From the Guidelines
Digoxin is not commonly associated with drug-induced liver injury, and when it does occur, it is typically mild and transient. When considering the use of digoxin, the primary concern is its cardiac toxicity effects rather than liver injury 1. The evidence suggests that digoxin is indicated in atrial fibrillation and symptomatic heart failure to slow ventricular rate and improve ventricular function and symptoms. Some key points to consider when using digoxin include:
- Monitoring for cardiac effects is crucial, with therapeutic drug monitoring targeting serum levels between 0.8-2.0 ng/mL to avoid toxicity.
- Regular assessment of kidney function is more critical than liver function when using digoxin, as renal impairment can lead to drug accumulation and toxicity 1.
- If abnormal liver function tests develop during digoxin therapy, clinicians should first consider other causes of liver injury, including concomitant medications, before attributing it to digoxin. The mechanism by which digoxin might affect liver function is not well established, but may relate to its effects on cellular Na+/K+-ATPase or potential immune-mediated reactions in rare cases. Management of suspected digoxin-related liver injury involves dose adjustment or discontinuation based on the severity of liver enzyme elevations and clinical symptoms. It is essential to note that the elimination of digoxin is renal, and it is less dependent on liver function compared to digitoxin, which is metabolized in the liver 1. Overall, the risk of liver injury from digoxin is relatively low, and its benefits in managing heart failure and atrial fibrillation often outweigh this risk.
From the Research
Digoxin Drug Induced Liver Injury
- There is limited evidence directly linking digoxin to liver injury, however, one study 2 suggests that digoxin may have a protective effect on the liver, mitigating diethylnitrosamine-induced acute liver injury in mice.
- The study found that digoxin pretreatments dose-dependently mitigated the rise of hepatocellular injury parameters and necroinflammation scores, and boosted the number of PCNA positive hepatocytes, leading to improvement of the reparative potential in hepatocytes.
- Another study 3 reports a case of hepatotoxicity associated with carvedilol, a beta-blocker, which may be relevant to patients taking digoxin, as carvedilol is sometimes used in conjunction with digoxin to treat heart failure.
- However, there is no direct evidence in this study to suggest that digoxin causes liver injury.
- Other studies 4, 5, 6 discuss the use of digoxin in various clinical settings, including heart failure and atrial fibrillation, but do not provide information on digoxin-induced liver injury.
Mechanism of Action
- The study 2 suggests that digoxin's ameliorative effect on liver injury may be attributed to its ability to reduce the production of proinflammatory mediators, such as IL-17A, IL-1β, and TNF-α, and impede the attraction and infiltration of monocytes to the liver.
- However, the exact mechanism of action of digoxin on the liver is not fully understood and requires further study.
Clinical Implications
- While there is limited evidence to suggest that digoxin causes liver injury, patients taking digoxin should be monitored for signs and symptoms of hepatotoxicity, as with any medication.
- The study 5 provides guidance on the diagnosis and management of digoxin toxicity, which may be relevant to patients experiencing liver injury.