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Ondansetron (ODSN) is a commonly used and well-tolerated anti-emetic used during pregnancy. Upon review, three cases were identified in which liver function tests (LFTs) were elevated after ODSN administration without concurrent chemotherapy. In this report, we present a case of a 28-year-old pregnant female experiencing psychosis who developed serum level elevation of aspartate transaminase (AST) and alanine transaminase (ALT). An extensive workup left drug-induced liver injury as the most likely etiology. On retrospective review, we were able to demonstrate a clear relationship between ODSN administration and the rise of ALT and AST serum levels.  A 28-year-old female gravida 3 para 2, who was 28 weeks pregnant, presented to a county hospital with new-onset psychotic features and persistent vomiting. She was diagnosed with major depressive disorder (MDD) with psychotic features and hyperemesis gravidarum (HG). She was started on medications to treat both conditions including as needed ODSN. Several days after admission, her serum levels of AST and ALT began to rise, eventually plateauing at an AST value of 267 units/liter (U/L) and an ALT value of 605 U/L on hospital day 10 and subsequently started decreasing. A comprehensive workup was performed to identify the cause of her hypertransaminasemia. Multiple causes were ruled out, with the most likely etiology determined to be drug-induced liver injury. She was admitted to the psychiatric emergency room (PER) on two separate occasions due to psychotic decompensation from medication noncompliance. On both occasions, her AST and ALT values were within normal limits. Ten weeks from the first admission she came for delivery. The patient had been medication compliant prior to delivery and displayed no features of psychosis. Notably, her AST and ALT were elevated and continued to rise until her delivery after which the serum levels decreased.  A sharp rise in the plasma concentration of ALT and AST indicates an acute injury liver. As noted in the case presentation, medical workup ruled out many possible etiologies of her hypertransaminasemia. An important differential to consider was HG, however, based on the history and timing of LFT rise, this differential was unlikely. With other differential diagnoses ruled out, medication-induced hepatotoxicity was the most likely diagnosis. Next, by reviewing the medication administration record we found a temporal relationship between the onset and discontinuation of ODSN and the pattern of AST and ALT levels. Temporal relationships between AST and ALT levels were able to be excluded from all other medications this patient received.  With limited reports indicating the hepatotoxicity potential of ODSN in the absence of concomitant chemotherapy administration, we hope this report adds to the literature and potentially assists future clinical decision making.

A Rise in Aspartate Transaminase and Alanine Transaminase Associated With Ondansetron Administration in a Pregnant Female