Digoxin

Pronunciation: (dih-JOX-in)

Class: Cardiac glycoside

Trade Names:

Digoxin

- Elixir, pediatric 0.05 mg/mL

Trade Names:
Lanoxicaps

- Capsules 0.1 mg

Trade Names:

Lanoxin

- Tablets 0.125 mg

- Tablets 0.25 mg

- Injection 0.25 mg/mL

- Injection, pediatric 0.1 mg/mL

Apo-Digoxin (Canada)

Digoxin Injection C.S.D. (Canada)

Digoxin Pediatric Injection C.S.D. (Canada)

PMS-Digoxin (Canada)

Pharmacology

Increases force and velocity of myocardial systolic contraction (positive inotropic action), slows heart rate, and decreases conduction through atrioventricular node.
Pharmacokinetics

Absorption

Bioavailability

100% (IV), 90% to 100% (capsules), 70% to 85% (elixir), 60% to 80% (tablets). T max is 1 to 3 h (oral). Food slows the rate of absorption after oral administration.

Distribution

6 to 8 h tissue distribution phase. Large apparent Vd. Crosses blood-brain barrier and placenta. Excreted in breast milk. Approximately 25% protein bound.

Metabolism

Approximately 16% metabolized; metabolites formed by hydrolysis, oxidation, and conjugation.

Elimination

Elimination follows first-order kinetics. 50% to 70% excreted unchanged in the urine (after IV administration). t ½ is 1.5 to 2 days.

Onset

0.5 to 2 h (oral), 5 to 30 min (IV).

Peak

2 to 6 h (oral), 1 to 4 h (IV).

Special Populations

Renal Function Impairment

Cl correlates with CrCl. Dosage adjustment recommended.

Indications and Usage

Treatment of CHF, atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia, cardiogenic shock.

Contraindications

Ventricular fibrillation; ventricular tachycardia except in certain cases; digitalis toxicity; beriberi heart disease; hypersensitivity to digoxin; some cases of hypersensitive carotid sinus syndrome.

Dosage and Administration

Rapid digitalization with loading dose

Adults

IV 0.4 to 0.6 mg or PO tablets 0.5 to 0.75 mg or capsules 0.4 to 0.6 mg in previously undigitalized patients; additional doses may be given cautiously at 6 to 8 h intervals ( IV 0.1 to 0.3 mg or PO tablets 0.125 to 0.375 mg or capsules 0.1 to 0.3 mg) until clinical response is achieved; thereafter adjust dosage based on levels (usual range 0.125 to 0.5 mg/day as single daily dose). In previously digitalized patients, adjust dosage in proportion to ratio of desired vs current serum levels.

Infants and children

Individualize dosage. Usual doses in children are listed at end of section.

General Advice

* For IV administration, digoxin injection may be diluted (up to 4-fold) with normal saline, D5W, or sterile water for injection. Infuse slowly, over 5 min or longer.
* Do not mix digoxin solution with other drugs.

Drug Interactions



Acarbose plasma concentration of digoxin possibly reduced by acarbose
Alprazolam plasma concentration of digoxin increased by alprazolam (increased risk of toxicity)
Amiodarone plasma concentration of digoxin increased by amiodarone (halve dose of digoxin) Amiodarone has a long half-life; there is a potential for drug interactions to occur for several weeks (or even months) after treatment with it has been stopped
Antacids absorption of digoxin possibly reduced by antacids Antacids should preferably not be taken at the same time as other drugs since they may impair absorption
Atorvastatin plasma concentration of digoxin possibly increased by atorvastatin
Captopril plasma concentration of digoxin possibly increased by captopril
Chloroquine and Hydroxychloroquine plasma concentration of digoxin possibly increased by chloroquine and hydroxychloroquine
Ciclosporin plasma concentration of digoxin increased by ciclosporin (increased risk of toxicity)
Cytotoxics absorption of digoxin tablets reduced by cytotoxics
Darifenacin plasma concentration of digoxin possibly increased by darifenacin
Diltiazem plasma concentration of digoxin increased by diltiazem
Gentamicin plasma concentration of digoxin possibly increased by gentamicin
Itraconazole plasma concentration of digoxin increased by itraconazole
Lercanidipine plasma concentration of digoxin increased by lercanidipine
Macrolides plasma concentration of digoxin increased by macrolides (increased risk of toxicity) See also Telithromycin
Mefloquine possible increased risk of bradycardia when digoxin given with mefloquine
Neomycin absorption of digoxin reduced by neomycin
Nicardipine plasma concentration of digoxin increased by nicardipine
Nifedipine plasma concentration of digoxin possibly increased by nifedipine
Penicillamine plasma concentration of digoxin possibly reduced by penicillamine
Phenytoin plasma concentration of digoxin possibly reduced by phenytoin
Prazosin plasma concentration of digoxin increased by prazosin
Propafenone plasma concentration of digoxin increased by propafenone (halve dose of digoxin)
Proton Pump Inhibitors plasma concentration of digoxin possibly slightly increased by proton pump inhibitors
Quinine plasma concentration of digoxin increased by quinine
Rifampicin plasma concentration of digoxin possibly reduced by rifampicin
Ritonavir plasma concentration of digoxin possibly increased by ritonavir
Salbutamol plasma concentration of digoxin possibly reduced by salbutamol
Sitagliptin plasma concentration of digoxin increased by sitagliptin
Spironolactone plasma concentration of digoxin increased by spironolactone
St John's Wort plasma concentration of digoxin reduced by St John's wort —avoid concomitant use
Sulfasalazine absorption of digoxin possibly reduced by sulfasalazine
Telithromycin plasma concentration of digoxin possibly increased by telithromycin
Telmisartan plasma concentration of digoxin increased by telmisartan
Trimethoprim plasma concentration of digoxin possibly increased by trimethoprim
Verapamil plasma concentration of digoxin increased by verapamil , also increased risk of AV block and bradycardia
Digoxin belongs to Cardiac Glycosides and will have the following interactions:

Acetazolamide increased cardiac toxicity with cardiac glycosides if hypokalaemia occurs with acetazolamide
Amphotericin increased cardiac toxicity with cardiac glycosides if hypokalaemia occurs with amphotericin Close monitoring required with concomitant administration of nephrotoxic drugs or cytotoxics
Beta-blockers increased risk of AV block and bradycardia when cardiac glycosides given with beta-blockers Since systemic absorption may follow topical application of beta-blockers to the eye the possibility of interactions, in particular, with drugs such as verapamil should be borne in mind
Calcium Salts arrhythmias can be precipitated when cardiac glycosides given with large intravenous doses of calcium salts see also Antacids
Colestipol absorption of cardiac glycosides possibly reduced by colestipol Other drugs should be taken at least 1 hour before or 4-6 hours after colestipol to reduce possible interference with absorption
Colestyramine absorption of cardiac glycosides possibly reduced by colestyramine Other drugs should be taken at least 1 hour before or 4-6 hours after colestyramine to reduce possible interference with absorption
Corticosteroids increased risk of hypokalaemia when cardiac glycosides given with corticosteroids Interactions do not generally apply to corticosteroids used for topical action (including inhalation) unless specified
Diuretics, Loop increased cardiac toxicity with cardiac glycosides if hypokalaemia occurs with loop diuretics
Diuretics, Thiazide and related increased cardiac toxicity with cardiac glycosides if hypokalaemia occurs with thiazides and related diuretics
NSAIDs plasma concentration of cardiac glycosides possibly increased by NSAIDs , also possible exacerbation of heart failure and reduction of renal function See also Aspirin. Interactions do not generally apply to topical NSAIDs
Sucralfate absorption of cardiac glycosides possibly reduced by sucralfate
Suxamethonium risk of ventricular arrhythmias when cardiac glycosides given with suxamethonium
Tizanidine possible increased risk of bradycardia when cardiac glycosides given with tizanidine


Adverse Reactions

Cardiovascular

Arrhythmias (supraventricular arrhythmias are more common in infants and children), including ventricular tachycardia and premature ventricular contractions.

CNS

Headache; weakness; apathy; drowsiness; mental depression; confusion; disorientation.

EENT

Visual disturbances (eg, blurred vision, halo effect).

GI

Anorexia; nausea; vomiting; diarrhea.

Precautions

Monitor

Monitor apical pulse for 1 full min before administering. Withhold dose and notify health care provider if pulse rate is less than 60 bpm in adult, less than 70 bpm in child, or less than 90 bpm in infant. Note signs of toxicity occur (eg, abdominal pain, anorexia, nausea, vomiting, visual disturbance, bradycardia, ECG changes, arrhythmias, headache, seizure). Be prepared to administer digoxin antibodies (digoxin-immune Fab) for severe overdose toxicity.

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Newborns show varying tolerance. Premature and immature infants are particularly sensitive; reduce and individualize dose as needed.

Elderly

Use with caution; renal Cl likely to be reduced.

Renal Function

Excretion may be decreased, leading to digoxin accumulation and toxicity; adjust dosage.

CV disease

Electrical conversion of arrhythmias may require dose reduction.

Digitalis toxicity

Anorexia, nausea, and vomiting may be associated with toxicity or CHF. Arrhythmias for which digoxin is indicated may also be a reflection of toxicity.

Electrolyte imbalance

Maintain normal serum potassium, calcium, and magnesium levels.

Lanoxicaps

Lanoxicaps have greater bioavailability than standard tablets. The 0.2 mg capsule is equivalent to 0.25 mg tablet; the 0.1 mg capsule to 0.125 mg tablet; the 0.05 mg capsule to 0.0625 mg tablet.
Usual Pediatric Digitalizing and Maintenance Dosages With Normal Renal Function Based on Lean Body Weight Age Digitalizing Dose (mcg/kg) Daily Maintenance Dose as % of Loading Dose (mcg/kg in 2 to 3 divided doses) PO IV Premature 20 to 30 15 to 25 20% to 30% Term 25 to 35 20 to 30 25% to 35% 1 to 24 mo 35 to 60 30 to 50 25% to 35% 2 to 5 yr 30 to 40 25 to 35 25% to 35% 5 to 10 yr 20 to 35 15 to 30 25% to 35% > 10 yr 10 to 15 8 to 12 25% to 35%

Overdosage

Symptoms

GI tract (eg, anorexia, nausea, vomiting, diarrhea); nervous system (eg, headache, weakness, apathy, drowsiness, visual disturbances such as blurred, yellow or green vision, halo effect), depression, confusion, restlessness, disorientation, seizures, EEG abnormalities, delirium, hallucinations, neuralgia and psychosis; cardiovascular system (eg, ventricular tachycardia, PVCs, paroxysmal and nonparoxysmal nodal rhythms, AV dissociation, accelerated nodal rhythm and premature atrial contraction with block, atrial fibrillation, ECG changes, all alterations in cardiac rate and rhythm). Conduction disturbances are common manifestations of toxicity in children.

Patient Information

* Instruct patient to take digoxin at same time each day to ensure steady-state dosing and to contact health care provider for instructions if dose is missed.
* Teach patient and family name, action, administration, adverse reactions, and toxic effects of particular digoxin preparation.
* Emphasize importance of regular follow-up exams to determine effectiveness and to monitor for toxicity.
* Caution patient to avoid taking otc medications without consulting health care provider. Antacids and antidiarrheals, for example, slow absorption of digoxin.
* Teach patient and family to take pulse and to seek health care provider's advice for rates less than 60 bpm or more than 100 bpm (adults).
* If patient is directed by health care provider, help identify ways to supplement potassium intake.