Do losartan (angiotensin II receptor antagonist) and amlodipine (calcium channel blocker) raise transaminases (liver enzymes)?

Effect of Losartan and Amlodipine on Liver Enzymes

Neither losartan nor amlodipine commonly causes significant elevation of transaminases, though rare cases of drug-induced liver injury have been reported with both medications.

Evidence on Losartan and Liver Function

Losartan, an angiotensin II receptor antagonist (ARB), has been associated with rare cases of hepatotoxicity:

• Elevation in transaminases occurs in less than 2% of patients taking losartan 1
• When drug-induced liver injury (DILI) does occur with losartan, it typically develops within 1-8 weeks of starting therapy 1
• Liver enzymes usually normalize within 2-4 months after discontinuation of the medication 1
• The mechanism of losartan-induced liver injury is not fully understood, but appears to be idiosyncratic rather than dose-dependent 1

Evidence on Amlodipine and Liver Function

Amlodipine, a calcium channel blocker, has similarly rare associations with liver enzyme elevations:

• Amlodipine is generally well-tolerated with minimal hepatic effects 2
• Case reports have documented idiosyncratic liver injury with amlodipine, with elevated transaminases occurring within days of initiation 2
• When amlodipine is discontinued, liver enzymes typically trend downward within 5 days 2

Comparative Safety Profile

When comparing the two medications:

• Neither drug is known to be significantly hepatotoxic in most patients
• Both medications have been extensively studied in large clinical trials without significant signals for hepatotoxicity
• The CASE-J trial specifically compared candesartan (an ARB like losartan) with amlodipine in patients with hypertension, including those with chronic kidney disease, without noting significant differences in liver function abnormalities 3
• In pharmacokinetic studies examining the combination of losartan and amlodipine, no significant hepatotoxic effects were reported 4

Risk Factors and Monitoring

Certain patient factors may increase risk of hepatotoxicity:

• Pre-existing liver disease
• Concomitant use of other potentially hepatotoxic medications
• Advanced age
• Genetic factors affecting drug metabolism

Management Recommendations

1. Baseline liver function tests should be obtained before starting either medication
2. Consider periodic monitoring of liver enzymes during the first few months of therapy, especially in high-risk patients
3. If transaminase elevations occur:
   • For mild elevations (<3 times upper limit of normal): continue monitoring
   • For moderate elevations (3-5 times upper limit): consider dose reduction or alternative agent
   • For significant elevations (>5 times upper limit): discontinue medication

Conclusion

Both losartan and amlodipine have favorable safety profiles regarding liver function. While rare cases of drug-induced liver injury have been reported with both medications, neither drug commonly causes significant elevation of transaminases in most patients. When choosing between these medications, liver safety should not be the primary determining factor for most patients without pre-existing liver disease.