Digoxin

Question 1

MoA

Answer 1

Cardiac glycose. Increases force of myocardial contraction and reduced conductivity within AV node

Question 2

What is the therapeutic range for serum digoxin concentration

Answer 2

0.7-2.0 nanograms/ml

Question 3

Major routes of elimination

Answer 3

Renal excretion
Hepatic metabolism to active metabolites

Question 4

Dose of digoxin to prescribe

Answer 4

Loading dose of 250mcg-750mcg daily for 7 days, followed by maintenance dose

Question 5

When is the clinical response usually seen by

Answer 5

Within 1 week

Question 6

Dose of digoxin to prescribe for elderly and renal impairment

Answer 6

Seek specialist advice for elderly and renal impairment - loading dose of digoxin will need to be reduced

Question 7

Usual maintenance dose

Answer 7

125mcg-250mcg daily - adjust according to renal function, initial loading dose, and heart rate response

Question 8

Dose to prescribe if a rapid response is needed

Answer 8

• 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

Question 9

If you take digoxin with some medications, it requires a dose adjustment. What are the medications and what is the dose change required?

Answer 9

Concurrent use of amiodarone, dronedarone and quinine: reduce dose of digoxin by half

Question 10

When may dose reductions of digoxin be required

Answer 10

• If digoxin (or another cardiac glycose) has been given in the preceding 2 weeks
• Concurrent use of amiodarone, dronedarone, quinine: halve dose of digoxin

Question 11

Switching from IV to oral digoxin

Answer 11

May need to increase dose by 20-33% to maintain the same plasma-digoxin concentration

Question 12

Contraindications

Answer 12

• 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

Question 13

Cautions

Answer 13

• 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)

Question 14

Use in pregnancy

Answer 14

May need dose adjustment

Question 15

Use in breastfeeding

Answer 15

Amount too small to be harmful

Question 16

Use in renal impairment

Answer 16

Consider reducing initial and maintenance doses

Question 17

Monitoring requirements

Answer 17

• 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

Question 18

Should you routinely measure serum digoxin

Answer 18

Not recommended - no evidence to indicate that this has better outcomes

Question 19

Concomitant use of PPIs

Answer 19

• Manufacturer’s SPC: PPIs cause increased plasma levels of digoxin (esp omeprazole)
• Use with caution

Question 20

Concomitant use of St John’s Wart

Answer 20

○ Plasma concentration of digoxin may be reduced
○ Counsel patients not to use St John’s wart

Question 21

Concomitant use of bupropion

Answer 21

○ May decrease digoxin levels - monitor
○ Digoxin levels may rise on discontinuation of bupropion
○ Monitor for possible digoxin toxicity when bupropion is discontinued

Question 22

Concomitant use of antidepressants

Answer 22

○ 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

Question 23

Concomitant use of beta blockers

Answer 23

○ 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

Question 24

Concomitant use with diuretics, acetazolamide, amphotericin

Answer 24

○ Increased cardiac toxicity if hypokalaemia occurs with these drugs
Monitor digoxin levels and adjust dose accordingly

Question 24

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

Answer 24

○ 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

Question 25

In which circumstances would you consider checking serum digoxin levels

Answer 25

○ 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

Question 26

Discuss the likelihood of toxicity when looking at serum digoxin concentrations

Answer 26

- 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

Question 27

What parameters should be checked at least annually

Answer 27

- 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

Question 28

Can digoxin toxicity occur in the therapeutic range

Answer 28

Yes - always interpret results in their clinical context

Question 29

When should serum digoxin concentrations be taken

Answer 29

○ 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