What is Amlodipine?
Amlodipine is a widely used dihydropyridine calcium channel blocker approved in the U.S. in 1992. It is commonly prescribed for hypertension, coronary artery disease, and angina. It works by blocking calcium entry into vascular smooth muscle and cardiac muscle, causing relaxation and vasodilation, which lowers blood pressure and decreases cardiac workload. Available as Norvasc and generic versions, it is also found in combination medications.
The Link Between Amlodipine and Liver Injury
Clinically apparent liver injury from amlodipine is considered rare. While mild, temporary liver enzyme elevations can occur with chronic use, these often happen at similar rates to control groups and may resolve even with continued medication. Some case reports have linked amlodipine to drug-induced liver injury (DILI), leading the NIH's LiverTox database to assign a 'C' likelihood score, indicating it is a probable but rare cause of clinically apparent liver injury. Large studies have not identified widespread cases despite its common use.
Mechanism of Injury
The exact cause of amlodipine hepatotoxicity is unclear but is thought to be an unpredictable, non-dose-dependent (idiosyncratic) reaction. This may result from toxic metabolites produced during the liver's metabolism of the drug, which is primarily done by CYP3A4 enzymes. The liver injury can manifest with mixed or cholestatic enzyme patterns, without typical allergic reactions like rash or fever.
Signs, Symptoms, and Onset
If amlodipine-induced liver injury occurs, symptoms typically appear 4 to 12 weeks after starting the medication, although delayed onset is possible.
Symptoms may include:
- Jaundice (yellowing of skin/eyes)
- Dark urine
- Fatigue
- Nausea and/or vomiting
- Right upper quadrant abdominal pain
- Itchy skin (pruritus)
Risk Factors and Management
Specific risk factors for this idiosyncratic reaction are not well-defined. However, individuals with existing liver problems may have reduced amlodipine clearance, leading to higher blood levels. A lower starting dose and closer monitoring may be necessary for these patients. There is also a potential for cross-reactivity with other calcium channel blockers.
Management involves stopping amlodipine as soon as liver injury is suspected. In most documented cases, liver enzyme levels improve within 4 to 8 weeks after discontinuation. There have been no reports of amlodipine causing chronic or acute liver failure.
Comparison with Other Antihypertensives
Compared to some other medications, calcium channel blockers like amlodipine are often considered safer options in cases of acute liver injury due to less reliance on hepatic metabolism.
| Medication Class | Drug Examples | General Liver Toxicity Risk | Notes |
|---|---|---|---|
| Calcium Channel Blockers | Amlodipine, Nifedipine | Low / Rare | Idiosyncratic injury, resolves on stopping. Safer in acute liver injury. |
| ACE Inhibitors | Lisinopril, Ramipril | Low / Rare | Rare cause of liver injury. |
| Angiotensin II Receptor Blockers (ARBs) | Losartan, Valsartan | Low / Rare | Generally well-tolerated. |
| Beta-Blockers | Metoprolol, Labetalol | Variable | Some, like labetalol, have a known risk. |
| Diuretics | Hydrochlorothiazide | Very Low | Rarely linked to significant injury. |
| Other | Methyldopa, Hydralazine | Higher | Methyldopa is a known cause of DILI. |
Conclusion
While amlodipine can cause liver damage, it is a very rare occurrence. This medication is generally well-tolerated, and for most patients, the benefits of managing blood pressure and angina outweigh the minimal risk of liver issues. Patients, particularly those with pre-existing liver conditions, should discuss any concerns with their doctor and undergo monitoring if necessary. Prompt medical attention is advised if symptoms of liver problems appear. The prognosis for amlodipine-induced liver injury is good, with expected full recovery after discontinuing the drug.
For more detailed information, consult the NIH's LiverTox database: https://www.ncbi.nlm.nih.gov/books/NBK548585/
