From the Guidelines
Amiodarone can cause liver function test (LFT) abnormalities, and discontinuation is recommended if liver enzyme levels are three times higher than normal, unless the patient is at high risk for recurrence of life-threatening arrhythmia. For patients starting amiodarone, baseline LFTs should be obtained before initiation, followed by monitoring every 6 months during therapy, as liver toxicity is common in patients receiving long-term amiodarone therapy, occurring at a rate of 0.6 percent annually 1. More frequent monitoring (every 3 months) is advised during the first year of treatment or in patients with pre-existing liver disease. If AST or ALT elevations exceed 2 times the upper limit of normal, dose reduction or discontinuation should be considered. Severe hepatotoxicity is rare but can occur, presenting as acute hepatitis or chronic liver injury resembling cirrhosis. The mechanism of amiodarone-induced liver injury involves direct hepatotoxicity and phospholipidosis, where the drug accumulates in lysosomes. Risk factors include higher doses, longer duration of treatment, advanced age, and pre-existing liver disease, and as a general rule, the longer the therapy and the higher the dose of amiodarone, the greater the likelihood that adverse side effects will require discontinuation of the drug 1. Most LFT abnormalities are mild and asymptomatic, but patients should be educated about symptoms of liver injury such as jaundice, abdominal pain, or unusual fatigue, which warrant immediate medical attention. Regular monitoring of lung, liver, and thyroid function is needed, as chronic administration of amiodarone is associated with complex drug interactions and a host of extracardiac side effects involving the thyroid, skin, and occasionally the lung and liver 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Amiodarone and Liver Function Tests (LFTs)
- Amiodarone is a commonly used antiarrhythmic drug that can cause hepatotoxicity, with an incidence of 1% to 3% in patients receiving chronic oral administration 2.
- The incidence of severe transaminitis (elevated liver enzymes) is low, but amiodarone can cause dramatic increases in serum transaminases, particularly in patients receiving intravenous administration 2.
- Predictors of amiodarone-induced liver injury (AILI) include the presence of cardiomyopathy, congestive hepatomegaly, increasing baseline total bilirubin, direct current cardioversion, and increasing dose of amiodarone 3.
- The severity of AILI is associated with compromised cardiac, hepatic, and hemodynamic conditions, as well as increasing dose of intravenous amiodarone 3.
- Amiodarone-induced liver dysfunction can lead to serious liver damage, including acute liver failure, cirrhosis, and the need for liver transplantation 4.
- Elevated C-reactive protein levels before amiodarone administration are a significant risk factor for drug-induced liver injury (DILI) 5.
- Close monitoring of liver function and consideration of alternative drugs may be necessary in patients with elevated C-reactive protein levels or other risk factors for AILI 5.
- Acute liver injury can occur within 24-36 hours of starting amiodarone, and discontinuation of the drug can lead to improvement in liver enzymes 6.