Practical information and advice on continuing or stopping drugs with associated hepatoxicity is available from a recent commentary (Gastroenterol Hepatol 2012; 8: 333-36).
Most drugs with a “bump” in aminotransferases do not need to be stopped. Many drugs induce an “adaptive response” in which elevated LFTs will spontaneously resolve; this is most common in the first 12 weeks of drug usage. This type of response must be distinguished from an immune reaction/hypersensitivity response which is much more likely to progress. A hypersensitivity response could include rash, fever, and eosinophilia.
Recommended STOP RULES:
- Drugs that cause symptomatic hepatitis: abdominal pain, jaundice, loss of appetite.
- ALT values that exceed 8 times the ULN
- ALT values >3 times the ULN and Bilirubin >2 times the ULN
- If the ALT value is >3 times the ULN but not associated with symptoms or rise in bilirubin, the drug can likely be continued with periodic monitoring.
- ALT values >5 times the ULN require more intensive monitoring.
- Hy’s law (named for Hyman Zimmerman): AST or ALT > 3 ULN AND bili > 3 ULN indicate serious hepatotoxicity with >10% mortality rate.
- Statins have similar rates of hepatotoxicity as the general population
- Acetaminophen accounts for 40-50% of the 2000-2500 U.S. cases per year of acute liver failure (ALF). Of the remaining cases of ALF, about 12% (250-300) are due to other cases of DILI. Isoniazid is the 2nd most common cause of ALF due to DILI with about 50 cases.
- Potential risk factors for DILI include alcohol usage, obesity, adult age group, and female gender.
Additional blog entries and references:
- -J Pediatr 2011; 158: 802. Developing liver toxicity with valproic acid (VPA) is a contraindication to OLTx (even in the absence of documented mitochondrial dz). Rx with carnitine and d/c VPA. 82% of 17 children died w/in 1 yr of OLTx. POLG1 mutations are associated with Alpers syndrome. (Ann Neurol 2004; 55: 706.)
- -NEJM 2009; 360: 1575. propylthiouracil assoc c liver failure in ~1 in 2000
- -JPGN 2008; 47: 395-405. Drug-related hepatotoxicity and acute liver failure.
- -NEJM 2003; 349: 474. (review)
- PDF] What Do We Mean by Looking? FDA powerpoint with related information