Digoxin

Question 1

What are Digoxin indications?

Answer 1

Most useful for controlling ventricular response in permanent and persistent AF and atrial flutter. Also has a role in HF

Question 2

For management of AF how is the maintenance dose of digoxin can be determined?

Answer 2

Determined by the ventricular rate at rest, which should not usually be allowed to fall persistently below 60 bpm.

Question 3

Patients who have HF and are in sinus rhythm, do they require loading dose of digoxin?

Answer 3

Loading dose is not required and satisfactory plasma digoxin conc can be achieved over a period of about a week.

Question 4

What is the dosing of digoxin? And what is the most important dterminant of digoxin dosage?

Answer 4

Dosing is OD, because digoxin has a long half life ( higher doses may be divided to avoid nausea). Renal function is the most important determinant of digoxin dosage.

Question 5

What digoxin concentrations would indicate likelihood of toxicity?

Answer 5

1.5 to 3 mcg/l

Question 6

What would predispose to digoxin toxicity and how can this be managed to prevent it?

Answer 6

Hypokalaemia predisposes the patient to digitalis toxicity; it is managed by giving a potassium-sparing diuretic or potassium supplementation.

Question 7

How does digoxin work?

Answer 7

Increases the force of myocardial contraction and reduces conductivity within the AV node.

Question 8

Digoxin doses for AF and HF?

Answer 8

AF: maintenance 125-250mcg OD.
HF: 62.5-125 mcg

Question 9

When would digoxin drug dose should be reduce by half? With concurrent use of which medications?

Answer 9

Amiodarone
Dronaderone
Quinine

Question 10

What electrolyte disturbances would predispose to digitalis toxicity?

Answer 10

Hypercalcaemia
Hypokalaemia
Hypomagnesaemia

Hypoxia

Question 11

Can digoxin be given during breast-feeding?

Answer 11

Yes amount to small to be harmful

Question 12

What are digoxin monitoring requirements?

Answer 12

For plasma-digoxin concentration assay, blood should be taken at least 6 hours after dose. Monitor serum electrolytes and renal function.

Question 13

Describe interactions between digoxin and anti-arrythmics- Amiodarone?

Answer 13

Amiodarone: plasma levels of digoxin are considerably increased by concurrent administration of amiodarone. This is due to a decrease in the renal and non-renal clearance of digoxin, a prolongation of its half life and a possible increase in absorption.

Question 14

Describe interactions between digoxin and anti-arrythmics- Disopyramide?

Answer 14

Disopyramide may modify the cardiovascular effects of digoxin and reduce its volume of distribution. The loading dose of digoxin should be reduced in patients who are also receiving disopyramide.

Question 15

Amiodarone and flecainide interaction with digoxin?

Answer 15

lasma levels of digoxin are increased by concurrent administration of flecainide. This is likely to be clinically significant only in patients with high plasma levels of digoxin or those with atrioventricular nodal dysfunction.

Question 16

Digoxin and anti-infective drugs?

Answer 16

Macrolides, tetracycline: presystemic metabolism of digoxin to inactive metabolites in the gastrointestinal tract occurs in about 10% of patients. Co-administration of macrolide antibiotics (azithromycin, clarithromycin, erythromycin, telithromycin), gentamicin or tetracycline to this sub-group of patients can result in a clinically significant increase in plasma digoxin levels. Neomycin: absorption of digoxin from the gastrointestinal tract is inhibited by neomycin and plasma levels are reduced. Rifampicin: the metabolism of digoxin may be increased by co-administration with rifampicin. The interaction may be enhanced in patients with renal impairment. Trimethoprim: the renal excretion of digoxin is decreased by concurrent administration with trimethoprim. The interaction is more significant in elderly patients or those with renal impairment and digoxin plasma levels should be monitored. Amphotericin: hypokalaemia due to amphotericin administration may potentiate digoxin toxicity. Patients should be monitored and given potassium supplements when necessary. Itraconazole can cause a marked increase in plasma digoxin levels and toxicity may occur if the dose of digoxin is not reduced. Itraconazole may also oppose the positive inotropic effects of digoxin. Quinine, hydroxychloroquine and chloroquine can increase plasma levels of digoxin by decreasing non-renal clearance.

Question 17

Digoxin and CCB?

Answer 17

Diltiazem and digoxin co-administration can result in increased digoxin plasma levels and toxicity and patients should be monitored. Nifedipine may increase digoxin plasma levels but there is considerable interindividual variation. Patients taking high doses of digoxin or those with renal impairment are most at risk. Nisoldipine may also increase plasma levels of digoxin but amlodipine, felodipine, isradipine, lercanidipine, nicardipine, nimodipine and nitrendipine do not appear to have significant effects on digoxin plasma levels but it is prudent to monitor the effects of co-administration. Verapamil increases plasma digoxin levels by inhibiting the active tubular secretion and non-renal clearance of digoxin. The dose of digoxin should be reduced and plasma levels monitored. Verapamil may also increase atrioventricular block and tachycardia in patients taking digoxin.

Question 18

Digoxin and Calcium salts and vitamin D analogues?

Answer 18

Intravenous administration of calcium salts to patients taking digoxin can result in dangerous cardiac arrhythmias and should be avoided. Vitamin D analogues can also increase digoxin toxicity due to elevations in plasma calcium concentrations.

Question 19

Digoxin and cardiovascular drugs?

Answer 19

ACE inhibitors and angiotensin II antagonists may cause hyperkalaemia which can reduce tissue binding of digoxin resulting in higher serum levels. These drugs may also cause a deterioration in renal function resulting in elevated serum levels of digoxin because of impaired renal excretion. Concurrent administration of captopril has been associated with increases in plasma digoxin levels but this may only be clinically significant in patients with impaired renal function or severe congestive heart failure. Telmisartan administration has been associated with increases in plasma digoxin levels and patients receiving both drugs should be monitored. No clinically significant interactions have been noted with other ACE inhibitors or angiotensin II antagonists examined (cilazapril, enalapril, imidapril, lisinopril, moexipril, perindopril, quinapril, ramipril and trandolapril; candesartan, eprosartan, irbesartan, losartan and valsartan)) but it is prudent to monitor the effects of co-administration. There is an increased risk of atrioventricular block and bradycardia when digoxin and beta blockers are taken concomitantly. Nitroprusside and hydralazine increase the renal clearance of digoxin by increasing renal blood flow and tubular secretion and lowering plasma digoxin levels.

Question 20

Digoxin and CNS drugs?

Answer 20

St John’s wort: co-administration of digoxin with St John’s wort should be avoided because plasma levels are significantly reduced. Nefazodone, trazodone: Plasma levels of digoxin are increased by concomitant administration of nefazodone or trazodone and it may be necessary to reduce the dose of digoxin. Phenytoin increases total clearance of digoxin and reduces its elimination half-life, resulting in a decrease in plasma levels. Intravenous phenytoin should not be used to treat digitalis induced arrhythmias or in patients with a high degree of heart block or marked bradycardia because of the risk of cardiac arrest. Topiramate: co-administration of digoxin and topiramate reduces the bioavailability of digoxin and patients should be monitored. Alprazolam and diazepam can decrease digoxin clearance, resulting in increased plasma concentrations. Patients should be monitored for digoxin toxicity, especially those aged over 65. Digoxin may have detrimental effects on the short term control of bipolar disorder in patients treated with lithium.

Question 21

Digoxin and diuretics?

Answer 21

Potassium depletion due to acetazolamide, loop diuretics and thiazide diuretics potentiates the effects of digoxin on the myocardium and may also have a small effect on reducing the renal tubular secretion of digoxin. Patients should be monitored for hypokalaemia and given potassium supplements when necessary. Spironolactone decreases renal excretion of digoxin, increasing plasma levels. The dose of digoxin should be decreased in susceptible patients.

Question 22

Digoxin and omeprazole?

Answer 22

Metabolism of digoxin in the gastrointestinal tract is inhibited by omeprazole, resulting in increased plasma levels of digoxin.

Question 23

Digoxin and NSAIDs?

Answer 23

NSAIDs have the potential to cause renal impairment, reducing the renal clearance of digoxin with a subsequent increase in plasma levels. Aspirin, azapropazone, diclofenac, fenbufen, ibuprofen, indometacin and tiaprofenic acid have all been shown to increase plasma concentrations of digoxin but this may only be clinically significant in patients with impaired renal function. Etoricoxib, ketoprofen, meloxicam, piroxicam and rofecoxib do not appear to increase plasma digoxin levels. Patients being treated with digoxin often need to take NSAIDs and digoxin plasma concentrations should be monitored whenever an NSAID is initiated or discontinued. Phenylbutazone stimulates hepatic metabolism of digoxin so plasma levels should be monitored in these drugs are given concurrently.

Question 24

Digoxin and Sympathomimetic?

Answer 24

Sympathomimetic drugs have direct positive chronotropic effects that can promote cardiac arrhythmias and may also lead to hypokalaemia, which can lead to or worsen cardiac arrhythmias. Concomitant use of digoxin and sympathomimetics may increase the risk of cardiac arrhythmias.