Medications That Increase Transaminases

High-Risk Lipid-Lowering Agents

The American College of Cardiology notes that lomitapide carries a black box warning for hepatotoxicity, requiring measurement of liver enzymes before initiation, with dose adjustment if liver enzymes are elevated, and discontinuation for clinically significant liver toxicity 2
Lomitapide increases hepatic fat, which may be a risk factor for progressive liver disease, and is only available through a REMS program, according to the American College of Cardiology 1, 2
Mipomersen causes injection site reactions, flu-like symptoms, and elevations in serum transaminases, with increases in hepatic fat that may lead to progressive liver disease, and is also available only through a REMS program, as stated by the American College of Cardiology 1
Both lomitapide and mipomersen are FDA-approved only for homozygous familial hypercholesterolemia and require intensive monitoring due to hepatotoxicity risk, according to the American College of Cardiology 1, 2

High-dose atorvastatin causes transaminase elevations in approximately 3.3% of patients, compared to 1.1% with pravastatin, with an odds ratio of 3.01, as reported by the American College of Cardiology 3
High-dose simvastatin shows 0.84% ALT elevation, versus 0.36% with lower doses, with an odds ratio of 2.35, according to the American College of Cardiology 3
Intensive statin therapy increases the risk for elevated hepatic transaminases, as stated by the American College of Cardiology 3
Persistent increases in serum transaminases occur in approximately 0.7-1% of patients receiving statins, according to the American College of Cardiology 3
Progression to liver failure due to statins is exceedingly rare, if it ever occurs, as reported by the American College of Cardiology 3

Approximately 5% of patients with ADPKD treated with tolvaptan display transaminase increases above 3× ULN, compared to 1% receiving placebo, as stated by the Kidney Disease: Improving Global Outcomes (KDIGO) guideline 4
Increases in ALT occur most often during the first 18 months of treatment and resolve within 1-4 months after tolvaptan cessation, according to the KDIGO guideline 4
Monthly monitoring of liver function tests is mandatory for the first 18 months, then every 3 months until drug discontinuation, as recommended by the KDIGO guideline 4

Obtain baseline liver function tests before initiating statin therapy to interpret potential future results, as recommended by the American College of Cardiology and the European Society of Cardiology 5, 3
Routine periodic monitoring of liver enzymes after statin initiation is not recommended, as serious liver injury is rare and unpredictable, according to the American College of Cardiology 3
Measure hepatic function only if symptoms of hepatotoxicity arise, as stated by the American College of Cardiology 3
Continue current statin dose and recheck liver enzymes at a shorter interval for elevations up to 2.5× ULN, as recommended by the American College of Cardiology 3
Reduce statin dose or temporarily withhold only if transaminases rise to >3× ULN, after ruling out other causes, according to the American College of Cardiology 3
Discontinue the statin only if liver enzymes remain >3× ULN despite dose reduction, as stated by the American College of Cardiology 3

Statins are safe and recommended in patients with compensated liver disease, including NAFLD, chronic hepatitis B and C, and compensated cirrhosis, as stated by the American Association for the Study of Liver Diseases (AASLD) and the American College of Cardiology 3, 6
Statins may actually improve transaminase elevations in individuals with fatty liver disease, rather than worsen them, according to the AASLD and the American College of Cardiology 3, 6
Statins are contraindicated only in decompensated cirrhosis, acute liver failure, and active hepatitis with fluctuating or worsening liver function tests, as stated by the AASLD and the American College of Cardiology 3
Pravastatin has the safest hepatic profile among statins, with only 1.1% ALT elevation in clinical trials, and is the statin of choice in liver transplant recipients, according to the American College of Cardiology 3