Asenapine Indications: FDA-Approved Uses
Source: Drug labeling information submitted to the Food and Drug Administration (FDA), updated by the National Library of Medicine (NLM).
Asenapine (SAPHRIS) is a second generation antipsychotic approved for the treatment of schizophrenia and manic episodes in bipolar I disorder.
The table below summarizes the dosing for each FDA-approved indication:
|Indication||Starting Dose||Recommended Dose||Maximum Dose|
|Acute treatment in adults||5 mg sublingually twice daily||5 mg sublingually twice daily||10 mg sublingually twice daily|
|Maintenance treatment in adults||5 mg sublingually twice daily for one week||10 mg sublingually twice daily||10 mg sublingually twice daily|
|Bipolar Disorder - Mania|
|Bipolar mania in adults- Monotherapy||10 mg sublingually twice daily||5-10 mg sublingually twice daily||10 mg sublingually twice daily
|Bipolar mania in adults- As adjunct to lithium or valproate||5 mg sublingually twice daily||5-10 mg sublingually twice daily||10 mg sublingually twice daily|
Data from Clinical Trials
The efficacy of SAPHRIS in the treatment of schizophrenia in adults was evaluated in three fixed-dose, short-term (6 week), randomized, double-blind, placebo-controlled, and active-controlled (haloperidol, risperidone, and olanzapine) trials of adult patients who met DSM-IV criteria for schizophrenia and were having an acute exacerbation of their schizophrenic illness. In two of the three trials SAPHRIS demonstrated superior efficacy to placebo. In a third trial, SAPHRIS could not be distinguished from placebo; however, an active control in that trial was superior to placebo.
In the two positive trials for SAPHRIS, the primary efficacy rating scale was the Positive and Negative Syndrome Scale (PANSS), which assesses the symptoms of schizophrenia. The primary endpoint was change from baseline to endpoint on the PANSS total score. The results of the SAPHRIS trials in schizophrenia follow:
In trial 1, a 6-week trial (n=174), comparing SAPHRIS (5 mg twice daily) to placebo, SAPHRIS 5 mg twice daily was statistically superior to placebo on the PANSS total score.
In trial 2, a 6-week trial (n=448), comparing two fixed doses of SAPHRIS (5 mg and 10 mg twice daily) to placebo, SAPHRIS 5 mg twice daily was statistically superior to placebo on the PANSS total score. SAPHRIS 10 mg twice daily showed no added benefit compared to 5 mg twice daily and was not significantly different from placebo.
An examination of population subgroups did not reveal any clear evidence of differential responsiveness on the basis of age, gender or race.
Maintenance of efficacy has been demonstrated in a placebo-controlled, double-blind, multicenter, flexible dose (5 mg or 10 mg twice daily based on tolerability) clinical trial with a randomized withdrawal design. A total of 700 patients entered open-label treatment with SAPHRIS for a period of 26 weeks. Of these, a total of 386 patients who met pre-specified criteria for continued stability (mean length of stabilization was 22 weeks) were randomized to a double-blind, placebo-controlled, randomized withdrawal phase. SAPHRIS was statistically superior to placebo in time to relapse or impending relapse defined as increase in PANSS ≥20% from baseline and a Clinical Global Impression–Severity of Illness (CGI-S) score ≥4 (at least 2 days within 1 week) or PANSS score ≥5 on “hostility” or “uncooperativeness” items and CGI-S score ≥4 (≥2 days within a week), or PANSS score ≥5 on any two of the following items: “unusual thought content,” “conceptual disorganization,” or “hallucinatory behavior” items, and CGI-S score ≥4 (≥2 days within 1 week) or investigator judgment of worsening symptoms or increased risk of violence to self (including suicide) or other persons. The Kaplan-Meier curves of the time to relapse or impending relapse during the double-blind, placebo-controlled, randomized withdrawal phase of this trial for SAPHRIS and placebo are shown in Figure 1.
Monotherapy: The efficacy of SAPHRIS in the treatment of acute mania was established in two similarly designed 3-week, randomized, double-blind, placebo-controlled, and active-controlled (olanzapine) trials of adult patients who met DSM-IV criteria for Bipolar I Disorder with an acute manic or mixed episode with or without psychotic features.
The primary rating instrument used for assessing manic symptoms in these trials was the Young Mania Rating Scale (YMRS). Patients were also assessed on the Clinical Global Impression – Bipolar (CGI-BP) scale. In both trials, all patients randomized to SAPHRIS were initially administered 10 mg twice daily, and the dose could be adjusted within the dose range of 5 to 10 mg twice daily from Day 2 onward based on efficacy and tolerability. Ninety percent of patients remained on the 10-mg twice daily dose. SAPHRIS was statistically superior to placebo on the YMRS total score and the CGI-BP Severity of Illness score (mania) in both studies.
An examination of subgroups did not reveal any clear evidence of differential responsiveness on the basis of age, gender or race.
Adjunctive Therapy: The efficacy of SAPHRIS as an adjunctive therapy in acute mania was established in a 12-week, placebo-controlled trial with a 3-week primary efficacy endpoint involving 326 patients with a manic or mixed episode of Bipolar I Disorder, with or without psychotic features, who were partially responsive to lithium or valproate monotherapy after at least 2 weeks of treatment. SAPHRIS was statistically superior to placebo in the reduction of manic symptoms (measured by the YMRS total score) as an adjunctive therapy to lithium or valproate monotherapy at week 3.
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