alpha-agonists as a class, may reduce heart rate and blood pressure. Although ophthalmic brimonidine administration generally does not have clinically significant effects on pulse and blood pressure, it should be used with caution with cardiac glycosides.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Bupropion: (Moderate) Monitor plasma digoxin concentrations during concomitant bupropion use. Concomitant use may decrease plasma digoxin concentrations. Digoxin exposure was decreased when a single oral dose of digoxin 0.5 mg was administered 24 hours after a single oral dose of extended-release bupropion 150 mg in healthy volunteers.
Bupropion; Naltrexone: (Moderate) Monitor plasma digoxin concentrations during concomitant bupropion use. Concomitant use may decrease plasma digoxin concentrations. Digoxin exposure was decreased when a single oral dose of digoxin 0.5 mg was administered 24 hours after a single oral dose of extended-release bupropion 150 mg in healthy volunteers.
Buspirone: (Minor) Buspirone can displace digoxin from plasma proteins, but the clinical significance of this effect has yet to be determined.
Butabarbital: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Butalbital; Acetaminophen: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Cabozantinib: (Minor) Monitor for an increase in digoxin-related adverse reactions if coadministration with cabozantinib is necessary; monitor digoxin levels as clinically appropriate. Digoxin is a P-glycoprotein (P-gp) substrate. Cabozantinib is a P-gp inhibitor and has the potential to increase plasma concentrations of P-gp substrates; however, the clinical relevance of this finding is unknown.
Calcifediol: (Moderate) Monitor serum calcium and patients for signs of digitalis toxicity in patients receiving calcifediol and digoxin concurrently. Monitor more frequently when initiating or adjusting the dose of calcifediol. Hypercalemia of any cause, including calcifediol therapy, increases the risk of digitalis toxicity.
Calcitriol: (Moderate) Monitor serum calcium concentration and for digoxin toxicity during concomitant calcitriol and digoxin use. Calcitriol may cause hypercalcemia, which may precipitate digoxin toxicity and cardiac arrhythmias.
Calcium Acetate: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium Carbonate: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium Carbonate; Simethicone: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium Chloride: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium Gluconate: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Calcium; Vitamin D: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Canagliflozin: (Moderate) When digoxin was coadministered with canagliflozin 300 mg, there was an increase in the AUC and Cmax of digoxin (20% and 36%, respectively). Patients taking canagliflozin concomitantly with digoxin should have their digoxin levels monitored periodically as clinically indicated. Monitor the patient's clinical response to therapy and for signs or symptoms of digoxin toxicity.
Canagliflozin; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary. (Moderate) When digoxin was coadministered with canagliflozin 300 mg, there was an increase in the AUC and Cmax of digoxin (20% and 36%, respectively). Patients taking canagliflozin concomitantly with digoxin should have their digoxin levels monitored periodically as clinically indicated. Monitor the patient's clinical response to therapy and for signs or symptoms of digoxin toxicity.
Candesartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Cannabidiol: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing cannabidiol. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for an increase in digoxin-related adverse reactions if coadministration with capmatinib is necessary. Measure serum digoxin concentrations before initiating concomitant drugs; adjust the digoxin dosage or dose frequency as indicated, and continue to monitor digoxin concentrations and clinical response to guide therapy. Digoxin is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor. Coadministration with capmatinib increased digoxin exposure by 47%.
Captopril: (Major) Coadministration of digoxin and captopril increases the serum concentration and AUC of digoxin by 58% and 39%, respectively. However, captopril and digoxin are administered together in patients with congestive heart failure. Measure serum digoxin concentrations before initiating captopril. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Captopril; Hydrochlorothiazide, HCTZ: (Major) Coadministration of digoxin and captopril increases the serum concentration and AUC of digoxin by 58% and 39%, respectively. However, captopril and digoxin are administered together in patients with congestive heart failure. Measure serum digoxin concentrations before initiating captopril. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Carbonic anhydrase inhibitors: (Moderate) Carbonic anhydrase inhibitors can result in hypokalemia. Patients receiving these drugs concurrently with cardiac glycosides are at an increased risk for digitalis toxicity if hypokalemia develops during treatment. Ventricular irritability may occur. Monitor for hypokalemia and supplement with potassium if needed.
Carmustine, BCNU: (Moderate) Use carmustine and digoxin together with caution; concomitant use may result in decreased digoxin tablet absorption and reduced digoxin effectiveness. Monitor digoxin levels prior to starting carmustine and during concomitant therapy. If necessary, increase the digoxin dose by 20% to 40%; continue to monitor digoxin levels. The digoxin AUC value was reduced approximately 50% in cancer patients who received digoxin (Lanoxin tablets) with high dose chemotherapy in a pharmacokinetic study (n = 6). Patients received a digoxin 0.25-mg dose within 3 days of starting chemotherapy (baseline) and another digoxin 0.25-mg dose within 5 days of completing high-dose chemotherapy which included carmustine 350 mg/m2 IV daily for 3 days with or without melphalan.
Carteolol: (Moderate) Because the pharmacologic effects of carteolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Carvedilol: (Major) Measure serum digoxin concentrations before initiating carvedilol. Reduce digoxin concentrations by decreasing the oral digoxin dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. No dosage adjustment is required when digoxin is administered intravenously. In addition, coadministration of digoxin with beta-blockers may produce additive effects on AV node conduction resulting in bradycardia and advanced or complete heart block. Coadministration of orally administered digoxin and carvedilol increases the serum concentration and AUC of digoxin by 16% and 14%, respectively. No significant changes in digoxin exposure were reported when digoxin was administered intravenously. Digoxin is a P-gp substrate and carvedilol is a P-gp inhibitor.
Celecoxib: (Moderate) Monitor digoxin concentrations before and during concomitant use of celecoxib and reduce the digoxin dose if necessary. Elevated digoxin concentrations and prolonged digoxin half-life have been observed when celecoxib has been coadministered with digoxin.
Celecoxib; Tramadol: (Moderate) An increased incidence of digoxin toxicity has been reported in some patients during postmarketing reports with the concurrent use of tramadol and digoxin. (Moderate) Monitor digoxin concentrations before and during concomitant use of celecoxib and reduce the digoxin dose if necessary. Elevated digoxin concentrations and prolonged digoxin half-life have been observed when celecoxib has been coadministered with digoxin.
Ceritinib: (Major) Avoid concomitant use of ceritinib with digoxin if possible due to the risk of additive bradycardia. Both ceritinib and digoxin can cause bradycardia. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if bradycardia occurs.
Charcoal: (Moderate) Decreased serum digoxin concentrations have been reported in patients who received digoxin and activated charcoal. Measure serum digoxin concentrations before initiating charcoal. Continue monitoring during concomitant treatment and increase the digoxin dose by 20% to 40% as necessary and clinically indicated. Patients who ingest dietary supplements containing activated charcoal should be aware that the effectiveness of digoxin may be decreased, and it is advisable to have the patient check with their health care professional before regularly taking such supplements.
Chlorambucil: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa. For the digoxin tablets, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean plus/minus SD) of the value before chemotherapy (p = 0.02), whereas for lanoxin capsules there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin tablets while they are receiving chemotherapy.
Chlordiazepoxide; Clidinium: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Chloroquine: (Moderate) Monitor serum digoxin concentrations in patients receiving digoxin and chloroquine as coadministration may result in increased serum digoxin concentrations. Digoxin serum concentrations have been reported to increase when hydroxychloroquine was added. Although this interaction has not been reported with chloroquine, chloroquine may similarly increase the plasma concentration of digoxin.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Chlorthalidone; Clonidine: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides.
Cholestyramine: (Moderate) Cholestyramine has been shown to significantly interfere with the absorption of digoxin. The administration of cholestyramine twice daily (8 hours before and after digoxin administration) or the use of digoxin solution may minimize this interaction. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of cholestyramine. Continue monitoring during concomitant treatment and increase the digoxin dose by 20-40% as necessary. Parenteral digoxin does not seem to interact with cholestyramine.
Cholinesterase inhibitors: (Moderate) The increase in vagal tone induced by some cholinesterase inhibitors may produce bradycardia, hypotension, or syncope. The vagotonic effect of these drugs may be increased when given with other medications known to cause bradycardia such as digoxin. In one study involving multiple doses of galantamine at 24 mg/day with digoxin at a dose of 0.375 mg/day, there was no effect on the pharmacokinetics of digoxin, except one healthy subject was hospitalized due to second and third degree heart block and bradycardia.
Chromium: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Cladribine: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa. For the digoxin tablets, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean plus/minus SD) of the value before chemotherapy (p = 0.02), whereas for lanoxin capsules there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin tablets while they are receiving chemotherapy.
Clarithromycin: (Major) Clarithromycin has been reported to increase the digoxin AUC by 70% when digoxin is administered orally. No significant changes in digoxin exposure were reported when digoxin was administered intravenously (IV). Originally, this interaction was thought to be due to inhibition of intestinal flora, which leads to decreased intestinal metabolism of digoxin to inactive digoxin reduction products (DRPs). While this may occur, only 5% of a digoxin dose is subject to metabolism by gut flora and this mechanism does not account for the large increases in digoxin levels that occur with the coadministration of clarithromycin. A more important factor is clarithromycin inhibition of P-glycoprotein (P-gp), an energy-dependent drug efflux pump. Digoxin is a P-gp substrate. Inhibition of this protein in the intestinal cell wall leads to increased oral absorption and decreased renal and non-renal clearance of digoxin. Measure serum digoxin concentrations before initiating clarithromycin. Reduce digoxin concentrations by decreasing the oral digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring. No dosage adjustment is required when digoxin is administered IV.
Clofarabine: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrati

ons that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Clonidine: (Moderate) Clonidine can produce bradycardia and should be used cautiously in patients who are receiving other drugs that lower the heart rate such as cardiac glycosides.
Clozapine: (Moderate) Because clozapine is highly protein bound, other highly protein bound medications such as digoxin can displace clozapine from its binding sites, predominantly alpha1-acid glycoprotein. Clozapine, in turn, can increase the serum concentrations of digoxin.
Cobicistat: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of digoxin with cobicistat. Digoxin is a substrate for P-gp; cobicistat is an inhibitor of this drug transporter. Concurrent use may result in elevated digoxin plasma concentration.
Cocaine: (Moderate) Monitor patients closely for cardiac arrhythmias during coadministration of cocaine and cardiac glycosides. Concomitant use of cardiac glycosides with drugs that have sympathomimetic activity, including cocaine, may increase the risk for arrhythmia.
Colchicine: (Major) According to the manufacturer of Colcrys, both digoxin and colchicine are substrates of P-glycoprotein (Pgp) and rhabdomyolysis has been reported in patients on concurrent therapy. If such agents are co-administered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
Colesevelam: (Moderate) Oral drugs with a narrow therapeutic range, with the potential for loss of efficacy with reduced absorption, include antiarrhythmics. The manufacturer recommends that when administering other drugs with a narrow therapeutic index, consideration should be given to separating the administration of the drug with colesevelam. Although not specifically studied, it may be prudent to administer antiarrhythmics at least 4 hours before colesevelam. Additionally, drug response and/or serum concentrations should also be monitored.
Colestipol: (Moderate) Although colestipol and cholestyramine have been reported to reduce the bioavailability of digitoxin, their effects on digoxin absorption are hypothesized to be less since digoxin undergoes less enterohepatic recycling than digitoxin. However, cholestyramine has been shown to significantly interfere with the absorption of digoxin. Colestipol is also expected to decrease the absorption of digoxin, and has been shown to produce a clinically significant decrease in the serum half-life of digoxin. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of colestipol or cholestyramine. Continue monitoring during concomitant treatment and increase the digoxin dose by 20-40% as necessary.
Conivaptan: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing conivaptan. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and conivaptan is a P-gp inhibitor. Coadministration of digoxin with conivaptan resulted in a 1.8- and 1.4-fold increase in digoxin peak and overall exposure, respectively.
Crizotinib: (Major) Avoid coadministration of crizotinib with agents known to cause bradycardia, such as digoxin, to the extent possible due to the risk of additive bradycardia. If concomitant use is unavoidable, monitor for heart rate and blood pressure regularly. An interruption of crizotinib therapy or dose adjustment may be necessary if bradycardia occurs.
Cyclosporine: (Major) Severe digitalis toxicity has been seen within days of starting cyclosporine in patients previously taking digoxin. Monitor serum digoxin concentrations if digoxin is used concomitantly with cyclosporine; a digoxin dosage reduction may be needed. Reduced clearance of digoxin has been observed when it is given concurrently with cyclosporine. Reduced clearance may be due to cyclosporine inhibition of P-glycoprotein (P-gp), an energy-dependent drug efflux pump. Inhibition of the P-gp-mediated renal tubular secretion of digoxin is the postulated mechanism for decreased renal clearance. A decrease in the apparent volume of distribution of digoxin has been reported after cyclosporine administration.
Daclatasvir: (Major) Coadministration of daclatasvir with digoxin may increase digoxin exposure leading to increased or prolonged therapeutic effects and adverse events. If digoxin is initiated in a patients already receiving daclatasvir, start digoxin at the lowest appropriate dose followed by gradual and caution dose adjustments. If daclatasvir is started in a patients already receiving digoxin, obtain digoxin serum concentrations before giving daclatasvir and decrease the digoxin dose by 30% to 50%. Alternatively, the digoxin dose may be reduced by prolonging the dosing interval. Digoxin is a substrate for P-glycoprotein (P-gp); daclatasvir is a P-gp inhibitor.
Dactinomycin, Actinomycin D: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Dapagliflozin; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Dapagliflozin; Saxagliptin: (Moderate) The AUC and Cmax of digoxin may be increased in the presence of saxagliptin. Dosage adjustment of digoxin is not recommended, but patients receiving these 2 drugs at the same time should be monitored closely.
Darifenacin: (Moderate) Oral formulations of digoxin can produce higher serum concentrations when administered concurrently with antimuscarinics because of decreased GI motility induced by the antimuscarinic agent. Darifenacin coadministered with digoxin resulted in a 16 percent increase in digoxin exposure. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Darunavir: (Major) The lowest dose of digoxin should initially be prescribed when given with darunavir/ritonavir, as increased serum concentrations of digoxin may occur. Monitor serum digoxin concentrations for dosage titration.
Darunavir; Cobicistat: (Major) The lowest dose of digoxin should initially be prescribed when given with darunavir/ritonavir, as increased serum concentrations of digoxin may occur. Monitor serum digoxin concentrations for dosage titration. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of digoxin with cobicistat. Digoxin is a substrate for P-gp; cobicistat is an inhibitor of this drug transporter. Concurrent use may result in elevated digoxin plasma concentration.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The lowest dose of digoxin should initially be prescribed when given with darunavir/ritonavir, as increased serum concentrations of digoxin may occur. Monitor serum digoxin concentrations for dosage titration. (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of digoxin with cobicistat. Digoxin is a substrate for P-gp; cobicistat is an inhibitor of this drug transporter. Concurrent use may result in elevated digoxin plasma concentration.
Dasatinib: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Daunorubicin Liposomal: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. Digoxin can reduce the uptake of doxorubicin into cardiac tissue and thus temper the cardiomyopathy caused by doxorubicin. Digoxin can be used to treat congestive heart failure due to doxorubicin cardiomyopathy and may offer improvement to some patients, although angiotensin-converting enzyme inhibitors may be of greater benefit. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy. It is not known if digoxin has similar effects on doxorubicin liposomal.
Daunorubicin Liposomal; Cytarabine Liposomal: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. Digoxin can reduce the uptake of doxorubicin into cardiac tissue and thus temper the cardiomyopathy caused by doxorubicin. Digoxin can be used to treat congestive heart failure due to doxorubicin cardiomyopathy and may offer improvement to some patients, although angiotensin-converting enzyme inhibitors may be of greater benefit. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy. It is not known if digoxin has similar effects on doxorubicin liposomal.
Demeclocycline: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of a tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
Dexlansoprazole: (Moderate) Dexlansoprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Becuase, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Dexmedetomidine: (Moderate) Dexmedetomidine has been associated with hypotension and bradycardia, and should be administered cautiously in combination with cardiac glycosides, such as digoxin, or other negative chronotropic agents.
Dextromethorphan; Bupropion: (Moderate) Monitor plasma digoxin concentrations during concomitant bupropion use. Concomitant use may decrease plasma digoxin concentrations. Digoxin exposure was decreased when a single oral dose of digoxin 0.5 mg was administered 24 hours after a single oral dose of extended-release bupropion 150 mg in healthy volunteers.
Dextromethorphan; Quinidine: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a P-gp substrate and quinidine inhibits P-gp. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
Diclofenac: (Moderate) Monitor digoxin concentrations before and during concomitant use of diclofenac and reduce the digoxin dose if necessary. Elevated digoxin concentrations and prolonged digoxin half-life have been observed when diclofenac has been coadministered with digoxin.
Diclofenac; Misoprostol: (Moderate) Monitor digoxin concentrations before and during concomitant use of diclofenac and reduce the digoxin dose if necessary. Elevated digoxin concentrations and prolonged digoxin half-life have been observed when diclofenac has been coadministered with digoxin.
Dicloxacillin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Dicyclomine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Digoxin Immune Fab: (Minor) Digoxin immune Fab can reverse desirable as well as toxic actions of cardiac glycosides.
Diltiazem: (Major) Measure serum digoxin concentrations before initiating diltiazem. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. In addition, coadministration of digoxin with calcium channel blockers may produce additive effects on AV node conduction resulting in bradycardia and advanced or complete heart block. Coadministration of digoxin and diltiazem increases the serum concentration of digoxin by 20%.
Dimenhydrinate: (Moderate) Patients receiving oral digoxin therapy should be monitored for increased digoxin effects when receiving drugs with substantial anticholinergic activity. Dimenhydrinate can theoretically increase the absorption of digoxin by decreasing gastrointestinal motility. Anticholinergics, because of their ability to cause tachycardia, can also antagonize the beneficial actions of digoxin in atrial fibrillation/flutter.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Diphenhydramine; Naproxen: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Diphenoxylate; Atropine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Dofetilide: (Major) Dofetilide does not affect the pharmacokinetics of digoxin; however, the concomitant administration of digoxin with dofetilide is associated with a higher occurrence of torsade de pointes.
Dolasetron: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Therefore, drugs known to prolong the PR interval, such as digoxin, should be avoided in patients taking dolasetron.
Donepezil; Memantine: (Moderate) Digoxin is eliminated by renal tubular secretion and may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or digoxin is recommended to assess for needed dosage adjustments. In selected individuals, digoxin serum concentration monitoring may be appropriate.
Dorzolamide; Timolol: (Moderate) Monitor heart rate during concomitant digoxin and timolol use due to increased risk for bradycardia. Both digoxin and timolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Doxercalciferol: (Moderate) Doxercalciferol should be administered with caution to patients receiving digoxin. Vitamin D analogs may cause hypercalemia which increases the risk of digitalis toxicity. In patients receiving doxercalciferol and digoxin concurrently, monitor serum calcium frequently and monitor the patient for signs of digitalis toxicity. More frequent monitoring is necessary when initiating or adjusting the dose of doxercalciferol.
Doxycycline: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
Dronabinol: (Major) Use caution if coadministration of dronabinol with digoxin is necessary, and monitor for an increase in digoxin levels and digoxin-related adverse effects. Dronabinol is highly bound to plasma proteins, and may displace and increase the free fraction of other concomitantly administered protein-bound drugs; caution is recommended with other drugs with a narrow therapeutic index.
Dronedarone: (Major) Dronedarone is an inhibitor of P-glycoprotein (P-gp). Digoxin is a substrate for P-gp. In clinical trials, the coadministration of dronedarone and digoxin resulted in an increase in the exposure of digoxin by 2.5-fold, with a subsequent increase in gastrointestinal adverse effects. Furthermore, digoxin can potentiate the electrophysiologic effects of dronedarone (e.g., decreased AV node conduction). In clinical trials, sudden death was more common in patients receiving combined therapy with dronedarone and digoxin than in patients on either therapy alone. It is unclear if combination therapy contributed to this increase or if this was related to the presence of advanced heart disease. According to the manufacturer of dronedarone, concurrent administration of dronedarone and digoxin should be avoided. However, if coadministration is unavoidable, a 50% reduction in the digoxin dose is recommended. The manufacturer of digoxin recommends measuring serum digoxin concentrations before initiating dronedarone and reducing digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency; continue monitoring.
Dupilumab: (Moderate) Coadministration of dupilumab may result in altered exposure to digoxin. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP450 enzymes could be normalized during dupilumab administration. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as digoxin. Monitor digoxin concentrations if dupilumab is initiated or discontinued in a patient taking digoxin; digoxin dose adjustments may be needed.
Edetate Calcium Disodium, Calcium EDTA: (Major) The pharmacodynamic actions of edetate disodium oppose those of the cardiac glycosides.
Elacestrant: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing elacestrant. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and elacestrant is a P-gp inhibitor. Concomitant use with elacestrant resulted in a 1.1-fold increase in the overall exposure of digoxin.
Elagolix: (Moderate) Clinical monitoring is recommended for digoxin when coadministered with elagolix. Monitor heart rate, clinical status and serum digoxin concentrations periodically and as clinically indicated. Elagolix is an inhibitor of P-glycoprotein (P-gp), and digoxin is a P-gp substrate. During drug interaction studies, the coadministration of elagolix with digoxin resulted in an increase in digoxin peak concentrations by a mean of 1.71 ( range, 1.53 to 1.91) and mean AUC of 1.26 (range 1.17 to 1.35).
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Clinical monitoring is recommended for digoxin when coadministered with elagolix. Monitor heart rate, clinical status and serum digoxin concentrations periodically and as clinically indicated. Elagolix is an inhibitor of P-glycoprotein (P-gp), and digoxin is a P-gp substrate. During drug interaction studies, the coadministration of elagolix with digoxin resulted in an increase in digoxin peak concentrations by a mean of 1.71 ( range, 1.53 to 1.91) and mean AUC of 1.26 (range 1.17 to 1.35).
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Administration of tezacaftor; ivacaftor may increase the systemic exposure of digoxin and increase or prolong the therapeutic effect and adverse reactions. Appropriate monitoring should be used. Digoxin is a sensitive P-gp substrate; ivacaftor is a weak inhibitor of P-gp. Coadministration of tezacaftor; ivacaftor with digoxin increased digoxin exposure by 1.3-fold. (Moderate) Coadministration of ivacaftor with digoxin may increase digoxin exposure leading to increased or prolonged therapeutic effects and adverse events. Digoxin is a substrate for P-glycoprotein (P-gp). Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Use caution when administering ivacaftor and digoxin concurrently.
Eliglustat: (Major) Coadministration of digoxin and eliglustat may result in increased digoxin concentrations, which may result in digoxin toxicity. Measure serum digoxin concentrations before initiating eliglustat, reduce the digoxin dose by 30%, and continue to monitor as clinically indicated. Eliglustat is a P-glycoprotein (P-gp) inhibitor, and digoxin is a P-gp substrate. During clinical trials, Cmax and AUC of digoxin increased by 1.7- and 1.5-fold, respectively, after multiple doses of eliglustat 127 mg PO twice daily in extensive and intermediate metabolizers or 84 mg PO twice daily in poor metabolizers. Of note, the only FDA-approved dose of eliglustat is 84 mg.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of digoxin with cobicistat. Digoxin is a substrate for P-gp; cobicistat is an inhibitor of this drug transporter. Concurrent use may result in elevated digoxin plasma concentration.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution and therapeutic drug concentrations monitoring, if available, is recommended during coadministration of digoxin with cobicistat. Digoxin is a substrate for P-gp; cobicistat is an inhibitor of this drug transporter. Concurrent use may result in elevated digoxin plasma concentration.
Empagliflozin; Linagliptin; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Empagliflozin; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Enalapril, Enalaprilat: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant enalapril use. A decline in GFR or tubular secretion, as from angiotensin-converting enzyme inhibitors, may impair the excretion of digoxin.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant enalapril use. A decline in GFR or tubular secretion, as from angiotensin-converting enzyme inhibitors, may impair the excretion of digoxin.
Enasidenib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing enasidenib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and enasidenib is a P-gp inhibitor. Coadministration of digoxin after multiple doses of enasidenib increased digoxin Cmax by 26% and AUC by 20%.
Entecavir: (Moderate) Both entecavir and digoxin are secreted by active tubular secretion. In theory, coadministration of entecavir with digoxin may increase the serum concentrations of either drug due to competition for the drug elimination pathway. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
Epoprostenol: (Moderate) Increased serum digoxin concentrations have been reported in patients who received digoxin and epoprostenol. Measure serum digoxin concentrations before initiating epoprostenol. Monitor patients who take both epoprostenol and digoxin for possible digoxin toxicity and reduce digoxin dose as necessary.
Eprosartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Erdafitinib: (Major) Avoid coadministration of digoxin with erdafitinib due to the risk of increased plasma concentrations of digoxin. If concomitant use is unavoidable, separate erdafitinib administration by at least 6 hours before or after administration of digoxin; monitor digoxin levels. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and erdafitinib is a P-gp inhibitor.
Ertugliflozin; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Erythromycin: (Moderate) Monitor digoxin concentrations as appropriate and watch for digoxin-related adverse reactions if coadministration with erythromycin is necessary. The dose of digoxin may need to be adjusted. Concurrent use may increase digoxin exposure by 100%. Digoxin is a P-gp substrate and erythromycin is a P-gp inhibitor.
Esmolol: (Moderate) A potentially clinically significant interaction between esmolol and digoxin may exist due to their additive effects on the AV node. The efficacy of esmolol in controlling ventricular response and in conversion to sinus rhythm may be improved with preoperative digitalization or with subsequent concomitant therapy for new-onset atrial fibrillation or flutter. The concomitant administration of esmolol and digoxin resulted in a 10-20% increase in serum digoxin concentrations. The clinical significance of this interaction is not known; however, the manufacturer warns that esmolol should be titrated cautiously in patients receiving digoxin.
Esomeprazole: (Moderate) Increased serum digoxin concentrations have been reported in patients who received digoxin and esomeprazole. Esomeprazole inhibits gastric acid secretion and increases the pH of the stomach. Changes in intragastric pH can potentially alter the bioavailability of other drugs with pH-dependent absorption, such as digoxin. Gastric acid pump-inhibitors may increase digoxin bioavailability; however, the magnitude of the interaction is small. Measure serum digoxin concentrations before initiating esomeprazole. Monitor patients for possible digoxin toxicity and reduce digoxin dose as necessary. In addition, proton pump inhibitors have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Estramustine: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Etodolac: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. Increased serum digoxin concentrations have been reported in patients who received digoxin and diclofenac sodium or ibuprofen. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Etravirine: (Moderate) Etravirine is a P-glycoprotein (PGP) inhibitor and digoxin is a substrate for PGP transport. Digoxin Cmax may increase by 19% and the AUC may increase by 18%. For patients starting both etravirine and digoxin, the lowest dose of digoxin should initially be prescribed. For patients on a stable digoxin regimen and initiating etravirine, no initial dose adjustment of either drug is necessary; however, serum digoxin concentrations should be monitored and used for digoxin dose titration.
Exenatide: (Moderate) Repeat doses of exenatide (10 mcg SQ twice daily) decreased the Cmax of digoxin (0.25 mg PO daily) by 17% and delayed Tmax by roughly 2.5 hours. Overall steady state AUC of digoxin was not altered. The mechanism of the interaction is not known (although it may be due to delayed gastric emptying), nor is the clinical significance of this potential interaction. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of exenatide. Continue monitoring during concomitant treatment and increase the digoxin dose by 20-40% as necessary.
Ezetimibe; Simvastatin: (Moderate) Simvastatin causes a slight elevation of serum digoxin levels. Simvastatin should be used cautiously in patients receiving digoxin.
Felodipine: (Moderate) Felodipine reduces the clearance of digoxin and may lead to digoxin toxicity. Although some reports show no effect on digoxin, it is prudent to monitor plasma levels of digoxin when felodipine is administered to patients receiving digoxin. Transient increases in serum digoxin concentrations have been reported with concomitant administration of felodipine. This effect is believed to be due to decreased renal and nonrenal clearance of digoxin induced by felodipine. When given concomitantly with extended-release felodipine tablets in one study, the pharmacokinetics of digoxin in patients with heart failure were not significantly altered. Adding digoxin to felodipine may have clinical significance in patients with serum digoxin concentrations which are at the high end of the therapeutic range.
Fenoprofen: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Fingolimod: (Major) If possible, do not start fingolimod in a patient who is taking a drug that slows the heart rate or atrioventricular conduction such as digoxin. Use of these drugs during fingolimod initiation may be associated with severe bradycardia or heart block. Seek advice from the prescribing physician regarding the possibility to switch to drugs that do not slow the heart rate or atrioventricular conduction before initiating fingolimod. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients who cannot stop taking drugs that slow the heart rate or atrioventricular conduction. Experience with fingolimod in patients receiving concurrent therapy with drugs that slow the heart rate or atrioventricular conduction is limited.
Flavoxate: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Flaxseed: (Moderate) Flaxseed fiber can impair the absorption of oral drugs when administered concomitantly. However, no drug interaction studies have been performed to assess the degree to which the absorption of oral drugs may be altered. Based on interactions of other plant seed fiber (e.g., psyllium) used as a bulk-forming laxative, flaxseed fiber may adsorb cardiac glycosides. Administration of prescribed oral agents should be separated from the administration of flaxseed fiber by at least 2 hours.
Flecainide: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant flecainide use. Small increases in plasma digoxin concentrations are seen during coadministration with flecainide; during administration of multiple oral doses of flecainide to healthy persons stabilized on a maintenance dose of digoxin, a 13% to 19% increase in plasma digoxin concentrations occurred at 6 hours postdose.
Flibanserin: (Major) The concomitant use of flibanserin, a P-glycoprotein (P-gp) inhibitor, and digoxin, a P-gp substrate, can increase digoxin concentrations, which may lead to digoxin toxicity. Increased monitoring of digoxin concentrations is recommended during concurrent use. In a controlled cross-over study in 24 healthy men and women, flibanserin 100 mg was administered once daily over 5 days followed by a single dose of 0.5 mg digoxin. Flibanserin increased the digoxin AUC by 2.0-fold and Cmax by 1.5-fold, compared to digoxin alone. Patients should be instructed to contact their healthcare provider if they experience symptoms of digoxin toxicity such as changes in color vision (more yellow color), blurred vision, eyes sensitive to light, light flashes, or halos around bright lights, changes in behavior, chest pain or palpitations, bradycardia, or loss of appetite.
Flurbiprofen: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Fluvastatin: (Moderate) Due to data that indicate high doses of fluvastatin, 80mg/day, increase digoxin serum concentrations, the manufacturer recommends closer monitoring of patients stabilized on digoxin if fluvastatin is added.
Folic Acid, Vitamin B9: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Fosamprenavir: (Moderate) Caution is advised when administering digoxin with fosamprenavir, as concurrent use may result in reduced digoxin plasma concentrations. Digoxin is a substrate for the drug transporter P-glycoprotein (P-gp). Amprenavir, the active metabolite of fosamprenavir, is a P-gp inducer.
Fosinopril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. In addition, fosinopril may cause a false low measurement of serum digoxin levels with the Digi-Tab RIA Kit for Digoxin. Other kits, such as the Coat-A-Count RIA Kit, may be used.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. In addition, fosinopril may cause a false low measurement of serum digoxin levels with the Digi-Tab RIA Kit for Digoxin. Other kits, such as the Coat-A-Count RIA Kit, may be used.
Fosphenytoin: (Moderate) Measure serum digoxin concentrations before starting and during concomitant fosphenytoin therapy; increase the digoxin dose by approximately 20% to 40% as necessary. Concomitant administration may result in decreased digoxin concentrations.
Fostamatinib: (Moderate) Monitor for digoxin toxicities that may require digoxin dose reduction if given concurrently with fostamatinib. Concomitant use of fostamatinib with a P-gp substrate may increase the concentration of the P-gp substrate. Fostamatinib is a P-gp inhibitor; digoxin is a substrate for P-gp. Coadministration of fostamatinib with digoxin increased digoxin AUC by 37% and Cmax by 70%.
Futibatinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing futibatinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and futibatinib is a P-gp inhibitor.
Gentamicin: (Major) The coadministration of gentamicin and digoxin resulted in a 129-212% increase in the serum concentration of digoxin. Measure serum digoxin concentrations before initiating gentamicin. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring.
Gilteritinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing gilteritinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and gilteritinib is a P-gp inhibitor.
Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of certain gingerol constituents of ginger; but it is unclear if whole ginger root exhibits these effects clinically in humans. It is theoretically possible that excessive doses of ginger could affect the action of inotropes; however, no clinical data are available.
Ginseng, Panax ginseng: (Major) A case of an elevated digoxin serum concentration was reported in a 74 year old man who was taking Siberian ginseng concomitantly. The serum digoxin concentration returned to an acceptable level after ginseng was discontinued. Although Panax ginseng has not been reported to alter digoxin serum concentrations, the possibility of an interaction should be considered.
Glecaprevir; Pibrentasvir: (Major) Coadministration of glecaprevir with digoxin may increase the serum concentrations of digoxin. Measure serum digoxin concentrations prior to initiating glecaprevir; reduce digoxin concentrations by decreasing digoxin dose by approximately 50% or by modifying the dosing frequency; continue monitoring during therapy. Digoxin is a substrate of P-glycoprotein (P-gp); glecaprevir is an inhibitor of P-gp. In drug interaction studies, coadministration of digoxin with glecaprevir; pibrentasvir resulted in a 48% increase in the AUC of digoxin. (Major) Coadministration of pibrentasvir with digoxin may increase the serum concentrations of digoxin. Measure serum digoxin concentrations prior to initiating pibrentasvir; reduce digoxin concentrations by decreasing digoxin dose by approximately 50% or by modifying the dosing frequency; continue monitoring during therapy. Digoxin is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp. In drug interaction studies, coadministration of digoxin with glecaprevir; pibrentasvir resulted in a 48% increase in the AUC of digoxin.
Glipizide; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Glyburide; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Glycopyrrolate: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Glycopyrrolate; Formoterol: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Heparin: (Minor) Digitalis (e.g., cardiac glycosides like digoxin or digitoxin) may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not of clinical significance since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
Homatropine; Hydrocodone: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Hydrocodone; Ibuprofen: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Hydroxychloroquine: (Moderate) Monitor serum digoxin concentrations in patients receiving digoxin and hydroxychloroquine as coadministration may result in increased serum digoxin concentrations.
Hyoscyamine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Ibritumomab Tiuxetan: (Major) Avoid coadministration of potassium phosphate and digoxin as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations. (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Ibrutinib: (Moderate) Use ibrutinib and digoxin together with caution; plasma concentrations of digoxin may increase resulting in increased toxicity. Ibrutinib is a P-glycoprotein (P-gp) inhibitor in vitro; digoxin is a P-gp substrate with a narrow therapeutic index. In addition, some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients.
Ibuprofen: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Ibuprofen; Famotidine: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Ibuprofen; Oxycodone: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Ibuprofen; Pseudoephedrine: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant ibuprofen use. A decline in GFR or tubular secretion, as from nonsteroidal anti-inflammatory drugs (NSAIDs), may impair the excretion of digoxin.
Imatinib: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Indacaterol; Glycopyrrolate: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Indapamide: (Moderate) Indapamide may induce hypokalemia, increasing the potential for proarrhythmic effects (e.g., torsade de pointes) of cardiac glycosides. Potassium levels should be within the normal range prior and during administration of these agents.
Indomethacin: (Major) Coadministration of digoxin and indomethacin increases the serum concentration of digoxin by 40%. Measure serum digoxin concentrations before initiating indomethacin. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. In addition, concomitant use of other nonsteroidal antiinflammatory drugs (NSAIDs), including COX-2 inhibitors, with digoxin may result in increased serum concentrations of digoxin. Increased serum digoxin concentrations have been reported in patients who received digoxin and diclofenac sodium or ibuprofen. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Insulin Glargine; Lixisenatide: (Moderate) Concomitant administration of lixisenatide 20 mcg and digoxin 0.25 mg (at steady state) delayed digoxin Tmax by approximately 1.5 hours and reduced Cmax by 26%. No clinically relevant effects on AUC were observed. The mechanism of this potential interaction has not been described (although it may be due to delayed gastric emptying) and the potential for clinical significance is unknown. Dosage adjustments of digoxin may be necessary.
Interferon Alfa-2b: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Ipratropium; Albuterol: (Moderate) Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol or levalbuterol and digoxin on a chronic basis is unclear. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of albuterol or levalbuterol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Irbesartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Isavuconazonium: (Moderate) Use caution and closely monitor digoxin serum concentrations when using digoxin and isavuconazonium concurrently. Coadministration results in increased digoxin exposure, and serum concentrations should guide digoxin dose titration. Isavuconazole, the active moiety of isavuconazonium, is an inhibitor of the drug transporter P-glycoprotein (P-gp); digoxin is a substrate for this transporter.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) It appears that rifampin decreases serum concentrations of digoxin by inducing intestinal P-glycoprotein and decreasing the oral bioavailability of digoxin by 30.1%. The Cmax and AUC of digoxin were decreased by 43% and 58%, respectively. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of rifampin. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Isoniazid, INH; Rifampin: (Moderate) It appears that rifampin decreases serum concentrations of digoxin by inducing intestinal P-glycoprotein and decreasing the oral bioavailability of digoxin by 30.1%. The Cmax and AUC of digoxin were decreased by 43% and 58%, respectively. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of rifampin. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Istradefylline: (Moderate) Monitor for digoxin-related adverse reactions if coadministration of istradefylline is necessary as digoxin exposure may be increased. Digoxin is a P-gp substrate; istradefylline is a P-gp inhibitor. Coadministration of digoxin and istradefylline 40 mg daily increased the exposure of digoxin by 21%.
Itraconazole: (Major) Measure serum digoxin concentrations before initiating itraconazole. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. Concomitant use of digoxin with itraconazole has resulted in an 80% increase in digoxin serum concentrations. Itraconazole is an inhibitor of P-glycoprotein (P-gp); digoxin is a substrate for P-gp.
Ivabradine: (Moderate) Monitor heart rate if ivabradine is coadministered with other negative chronotropes like digoxin. Most patients receiving ivabradine will receive concomitant beta-blocker therapy. Coadministration of drugs that slow heart rate increases the risk for bradycardia.
Ivacaftor: (Moderate) Coadministration of ivacaftor with digoxin may increase digoxin exposure leading to increased or prolonged therapeutic effects and adverse events. Digoxin is a substrate for P-glycoprotein (P-gp). Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Use caution when administering ivacaftor and digoxin concurrently.
Ketoconazole: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing ketoconazole. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and ketoconazole is a P-gp inhibitor.
Ketoprofen: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Ketorolac: (Moderate) Monitor serum digoxin concentrations during concomitant use of ketorolac. A decline in glomerular filtration or tubular secretion as from nonsteroidal antiinflammatory drugs (NSAIDs) may impair the excretion of digoxin. The concomitant use of digoxin and ketorolac has been reported to increase the serum concentration and prolong the half-life of digoxin.
Labetalol: (Moderate) Monitor heart rate during concomitant digoxin and labetalol use due to increased risk for bradycardia. Both digoxin and labetalol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Lacosamide: (Moderate) Lacosamide causes PR interval prolongation in some patients. Caution is advised during coadministration of lacosamide with other drugs that cause PR prolongation, such as digoxin, since further PR prolongation is possible. If concurrent use is necessary, an ECG is recommended prior to initiation of lacosamide and after the drug is titrated to the maintenence dose. Patients receiving intravenous lacosamide should be closely monitored due to the potential for profound bradycardia and AV block during coadministration.
Lansoprazole: (Moderate) Lansoprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Becuase, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Clarithromycin has been reported to increase the digoxin AUC by 70% when digoxin is administered orally. No significant changes in digoxin exposure were reported when digoxin was administered intravenously (IV). Originally, this interaction was thought to be due to inhibition of intestinal flora, which leads to decreased intestinal metabolism of digoxin to inactive digoxin reduction products (DRPs). While this may occur, only 5% of a digoxin dose is subject to metabolism by gut flora and this mechanism does not account for the large increases in digoxin levels that occur with the coadministration of clarithromycin. A more important factor is clarithromycin inhibition of P-glycoprotein (P-gp), an energy-dependent drug efflux pump. Digoxin is a P-gp substrate. Inhibition of this protein in the intestinal cell wall leads to increased oral absorption and decreased renal and non-renal clearance of digoxin. Measure serum digoxin concentrations before initiating clarithromycin. Reduce digoxin concentrations by decreasing the oral digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring. No dosage adjustment is required when digoxin is administered IV. (Moderate) Lansoprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may s lightly increase digoxin bioavailability. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Becuase, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Lapatinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing lapatinib; if the digoxin serum concentration is greater than 1.2 ng/mL, the digoxin dose should be reduced by half. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and lapatinib is a P-gp inhibitor. The systemic exposure of oral digoxin increased by approximately 2.8-fold following administration with lapatinib.
Lasmiditan: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing lasmiditan. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and lasmiditan is a P-gp inhibitor. Lasmiditan has also been associated with a lowering of heart rate (approximately 5 to 10 beats per minute), which may be additive to digoxin's effect on heart rate. Use this combination with caution if this magnitude of heart rate decrease may pose a concern for the patient.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoing of digoxin therapeutic concentrations is advised when administering digoxin with ledipasvir. Digoxin is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase digoxin plasma concentrations.
Lenacapavir: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing lenacapavir. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and lenacapavir is a P-gp inhibitor.
Lenalidomide: (Moderate) Concomitant use of lenalidomide and digoxin may result in increased digoxin levels and exposure; use these drugs together with caution. Monitor digoxin levels periodically and as clinically indicated in patients who require both lenalidomide and digoxin. The Cmax and AUC values of digoxin were increased by 14% in patients who received digoxin following multiple oral doses of lenalidomide 10 mg/day.
Levalbuterol: (Moderate) Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol or levalbuterol and digoxin on a chronic basis is unclear. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of albuterol or levalbuterol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Levoketoconazole: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing ketoconazole. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and ketoconazole is a P-gp inhibitor.
Levomilnacipran: (Major) Postural hypotension and tachycardia may occur during concurrent use of intravenous digoxin and milnacipran, a racemic mixture containing levomilnacipran. Because the manufacturer of milnacipran recommends against use of milnacipran and intravenous digoxin, use of levomilnacipran with intravenous digoxin should be approached with extreme caution.
Linagliptin; Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Lisinopril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Lixisenatide: (Moderate) Concomitant administration of lixisenatide 20 mcg and digoxin 0.25 mg (at steady state) delayed digoxin Tmax by approximately 1.5 hours and reduced Cmax by 26%. No clinically relevant effects on AUC were observed. The mechanism of this potential interaction has not been described (although it may be due to delayed gastric emptying) and the potential for clinical significance is unknown. Dosage adjustments of digoxin may be necessary.
Lomitapide: (Moderate) Concomitant use of lomitapide and digoxin may result in increased serum concentrations of digoxin. According to the manufacturer of lomitapide, dose reduction of digoxin should be considered during concurrent use. Lomitapide is an inhibitor of P-glycoprotein (P-gp) and digoxin is a P-gp substrate.
Lomustine, CCNU: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Lonafarnib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing lonafarnib. Concurrent use may increase digoxin exposure. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and lonafarnib is a P-gp inhibitor.
Loop diuretics: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and loop diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Lopinavir; Ritonavir: (Major) In a pharmacokinetic study of 11 healthy men, increases in digoxin AUC (86%), volume of distribution, and half-life were seen, while renal and non-renal clearance decreased, when coadministered with ritonavir. It appears that this interaction is mediated by ritonavir's inhibition or P-glycoprotein-mediated renal tubular secretion of digoxin. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including digoxin) has not been evaluated. Measure serum digoxin concentrations before initiating ritonavir or lopinavir; ritonavir. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
Lorlatinib: (Moderate) Increase monitoring of serum digoxin concentrations when starting, adjusting, or discontinuing lorlatinib. Concurrent use may decrease digoxin exposure. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and lorlatinib is a P-gp inducer.
Losartan: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant losartan use. A decline in GFR or tubular secretion, as from angiotensin receptor blockers, may impair the excretion of digoxin.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant losartan use. A decline in GFR or tubular secretion, as from angiotensin receptor blockers, may impair the excretion of digoxin.
Lumacaftor; Ivacaftor: (Moderate) Coadministration of ivacaftor with digoxin may increase digoxin exposure leading to increased or prolonged therapeutic effects and adverse events. Digoxin is a substrate for P-glycoprotein (P-gp). Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Use caution when administering ivacaftor and digoxin concurrently.
Lumacaftor; Ivacaftor: (Moderate) Concomitant use of digoxin and lumacaftor; ivacaftor may alter digoxin exposure. Monitor digoxin serum concentrations closely and titrate the dosage to achieve the desired therapeutic effect. Digoxin is a substrate for the P-glycoprotein (P-gp) efflux transporter. In vitro studies suggest lumacaftor; ivacaftor has the potential to both inhibit and induce P-gp.
Magnesium Hydroxide: (Moderate) Monitor digoxin concentrations as appropriate and watch for decreased digoxin efficacy if coadministration with antacids is necessary. The dose of digoxin may need to be adjusted. Antacids may decrease the absorption of digoxin.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Moderate) Administer digoxin at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of digoxin may be reduced by chelation with magnesium sulfate.
Mannitol: (Moderate) Mannitol-induced diuresis increases the excretion of potassium and can lead to hypokalemia. Administration of mannitol to patients receiving cardiac glycosides can increase the risk of developing cardiac toxicity secondary to mannitol-induced hypokalemia. Serum potassium concentrations should be monitored.
Maribavir: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing maribavir. Concurrent use may increase digoxin exposure. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and maribavir is a P-gp inhibitor. Coadministration with maribavir increased the exposure of digoxin by approximately 20%.
Meclizine: (Moderate) Patients receiving oral digoxin therapy should be monitored for increased digoxin effects when receiving drugs with substantial anticholinergic activity. Meclizine can theoretically increase the absorption of digoxin by decreasing gastrointestinal motility. Anticholinergics, because of their ability to cause tachycardia, can also antagonize the beneficial actions of digoxin in atrial fibrillation/flutter.
Meclofenamate Sodium: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Mefenamic Acid: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Melphalan Flufenamide: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa. For the digoxin tablets, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean plus/minus SD) of the value before chemotherapy (p = 0.02), whereas for lanoxin capsules there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin tablets while they are receiving chemotherapy.
Melphalan: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa. For the digoxin tablets, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean plus/minus SD) of the value before chemotherapy (p = 0.02), whereas for lanoxin capsules there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin tablets while they are receiving chemotherapy.
Memantine: (Moderate) Digoxin is eliminated by renal tubular secretion and may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or digoxin is recommended to assess for needed dosage adjustments. In selected individuals, digoxin serum concentration monitoring may be appropriate.
Metformin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Metformin; Repaglinide: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Metformin; Rosiglitazone: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Metformin; Saxagliptin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary. (Moderate) The AUC and Cmax of digoxin may be increased in the presence of saxagliptin. Dosage adjustment of digoxin is not recommended, but patients receiving these 2 drugs at the same time should be monitored closely.
Metformin; Sitagliptin: (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Methimazole: (Minor) Serum concentrations of digoxin can increase as hyperthyroidism is corrected. In patients receiving antithyroid therapy, the dosage of digoxin may need to be reduced as the patient becomes euthyroid.
Methohexital: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Methotrexate: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa. For the digoxin tablets, there was a significant reduction in the AUC after chemotherapy to 54.4% +/- 35.5% (mean plus/minus SD) of the value before chemotherapy (p = 0.02), whereas for lanoxin capsules there was an insignificant reduction in AUC to 85.1% +/- 42.7% of the value before chemotherapy. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin tablets while they are receiving chemotherapy.
Methoxsalen: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Methscopolamine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Metoclopramide: (Moderate) Digoxin absorption and bioavailability may be diminished in some patients on metoclopramide due to the increased rate of transit from the stomach, where digoxin is normally absorbed. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of metoclopramide. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Metoprolol: (Moderate) Monitor heart rate during concomitant digoxin and metoprolol use due to increased risk for bradycardia. Both digoxin and metoprolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate during concomitant digoxin and metoprolol use due to increased risk for bradycardia. Both digoxin and metoprolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Miglitol: (Moderate) Acarbose, an alpha-glucosidase inhibitor, has been found to decrease the mean bioavailability (AUC) of digoxin by 16% (90% confidence interval: range 8-23%), decrease the mean Cmax of digoxin by 26% (90% confidence interval: range 16-34%), and decrease the mean trough concentration of digoxin by 9% (90% confidence limit: 19% decrease to 2% increase). Miglitol, also an alpha-glucosidase inhibitor, may impair the oral absorption of digoxin and lead to subtherapeutic serum digoxin concentrations in some patients. In healthy volunteers, coadministration of miglitol 50 mg or 100 mg with digoxin reduced the average plasma concentrations of digoxin by 19% and 28%, respectively. However, in diabetic patients under treatment with digoxin, plasma digoxin concentrations were not altered when coadministered with miglitol. The mechanism of the interaction is not well understood. The manufacturer of digoxin recommends measuring digoxin concentrations prior to initiating acarbose or miglitol. Continue monitoring during concomitant treatment and increase the digoxin dose by 20-40% as necessary. Some experts have recommended that these agents be administered 6 hours after an oral digoxin dose to ensure time for adequate digoxin absorption.
Milnacipran: (Major) Postural hypotension and tachycardia have occurred during concurrent use of intravenous digoxin and milnacipran. Use of this combination is not recommended. Per the product labeling, there was no pharmacokinetic interaction between milnacipran and orally administered digoxin in healthy subjects. The possibility of a pharmacodynamic interaction should not be excluded.
Minocycline: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism. Additionally, injectable minocycline contains magnesium sulfate heptahydrate. Magnesium salts, such as magnesium sulfate, can antagonize the electrophysiologic effects of cardiac glycosides such as digoxin.
Mirabegron: (Major) Mirabegron increases digoxin exposure approximately 30% with concomitant use. Measure serum digoxin concentrations prior to initiating mirabegron. Reduce the digoxin dose by approximately 15% to 30% or modify the dosing frequency when given together. Monitor digoxin concentrations and titrate the dose to obtain the desired clinical effect.
Mitapivat: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing mitapivat. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and mitapivat is a P-gp inhibitor.
Mitoxantrone: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Moexipril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Nabumetone: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Nadolol: (Moderate) Because the pharmacologic effects of nadolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Nafcillin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Naproxen: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Naproxen; Esomeprazole: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary. (Moderate) Increased serum digoxin concentrations have been reported in patients who received digoxin and esomeprazole. Esomeprazole inhibits gastric acid secretion and increases the pH of the stomach. Changes in intragastric pH can potentially alter the bioavailability of other drugs with pH-dependent absorption, such as digoxin. Gastric acid pump-inhibitors may increase digoxin bioavailability; however, the magnitude of the interaction is small. Measure serum digoxin concentrations before initiating esomeprazole. Monitor patients for possible digoxin toxicity and reduce digoxin dose as necessary. In addition, proton pump inhibitors have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Naproxen; Pseudoephedrine: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Nebivolol: (Moderate) Monitor heart rate during concomitant digoxin and nebivolol use due to increased risk for bradycardia. Both digoxin and nebivolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Nebivolol; Valsartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity. (Moderate) Monitor heart rate during concomitant digoxin and nebivolol use due to increased risk for bradycardia. Both digoxin and nebivolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Nefazodone: (Major) Coadministration of digoxin and nefazodone increases the serum concentration and AUC of digoxin by 27% and 15%, respectively. Measure serum digoxin concentrations before initiating nefazodone. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring.
Nelarabine: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Neomycin: (Moderate) Large doses of neomycin have been reported to reduce the absorption of digoxin leading to reduced steady-state digoxin concentrations of 28%. It is thought that the decrease in digoxin absorption is due to alterations in the properties of the gut wall. Therefore, separating the time of administration between these drugs and digoxin will probably not reduce the potential interaction. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of neomycin. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Neostigmine; Glycopyrrolate: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Neratinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing neratinib. Concurrent use may increase digoxin exposure. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and neratinib is a P-gp inhibitor. Coadministration with neratinib increased the mean Cmax and AUC of digoxin by 54% and 32%, respectively.
Nesiritide, BNP: (Major) Nesiritide may have additive inoptropic effects with cardiac glycosides.
Niacin; Simvastatin: (Moderate) Simvastatin causes a slight elevation of serum digoxin levels. Simvastatin should be used cautiously in patients receiving digoxin.
Nicardipine: (Minor) Some calcium-channel blockers cause serum digoxin concentrations to rise. Although this reaction has not been reported with nicardipine, patients should be monitored closely for this possibility if nicardipine is added to digoxin therapy.
Nifedipine: (Major) Measure serum digoxin concentrations before initiating nifedipine. If necessary, reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Coadministration of digoxin and nifedipine increases the serum concentration of digoxin by 45%. This is believed to be due to decreased renal and nonrenal clearance of digoxin by nifedipine.
Nirmatrelvir; Ritonavir: (Major) In a pharmacokinetic study of 11 healthy men, increases in digoxin AUC (86%), volume of distribution, and half-life were seen, while renal and non-renal clearance decreased, when coadministered with ritonavir. It appears that this interaction is mediated by ritonavir's inhibition or P-glycoprotein-mediated renal tubular secretion of digoxin. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including digoxin) has not been evaluated. Measure serum digoxin concentrations before initiating ritonavir or lopinavir; ritonavir. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
Nisoldipine: (Moderate) The manufacturer of Sular reports that there are no significant interactions between nisoldipine core-coat and warfarin or digoxin. However, in a study of chronic coadministration of immediate release nisoldipine and digoxin in 10 patients with heart failure, nisoldipine was shown to elevate trough digoxin plasma concentrations by about 15%. A structurally related dihydropyridine, nifedipine, has been reported to increase digoxin levels up to 45%. In individual patients, significant elevation of digoxin plasma levels could occur with nisoldipine coadministration; monitoring of digoxin levels is advised.
Olmesartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Omeprazole: (Moderate) Omeprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Omeprazole increases the AUC of digoxin by about 10%. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Omeprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Omeprazole increases the AUC of digoxin by about 10%. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement. (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Omeprazole; Sodium Bicarbonate: (Moderate) Omeprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. Omeprazole increases the AUC of digoxin by about 10%. Patients with digoxin serum levels at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin levels when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Because, low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in addition to magnesium replacement.
Oxacillin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Oxaprozin: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Oxybutynin: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Oxymetazoline: (Major) Caution is advised when taking cardiac glycosides with alpha adrenergic agonists, such as oxymetazoline. Alpha adrenergic agonist can enhance ectopic pacemaker activity; thus, concurrent use with cardiac glycosides may result in arrhythmias.
Pacritinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing pacritinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and pacritinib is a P-gp inhibitor.
Pancuronium: (Moderate) Use pancuronium with caution in patients receiving digoxin due to an increased risk of dysrhythmia.
Pantoprazole: (Moderate) Monitor serum magnesium concentrations periodically in patients taking pantoprazole and digoxin concomitantly. Patients who develop hypomagnesemia may require pantoprazole discontinuation in addition to magnesium replacement. Proton pump inhibitors (PPIs) have been associated with hypomagnesemia which may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias. Additionally, monitor patients with digoxin serum concentrations at the upper end of the therapeutic range for potential increases in serum digoxin concentrations when coadministered with pantoprazole. Although pantoprazole has not been shown to increase digoxin bioavailability, other PPIs have slightly increased digoxin levels due to the long-lasting effect of the PPIs on gastric acid secretion, which affects the absorption of digoxin.
Parathyroid Hormone: (Moderate) Caution is warranted in patients receiving digoxin with parathyroid hormone (PTH) therapy. PTH therapy causes transient increases in serum calcium concentrations. Since the inotropic effects of digoxin are affected by serum calcium concentrations, hypercalcemia may predispose patients to digoxin toxicity. Digoxin efficacy is reduced if hypocalcemia is present. Monitor the patient's serum calcium and digoxin concentrations and for signs or symptoms of digitalis toxicity. Adjustment of digoxin and/or parathyroid hormone may be necessary. There has not been a formal drug interaction study of these 2 drugs together.
Paricalcitol: (Moderate) Paricalcitol should be administered with caution to patients receiving digoxin. Vitamin D analogs may cause hypercalemia which increases the risk of digitalis toxicity. In patients receiving paricalcitol and digoxin concurrently, monitor serum calcium frequently and monitor the patient for signs of digitalis toxicity. More frequent monitoring is necessary when initiating or adjusting the dose of paricalcitol.
Paromomycin: (Moderate) In approximately 10% of patients, a small portion of oral digoxin is metabolized by GI flora. Administration of a nonabsorbable aminoglycoside antibiotic such as paromomycin can depress colonic bacteria and increase the oral bioavailability of digoxin in these patients. Large doses of neomycin have been reported to reduce the absorption of digoxin leading to reduced steady-state digoxin concentrations of 28%. Since paromomycin is structurally related to neomycin, it is possible that paromomycin could also reduce digoxin bioavailability. It is thought that the decrease in digoxin absorption is due to alterations in the properties of the gut wall. Therefore, separating the time of administration between these drugs and digoxin will probably not reduce the potential interaction. Since it is impossible to predict which patients will be affected in this manner, digoxin serum concentrations should be monitored closely if oral paromomycin is added.
Paroxetine: (Minor) Paroxetine may slightly decrease mean digoxin area under the curve values. Until more clinical data are known, patients should be monitored for loss of digoxin clinical effect if paroxetine is added.
Pegaspargase: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Penicillamine: (Moderate) Decreased serum digoxin concentrations have been reported in patients who received digoxin and penicillamine. Measure serum digoxin concentrations before initiating penicillamine. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Penicillin G Benzathine: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Penicillin G Benzathine; Penicillin G Procaine: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Penicillin G Procaine: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Penicillin G: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Penicillin V: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Penicillins: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Pentobarbital: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Perindopril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Perindopril; Amlodipine: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Phenobarbital: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known. (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Phentermine; Topiramate: (Moderate) Serum digoxin AUC was decreased by 12% when coadministered with topiramate. Although the clinical relevance has not been determined, the clinician should be aware that serum digoxin concentrations may be affected when digoxin and topiramate are used concomitantly.
Phenytoin: (Moderate) Measure serum digoxin concentrations before starting and during concomitant phenytoin therapy; increase the digoxin dose by approximately 20% to 40% as necessary. Concomitant administration may result in decreased digoxin concentrations.
Pindolol: (Moderate) Because the pharmacologic effects of pindolol include depression of AV nodal conduction and myocardial function, additive effects are possible when used in combination with cardiac glycosides, especially in patients with pre-existing left ventricular dysfunction. The risk of additive inhibition of AV conduction is symptomatic bradycardia with hypotension or advanced AV block; whereas additive negative inotropic effects could precipitate overt heart failure in some patients. Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients.
Pioglitazone: (Moderate) Concentrations of digoxin may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of digoxin was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with digoxin 0.2 mg twice daily (loading dose) then 0.25 mg daily (maintenance dose, 7 days) resulted in a 15% and 17% increase in digoxin AUC and Cmax, respectively. Carefully monitor serum digoxin concentrations; observe patients carefully for signs of digoxin toxicity.
Pioglitazone; Glimepiride: (Moderate) Concentrations of digoxin may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of digoxin was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with digoxin 0.2 mg twice daily (loading dose) then 0.25 mg daily (maintenance dose, 7 days) resulted in a 15% and 17% increase in digoxin AUC and Cmax, respectively. Carefully monitor serum digoxin concentrations; observe patients carefully for signs of digoxin toxicity.
Pioglitazone; Metformin: (Moderate) Concentrations of digoxin may be increased with concomitant use of pioglitazone. The effect of pioglitazone capistration on the systemic exposure of digoxin was determined in a drug-drug interaction study. Coadministration of pioglitazone 45 mg once daily with digoxin 0.2 mg twice daily (loading dose) then 0.25 mg daily (maintenance dose, 7 days) resulted in a 15% and 17% increase in digoxin AUC and Cmax, respectively. Carefully monitor serum digoxin concentrations; observe patients carefully for signs of digoxin toxicity. (Moderate) Metformin may increase digoxin concentrations, but the magnitude is unclear. Measure serum digoxin concentrations before initiating metformin, and periodically after that. Monitor heart rate and other clinical parameters. Adjust digoxin dose as necessary.
Piperacillin; Tazobactam: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Piroxicam: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Pirtobrutinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing pirtobrutinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and pirtobrutinib is a P-gp inhibitor. Concomitant use was observed to increase digoxin overall exposure by 35%.
Polycarbophil: (Major) Since electrolyte disorders modify the actions of cardiac glycosides (e.g., digoxin and digitoxin), drugs that can affect electrolyte balance can potentially affect the response to digoxin. Hypercalcemia increases digoxin's effect, and each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). It is recommended that serum calcium be monitored regularly in patients receiving digoxin.
Polyethylene Glycol; Electrolytes: (Moderate) Administer digoxin at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of digoxin may be reduced by chelation with magnesium sulfate.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Moderate) Administer digoxin at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of digoxin may be reduced by chelation with magnesium sulfate.
Ponesimod: (Major) Avoid concomitant use of ponesimod and medications that may decrease heart rate such as digoxin due to the risk for severe bradycardia and heart block. Consider consultation from a cardiologist if concomitant use is necessary.
Posaconazole: (Moderate) Posaconazole and digoxin should be used together with caution due to the potential for digoxin-related adverse events. If used in combination, carefully monitor digoxin plasma concentrations during and at discontinuation of posaconazole therapy. Both posaconazole and digoxin are substrates of the drug efflux protein, P-glycoprotein, which when administered together may increase the absorption or decrease the clearance of the other drug. Increased plasma concentrations of digoxin have been reported during coadministration with posaconazole.
Potassium Phosphate: (Major) Avoid coadministration of potassium phosphate and digoxin as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium Phosphate; Sodium Phosphate: (Major) Avoid coadministration of potassium phosphate and digoxin as concurrent use may increase the risk of severe and potentially fatal hyperkalemia, particularly in high-risk patients (renal impairment, cardiac disease, adrenal insufficiency). If concomitant use is necessary, closely monitor serum potassium concentrations.
Potassium: (Minor) Potassium levels should be monitored closely in patients receiving digoxin and potassium supplementation. Both hypokalemia and hyperkalemia increase the risk of digoxin toxicity. Some patients at increased risk are patients with renal impairment, patients on diuretics, and patients who are on potassium-sparing medications concurrently. Monitor renal function, potassium concentrations, and digoxin concentrations and clinical response during concurrent treatment.
Pretomanid: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing pretomanid. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and pretomanid is a P-gp inhibitor.
Primidone: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Probenecid; Colchicine: (Major) According to the manufacturer of Colcrys, both digoxin and colchicine are substrates of P-glycoprotein (Pgp) and rhabdomyolysis has been reported in patients on concurrent therapy. If such agents are co-administered, advise patients to report signs and symptoms of myotoxicity including muscle tenderness, pain, or weakness; monitoring creatine phosphokinase may not predict the development of severe myopathy.
Propafenone: (Major) Propafenone reduces the clearance of digoxin and may lead to digoxin toxicity. Increases in digoxin serum concentrations may occur in over 80% of patients when propafenone is added to the regimen. Concomitant use of propafenone and digoxin has been reported to increase the steady-state AUC of orally administered digoxin by 60 to 270%, and decrease digoxin clearance by 31 to 67%. When propafenone is coadministered with intravenous (IV) digoxin, the serum concentration of digoxin is increased by 28%. Although the exact mechanism for this interaction has not been established, several mechanisms have been proposed including reduced distribution volume and nonrenal clearance of digoxin, as well as potential inhibition of P-glycoprotein renal tubular transport of digoxin. Measure serum digoxin concentrations before initiating propafenone. Reduce digoxin concentrations by decreasing the oral digoxin dose by approximately 30 to 50%, decreasing the IV digoxin dose by 15 to 30%, or by modifying the dosing frequency and continue monitoring.
Propantheline: (Major) Coadministration of digoxin and propantheline increases both the serum concentration and AUC of digoxin by 24%. Measure serum digoxin concentrations before initiating propantheline. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Anticholinergics, because of their ability to cause tachycardia, can also antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Propranolol: (Moderate) Monitor heart rate during concomitant digoxin and propranolol use due to increased risk for bradycardia. Both digoxin and propranolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor heart rate during concomitant digoxin and propranolol use due to increased risk for bradycardia. Both digoxin and propranolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Propylthiouracil, PTU: (Minor) Serum concentrations of digoxin can increase as hyperthyroidism is corrected. In patients receiving antithyroid therapy, the dosage of digoxin may need to be reduced as the patient becomes euthyroid.
Psyllium: (Moderate) Psyllium can interfere with the absorption of certain oral drugs if administered together. Psyllium can adsorb cardiac glycosides. Per the manufacturer, administration of other oral drugs should be separated from the administration of psyllium by at least 2 hours.
Pyridoxine, Vitamin B6: (Moderate) Monitor for signs and symptoms of digoxin toxicity during concomitant calcium use. Hypercalcemia may predispose persons to digoxin toxicity. If IV calcium is administered rapidly in a person receiving digoxin, serious arrhythmias may occur. Monitor ECG and calcium concentrations closely during IV calcium and digoxin administration.
Quinapril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Quinidine: (Major) Coadministration of quinidine and oral digoxin has resulted in a 100% increase in digoxin serum concentrations. When quinidine is coadministered with intravenous (IV) digoxin, the digoxin AUC is increased by 54 to 83%. Digoxin is a P-gp substrate and quinidine inhibits P-gp. The inhibition of P-gp in the intestinal cell wall may lead to increased oral absorption of digoxin. It also has been shown that quinidine inhibits the secretion of digoxin by P-gp transporters in the kidney leading to decreased renal tubular elimination of digoxin and increased serum concentrations. Measure serum digoxin concentrations before initiating quinidine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
Quinine: (Major) Coadministration of digoxin and quinine increases the AUC of digoxin by 33%. Both digoxin and quinine are substrates for P-glycoprotein (P-gp). Measure serum digoxin concentrations before initiating quinine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. Lower doses of quinine may have no effect on digitalis clearance.
Rabeprazole: (Moderate) Rabeprazole or other proton pump inhibitors (PPIs) can affect digoxin absorption due to their long-lasting effect on gastric acid secretion. Additionally, PPIs may slightly increase digoxin bioavailability. When rabeprazole was co-administered with digoxin, the AUC and Cmax for digoxin increased 19% and 29%, respectively. Patients with digoxin serum concentrations at the upper end of the therapeutic range may need to be monitored for potential increases in serum digoxin concentrations when a PPI is coadministered with digoxin. Finally, PPIs have been associated with hypomagnesemia. Because low serum magnesium may lead to irregular heartbeat and increase the likelihood of serious cardiac arrhythmias, clinicians should monitor serum magnesium concentrations periodically in patients taking a PPI and digoxin concomitantly. Patients who develop hypomagnesemia may require PPI discontinuation in a ddition to magnesium replacement.
Ramipril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Ranolazine: (Major) In vitro studies suggest that ranolazine is a P-glycoprotein inhibitor. Ranolazine increases digoxin concentrations by 1.5-fold in healthy volunteers receiving ranolazine (1000 mg PO twice daily) and digoxin (0.125 mg PO once daily). Measure serum digoxin concentrations before initiating ranolazine. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring. In contrast, digoxin does not increase the plasma concentrations of ranolazine. No dose adjustment of ranolazine is required for patients treated with digoxin.
Regadenoson: (Major) Because of the potential for additive or synergistic depressant effects on SA and AV nodes, regadenoson should be used with caution in the presence of agents that slow cardiac conduction, such as digoxin.
Rifampin: (Moderate) It appears that rifampin decreases serum concentrations of digoxin by inducing intestinal P-glycoprotein and decreasing the oral bioavailability of digoxin by 30.1%. The Cmax and AUC of digoxin were decreased by 43% and 58%, respectively. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of rifampin. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Ritonavir: (Major) In a pharmacokinetic study of 11 healthy men, increases in digoxin AUC (86%), volume of distribution, and half-life were seen, while renal and non-renal clearance decreased, when coadministered with ritonavir. It appears that this interaction is mediated by ritonavir's inhibition or P-glycoprotein-mediated renal tubular secretion of digoxin. Ritonavir also prolongs the PR interval in some patients; however, the impact on the PR interval of coadministration of ritonavir with other drugs that prolong the PR interval (including digoxin) has not been evaluated. Measure serum digoxin concentrations before initiating ritonavir or lopinavir; ritonavir. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring.
Rolapitant: (Moderate) Avoid the concurrent use of digoxin and rolapitant if possible; if coadministration is necessary, monitor digoxin levels and watch for digoxin-related adverse effects. Digoxin is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Sacubitril; Valsartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Saquinavir: (Major) The concurrent use of saquinavir boosted with ritonavir and digoxin should be used very cautiously due to the potential for increased serum digoxin concentrations and possible cardiac arrhythmias. The increase in serum concentrations may be greater in females, as compared to males. Additionally, saquinavir boosted with ritonavir causes dose-dependent PR prolongation; if possible, avoid use with other drugs that may prolong the PR interval, such as digoxin. If concomitant therapy cannot be avoided, measure serum digoxin concentrations before initiating saquinavir boosted with ritonavir. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30-50% or by modifying the dosing frequency and continue monitoring.
Sarecycline: (Major) Measure serum digoxin concentrations before initiating sarecycline. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30% to 50% or by modifying the dosing frequency and continue monitoring. Coadministration may increase serum concentrations of digoxin. Digoxin is a substrate for P-glycoprotein (P-gp); sarecycline is an inhibitor of P-gp. Coadministration of a single dose of sarecycline 150 mg resulted in a 26% increase in the Cmax of digoxin.
Saxagliptin: (Moderate) The AUC and Cmax of digoxin may be increased in the presence of saxagliptin. Dosage adjustment of digoxin is not recommended, but patients receiving these 2 drugs at the same time should be monitored closely.
Scopolamine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Secobarbital: (Moderate) Hepatic enzyme inducing drugs, such as barbiturates, can accelerate the metabolism of digoxin, decreasing its serum concentrations. It is recommended that digoxin concentrations be monitored if used with barbiturates.
Selpercatinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing selpercatinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and selpercatinib is a P-gp inhibitor.
Semaglutide: (Moderate) Consider increased clinical or laboratory monitoring for digoxin if administered with oral semaglutide as the oal absorption of digoxin may be altered. Semaglutide delays gastric emptying and therefore has the potential to affect absorption of other orally administered medications. Be sure to administer oral semaglutide as directed, separately from other oral medications. This interaction does not occur with subcutaneous semaglutide or IV digoxin.
Simvastatin: (Moderate) Simvastatin causes a slight elevation of serum digoxin levels. Simvastatin should be used cautiously in patients receiving digoxin.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving digoxin due to the potential for additive effects on heart rate. Consult a cardiologist regarding appropriate monitoring if siponimod use is required.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing taurursodiol. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and taurursodiol is a P-gp inhibitor.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Digoxin may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, digoxin should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution. In addition, the manufacturer cautions the use of sodium picosulfate; magnesium oxide; anhydrous citric acid solution in patients receiving drugs where hypokalemia is a particular risk, such as digoxin.
Sodium Polystyrene Sulfonate: (Moderate) Since electrolyte disorders modify the actions of digoxin, drugs that can affect electrolyte balance, such as sodium polystyrene sulfonate, potentially can increase the effect and potentiate the toxicity of digoxin.
Sofosbuvir; Velpatasvir: (Moderate) Therapeutic serum concentration monitoring of digoxin is recommended when coadministered with velpatasvir due to the potential for increased digoxin serum concentrations. A digoxin dose modification may be necessary. A single-dose pharmacokinetic study showed increases in the Cmax (188%) and AUC (134%) of digoxin when administered with velpatasvir compared to no coadministration. Digoxin is a P-glycoprotein (P-gp) substrate and velpatasvir inhibits P-gp.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Increased digoxin serum concentrations may occur when digoxin is coadministered with voxilaprevir. Monitor digoxin serum concentrations and adjust digoxin dose as necessary. Digoxin is a P-glycoprotein (P-gp) substrate and voxilaprevir inhibits P-gp. (Moderate) Therapeutic serum concentration monitoring of digoxin is recommended when coadministered with velpatasvir due to the potential for increased digoxin serum concentrations. A digoxin dose modification may be necessary. A single-dose pharmacokinetic study showed increases in the Cmax (188%) and AUC (134%) of digoxin when administered with velpatasvir compared to no coadministration. Digoxin is a P-glycoprotein (P-gp) substrate and velpatasvir inhibits P-gp.
Sorafenib: (Moderate) Monitor for an increase in digoxin plasma concentrations and digoxin-related adverse reactions if coadministration with sorafenib is necessary. Digoxin is a P-glycoprotein (P-gp) substrate and sorafenib inhibits P-gp in vitro. Sorafenib may increase the concentrations of concomitantly administered drugs that are P-gp substrates.
Sotagliflozin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing sotagliflozin. Concurrent use may increase digoxin exposure; concomitant use with digoxin increased overall exposure by 131%.
Sotalol: (Moderate) Sotalol and digoxin should be used together cautiously. Digoxin and sotalol slow AV conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. In addition, digoxin used concomitantly with sotalol can increase the possibility of proarrhythmia. Proarrhythmic events were more common in sotalol-treated patients also receiving digoxin; it is not clear whether this represents an interaction or is related to the presence of CHF, a known risk factor for proarrhythmia. Single and multiple doses of sotalol do not appear to interfere substantially with digoxin serum concentrations.
Sotorasib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing sotorasib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and sotorasib is a P-gp inhibitor.
Sparsentan: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing sparsentan. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and sparsentan is a P-gp inhibitor.
Spironolactone: (Major) Monitor serum digoxin concentrations before initiating concomitant spironolactone. Reduce digoxin concentrations by decreasing the dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. Concomitant use increased digoxin concentrations by 25%. Spironolactone and its metabolites interfere with radioimmunoassays for digoxin and increase the apparent exposure to digoxin. It is unknown to what extent, if any, spironolactone may increase actual digoxin exposure. In persons taking concomitant digoxin, use an assay that does not interact with spironolactone.
Spironolactone; Hydrochlorothiazide, HCTZ: (Major) Monitor serum digoxin concentrations before initiating concomitant spironolactone. Reduce digoxin concentrations by decreasing the dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. Concomitant use increased digoxin concentrations by 25%. Spironolactone and its metabolites interfere with radioimmunoassays for digoxin and increase the apparent exposure to digoxin. It is unknown to what extent, if any, spironolactone may increase actual digoxin exposure. In persons taking concomitant digoxin, use an assay that does not interact with spironolactone.
St. John's Wort, Hypericum perforatum: (Moderate) Consider if St. John's Wort supplementation is appropriate in patients receiving digoxin. Monitor serum digoxin concentrations before starting St. John's Wort. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary. Conversely, the discontinuation of St. John's wort could lead to increased digoxin exposure and potential toxicity. An interaction between St. John's wort, Hypericum perforatum and digoxin has been studied. After the achievement of steady-state digoxin levels, 25 healthy volunteers received digoxin (0.25 mg/day) either with placebo or with St. John's wort extract (900 mg/day),patients receiving St. John's Wort had a reduction in digoxin AUC of approximately 25%. Digoxin trough concentrations and Cmax decreased by 33% and 26%, respectively. St. John's wort appears to induce the P-glycoprotein intestinal drug transporter, which extrudes digoxin back into the GI tract and results in decreased systemic bioavailability.
Succinylcholine: (Moderate) Succinylcholine-induced potassium release from muscle cells may cause arrhythmias in patients receiving digoxin.
Sucralfate: (Moderate) Sucralfate, because it contains aluminum in its structure and due to its mechanism of action, can bind with digoxin in the GI tract, reducing its bioavailability. Sucralfate should be given 2 hours before or after the oral administration of digoxin. In addition, the manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of sucralfate. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) Monitor serum digoxin concentrations before initiating concomitant trimethoprim. Reduce digoxin concentrations by decreasing the dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. Concomitant use increased digoxin concentrations by 22% to 28%.
Sulfasalazine: (Moderate) Sulfasalazine has been reported to reduce the absorption of digoxin by 20%. It is thought that the decrease in digoxin absorption is due to alterations in the properties of the gut wall. Therefore, separating the time of administration between sulfasalazine and digoxin will probably not reduce the potential interaction. The manufacturer of digoxin recommends measuring serum digoxin concentrations prior to initiation of sulfasalazine. Continue monitoring during concomitant treatment and increase the digoxin dose by 20 to 40% as necessary.
Sulindac: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Sumatriptan; Naproxen: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Suvorexant: (Major) Digoxin concentrations should be monitored during use with suvorexant. In one evaluation, concomitant administration of digoxin and suvorexant slightly increased digoxin levels presumably due to inhibition of intestinal P-glycoprotein (P-gp) by suvorexant.
Teduglutide: (Moderate) Teduglutide may increase absorption of digoxin because of it's pharmacodynamic effect of improving intestinal absorption. Careful monitoring and possible dose adjustment of digoxin is recommended.
Tegaserod: (Minor) When digoxin is combined with tegaserod, a reduction in digoxin peak plasma concentration occurs. Digoxin dose adjustments are unlikely to be required when combined with tegaserod. Until further clinical use is gained with tegaserod, use caution and consider monitoring digoxin levels more frequently if combined with tegaserod.
Telmisartan: (Major) When telmisartan is coadministered with digoxin, median increases in digoxin peak concentration (49%) and in trough concentration (20%) are observed. Measure serum digoxin concentrations before initiating telmisartan. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Telmisartan; Amlodipine: (Major) When telmisartan is coadministered with digoxin, median increases in digoxin peak concentration (49%) and in trough concentration (20%) are observed. Measure serum digoxin concentrations before initiating telmisartan. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Telmisartan; Hydrochlorothiazide, HCTZ: (Major) When telmisartan is coadministered with digoxin, median increases in digoxin peak concentration (49%) and in trough concentration (20%) are observed. Measure serum digoxin concentrations before initiating telmisartan. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 15-30% or by modifying the dosing frequency and continue monitoring. In addition, caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Temsirolimus: (Moderate) Monitor digoxin levels and watch for an increase in digoxin -related adverse reactions if coadministration with temsirolimus is necessary. Digoxin is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. Concomitant use is likely to lead to increased concentrations of digoxin.
Tepotinib: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing tepotinib. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and tepotinib is a P-gp inhibitor.
Teriparatide: (Minor) Sporadic case reports have suggested that hypercalcemia may predispose patients to digitalis toxicity. Because teriparatide increases serum calcium it should be used with caution in patients taking digoxin. Administering a single dose of teriparatide to patients with steady state digoxin levels did not alter the effect of digoxin on the systolic time interval.
Tetracycline: (Major) Measure serum digoxin concentrations before initiating tetracyclines. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30 to 50% or by modifying the dosing frequency, and continue monitoring. In approximately 10% of patients, a small portion of a digoxin dose is metabolized in the gut by intestinal Eubacterium lentum, an anaerobic bacillus, to inactive digoxin reduction products (DRPs). DRPs have little cardiac activity due to poor cardiac receptor binding and rapid excretion. Certain antibiotics can reduce the activity of intestinal bacteria, which, in turn, may enhance digoxin bioavailability via decreased DRP formation and increased enterohepatic recycling of digoxin in some patients. The addition of tetracycline to digoxin therapy has been reported to increase the serum digoxin concentration by 100%. Digoxin toxicity has been reported in patients previously stabilized on digoxin who receive antibiotics that affect E. lentum, such as tetracyclines. Other antibiotics that have activity against E. lentum may produce similar effects on digoxin metabolism.
Tezacaftor; Ivacaftor: (Moderate) Administration of tezacaftor; ivacaftor may increase the systemic exposure of digoxin and increase or prolong the therapeutic effect and adverse reactions. Appropriate monitoring should be used. Digoxin is a sensitive P-gp substrate; ivacaftor is a weak inhibitor of P-gp. Coadministration of tezacaftor; ivacaftor with digoxin increased digoxin exposure by 1.3-fold. (Moderate) Coadministration of ivacaftor with digoxin may increase digoxin exposure leading to increased or prolonged therapeutic effects and adverse events. Digoxin is a substrate for P-glycoprotein (P-gp). Ivacaftor is an inhibitor of P-glycoprotein (P-gp). Use caution when administering ivacaftor and digoxin concurrently.
Thalidomide: (Moderate) Thalidomide and digoxin should be used cautiously due to the potential for additive bradycardia. The pharmacokinetic parameters of thalidomide and digoxin were not affected when a single dose of digoxin 0.5 mg was administered in 16 healthy men who were receiving thalidomide 200 mg/day (at steady state levels).
Thiazide diuretics: (Moderate) Monitor serum magnesium and potassium during concomitant cardiac glycoside and thiazide diuretic use. Potassium-depleting diuretics are a major contributing factor to digoxin toxicity.
Thyroid hormones: (Minor) Thyroid disease is known to alter the response to digoxin. Digoxin toxicity is more likely to occur in patients with hypothyroidism, while the response to digoxin is diminished in patients with hyperthyroidism. These reactions should be kept in mind when therapy with thyroid hormones is begun or interrupted. When hypothyroid patients are administered thyroid hormone, the dose requirement of digoxin may be increased.
Ticagrelor: (Moderate) Monitor digoxin concentrations when used concomitantly with ticagrelor. Ticagrelor is a P-gp inhibitor and digoxin is metabolized by P-gp.
Ticlopidine: (Minor) Ticlopidine has been shown to slightly decrease digoxin plasma levels. The magnitude of this pharmacokinetic interaction may not be clinically significant.
Timolol: (Moderate) Monitor heart rate during concomitant digoxin and timolol use due to increased risk for bradycardia. Both digoxin and timolol slow atrioventricular conduction (AV) and decrease heart rate; additive effects on AV node conduction can result in bradycardia and advanced or complete heart block.
Tolmetin: (Moderate) Concomitant use of nonsteroidal antiinflammatory drugs (NSAIDs) with digoxin may result in increased serum concentrations of digoxin. NSAIDs may cause a significant deterioration in renal function. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Monitor patients during concomitant treatment for possible digoxin toxicity and reduce digoxin dose as necessary.
Tolterodine: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Tolvaptan: (Moderate) Monitor serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing tolvaptan. Concurrent use may increase digoxin exposure. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and tolvaptan is a P-gp inhibitor. Coadministration of digoxin and tolvaptan increased digoxin peaks by 30% and overall exposure by 20%.
Topiramate: (Moderate) Serum digoxin AUC was decreased by 12% when coadministered with topiramate. Although the clinical relevance has not been determined, the clinician should be aware that serum digoxin concentrations may be affected when digoxin and topiramate are used concomitantly.
Tositumomab: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Tramadol: (Moderate) An increased incidence of digoxin toxicity has been reported in some patients during postmarketing reports with the concurrent use of tramadol and digoxin.
Tramadol; Acetaminophen: (Moderate) An increased incidence of digoxin toxicity has been reported in some patients during postmarketing reports with the concurrent use of tramadol and digoxin.
Trandolapril: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Trandolapril; Verapamil: (Major) Consider an empiric digoxin dosage reduction when used with verapamil. Follow digoxin concentrations closely and monitor for signs and symptoms of digoxin toxicity. Concomitant use may increase digoxin exposure and the risk for digoxin related adverse effects. The risk for bradycardia and hypotension may also increase. Chronic verapamil treatment has been observed to increase digoxin levels by 50% to 75% during the first week of digoxin therapy. Digoxin is a P-gp substrate and verapamil is a P-gp inhibitor. (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin-converting enzyme inhibitors (ACE inhibitors). A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Trazodone: (Moderate) Monitor digoxin concentrations before initiating concomitant trazodone and continually during therapy; decrease digoxin dose as clinically necessary. Trazodone may increase digoxin concentrations.
Tretinoin, ATRA: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Trihexyphenidyl: (Moderate) Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Trimethoprim: (Major) Monitor serum digoxin concentrations before initiating concomitant trimethoprim. Reduce digoxin concentrations by decreasing the dose by approximately 15% to 30% or by modifying the dosing frequency and continue monitoring. Concomitant use increased digoxin concentrations by 22% to 28%.
Trospium: (Moderate) Oral formulations of digoxin can produce higher serum concentrations when administered concurrently with antimuscarinics (e.g., propantheline) because of decreased GI motility induced by the antimuscarinic agent. This interaction has mostly occurred in the literature with slowly-dissolving, large-particle formulations of digoxin tablets; the manufacture of oral digoxin products today, utilizing liquid formulations and/or smaller particle sizes, theoretically reduces the potential for absorption interactions. However, there is wide variability expected in individual responses to many digoxin-drug interactions. Other pharmacodynamic and pharmacokinetic systemic interactions are possible between digoxin and select antimuscarinic agents. Both trospium (a selective antimuscarinic) and digoxin are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or digoxin due to competition for the drug elimination pathway. Darifenacin (30 mg daily) coadministered with digoxin (0.25 mg daily) resulted in a 16% increase in digoxin exposure. Anticholinergics, because of their ability to cause tachycardia, can also antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
Tucatinib: (Moderate) Monitor for an increase in digoxin-related adverse reactions if coadministration with tucatinib is necessary; monitor digoxin concentrations as clinically appropriate. Concurrent use may increase digoxin exposure. Digoxin is a P-glycoprotein (P-gp) substrate with a narrow therapeutic index and tucatinib is a P-gp inhibitor. Coadministration with tucatinib increased digoxin exposure by 50%.
Uridine Triacetate: (Moderate) Coadministration of uridine triacetate and digoxin may increase digoxin serum concentrations; monitor digoxin serum concentrations and therapeutic/adverse effects if these drugs are administered together. Both digoxin and uridine triacetate are substrates for P-glycoprotein (P-gp). Due to the potential for high local gut concentrations of the drug after dosing, the interaction of uridine triacetate with digoxin and other orally administered P-gp substrate drugs cannot be ruled out.
Valbenazine: (Major) Digoxin concentrations should be monitored during concurrent use of valbenazine. During co-administration of valbenazine and digoxin, the Cmax of digoxin increased nearly 2-fold and the AUC increased over 1-fold due to inhibition of intestinal P-glycoprotein (P-gp) by valbenazine. An increase in digoxin exposure may result in digoxin toxicity (e.g., cardiac arrhythmias, nausea and vomiting, and visual disturbances), A dosage adjustment of digoxin may be necessary.
Valsartan: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution should be exercised when administering digoxin with drugs that may cause a significant deterioration in renal function including angiotensin II receptor antagonists. A decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. Close monitoring of serum digoxin concentrations is essential to avoid enhanced toxicity.
Vandetanib: (Moderate) Monitor closely for digoxin-related toxicities (e.g., arrhythmias, confusion, vision changes, and nausea) if coadministration with vandetanib is necessary. Digoxin is a substrate of P-glycoprotein (P-gp). Coadministration with a single dose of vandetanib increased the Cmax and AUC of digoxin by 29% and 23%, respectively.
Vasopressors: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and digoxin; increased digoxin exposure has been reported. If coadministration is unavoidable, consider a digoxin dose reduction and monitor patients carefully for signs and symptoms of digoxin toxicity (e.g., arrhythmias, heart block). Vemurafenib is a substrate and inhibitor P-glycoprotein (P-gp) and digoxin is a sensitive P-gp substrate with a narrow therapeutic index. The digoxin AUC and Cmax values were increased by 1.8-fold (90% CI, 1.6 to 2) and 1.5-fold (90% CI, 1.3 to 1.7), respectively, in 26 cancer patients who received vemurafenib 960 mg PO twice daily for 22 days and a single 0.25 mg-dose of digoxin.
Venetoclax: (Major) Avoid the concomitant use of venetoclax and digoxin as digoxin levels may be increased. If concomitant use of these drugs is required, administer digoxin at least 6 hours before venetoclax. Monitor patients for signs and symptoms of digoxin toxicity. Venetoclax is an inhibitor of P-glycoprotein (P-gp) and digoxin is a P-gp substrate with a narrow therapeutic index. Coadministration of a single 100-mg dose of venetoclax with digoxin led to an increase in digoxin Cmax and AUC values by 35% and 9%, respectively.
Verapamil: (Major) Consider an empiric digoxin dosage reduction when used with verapamil. Follow digoxin concentrations closely and monitor for signs and symptoms of digoxin toxicity. Concomitant use may increase digoxin exposure and the risk for digoxin related adverse effects. The risk for bradycardia and hypotension may also increase. Chronic verapamil treatment has been observed to increase digoxin levels by 50% to 75% during the first week of digoxin therapy. Digoxin is a P-gp substrate and verapamil is a P-gp inhibitor.
Vibegron: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing vibegron. Concurrent use may increase digoxin exposure. Concomitant administration of vibegron increased digoxin Cmax by 21% and AUC by 11%.
Vilazodone: (Moderate) Concomitant use of digoxin, a P-gp substrate, and vilazodone may increase digoxin concentrations. Because digoxin is a narrow therapeutic index drug, serum digoxin concentrations should be measured before initiating vilazodone, with periodic monitoring throughout concurrent treatment. Adjust the digoxin dose as necessary.
Voclosporin: (Moderate) Increase monitoring of serum digoxin concentrations and watch for potential signs and symptoms of clinical toxicity when starting, adjusting, or discontinuing voclosporin. Concurrent use may increase digoxin exposure. Digoxin is a P-gp substrate with a narrow therapeutic index and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Clarithromycin has been reported to increase the digoxin AUC by 70% when digoxin is administered orally. No significant changes in digoxin exposure were reported when digoxin was administered intravenously (IV). Originally, this interaction was thought to be due to inhibition of intestinal flora, which leads to decreased intestinal metabolism of digoxin to inactive digoxin reduction products (DRPs). While this may occur, only 5% of a digoxin dose is subject to metabolism by gut flora and this mechanism does not account for the large increases in digoxin levels that occur with the coadministration of clarithromycin. A more important factor is clarithromycin inhibition of P-glycoprotein (P-gp), an energy-dependent drug efflux pump. Digoxin is a P-gp substrate. Inhibition of this protein in the intestinal cell wall leads to increased oral absorption and decreased renal and non-renal clearance of digoxin. Measure serum digoxin concentrations before initiating clarithromycin. Reduce digoxin concentrations by decreasing the oral digoxin dose by approximately 30 to 50% or by modifying the dosing frequency and continue monitoring. No dosage adjustment is required when digoxin is administered IV. (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Vorinostat: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Zonisamide: (Minor) Zonisamide is a weak inhibitor of P-glycoprotein (P-gp), and digoxin is a substrate of P-gp. There is theoretical potential for zonisamide to affect the pharmacokinetics of drugs that are P-gp substrates. Use caution when starting or stopping zonisamide or changing the zonisamide dosage in patients also receiving drugs which are P-gp substrates.

How Supplied

Digitek/Digoxin/Lanoxin Oral Tab: 0.0625mg, 0.125mg, 0.25mg
Digoxin/Lanoxin Oral Sol: 0.05mg, 1mL
Digoxin/Lanoxin/Lanoxin Pediatric Intramuscular Inj Sol: 0.1mg, 0.25mg, 1mL, 2mL, 500mcg
Digoxin/Lanoxin/Lanoxin Pediatric Intravenous Inj Sol: 0.1mg, 0.25mg, 1mL, 2mL, 500mcg

Maximum Dosage

Digoxin has a narrow therapeutic index. In all populations, the dosage is individualized based on patient weight, renal function, clinical goals, patient response, and when needed, serum digoxin concentrations.

Mechanism Of Action

Digoxin inhibits the Na-K-ATPase membrane pump. Na-K-ATPase regulates intracellular sodium and potassium. Inhibition of this enzyme leads to an increase in intracellular sodium concentration (i.e., decreased outward transport) and ultimately to an increase in intracellular calcium as sodium-calcium exchange is stimulated by high intracellular sodium concentrations. It is believed that increased intracellular concentrations of calcium allow for greater activation of contractile proteins (e.g., actin, myosin). While the contractile proteins and the troponin-tropomysin system are directly involved in muscular contraction, it is not clear how digoxin augments their action. Digoxin does not directly affect these proteins or the cellular mechanisms that provide energy for contraction, nor does it affect contraction in skeletal muscle. Digoxin also increases sympathetic tone, however, this does not account for the positive inotropic effect which persists even in the presence of beta-adrenergic blockade.
 
Digoxin directly increases the force and velocity of myocardial contraction in both healthy and failing hearts. In the failing heart, an increased force of contraction raises cardiac output, resulting in greater systolic emptying and a smaller diastolic heart size. End-diastolic pressures decrease, leading to a reduction in pulmonary and systemic venous pressures. In patients with normal hearts, however, cardiac output remains unchanged. Digoxin also possesses direct vasoconstrictive properties and reflex CNS-mediated peripheral vasoconstriction. Although this increases vascular resistance, in patients with failing hearts, increased myocardial contractility predominates and total peripheral resistance drops. In patients with congestive heart failure, an increased cardiac output will decrease sympathetic tone, thereby reducing the heart rate and causing diuresis in edematous patients and improving coronary blood flow.
 
In addition to its inotropic effects, digoxin also possesses significant actions on the electrical activity of the heart. It increases the slope of phase 4 depolarization, shortens the action potential duration, and decreases the maximal diastolic potential. The increase in vagal activity mediated by cardiac glycosides decreases conduction velocity through the atrioventricular (AV) node, prolonging its effective refractory period. In atrial flutter or fibrillation, digoxin decreases the number of atrial depolarizations that reach the ventricle, thereby slowing ventricular rate. Sympathetic stimulation, however, easily overrides the beneficial inhibitory effects of digoxin on AV nodal conduction. Thus, verapamil and diltiazem are gradually replacing digoxin as the agent to control ventricular rate in atrial tachyarrhythmias. While digoxin is somewhat effective in controlling ventricular rate in atrial fibrillation, it appears to be no better than placebo for converting recent-onset atrial fibrillation to normal sinus rhythm.

Pharmacokinetics

Digoxin is administered orally, intravenously, or intramuscularly. After administration, digoxin undergoes a 6- to 8-hour distribution phase in which serum concentrations fall more rapidly followed by a slower elimination phase. Digoxin distributes throughout the body tissues, with the highest concentrations found in the heart, kidneys, intestine, liver, stomach, and skeletal muscle. Small amounts can be found in the brain. Since digoxin concentrates in the tissues, it has a large volume of distribution. Early serum concentrations do not represent digoxin concentrations at the sites of action; however, an equilibrium is obtained between serum and tissue concentrations at steady-state, post-distribution with chronic digoxin therapy. The presence of congestive heart failure slows the rate at which steady-state distribution is achieved. Approximately 25% of the drug is plasma protein-bound. Digoxin crosses the placenta, and maternal and fetal plasma concentrations of the drug are equal.
 
A small amount of digoxin (approximately 13 to 16%) is metabolized in the liver via hydrolysis, oxidation, and conjugation; the cytochrome P450 system is not involved in the metabolism of digoxin. Fifty to 70% of an intravenous dose is excreted unchanged in the urine. The elimination half-life in adults is normally 36 to 48 hours, but heart failure or renal impairment can prolong digoxin elimination.
 
Affected cytochrome P450 isoenzymes and drug transporters: P-glycoprotein (P-gp)
Digoxin is a substrate for P-glycoprotein transport; drug-drug interactions may occur with drugs that are P-gp inducers or inhibitors.

Oral Route

In general, digoxin is rapidly absorbed from the GI tract following an oral dose. In approximately 10% of patients, 40% or more of an orally ingested digoxin is converted to inactive metabolites, such as dihydrodigoxin, in the gut by colonic bacteria.
Oral Tablet: Peak serum concentrations occur within 1 to 3 hours after oral digoxin administration. Bioavailability is approximately 60 to 80% from oral tablets. Onset of therapeutic effects generally occurs within 30 minutes to 2 hours and peak effect within 2 to 6 hours after oral administration of a dose. The rate of digoxin absorption is slower, but the amount absorbed is usually unchanged when digoxin tablets are taken after meals. However, when digoxin tablet are administered with a high fiber meal, digoxin absorption is reduced.
Oral Solution: Peak serum concentrations occur within 30 to 90 minutes after oral digoxin administration. Bioavailability is approximately 70 to 85% from the oral solution. Peak serum concentrations increase by 20% and total absorption increases by 43% when the digoxin solution is taken after meals, but absorption rate is unchanged. Administration after a high fiber meal reduces digoxin absorption.

Intravenous Route

Onset of therapeutic effects generally occurs within 5 to 30 minutes and peak effect within 1 to 4 hours after IV administration.

Pregnancy And Lactation
Pregnancy

Published retrospective clinical studies and case reports with digoxin use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse fetal or maternal outcomes. Low birth weight has been observed in infants born to patients who received digoxin therapy during pregnancy. Animal reproduction studies have not been conducted with digoxin. Digoxin crosses the placenta and is found in amniotic fluid. Monitor neonates exposed to digoxin in utero for signs and symptoms of digoxin toxicity, including vomiting and cardiac arrhythmias. Digoxin requirements may increase during pregnancy and decrease in the postpartum period; closely monitor serum digoxin concentrations during pregnancy and the postpartum period. Serum concentrations of digoxin may be altered during pregnancy due to circulating digoxin-like fragments that can falsely increase concentrations. Evaluate for signs of digoxin toxicity (e.g., arrhythmia and vomiting) at any digoxin serum concentration. The risk of arrhythmia may be increased during labor and obstetric delivery; monitor patients continually during labor and delivery. Untreated underlying maternal conditions (e.g., heart failure and atrial fibrillation) during pregnancy pose a risk to the mother and fetus, including maternal or fetal death. Pregnant women with heart failure are at increased risk for preterm birth, and pregnant women with atrial fibrillation are at an increased risk of delivering a low birth weight infant.[28272] Based upon available data and guidelines, use of digoxin during pregnancy is generally considered safe.