Pharmacology Update
Asenapine Sublingual Tablets (Saphris®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Elliott and Chan report no financial relationship to this field of study.
The ninth atypical antipsychotic agent has been approved by the FDA. Asenapine is somewhat unique in the class with different receptor binding than risperidone and olanzapine. It is marketed by Schering-Plough as Saphris® as a sublingual tablet.
Indications
Asenapine is indicated for the acute treatment of schizophrenia, manic, or mixed episodes associated with bipolar disease in adults.1
Dosage
The recommended dose is 5 mg sublingually twice daily for schizophrenia and 10 mg twice daily for bipolar disorders.1 The tablets should be allowed to dissolve under the tongue and should not be swallowed. Eating and drinking should be avoided for 10 minutes after taking.
Asenapine is available as 5 mg and 10 mg sublingual tablets.
Potential Advantages
Asenapine has been associated with minimal weight gain, metabolic disturbance, and cardiovascular adverse events.2
Potential Disadvantages
Adverse events reported in schizophrenia include akathisia, oral hypoesthesia, and somnolence. For bipolar patients, somnolence, dizziness, extrapyramidal symptoms (other than akathisia), and weight gain were reported.1 Asenapine carries the same warning and contraindications as other atypical antipsychotics. Strong CYP1A2 inhibitors (fluvoxamine) and CYP2D substrate and inhibitors (paroxetine) should be used concomitantly with asenapine with caution.1 Asenapine should not be used with other drugs that may prolong QT interval or in patients at risk for prolonged QT interval.1
Comments
Asenapine is chemically different from currently available atypical antipsychotics. It differs in its receptor-binding profile, showing a high affinity for various serotonergic (e.g., 5-HT2A, 5-HT2C), noradrenergic, and dopaminergic (D3, D4) receptors, rather than D2 receptors, and has low affinity for muscarinic receptors. These receptor-binding characteristics suggest improvement of positive, negative, and cognitive symptoms, and minimal muscarinic adverse events.2,3 In phase 3 short-term (6-week), acute treatment, placebo-controlled and active-controlled studies, asenapine (5 mg twice daily) was more efficacious than placebo in 2 of 3 studies in patients with schizophrenia, as assessed by change from baseline of the total score on the Positive and Negative Syndrome Scale (PANSS). Asenapine was associated with less weight gain and hyperprolactinemia than risperidone.4 In a phase 3, relapse prevention, 26-week study in patients (n = 386) with stable schizophrenia, the relapse rate was 12% for asenapine (5 mg or 10 mg) compared to 47% for placebo.5 The frequency of weight gain was 6.7% for asenapine compared to 3.7% for placebo. In two 3-week studies involving patients with bipolar disorder, asenapine (5 mg and 10 mg twice daily) was more efficacious than placebo as assessed by changes from baseline in the Young Mania Rating Scale (YMRS) total score. In a long-term schizophrenia comparative trial with olanzapine, asenapine-treated subjects had a mean weight gain of 1.6 kg from baseline compared to 5.6 kg for olanzapine.6 Clinically meaningful weight gain (at least 7% increase from baseline) occurred in 14.7% of asenapine-treated patients compared to 36.1% for olanzapine-treated patients.1,6
Clinical Implications
Asenapine is the latest atypical antipsychotic to enter a crowded market. While its receptor-binding profile may suggest therapeutic advantage compared to existing agents, further studies are needed to substantiate such advantage.
References
1. Saphris Prescribing Information. Kenilworth, NH: Schering-Plough; July 2009.
2. Bihar D, Taylor D. Upcoming agents for the treatment of schizophrenia: Mechanism of action, efficacy and tolerability. Drugs 2008;68:2269-2292.
3. Shahid M, et al. Asenapine: A novel psychopharmacologic agent with a unique human receptor signature. J Psychopharmacol 2009;23:65-73.
4. Potkin SG, et al. Efficacy and tolerability of asenapine in acute schizophrenia: A placebo- and risperidone-controlled trial. J Clin Psychiatry 2007;68:1492-1500.
5. Reuters. Schering-Plough reports data from Saphris long-term schizophrenia relapse prevention study. Available at: www.reuters.com/article/pressRelease/idUS89304+14-Sep-2009+PRN20090914. Accessed Oct. 3, 2009.
6. Psychiatry News. Asenapine adds to arsenal to treat psychotic disorders. Psychiatr News 2009;44:2-28. Available at: http://pn.psychiatryonline.org/cgi/content/full/44/17/2?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=asenapine&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT. Accessed Oct. 3, 2009.
The ninth atypical antipsychotic agent has been approved by the FDA. Asenapine is somewhat unique in the class with different receptor binding than risperidone and olanzapine.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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