Liver, extensive; active metabolites include amoxapine and 8-hydroxyloxapine. Inhibits P-glycoprotein and is a substrate of CYP1A2, CYP3A4 and CYP2D6[1]
Loxapine is a typical antipsychoticmedication, used primarily in the treatment of schizophrenia. Trade names for loxapine taken by mouth include Loxapac and Loxitane; the inhalable form is approved as Adasuve. The drug is a member of the dibenzoxazepine class and structurally related to clozapine (which belongs to the chemically akin class of dibenzodiazepines). Several researchers have argued that loxapine may behave as an atypical antipsychotic.[2]
The typical starting dosage is 10 mg twice daily; usual dose range 30–50 mg twice daily; maximum recommended dosage is 250 mg per day. The US Food and Drug Administration (FDA) has approved loxapine inhalation powder 10 mg (Adasuve, Alexza Pharmaceuticals) for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults.[4]
A brief review of loxapine[5] found no conclusive evidence that it was particularly effective in patients with paranoid schizophrenia. A subsequent systematic review considered that the limited evidence did not indicate a clear difference in its effects from other antipsychotics.[6]
Loxapine was one of five antipsychotics used in a study on the structure of neurons in parts of the brain thought to be involved in schizophrenia. Only loxapine was linked to the development of new connections between neurons.[7]
Precautions
This drug is unrelated to the habit-forming benzodiazepines, and misuse is rare.[8] The risks and side effect profile are comparable to other antipsychotics.
Extrapyramidal disease (dose-dependent. At lower dosages its propensity for causing extrapyramidal side effects appears to be similar to that of atypical antipsychotics[9]
The data in the following table was obtained from the PDSP Ki database and they are for binding towards human cloned proteins (receptor and transporter) unless otherwise specified.[11]
^ abcdefgTruven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 21]. Greenwood Village, CO: Thomsen Healthcare; 2013.
^Glazer WM (1999). "Does loxapine have "atypical" properties? Clinical evidence". The Journal of Clinical Psychiatry60 (Suppl 10): 42–6. PMID10340686.
^Cheung SW, Tang SW, Remington G (March 1991). "Simultaneous quantitation of loxapine, amoxapine and their 7- and 8-hydroxy metabolites in plasma by high-performance liquid chromatography". Journal of Chromatography564 (1): 213–21. doi:10.1016/0378-4347(91)80083-O. PMID1860915.
^Harrison, Pam: Inhalant Approved for Agitation in Bipolar I, Schizophrenia. Medscape. Dec 24, 2012.
^"Clozapine and loxapine for schizophrenia". Drug and Therapeutics Bulletin29 (11): 41–2. May 1991. PMID1747161.
^Chakrabarti A, Bagnall A, Chue P et al. (2007). Chakrabarti A, ed. "Loxapine for schizophrenia". Cochrane Database of Systematic Reviews (Online) (4): CD001943. doi:10.1002/14651858.CD001943.pub2. PMID17943763.
^Nordstrom K. Inhaled loxapine for rapid treatment of agitation in schizophrenia and bipolar disorder: an update. Neuropsychiatry [Internet]. 2012 Jun [cited 2013 Sep 21];2(3):253–60. Available from: http://www.futuremedicine.com/doi/abs/10.2217/npy.12.23
^Taylor D, Paton C, Kapur S, Taylor D, South London and Maudsley NHS Trust. The Maudsley prescribing guidelines in psychiatry [Internet]. Chichester, West Sussex: John Wiley & Sons; 2012 [cited 2013 Sep 21]. Available from: http://site.ebrary.com/lib/uqat/Doc?id=10531429
^National Institute of Mental Health. PDSD Ki Database (Internet) [cited 2013 Aug 3]. Chapel Hill (NC): University of North Carolina. 1998-2013. Available from: http://pdsp.med.unc.edu/pdsp.php