From the Guidelines
Amlodipine rarely causes liver injury, and it is considered safe for most patients, including those with pre-existing liver disease, when used at recommended doses. This calcium channel blocker, commonly prescribed for hypertension and angina at doses of 2.5-10 mg daily, has an excellent safety profile regarding liver health, as supported by various studies, including those that did not specifically focus on liver injury but demonstrated its overall safety in a wide range of patients 1. While mild, transient elevations in liver enzymes can occur in some patients, clinically significant liver damage from amlodipine is extremely uncommon. If liver injury does occur, it typically presents within the first few months of treatment with symptoms like fatigue, nausea, and jaundice. The mechanism behind the rare cases of amlodipine-related liver injury is believed to be an idiosyncratic immune-mediated reaction rather than direct toxicity.
Key points to consider:
- Amlodipine's safety profile is well-established, with a low risk of liver injury.
- Patients with pre-existing liver disease can generally take amlodipine safely, though they may require closer monitoring.
- If a patient develops signs of liver problems while taking amlodipine, their healthcare provider should evaluate them promptly, as discontinuation of the medication typically leads to resolution of liver abnormalities within weeks to months.
- The choice of amlodipine should be based on its efficacy for the patient's condition, considering its benefits and the low risk of liver injury, as evidenced by studies such as the ALLHAT trial, which compared different antihypertensive therapies without highlighting amlodipine as a significant risk for liver injury 1.
Given the available evidence, the use of amlodipine is not significantly associated with an increased risk of liver injury, making it a viable treatment option for patients with hypertension and angina, including those with concerns about liver health, under the guidance of a healthcare provider.
From the FDA Drug Label
In postmarketing experience, jaundice and hepatic enzyme elevations (mostly consistent with cholestasis or hepatitis), in some cases severe enough to require hospitalization, have been reported in association with use of amlodipine.
Amlodipine may cause liver injury, as evidenced by reports of jaundice and hepatic enzyme elevations in postmarketing experience 2. These events were sometimes severe enough to require hospitalization.
- Key points:
- Jaundice and hepatic enzyme elevations have been reported.
- These events were mostly consistent with cholestasis or hepatitis.
- Some cases were severe enough to require hospitalization. It is essential to monitor patients for signs of liver injury when taking amlodipine.
From the Research
Amlodipine and Liver Injury
- Amlodipine, a commonly prescribed antihypertensive drug, has been associated with liver injury in several case reports 3, 4, 5.
- These case reports describe patients who developed elevated liver enzymes after starting amlodipine, with improvements in liver function after discontinuation of the drug.
- The mechanisms of amlodipine-induced liver injury are not fully understood, but may involve idiosyncratic reactions or alterations in the gut microbiome 6.
Gut Microbiome and Liver Injury
- A study in rats found that S-amlodipine induced liver inflammation and dysfunction through alterations in the gut microbiome, including an increase in E. coli and a decrease in A. muciniphila and B. uniformis 6.
- Another study found that amlodipine besylate and amlodipine aspartate improved liver function and reduced liver injury in mice with non-alcoholic fatty liver disease (NAFLD) by modulating the gut microbiota and enhancing taurine and hypotaurine metabolism 7.
Clinical Implications
- Clinicians should be aware of the potential for amlodipine to cause liver injury, particularly in patients with pre-existing liver disease or those taking other medications that may increase the risk of liver injury 3, 4, 5.
- Further studies are needed to fully understand the mechanisms of amlodipine-induced liver injury and to determine the clinical significance of these findings.