Asenapine for pediatric bipolar disorder: New indication

Asenapine an atypical antipsychotic sold under the brand name Saphris, was granted a second, pediatric indi­cation by the FDA in March 2015 as mono­therapy for acute treatment of manic or mixed episodes of bipolar I disorder in chil­dren and adolescents age 10 to 17 (Table 1).¹ (Asenapine was first approved in August 2009 as monotherapy or adjunctive therapy to lithium or valproate in adults for schizo­phrenia and bipolar I disorder.^1,2)

Dosage and administration
Asenapine is available as 2.5-, 5-, and 10-mg sublingual tablets, the only atypical anti­psychotic with this formulation.¹ The rec­ommended dosage for the new indication is 2.5 mg twice daily for 3 days, titrated to 5 mg twice daily, titrated again to 10 mg twice daily after 3 days.³ In a phase I study, pedi­atric patients appeared to be more sensitive to dystonia when the recommended dosage escalation schedule was not followed.³

In clinical trials, drinking water 2 to 5 minutes after taking asenapine decreased exposure to the drug. Instruct patients not to swallow the tablet and to avoid eating and drinking for 10 minutes after administration.³

For full prescribing information for pediat­ric and adult patients, see Reference 3.

Safety and efficacy
In a 3-week, placebo-controlled, double-blind trial of 403 patients, 302 children and adolescents age 10 to 17 received asenap­ine at fixed dosages of 2.5 to 10 mg twice daily; the remainder were given placebo. The Young Mania Rating Scale (YMRS) total score and Clinical Global Impressions Severity of Illness scores of patients who received asenapine improved significantly compared with those who received placebo, as measured by change from baseline to week 3 (Table 2).¹

The safety and efficacy of asenapine has not been evaluated in pediatric bipolar dis­order patients age ≤10 or pediatric schizo­phrenia patients age ≤12, or as an adjunctive therapy in pediatric bipolar disorder patients.

Asenapine was not shown to be effective in pediatric patients with schizophrenia in an 8-week, placebo-controlled, double-blind trial.

The pharmacokinetics of asenapine in pediatric patients are similar to those seen in adults.

Adverse effects
In pediatric patients, the most common reported adverse effects of asenapine are:
• dizziness
• dysgeusia
• fatigue
• increased appetite
• increased weight
• nausea
• oral paresthesia
• somnolence.

Similar adverse effects were reported in the pediatric bipolar disorder and adult bipolar disorder clinical trials (Table 3).³ A complete list of reported adverse effects is given in the package insert.³

When treating pediatric patients, moni­tor the child’s weight gain against expected normal weight gain.

Asenapine is contraindicated in patients with hepatic impairment and those who have a hypersensitivity to asenapine or any components in its formulation.³