From the Guidelines
Amlodipine can affect the liver, particularly in patients with pre-existing liver disease or impaired liver function, as it is primarily metabolized by the liver and may accumulate in the body, leading to higher blood levels and increased side effects 1.
Key Points to Consider
- Amlodipine is a calcium channel blocker that is metabolized by the liver, and its clearance may be decreased in patients with liver disease, leading to increased blood levels and potential side effects 1.
- Patients with liver disease or impaired liver function may require lower doses of amlodipine and closer monitoring of liver function 1.
- Rarely, amlodipine can cause liver injury, with symptoms such as jaundice, dark urine, abdominal pain, or elevated liver enzymes on blood tests.
- Amlodipine is a substrate of CYP3A4, and its plasma concentrations may be affected by inhibitors or inducers of this enzyme, which can further impact its metabolism and potential liver effects 1.
Clinical Implications
- Patients taking amlodipine should be monitored for signs of liver problems, such as jaundice, dark urine, or abdominal pain, and should contact their healthcare provider promptly if they experience any of these symptoms.
- Regular check-ups and liver function tests may be recommended for long-term users of amlodipine, especially those with existing liver conditions.
- Healthcare providers should consider the potential liver effects of amlodipine when prescribing the medication, particularly in patients with pre-existing liver disease or impaired liver function.
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 is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine. Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40 to 60%, and a lower initial dose may be required.
Amlodipine can affect the liver, as evidenced by reports of jaundice and hepatic enzyme elevations in postmarketing experience. Additionally, amlodipine undergoes extensive hepatic metabolism, and patients with hepatic insufficiency may require a lower initial dose due to decreased clearance of the drug 2.
From the Research
Amlodipine's Effect on the Liver
- Amlodipine, a commonly prescribed antihypertensive drug, has been reported to cause liver enzyme elevations in some cases 3, 4.
- A case report published in 2020 described a 47-year-old male patient who developed markedly elevated liver transaminases after starting amlodipine, which resolved after the drug was suspended 3.
- Another case report published in 2022 described an 88-year-old female who developed intermittent right upper quadrant pain and pruritus after starting amlodipine, with significantly elevated liver enzymes that normalized after the drug was discontinued 4.
- A study published in 2024 found that S-amlodipine induced liver inflammation and dysfunction in a rat model by altering the intestinal microbiome, leading to an increase in gut bacterial lipopolysaccharide content and subsequent activation of the TLR4 pathway 5.
Mechanism of Amlodipine-Induced Liver Injury
- The exact mechanism of amlodipine-induced liver injury is not fully understood, but it is thought to be idiosyncratic and may involve alterations in the gut microbiome 3, 5.
- A study published in 2022 found that amlodipine besylate and amlodipine aspartate improved liver injury and hepatic steatosis in mice with non-alcoholic fatty liver disease (NAFLD) and hypertension by modulating gut microbiota and enhancing taurine and hypotaurine metabolism 6.
Clinical Implications
- These findings suggest that amlodipine may have adverse effects on the liver, particularly in individuals with pre-existing liver disease or those taking other medications that may interact with amlodipine 3, 5, 4.
- However, amlodipine may also have beneficial effects on the liver in certain contexts, such as in the treatment of NAFLD and hypertension 6.