Related Experiment Videos
Effect of aging on the incidence of digoxin toxicity
1Department of Pharmacy Services, Kosei Hospital, Anjo, Japan. miura@kosei.anjo.aichi.jp
Objective:
To evaluate the relationship of the therapeutic serum digoxin concentration (SDC) range (0.5-2 ng/mL, as recommended in previous clinical studies) with the incidence of digoxin toxicity during digoxin maintenance therapy.
Methods:
Subjects included all inpatients (n = 462) and outpatients (n = 437) receiving digoxin oral maintenance therapy for heart failure and/or atrial fibrillation with tachycardia at Kosei Hospital, Anjo, Japan. SDC and blood chemistry analysis were determined, and a 24-hour Holter electrocardiographic recording was performed when the SDC was at the presumed steady-state concentration.
Results:
Analysis of clinical data showed that there was an overlapping (toxic and nontoxic) range of SDCs in which the incidence of digoxin toxicity was patient-dependent (1.4-2.9 ng/mL). No patient exhibited signs or symptoms of digoxin toxicity when the SDC was <1.4 ng/mL; all patients had evidence of toxicity when the SDC was >3 ng/mL. Additionally, it was shown that the concentration range of this overlapping range tended to broaden and shift to lower concentrations with increasing age. Patients with signs of toxicity when their SDCs were in the overlapping range had normal serum creatinine, blood urea nitrogen, digoxin clearance, creatinine clearance, and potassium concentrations, except for a significantly higher mean age than patients without toxicity. The incidence of digoxin toxicity was dependent on increasing age in patients whose SDCs were within the recommended therapeutic range. Moreover, clinical evidence of digoxin toxicity in patients >71 years old was 26.5%, despite their SDCs falling between 1.4 and 2 ng/mL.
Conclusions:
Increased age is most likely associated with enhanced susceptibility to digoxin toxicity, possibly due to unknown pharmacodynamic changes. This raises the possibility that patients >71 years show clinical evidence of digoxin toxicity despite having SDCs within the recommended therapeutic range.
Insights
Older patients are more susceptible to digoxin toxicity, even within the recommended therapeutic serum digoxin concentration range. Age significantly influences the risk of adverse effects during digoxin maintenance therapy.
Area of Science:
- Pharmacology
- Geriatrics
- Cardiology
Background:
- Digoxin is commonly prescribed for heart failure and atrial fibrillation.
- The established therapeutic serum digoxin concentration (SDC) range is 0.5-2 ng/mL.
- The relationship between SDC and digoxin toxicity, particularly in specific patient populations, requires further investigation.
Purpose of the Study:
- To evaluate the association between the recommended therapeutic serum digoxin concentration (SDC) range and the incidence of digoxin toxicity.
- To identify patient factors influencing digoxin toxicity risk within the therapeutic SDC range.
Main Methods:
- A study involving 462 inpatients and 437 outpatients receiving digoxin maintenance therapy.
- Serum digoxin concentration (SDC) and blood chemistry were analyzed.
- 24-hour Holter electrocardiographic recordings were performed at steady-state SDC.
Main Results:
- An overlapping SDC range (1.4-2.9 ng/mL) showed patient-dependent digoxin toxicity.
- No toxicity was observed below 1.4 ng/mL, while toxicity occurred above 3 ng/mL.
- Increased age correlated with a broader, lower-shifted overlapping SDC range and higher toxicity incidence, especially in patients >71 years.
Conclusions:
- Advanced age is a significant risk factor for enhanced susceptibility to digoxin toxicity.
- Pharmacodynamic changes associated with aging may increase digoxin sensitivity.
- Current therapeutic SDC ranges may need age-specific adjustments to prevent toxicity in elderly patients.