Case Presentation: Asenapine is widely acknowledged as a well-tolerated medication, exhibiting only infrequent severe adverse events1. The necessity of liver enzyme testing remains a topic without a unanimous consensus2. This case study discusses a patient who experienced significant liver damage upon initiating asenapine. As far as our understanding goes, this represents the initial documented instance of such an occurrence. In this presented case, a 39-year-old visually impaired female with a medical history notable for gastric bypass and hypertension exhibited enduring symptoms of nausea, vomiting, and abrupt right upper quadrant pain. Absent were indications of infection or other alarming factors. Laboratory analyses exposed elevated levels of liver enzymes, specifically alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as shown in Table 1. high international normalized ratio (INR) was also present An extensive liver viral panel and serology yielded negative results, as did drug toxicity assessments for aspirin and Tylenol.Subsequent abdominal CT scans excluded surgical complications, obstructions, or immediate pathologies.Of note, the recent introduction of a transdermal antipsychotic, Asenapine, emerged as a plausible instigator of hepatotoxicity, commencing two weeks prior but discontinued on admission. A subsequent liver biopsy unveiled widespread ballooning degeneration and necrosis, predominantly localized to zone 3 of the liver, consistent with acute liver injury. Given the imminent peril of acute liver failure, inclusion on a liver transplant waitlist was contemplated, although transfer was eventually obviated due to her stabilized condition. On her day of discharge, approximately 7 days after the initial assessment, the patient exhibited a significant diminution in liver enzyme levels. Upon a two-week follow-up, her AST levels trended toward 77 units/l and ALT toward 139 units/l.
Discussion: The literature review revealed that 50% of patients treated with atypical antipsychotics experienced asymptomatic elevation of liver enzymes. However, instances of severe hepatotoxicity were sporadic, with only a few reported cases associated with clozapine, olanzapine, risperidone, and questiapine2. Overall, safety considerations for transdermal asenapine mirror those of its sublingual counterpart3. Liver test irregularities were observed in approximately 1% to 2.5% of patients taking sublingual asenapine, a rate akin to placebo treatment (ranging from 0.6% to 1.3%). Typically, ALT elevations tend to be mild and fleeting, often resolving even without medication adjustments or discontinuation of the medication3.This case marks the initial instance of liver failure, involving elevated liver enzymes and an elevated INR level, necessitating hospitalization3.The liver injury commonly manifests within the initial weeks of treatment, although it can exhibit variability, extending up to several months, as previously reported for risperidone. In this particular instance, the elevation of liver enzymes was identified 2 weeks after initiating the asenapine patch.2
Conclusions: This case study highlights the potential for severe hepatotoxic effects associated with asenapine and underscores the importance of regular enzyme level monitoring as deemed necessary.
