Treatment with digoxin: Initial dosing, monitoring, and dose modification
- Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
- Professor of Medicine
- Director, Center for Women’s Health
- Columbia University Medical Center
- Lynne Sylvia, PharmD
Lynne Sylvia, PharmD
- Senior Clinical Pharmacy Specialist, Tufts Medical Center
- Clinical Professor, Northeastern University, School of Pharmacy
Cardiac glycosides have important positive inotropic, neurohormonal, and electrophysiologic actions, which are the basis for its use in two clinical situations: heart failure due to systolic dysfunction, and in certain supraventricular tachyarrhythmias. The ability of digoxin to reduce sympathetic activation has also been recognized. For maximal early benefits, digoxin requires loading doses, which can be administered intravenously or orally. (See "Use of digoxin in heart failure with reduced ejection fraction", section on 'Mechanism of action' and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Digoxin'.)
While two cardiac glycosides (digoxin and digitoxin) were previously used, digitoxin has not been widely available since the 1980s. As digoxin is now the only cardiac glycoside available in most countries, the method of initiating therapy with digoxin is presented here. Recommendations regarding the use of digoxin in the management of heart failure or arrhythmias are discussed separately. (See "Use of digoxin in heart failure with reduced ejection fraction" and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Digoxin'.)
INITIATION OF THERAPY
The electrolyte and renal status of each patient should be ascertained prior to initiating treatment and periodically thereafter. Hypokalemia or hypomagnesemia, for example, may promote the development of digoxin-induced arrhythmias, while impaired renal function may result in higher than anticipated serum drug levels. (See 'Dose adjustments' below.)
The initiation of digoxin therapy has been divided into rapid and slow digitalization followed by the maintenance digoxin dose, and the proposed regimens vary considerably. The following principles should be viewed as a general guide to the use of digoxin for its inotropic or electrophysiologic effects, which must be modified according to clinical circumstances. Patients receiving digoxin for ventricular rate control in atrial fibrillation or flutter will usually require more rapid loading than those treated with digoxin for heart failure, in whom a loading dose is typically not required. The use of digoxin primarily for heart failure is discussed separately. (See "Use of digoxin in heart failure with reduced ejection fraction".)
Rapid digoxin loading — Rapid intravenous and oral digitalization is often used to control the ventricular response in atrial fibrillation and flutter. However, other drugs may be more effective and/or have a more rapid onset of action on the ventricular response in these arrhythmias; therefore, rapid digitalization is rarely needed unless alternative drugs are contraindicated or have not been effective. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Pharmacologic treatment' and "Control of ventricular rate in atrial flutter", section on 'Rate control with drugs'.)
Subscribers log in hereLiterature review current through: Jul 2017. | This topic last updated: Jun 08, 2017.References
- Aronson JK. Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. Clin Pharmacokinet 1983; 8:155.
- Cheng JW, Charland SL, Shaw LM, et al. Is the volume of distribution of digoxin reduced in patients with renal dysfunction? Determining digoxin pharmacokinetics by fluorescence polarization immunoassay. Pharmacotherapy 1997; 17:584.
- Matzke GR, Frye RF. Drug administration in patients with renal insufficiency. Minimising renal and extrarenal toxicity. Drug Saf 1997; 16:205.
- Ewy GA, Groves BM, Ball MF, et al. Digoxin metabolism in obesity. Circulation 1971; 44:810.
- Abernethy DR, Greenblatt DJ. Drug disposition in obese humans. An update. Clin Pharmacokinet 1986; 11:199.
- Erstad BL. Dosing of medications in morbidly obese patients in the intensive care unit setting. Intensive Care Med 2004; 30:18.
- DiDomenico RJ, Bress AP, Na-Thalang K, et al. Use of a simplified nomogram to individualize digoxin dosing versus standard dosing practices in patients with heart failure. Pharmacotherapy 2014; 34:1121.
- Vallakati A, Chandra PA, Pednekar M, et al. Dronedarone-induced digoxin toxicity: new drug, new interactions. Am J Ther 2013; 20:e717.
- Dorian P. Clinical pharmacology of dronedarone: implications for the therapy of atrial fibrillation. J Cardiovasc Pharmacol Ther 2010; 15:15S.
- Dronedarone tablet. US Food & Drug Administration (FDA) approved product information. Revised March, 2014. US National Library of Medicine. Available online at http://www.dailymed.nlm.nih.gov/.
- Kirby BJ, Collier AC, Kharasch ED, et al. Complex drug interactions of the HIV protease inhibitors 3: effect of simultaneous or staggered dosing of digoxin and ritonavir, nelfinavir, rifampin, or bupropion. Drug Metab Dispos 2012; 40:610.
- He J, Yu Y, Prasad B, et al. Mechanism of an unusual, but clinically significant, digoxin-bupropion drug interaction. Biopharm Drug Dispos 2014; 35:253.
- Bupropion US prescribing information (revision May 10, 2017) https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020711s045s046s047lbl.pdf.
- Hauptman PJ, Kelly RA. Digitalis. Circulation 1999; 99:1265.
- Rubinow A, Skinner M, Cohen AS. Digoxin sensitivity in amyloid cardiomyopathy. Circulation 1981; 63:1285.
- Falk RH. Diagnosis and management of the cardiac amyloidoses. Circulation 2005; 112:2047.
- Broeren MA, Geerdink EA, Vader HL, van den Wall Bake AW. Hypomagnesemia induced by several proton-pump inhibitors. Ann Intern Med 2009; 151:755.
- INITIATION OF THERAPY
- Rapid digoxin loading
- Slow digoxin loading
- Loading dose adjustments
- - Renal impairment
- - Lean body weight
- - Patients with low body weight
- - Patients who are obese
- Maintenance digoxin dosing
- Dose adjustments
- - Dose adjustment in renal disease
- - Dose adjustment with hepatic disease
- - Dose adjustment with concomitant medications
- - Digoxin in pregnancy
- - Digoxin in patients with amyloidosis
- MONITORING SERUM DIGOXIN
- Adjusting the digoxin dose
- Heart failure
- Atrial fibrillation
- Relation to digoxin toxicity
- SUMMARY AND RECOMMENDATIONS