ADMINISTRATION ROUTES:
IV, PO
ALTERNATIVE NAMES:
Lanoxin
ICU INDICATIONS:
- Atrial fibrillation
Note: As digoxin is rarely initiated for heart failure, particularly in ICU settings, dosing for this indication is not included in this monograph
PRESENTATION AND ADMINISTRATION:
PO:
Lanoxin PG tablets 62.5 microgram tablets (blue), Lanoxin 250 microgram tablets (white), Lanoxin Paediatric Elixir 50 microgram/mL
IV:
Digoxin 500 microgram/2 mL vial
Vials should be stored at room temperature and protected from light
Dilute required dose with at least four times its volume of a compatible fluid (e.g. 2 mL with at least 8 mL of compatible fluid) and administer slowly over 10 - 30 minutes
Discard any solution immediately
Compatible with the following IV fluids: Sodium chloride 0.9%, glucose 5%, glucose 4% with sodium chloride 0.18%
DOSAGE:
Before administering a digoxin loading dose, confirm no prior digoxin has been given during this admission. If previously administered, consult the prescriber before proceeding.
Loading dose:
Loading doses should be calculated using ideal body weight and knowledge of patient’s renal function (see Dosing in Renal Impairment and Renal Replacement Therapy section below).
IV:
8 – 12 mcg/kg
PO:
10 – 15 mcg/kg
Oral doses should be rounded to the nearest 125 mcg
Note: Loading dose (IV or PO) is administered in increments:
- Initially: Give half the total calculated loading dose (1st dose)
- 6 hours later: Give one quarter of calculated loading dose (2nd dose)
- 6 hours after 2nd dose: Give remaining quarter of calculated loading dose
Average adult will receive the following oral loading regime:
- Initially 500 mcg followed by
- 250 mcg 6 hours later and then further
- 250 mcg 6 hours after the 2nd dose
Maintenance dose:
IV / PO:
250 mcg OD
Maintenance doses should be given at 6 pm for ease of monitoring and dose adjustment in primary care
Consider lower starting maintenance doses in elderly patients, patients on concomitant amiodarone and/or with renal impairment, hypothyroidism or heart failure
Note: When converting from oral to IV formulation, the dose should be reduced by 33% to account for the difference in bioavailability
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose in renal impairment
Loading dose:
For patients with eGFR <50 mL/min:
IV:
4 – 7 mcg/kg
PO:
6 – 10 mcg/kg
Oral doses should be rounded to the nearest 125 micrograms
Note: Loading dose (IV or PO) should be split in increments as per the guidance for patients with normal renal function above.
Maintenance dose:
| GFR (ml/min) | DOSE |
|---|---|
| 20 - 50 | 125 mcg OD |
| 10 - 20 | 62.5 mcg OD |
| < 10 | 62.5 mcg three times a week |
Dose in renal replacement therapy
| MODALITY | DOSE |
|---|---|
| CAPD | 62.5 mcg three times a week to OD |
| HD | 62.5 mcg three times a week to OD |
| CVVHDF | 125 mcg OD |
DOSAGE IN PAEDIATRICS:
Loading dose:
IV:
15 mcg/kg stat then 5 mcg/kg 6 hours later
Maintenance dose:
IV / PO:
3 - 5 mcg/kg BD
Note: when converting from oral to IV formulation, the dosage should be reduced by 33% to account for the difference in bioavailability
CLINICAL PHARMACOLOGY:
Lanoxin (digoxin) is one of the cardiac (or digitalis) glycosides, a closely related group of drugs having in common specific effects on the myocardium. Digoxin inhibits sodium-potassium ATPase, an enzyme that regulates the quantity of sodium and potassium inside cells. Inhibition of the enzyme leads to an increase in the intracellular concentration of sodium and thus (by stimulation of sodium-calcium exchange) an increase in the intracellular concentration of calcium. The beneficial effects of digoxin result from direct actions on cardiac muscle, as well as indirect actions on the cardiovascular system mediated by effects on the autonomic nervous system.
CONTRAINDICATIONS:
- Hypersensitivity to digoxin
- Ventricular fibrillation
WARNINGS:
Digoxin Toxicity
Digoxin toxicity in both adult and paediatric patients is associated with serum levels > 2 ng/mL. However, because of digoxin’s narrow therapeutic index, toxicity can still occur at levels within the therapeutic range. Serum concentrations measured within 6 hours of ingestion may be falsely elevated and not accurately reflect toxicity.
Clinical signs of digoxin toxicity may include:
- gastrointestinal symptoms (nausea, vomiting)
- visual disturbances (such as blurred vision, yellow-tinted vision, or 'halos)
- llethargy
- potentially life-threatening arrhythmias, including paroxysmal atrial tachycardia, various degrees of atrioventricular (AV) block (first-degree, second-degree, or complete AV block - though Mobitz type II is less common), and ventricular premature beats. In more severe cases, arrhythmias may progress to bidirectional ventricular tachycardia or ventricular fibrillation.
In children, digoxin toxicity most often presents with cardiac arrhythmias, while neurological & gastrointestinal symptoms are less common. Common arrhythmias include atrial tachycardia (with or without block), junctional tachycardia, and sinus bradycardia, especially in infants. Ventricular arrhythmias are less common. Sinus bradycardia may be a sign of impending digoxin intoxication, especially in infants, even in the absence of first-degree heart block. Any arrhythmia or alteration in cardiac conduction that develops in a child taking digoxin should be assumed to be caused by digoxin, until further evaluation proves otherwise. Cardiac arrhythmias, which may occur without other symptoms, are the primary cause of death in digoxin toxicity.
Digoxin toxicity is reversible upon discontinuation or administration of digoxin immune Fab (Digibind).
Sinus Node Disease and AV Block
Because digoxin slows sinoatrial and AV conduction, the drug commonly prolongs the PR interval. It may cause severe sinus bradycardia or sinoatrial block in patients with pre-existing sinus node disease and may cause advanced or complete heart block in patients with pre-existing incomplete AV block. In such patients consideration should be given to the insertion of a pacemaker before treatment with digoxin.
Accessory AV Pathway (Wolff-Parkinson-White syndrome)
After intravenous digoxin therapy, some patients with paroxysmal atrial fibrillation or flutter and a coexisting accessory AV pathway have developed increased antegrade conduction across the accessory pathway bypassing the AV node, leading to a very rapid ventricular response or ventricular fibrillation.
PRECAUTIONS:
General:
Use in Patients with Electrolyte Disorders
In patients with hypokalaemia or hypomagnesaemia, toxicity may occur despite serum digoxin concentrations < 2.0 nmol/L, because potassium or magnesium depletion sensitizes the myocardium to digoxin. Therefore, it is desirable to maintain normal serum potassium and magnesium concentrations in patients being treated with digoxin. Hypercalcaemia from any cause predisposes the patient to digitalis toxicity. Calcium, particularly when administered rapidly by the intravenous route, may produce serious arrhythmias in digitalised patients. On the other hand, hypocalcaemia can nullify the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal.
Use in Thyroid Disorders and Hypermetabolic States:
Hypothyroidism may reduce the requirements for digoxin due to significant reduction in digoxin clearance.
In patients with hyperthyroidism, lower digoxin concentrations may result due to an increase in renal clearance of digoxin.
Heart failure and/or atrial arrhythmias resulting from hypermetabolic or hyperdynamic states (e.g. hyperthyroidism, hypoxia, or arteriovenous shunt) are best treated by addressing the underlying condition. Atrial arrhythmias associated with hypermetabolic states are particularly resistant to digoxin treatment. Care must be taken to avoid toxicity if digoxin is used.
Laboratory Tests:
Indications for monitoring:
- 7-10 days after initiation or dose change to ensure therapeutic range reached (after 5 half-lives)
- For suspected toxicity: bradycardia, heart block (especially when used alongside beta-blockers, calcium channel blockers, or amiodarone), arrhythmias, visual disturbances, nausea, fatigue, or neuropsychiatric symptoms
- When starting or discontinuing interacting drugs or if renal function declines (see Important Drug Interactions in ICU section below)
- In cases of therapeutic failure (such as poorly controlled AF/CHF), to assess if the dose can be increased safely without causing toxicity
Blood Specimen Collection:
- Adults: Plain (red) or SST (yellow) tubes
- Paediatric and Neonatal only: 0.4 mL green microtainer
Take sample 8 - 24 hours after dose. Early sampling during the distribution phase of digoxin will result in falsely elevated plasma levels being reported.
Therapeutic Range:
- Atrial Fibrillation: 1 -2 nmol/L
- Heart Failure: 0.6 – 2 nmol/L
In congestive heart failure, there is evidence that lower concentrations (revised lower limit of 0.6 nmol/L) are still efficacious. Toxicity risk rises significantly with serum digoxin concentrations over 2.6 nmol/L and becomes almost certain above 3.8 nmol/L
Drug/Laboratory Test Interactions:
None of note
IMPORTANT DRUG INTERACTIONS IN ICU:
Potassium-depleting diuretics are a major contributing factor to digitalis toxicity. Calcium, particularly if administered rapidly by the intravenous route, may produce serious arrhythmias in digitalised patients.
Quinidine, verapamil, amiodarone, propafenone, indomethacin, itraconazole, alprazolam, and spironolactone raise the serum digoxin concentration due to a reduction in clearance and/or in volume of distribution of the drug, with the implication that digitalis intoxication may result.
Erythromycin and clarithromycin (and possibly other macrolide antibiotics) and tetracycline may increase digoxin absorption in patients who inactivate digoxin by bacterial metabolism in the lower intestine, so that digitalis toxicity may result.
Rifampin may decrease serum digoxin concentration, especially in patients with renal dysfunction, by increasing the non-renal clearance of digoxin.
ADVERSE REACTIONS:
Cardiovascular System:
Ventricular extrasystoles, tachycardia, bradycardias, heart block, cardiac arrest
Dermatologic:
Skin rash (bullous, erythematous, maculopapular [most common], papular, scarlatiniform, vesicular)
Endocrine:
Gynecomastia
Gastrointestinal System:
Anorexia, nausea, vomiting, diarrhoea, abdominal pain, intestinal necrosis (haemorrhagic), mesenteric ischemia
Heamatologic:
Thrombocytopenia
Nervous System:
Altered mental status, anxiety, apathy, confusion, delirium, depression, dizziness, hallucination, headache, lethargy
Neuromuscular & skeletal:
Asthenia
Ophthalmic:
Blurred vision, visual disturbances (blurred or yellow vision)