Digoxin Flashcards
MoA
Cardiac glycose. Increases force of myocardial contraction and reduced conductivity within AV node
What is the therapeutic range for serum digoxin concentration
0.7-2.0 nanograms/ml
Major routes of elimination
Renal excretion
Hepatic metabolism to active metabolites
Dose of digoxin to prescribe
Loading dose of 250mcg-750mcg daily for 7 days, followed by maintenance dose
When is the clinical response usually seen by
Within 1 week
Dose of digoxin to prescribe for elderly and renal impairment
Seek specialist advice for elderly and renal impairment - loading dose of digoxin will need to be reduced
Usual maintenance dose
125mcg-250mcg daily - adjust according to renal function, initial loading dose, and heart rate response
Dose to prescribe if a rapid response is needed
- More rapid response may be achieved by prescribing 750mcg-1500mcg in divided dose over 24 hours
- However, Previous expert reviews suggest usually no more than 1000mcg (1mg) needed in 25 hours
- If more rapid clinical response is required, consider referral to secondary care
If you take digoxin with some medications, it requires a dose adjustment. What are the medications and what is the dose change required?
Concurrent use of amiodarone, dronedarone and quinine: reduce dose of digoxin by half
When may dose reductions of digoxin be required
- If digoxin (or another cardiac glycose) has been given in the preceding 2 weeks
- Concurrent use of amiodarone, dronedarone, quinine: halve dose of digoxin
Switching from IV to oral digoxin
May need to increase dose by 20-33% to maintain the same plasma-digoxin concentration
Contraindications
- Constrictive pericarditis (unless to control AF or improve systolic dysfunction, but use with caution)
- Hypertrophic cardiomyopathy (unless concomitant AF and heart failure, but use with caution)
- Intermittent complete heart block
- Myocarditis
- Second degree AV block
- Supra ventricular arrhythmias associated with accessory conducting pathways e.g. Wolff-Parkinson-White syndrome (although can be used in infancy)
- Ventricular tachycardia or fibrillation
Cautions
- Hypercalcaemia - risk of digitalis toxicity
- Hypokalaemia - risk of digitalis toxicity
- Hypomagnesaemia - risk of digitalis toxicity
- Hypoxia - risk of digitalis toxicity
- Recent MI
- Severe respiratory disease
- Sick sinus syndrome
- Thyroid disease
- Elderly - prescription potentially inappropriate (STOPP criteria)
○ In heart failure with normal systolic ventricular function (no clear evidence of benefit)
○At long term dose greater than 125mcy daily if eGFR less than 30ml/min/1.73m2 (risk of digoxin toxicity if plasma levels not measured) In heart failure with normal systolic ventricular function (no clear evidence of benefit)
At long term dose greater than 125mcy daily if eGFR less than 30ml/min/1.73m2 (risk of digoxin toxicity if plasma levels not measured)
Use in pregnancy
May need dose adjustment
Use in breastfeeding
Amount too small to be harmful
Use in renal impairment
Consider reducing initial and maintenance doses
Monitoring requirements
- Therapeutic drug monitoring - NTI Drug!!!
○ For plasma-digoxin concentration assay, blood should be taken at least 6 hours after a dose
○ Therapeutic range 0.7-2.0ng/ml - Monitoring patient parameters
○ Monitor serum electrolytes and renal function
○ Toxicity increased by electrolyte disturbances
Should you routinely measure serum digoxin
Not recommended - no evidence to indicate that this has better outcomes
Concomitant use of PPIs
- Manufacturer’s SPC: PPIs cause increased plasma levels of digoxin (esp omeprazole)
- Use with caution
Concomitant use of St John’s Wart
○ Plasma concentration of digoxin may be reduced
○ Counsel patients not to use St John’s wart
Concomitant use of bupropion
○ May decrease digoxin levels - monitor
○ Digoxin levels may rise on discontinuation of bupropion
○ Monitor for possible digoxin toxicity when bupropion is discontinued
Concomitant use of antidepressants
○ Avoid TCAs - possibly proarrhytmiac in cardiac disease
○ Consider SSRIs or mirtazapine instead
○ Avoid venlafaxine with digoxin in people at risk of arrhythmias - consider SSRIs or mirtazapine instead
○ Avoid trazodone - increases digoxin plasma levels; consider SSRIs or mirtazapine instead
Concomitant use of beta blockers
○ Concomitant use can reduce HR and prolong AV conduction time, increasing risk of AV block and brady cardia - monitor pulse
○ Carvedilol: increases plasma digoxin levels
○ Monitor for toxicity: confusion, anorexia, nausea, disturbance of colour vision) when starting, adjusting or stopping carvedilol
Concomitant use with diuretics, acetazolamide, amphotericin
○ Increased cardiac toxicity if hypokalaemia occurs with these drugs
Monitor digoxin levels and adjust dose accordingly
Monitor for signs and symptoms of digoxin toxicity and adjust doses accordingly) if digoxin is given with the following drug which may increase plasma concentrations of digoxin
○ Amiodarone
○ Antimicrobials (itraconazole, macrolide abx, tetracycline, trimethoprim)
○ CCBs (diltiazem, verapamil, possibly nifedipine)
§ Verapamil: also increases risk of AV bloc and bradycardia
○ Chloroquine and hydroxychloroquine
Spironolactone
In which circumstances would you consider checking serum digoxin levels
○ Adverse effects suggestive of toxicity e.g. confusion, nausea, anorexia, disturbance of colour vision
○ Other factors may affect serum digoxin level e.g. use of concomitant drugs like amiodarone, diltiazem, verapamil, or deteriorating renal function, thyroid disease and advancing age
○ Poor adherence suspected
Discuss the likelihood of toxicity when looking at serum digoxin concentrations
- Likelihood of toxicity depends on serum dogoxin concentration
○ Levels less than 1.5 nanograms/ml with no hypokalamia - toxicity unlikely
○ Levels more than 3.0 nanograms/ml - toxicity likely
○ Levels between 1.5 and 3.0 nanograms/ml - toxicity possible
What parameters should be checked at least annually
- Also need to check blood chemistry (U&E, creatinine) at least annually
○ More frequently in elderly and renal impairment
○ Tests often done routinely as renal function is likely to be monitored owing to the use of nephrotoxic drugs e.g. diuretics and drugs affecting renin-angiotensin system
Can digoxin toxicity occur in the therapeutic range
Yes - always interpret results in their clinical context
When should serum digoxin concentrations be taken
○ Take blood samples at least 6 hours after previous dose, but ideally 8-12 hours afterwards
○ Monitor digoxin levels several days after the last dose change
