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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: July 27, 2017.



Asenapine is a second generation (atypical) antipsychotic agent that is taken sublingually and used in the treatment of schizophrenia and manic or mixed episodes associated with bipolar 1 disorder. Asenapine is associated with a low rate of transient and mild serum aminotransferase elevations during therapy, but has not been linked to instances of clinically apparent acute liver injury.


Asenapine (a sen' a peen) is a second generation antipsychotic agent which appears to act as a dopamine type 2 (D2) and serotonin (5-HT)-2A receptor antagonist. It is a somewhat unique antipsychotic agent that has a tetracyclic structure similar to that of mirtazapine, and it is administered as a sublingual tablet, being poorly absorbed by the oral route. Several randomized controlled trials have shown that sublingual asenapine improves symptoms of schizophrenia with effects comparable to risperidone and olanzapine. It also has beneficial activity in acute manic and mixed episodes associated with bipolar 1 disorder. Asenapine was approved for use in the United States in 2009 and is available in sublingual tablets of 2.5, 5 and 10 mg under the brand name Saphris. The typical maintenance dose in adults is 2.5 to 10 mg twice daily. Common side effects of include dizziness, somnolence, fatigue, nausea, anxiety, restlessness (akathisia) and weight gain. Rare, but potentially severe adverse reactions (mentioned in most antipsychotic and antidepressant product labels) include tardive dyskinesia, major neurologic events, neuroleptic malignant syndrome, orthostatic hypotension, seizures, neutropenia, hypersensitivity reactions, prolongation of the QTc interval and suicidal ideation or behavior.


Liver test abnormalities occur in 1% to 2.5% of patients receiving asenapine, but similar rates are reported with placebo therapy (0.6% to 1.3%) and with comparator agents. The ALT elevations are usually mild, transient and often resolve even without dose modification or drug discontinuation. There has been a single case report of cholestatic serum enzyme elevations arising 3 to 4 weeks after starting asenapine, resolving within a month of stopping. Thus, asenapine may be a rare cause of mild cholestatic liver injury.

Likelihood score: D (possible rqaare cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which asenapine might cause serum enzyme elevations or liver injury is not known. Asenapine is metabolized to some extent by the cytochrome P450 system (CYP 2D6 and 3A4), but is an uncommon cause of significant drug-drug interactions with agents that inhibit or induce these microsomal enzymes.

Outcome and Management

The serum aminotransferase elevations that occur with asenapine therapy are usually self-limited and often do not require dose modification or discontinuation. No instances of acute liver failure, chronic hepatitis or vanishing bile duct syndrome have been attributed to asenapine. Cross sensitivity to liver related or other hypersensitivity reactions between asenapine and other antipsychotic agents have not been demonstrated.

Drug Class: Antipsychotic Agents, Atypicals



Asenapine – Saphris®


Antipsychotic Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Asenapine Chemical Structure


References updated: 27 July 2017

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