Can Amlodipine, Losartan, or Lorazepam Cause Hepatocellular Carcinoma?
None of these three medications—amlodipine 5mg, losartan 50mg, or lorazepam (Ativan) 0.5mg—are established causes of hepatocellular carcinoma (HCC), and there is no evidence linking them to HCC development.
Evidence from FDA Drug Labels
Amlodipine
- Long-term carcinogenicity studies in rats and mice showed no evidence of carcinogenic effects at doses up to 2.5 mg/kg/day for up to two years 1
- The highest tested dose in mice was similar to the maximum recommended human dose of 10 mg/day on a mg/m² basis 1
- No drug-related mutagenic effects were observed at either gene or chromosome level 1
Losartan
- Losartan was not carcinogenic when administered at maximally tolerated doses to rats (105 weeks) and mice (92 weeks) 2
- Female rats at the highest dose (270 mg/kg/day) showed only a slightly higher incidence of pancreatic acinar adenoma, not hepatocellular carcinoma 2
- The tested exposures were approximately 160 times (rats) and 30 times (mice) the human exposure at 100 mg/day 2
- Losartan was negative in all mutagenesis assays, including microbial mutagenesis and chromosomal aberration tests 2
Lorazepam (Ativan)
- No FDA drug label evidence was provided regarding carcinogenicity, and there is no established link to HCC in the medical literature
Paradoxical Protective Effect of Losartan
Interestingly, research suggests losartan may actually inhibit HCC progression rather than cause it:
- In animal models, losartan (10 mg/kg) inhibited diethylnitrosamine-induced HCC progression through inactivation of the nuclear transcription factor kappa-B (NF-κB) pathway 3
- This effect resulted in improved liver function, reduced AFP levels, and better histologic outcomes 3
- The mechanism involves blocking angiotensin II type 1 receptors (AT1R), which reduces tumor-promoting inflammation 3
Actual Risk Factors for HCC
The established causes of HCC are entirely different from these medications 4:
- Viral hepatitis (hepatitis B and C)
- Alcohol-related liver disease
- Non-alcoholic fatty liver disease (NAFLD) - rapidly becoming the dominant cause
- Cirrhosis of any etiology
Hepatotoxicity vs. Carcinogenicity: An Important Distinction
While losartan can rarely cause drug-induced liver injury (DILI) with elevated transaminases in <2% of cases 5, this acute hepatotoxicity is fundamentally different from causing cancer:
- DILI from losartan typically occurs within 1-8 weeks of therapy 5
- Hepatic enzymes usually normalize 2-4 months after drug suspension 5
- Acute liver injury does not equal carcinogenicity - only seven cases of losartan-induced hepatitis have been described in the literature 5
Clinical Bottom Line
These three medications can be safely continued without concern for HCC causation. If a patient on these medications develops HCC, the investigation should focus on the established risk factors listed above (viral hepatitis, alcohol, NAFLD, cirrhosis) rather than attributing it to their antihypertensive or anxiolytic therapy 4.