Loxapine is a conventional antipsychotic used in the therapy of schizophrenia. Loxapine therapy is commonly associated with minor serum aminotransferase elevations and in very rare instances has been linked to clinically apparent acute liver injury.
Loxapine (lox' a peen) is a dibenzoxazepine tricyclic derivative which appears to act by blocking dopamine type 2 (D2) receptors. Loxapine has other central and peripheral effects including anticholinergic and α-adrenergic blockade. Loxapine is indicated for the therapy of psychotic disorders and was approved for this use in the United States in 1976. In recent years, loxapine has been replaced in large part by the atypical antipsychotics, which have fewer extrapyramidal side effects. Loxapine is available as tablets of 5, 10, 25 and 50 mg and in generic forms and under the brand name Loxitane. Recommended doses of oral loxapine are 10 mg twice daily initially, increasing to a maximum of 100 mg in divided doses daily. An aerosol formulation of loxapine has recently been developed that is recommended for use in acute agitation in patients with bipolar disorder or schizophrenia. Common side effects include drowsiness, dizziness, headache, blurred vision, dry mouth, and tremor. Loxapine, unlike many antipsychotic agents, is not associated with significant weight gain.
Liver test abnormalities have been reported to occur in a small proportion of patients on long term therapy with loxapine, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury have been reported due to loxapine and to the structurally related tricylic amoxapine (not available in the United States), but cases are rare. The onset of jaundice is within 4 to 8 weeks, and the pattern of serum enzyme elevations is typically hepatocellular. Immunoallergic features and autoantibody formation are not typical.
Mechanism of Injury
The mechanism by which loxapine causes serum aminotransferase elevations is not known, but is likely due to production of a toxic intermediate by its metabolism. Loxapine is extensively metabolized by the liver via sulfoxidation and oxidation, partially via P450 system.
Outcome and Management
The serum aminotransferase elevations that occur on loxapine therapy are usually self-limited and do not require dose modification or discontinuation of therapy. No instances of acute liver failure or vanishing bile duct syndrome due to loxapine have been reported. Patients with loxapine induced liver injury probably do not have cross sensitivity to atypical antipsychotics.
REPRESENTATIVE TRADE NAMES
Loxapine – Generic, Loxitane®
Product labeling at DailyMed, National Library of Medicine, NIH
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References Last Updated: 24 February 2014
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