Can brexipiprazole or mirtazapine cause cholestatic or hepatocellular injury?

Hepatotoxicity Risk with Brexipiprazole and Mirtazapine

Both brexipiprazole and mirtazapine can cause hepatotoxicity, but the evidence is limited and differs between the two agents: mirtazapine has documented cases of severe hepatocellular injury with prolonged jaundice, while brexipiprazole lacks specific published evidence regarding cholestatic or hepatocellular injury patterns.

Mirtazapine Hepatotoxicity

Documented Hepatocellular Injury

• Mirtazapine has been associated with severe hepatotoxicity presenting as hepatocellular injury with prolonged jaundice in documented case reports 1
• Two cases demonstrated severe hepatotoxicity with prolonged jaundice that required 3 months or longer to resolve after drug withdrawal 1
• The mechanism of mirtazapine-induced liver toxicity remains unknown 1

Clinical Characteristics

• Elevated alanine aminotransferase (ALT) levels have been reported with mirtazapine, though most cases were mild and returned to normal with continued administration 2
• Granulocytopenia and elevated ALT represent the most commonly reported laboratory abnormalities 2
• The injury pattern appears predominantly hepatocellular rather than cholestatic, based on the presentation with jaundice and elevated transaminases 1

Monitoring Recommendations

• Regular and close monitoring for adverse events is recommended, particularly in patients with hepatic insufficiency 2
• Careful dosage titration is essential in patients with pre-existing liver disease 2

Brexipiprazole Hepatotoxicity

Limited Evidence

• No specific published evidence was identified in the provided literature regarding brexipiprazole causing cholestatic or hepatocellular injury
• As an atypical antipsychotic, brexipiprazole belongs to a drug class that has variable hepatotoxicity profiles across different agents

General Drug-Induced Liver Injury Context

Pattern Classification

• Drug-induced liver injury (DILI) is classified using the R value: R = (ALT/ULN) / (ALP/ULN) 3
• R ≥5 indicates hepatocellular injury, R <2 indicates cholestatic injury, and R between 2-5 indicates mixed injury 3
• Cholestatic DILI accounts for approximately 30% of all DILI cases 4, 5

Management Principles

• The only effective treatment for drug-induced cholestasis or hepatocellular injury is immediate withdrawal of the suspected drug 4, 5
• Early detection of abnormal liver tests and prompt drug withdrawal are crucial for preventing progression 4
• Cholestatic injury generally has a better prognosis than hepatocellular injury 4

Clinical Pitfalls to Avoid

• Do not confuse drug-induced cholestatic injury with drug-induced autoimmune-like hepatitis, which requires different management 4
• Patients with pre-existing liver disease who develop DILI have increased morbidity and mortality compared to those with healthy livers 3
• Monitor liver function tests within 7-10 days after drug discontinuation to confirm the injury pattern and assess trends 4

Practical Clinical Approach

For Mirtazapine

• Obtain baseline liver function tests before initiating therapy
• Monitor ALT, AST, alkaline phosphatase, and bilirubin periodically during treatment
• Discontinue immediately if ALT/AST rise significantly or if jaundice develops 1
• Be aware that recovery may take 3 months or longer after discontinuation 1

For Brexipiprazole

• While specific hepatotoxicity data is lacking, apply standard monitoring practices for atypical antipsychotics
• Obtain baseline and periodic liver function tests, particularly in patients with risk factors
• Maintain heightened vigilance for any signs of liver injury