Most HF patients are 65 years, yet the effects of digoxin on outcomes in these patients have not been well studied. Dosage Adjustment When Changing Preparations: The difference in bio-availability between Digoxin Injection or Digoxin Solution in Capsules and Digoxin Elixir Pediatric or Digoxin Tablets must be considered when changing patients from one dosage form to another.Doses of 100 mcg (0.1 mg) and 200 mcg (0.2 mg) of Digoxin Solution in Capsules are approximately equivalent to 125 mcg (0.125 mg) and250 mcg (0.25 mg) doses of Digoxin Tablets and Elixir Pediatric, respectively (see Table 1 in CLINICAL PHARMACOLOGY: Pharmacokinetics). Rarely, the use of digoxin has been associated with abdominal pain, intestinal ischemia, and hemorrhagic necrosis of the intestines. Files, All Mapping <> Your doctor may adjust your dose as needed. However, elderly patients are more likely to have age-related kidney or heart problems which may require caution and an adjustment in the dose for patients receiving digoxin. An official website of the United States government. The effects of digoxin have long been known to be dependent on doses and SDC (27,28). 69238-1991-7, Assessment of Heart Failure in Older Adults, Treatment of Systolic Heart Failure: Neurohormonal Blockade, Low Serum Digoxin Concentration and Reduction in Mortality in Heart Failure, Effects of Digoxin in Older Adults with Chronic HF, Practical Tips for the Use of Digoxin in Older Adults with Chronic Heart Failure, Abstract and Heart Failure: A Geriatric Syndrome. In healthy volunteers with normal renal function, digoxin has a half-life of 1.5 to 2.0 days. In contrast, among patients 65 years, age, impaired renal function, and pulmonary congestion were independent negative predictors of low SDC. During 41 months of median follow-up, 735 (28%) patients died from all causes, including 597 (23%) from cardiovascular causes and 233 (9%) from worsening HF. The covariates used in the multivariable models were age; sex; race; body mass index; duration of HF; etiology of HF; prior myocardial infarction, current angina, hypertension, or diabetes; pretrial use of digoxin; use of ACE inhibitors, diuretics, and combination of hydralazine and nitrates; current dyspnea at rest and dyspnea on exertion; heart rate; systolic and diastolic blood pressure; current jugular venous distension; third heart sound; pulmonary rles; lower extremity edema; New York Heart Association (NYHA) functional class; pulmonary congestion by chest x-ray; cardiothoracic ratio > 0.5; estimated GFR; and ejection fraction. In addition, at low SDC, use of digoxin was also associated with reduction in all-cause mortality and all-cause hospitalization in both age groups. ,O&x";>:,$9_JT/GT$cI If rapid digitalization is considered medically appropriate, it may be achieved by administering a loading dose based upon projected peak digoxin body stores. -, Circulation. However, digoxin is used in low doses and care is taken to achieve low SDC, digoxin may also reduce all-cause mortality and all-cause hospitalizations. 2018 Jun;43(3):377-384. doi: 10.1111/jcpt.12667. An official website of the United States government. It is thus prudent to treat older adults with HF with digoxin 0.125 mg/d. In this trial, the most common manifestations of digoxin toxicity included gastrointestinal and cardiac disturbances; CNS manifestations were less common. Independent predictors of low (0.5 0.9 ng/ml) serum digoxin concentrations among patients < 65 years (left panel: n=806; median age, 58 years) and 65 years (right panel: n=881; median age, 72 years) [Chronic kidney disease=estimated glomerular filtration rate <60 ml/m/1.73 square meters; OR=odds ratio, CI=confidence interval. Reduction was not influenced by age, sex, dose, or blood level of digoxin. On the other hand, hypocalcemia can nullify the effects of digoxin in humans; thus, digoxin may be ineffective until serum calcium is restored to normal. We aimed to investigate the usefulness of the HUGE value to predict the initial dose of digoxin in patients aged older than 70 years. Maintenance, for atrial fibrillation or flutter By mouth Adult Maintenance 125-250 micrograms daily, dose according to renal function and initial loading dose, reduce dose in the elderly. If this is not possible, sampling should be done at least 6 to 8 hours after the last dose, regardless of the route of administration or the formulation used. This Manuscript was prepared using a limited access dataset obtained from the NHLBI and does not necessarily reflect the opinions or views of the DIG Study or the NHLBI., National Library of Medicine Digoxin reduces hospitalizations due to heart failure (HF) and may also reduce mortality at low serum digoxin concentrations (SDC). Slatton ML, Irani WN, Hall SA, et al. Digoxin is approved by the U.S. Food and Drug Administration (FDA) for use in HF, and national HF guidelines recommend use of digoxin to reduce HF symptoms and HF hospitalizations (6,7). Maintenance dose Oral: Adult: 125 to 250 micrograms once daily (rarely increased up to 500 . Low-dose digoxin in patients with heart failure. Digoxin Adult Medication Guideline Page 2 of 5 Adult: 250 to 500 micrograms every 4 to 6 hours according to response, up to a total of 1.5mg. The randomized placebo-controlled DIG trial was conducted during 19911995 in the United States (186 centers) and Canada (116 centers). However, unlike in younger adults, age and digoxin dose were independent predictors of SDC in older adults, suggesting important age-related changes in digoxin pharmacokinetics with aging. The assessment of HF in older adults is often complicated by underreporting of symptoms, functional impairment, other morbidities with symptoms similar to those of HF, and the presence of a normal left ventricular ejection fraction.[3,4]. Rarely, there are patients who are unable to tolerate digoxin at serum concentrations below 0.8 ng/mL. There have been no long-term studies performed in animals to evaluate carcinogenic potential, nor have studies been conducted to assess the mutagenic potential of digoxin or its potential to affect fertility. The present article reviews the current role of digitalis in the management of heart failure and atrial fibrillation (AF) in light of recent study findings. Use in Patients with Impaired Renal Function: Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of digoxin (see DOSAGE AND ADMINISTRATION). 3 0 obj Recent evidence suggests that digoxin inhibits sympathetic nervous system activities in HF by inhibiting the sodiumpotassium (Na+K+) adenosine triphosphatase (ATPase) enzyme in vagal afferent nerve fibers (24,25). The clearance of digoxin can be primarily correlated with renal function as indicated by creatinine clearance. 2004;64(16):1779-800. doi: 10.2165/00003495-200464160-00005. Treatment of Adverse Reactions Produced by Overdosage: Digoxin should be temporarily discontinued until the adverse reaction resolves. 2010 Oct;8(5):419-27. doi: 10.1016/j.amjopharm.2010.10.001. Gheorghiade M, Zannad F, Sopko G, et al. Multivariable adjustment for baseline covariates did not significantly alter these associations of low and high SDC with all-cause hospitalization (Table 4). Smith TW, Butler VP, Jr, Haber E. Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay. In general, the adverse reactions of digoxin are dose-dependent and occur at doses higher than those needed to achieve a therapeutic effect. https://dailymed.nlm.nih.gov/dailymed/labelrss.cfm?setid=f3d29508-e7cc-47ff-845d-b5375ee30407, https://dailymed.nlm.nih.gov/dailymed/rss.cfm. The .gov means its official. Double-blind placebo-controlled study of ibopamine and digoxin in patients with mild to moderate heart failure: results of the Dutch Ibopamine Multicenter Trial (DIMT). Specifically, digoxin should be considered for treatment of HF symptoms before high-dose non-potassium-sparing diuretics. The administration of more than 10 mg of digoxin in a previously healthy adult, or more than 4 mg in a previously healthy child, or a steady-state serum concentration greater than 10 ng/mL often results in cardiac arrest. Distribution: Following drug administration, a 6- to 8-hour tissue distribution phase is observed. Call your doctor for medical advice about side effects. 2003;20(6):445-63. doi: 10.2165/00002512-200320060-00004. In the smaller trial, these trended in favor of a treatment benefit. Concomitant use of digoxin and sympathomimetics increases the risk of cardiac arrhythmias. Digoxin has been shown to reduce hospitalization due to worsening HF. In high doses, digoxin increases sympathetic outflow from the central nervous system (CNS). Finally, we examined the association between low-dose ( 0.125 mg/d) digoxin and low SDC (0.50.9 ng/mL) among patients receiving digoxin (n = 1687), separately for patients < 65 (n = 881) and 65 years (n = 806). The magnitude of rise in serum digoxin concentration relates to the extent of bacterial inactivation, and may be as much as two-fold in some cases. Emesis or gastric lavage may be indicated especially if ingestion has occurred withing 30 minutes of the patients presentation at the hospital. Hence, adverse reactions are less common when digoxin is used within the recommended dose range or therapeutic serum concentration range and when there is careful attention to concurrent medications and conditions. Digoxin is concentrated in tissues and therefore has a large apparent volume of distribution. information submitted for this request. The patients age. Although digoxin may produce anorexia, nausea, vomiting, diarrhea, and CNS disturbances in young patients, these are rarely the initial symptoms of overdosage. Elderly: 125 to 250 micrograms every 4 to 6 hours according to response, up to a total of 500 micrograms. this version. Digoxin Tablets, USP, 125 mcg (0.125 mg), Scored I.D. This is the first comprehensive analysis of the DIG trial that demonstrates that digoxin at low SDC is as effective in older adults as in younger adults suggesting that the pharmacodynamic (what drug does to the body) properties of digoxin are similar, regardless of age. Results: Haldeman GA, Croft JB, Giles WH, Rashidee A. Digoxin inhibits sodium-potassium ATPase, an enzyme that regulates the quantity of sodium and potassium inside cells. The drug 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. Acute heart failure syndromes: current state and framework for future research. About two-thirds of adult patients with clinical toxicity have serum digoxin concentrations greater than 2.0 ng/mL. Although beta-adrenergic blockers or calcium channel blockers and digoxin may be useful in combination to control atrial fibrillation, their additive effects on AV node conduction can result in advanced or complete heart block. Digoxin is used to treat heart failure, usually along with other medications. CrCl <60mL/minute: Reduce loading dose by half. Use of digoxin for heart failure and atrial fibrillation in elderly patients. Hypomagnesemia (low magnesium in the blood)Increased risk of digoxin toxicity. 8600 Rockville Pike Reduction in hospitalizations for HF occurred in both low and high SDC groups. PMC This site needs JavaScript to work properly. 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. Digitalis glycosides are contraindicated in patients with ventricular fibrillation or in patients with a known hypersensitivity to digoxin. -, J Am Coll Cardiol. For women, this result should be multiplied by 0.85. Administration of a digitalis glycoside other than digoxin. However, digoxin may produce clinical benefits even at serum concentrations below this range. Newborn infants display considerable variability in their tolerance to digoxin. Please see our. The following formula has had wide clinical use: Maintenance Dose = Peak Body Stores (i.e., Loading Dose)x % Daily Loss/100Where: % Daily Loss = 14 + Ccr/5, (Ccr is creatinine clearance, corrected to 70 kg body weight or 1.73 m2 body surface area.). The HUGE value is a tool for differentiating the presence or absence of chronic kidney disease in elderly patients. Hosmer and Lemeshow goodness of fit test Chi-square at the final steps for < 65 and 65 years were, respectively, 7.2 (p = .512) and 7.8 (p = .455). The elderly are at an increased risk of digoxin toxicity. The .gov means its official. View NDC Code(s)NEW! and transmitted securely. The KaplanMeier plots for first HF hospitalization are displayed in Figure 2a. Severe digitalis intoxication can cause a massive shift of potassium from inside to outside the cell, leading to life-threatening hyperkalemia. Patients were randomized to placebo or Digoxin, the dose of which was adjusted for the patients age, sex, lean body weight, and serum creatinine (see DOSAGE AND ADMINISTRATION), and followed for up to 58 months (median 37 months). Med Clin North Am. These hemodynamic effects are accompanied by an increase in the left ventricular ejection fraction and a decrease in end-systolic and end-diastolic dimensions. x\YsF~W RTeCZ%n(R!_Oc('rev]?9-bN~?qrx80Ygr>|\Gob9ys4I?Js% g$4).~dH -, Am J Cardiol. Digoxin was associated with a 25% reduction in the number of hospitalizations for heart failure, a 28% reduction in the risk of a patient having at least one hospitalization for heart failure, and a 6.5% reduction in total hospitalizations (for any cause). Background: 12 Citations Metrics Summary Digitalis has been widely used in the treatment of cardiac disease for more than 200 years. J Gerontol A Biol Sci Med Sci. Click here for an email preview. Patients with massive digitalis ingestion should receive large doses of activated charcoal to prevent absorption and bind digoxin in the gut during enteroenteric recirculation. Would you like email updates of new search results? Drugs Aging. Digoxin reduced HF hospitalizations in older adults with HF regardless of SDC. Repeat prescribing: scale, problems and quality management in ambulatory care patients. Heart failure (HF) is common, and with the aging of the population, its incidence and prevalence are projected to rise. The body weight of the patient. Both models were fit to data during all steps of the regression analyses. Pharmacodynamic and Clinical Effects: The times to onset of pharmacologic effect and to peak effect of preparations of digoxin are shown in Table 2: Documented for ventricular response rate in atrial fibrillation, inotropic effects and electrocardiographic changes. Such disorders include restrictive cardiomyopathy, constrictive pericarditis, amyloid heart disease, and acute cor pulmonale. Therefore, digoxin can play an important role in reducing HF hospitalization in older adults with symptomatic HF (4,37) and thus improve quality of life and ease the burden on the health care system. Furthermore, caution should be exercised when combining digoxin with any drug that may cause a significant deterioration in renal function, since a decline in glomerular filtration or tubular secretion may impair the excretion of digoxin. We noted that kidney function, a major determinant of excretion of digoxin, had similar effect of SDC, regardless of age. -. The presence of other medical problems may affect the use of this medicine. Digoxin Injection is frequently used to achieve rapid digitalization, with conversion to digoxin tablets or digoxin solution in capsules for maintenance therapy. New data suggest that at low doses (0.125 mg/day or lower) digoxin not only reduces hospitalization due to HF, but may also reduce mortality. Compared with 70% of patients receiving placebo, 68% with low SDC (HR = 0.83; 95% CI = 0.730.93; p = .002) and 72% of high SDC (HR = 0.98; 95% CI = 0.861.11; p = .712) patients were hospitalized due to all causes (Table 4). Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. The KaplanMeier plots for mortality among HF patients 65 years receiving placebo and among those with low and high SDC are displayed in Figure 1b. 2014 Nov;34(11):1121-31. doi: 10.1002/phar.1480. 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. [ ABPI, 2019d; Joint Formulary Committee, 2019] government site. All rights reserved. 4 UNI | 4.95 per 1UNI. van Veldhuisen DJ. Potassium is usually administered orally, but when correction of the arrhythmia is urgent and the serum potassium concentration is low, potassium may be administered cautiously by the intravenous route. 6 hours according to response, up to a total of 500 micrograms unable to tolerate digoxin at concentrations... 4 ) the aging of the HUGE value to predict the initial dose digoxin. Hospitalizations in older adults with HF with digoxin 0.125 mg/d abdominal pain, intestinal,. 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Known to be dependent on doses and SDC ( 27,28 ) ischemia, and hemorrhagic of. For HF occurred in both low and high SDC with all-cause hospitalization ( Table 4 ) displayed. Volunteers with normal renal function, a 6- to 8-hour tissue distribution is. Older than 70 years your dose as needed women, this result should be multiplied by.!