TABLE 2.

Overview of pharmacologic agents used in treatment of substance use disorder and their associated hepatotoxicity

Drug	Proposed mechanism of DILI	Clinical findings	Outcomes	References
Buprenorphine	Unknown	Hepatocellular injury Case report demonstrated ALT elevation 300 × ULN, prolonged PT, and renal impairment	Most cases appear to be self-limited Severe hepatitis with acute liver failure may occur	10
Gabapentin (Used off label for cannabis use disorder)	Unknown	Mixed pattern of liver injury Case reports demonstrate peak ALT/AST levels ranging from 300 to 800. One case showed primarily cholestatic injury, with significantly elevated ALP in the 1200s.	Clinical resolution with removal of the drug	13
Methadone	No clearly established hepatotoxic effects			11
Naltrexone	Unknown	Mild, asymptomatic hepatocellular injury Case reports do not show liver enzyme elevation at therapeutic doses	Spontaneous resolution often occurs without discontinuation of the drug	12
Topiramate (used off label for cocaine use disorder)	Induction of CYP3A4, or inhibition of CYP2C19 enzymes by topiramate potentiates hepatotoxic effects of other medications (eg, antipsychotics)	Hepatocellular injury Case reports demonstrate ALT/AST elevations ranging from 3 to 6 × ULN	Clinical resolution with removal of the drug and supportive care	14

Abbreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; PT, prothrombin time; ULN, upper limit of normal.