The Medical Letter on Drugs and Therapeutics
In Brief: Iloperidone (Fanapt) — A New Indication for Bipolar Disorder
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Med Lett Drugs Ther. 2024 Jun 10;66(5075):1-2   doi:10.58347/tml.2024.5075a

Iloperidone (Fanapt – Vanda), an oral second-generation antipsychotic drug, has been approved by the FDA for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. First approved in 2009 for treatment of schizophrenia, iloperidone is the eighth second-generation antipsychotic to be approved for acute treatment of manic or mixed episodes of bipolar I disorder (see Table 1).

TREATMENT OF MANIA — Bipolar I disorder is characterized by a history of at least one manic episode with or without a history of depression. Lithium, valproate, carbamazepine, and second-generation antipsychotic drugs are effective for treatment of acute manic episodes, but lithium and valproate may take days to weeks to have a full therapeutic effect. Second-generation antipsychotic drugs can be used as monotherapy or in combination with lithium or valproate.1,2

CLINICAL STUDIES ― FDA approval of iloperidone for the new indication was based on the results of a double-blind trial in 392 patients with bipolar mania, with or without mixed features, who were randomized to receive iloperidone or placebo twice daily for 4 weeks. The least-squares mean change from baseline to week 4 in the Young Mania Rating Scale (measures irritability, speech, thought content, disruptive/aggressive behavior, etc.), the primary endpoint, was statistically significantly greater with iloperidone than with placebo (-14.0 vs -10.0; mean score at baseline = 29).3

ADVERSE EFFECTS ― The most common adverse effects of iloperidone in the clinical trial were tachycardia, dizziness, dry mouth, hepatic enzyme elevations, nasal congestion, weight gain, orthostatic hypotension, and somnolence. Neuroleptic malignant syndrome, akathisia, tardive dyskinesia, dyslipidemia, hyperglycemia, falls, seizures, leukopenia, neutropenia, agranulocytosis, and priapism can occur. Patients with bipolar disorder are particularly susceptible to extrapyramidal symptoms. Iloperidone can also prolong the QT interval and increase the risk of arrhythmias and sudden death.

PREGNANCY AND LACTATION ― Data on use of second-generation antipsychotic drugs during pregnancy are limited; increased birth weight has been reported. Neonates whose mothers were exposed to antipsychotic drugs during the third trimester are at increased risk for extrapyramidal and withdrawal symptoms after delivery. No data are available on the presence of iloperidone in human milk or its effects on the breastfed infant or milk production. Breastfeeding is not recommended during treatment with iloperidone.

DRUG INTERACTIONS ― Concomitant use of iloperidone with other drugs that prolong the QT interval or with alpha-adrenergic blockers should be avoided. The dose of iloperidone should be reduced by half in patients who are CYP2D6 poor metabolizers or are taking strong CYP2D6 or CYP3A4 inhibitors concurrently.4

DOSAGE, ADMINISTRATION, AND COST ― Iloperidone is supplied in 1-, 2-, 4-, 6-, 8-, 10-, and 12-mg tablets. Because of the risk of hypotension, the dosage should be increased gradually, starting with 1 mg twice daily, with daily increases to 3, 6, 9, and 12 mg twice daily thereafter. Iloperidone is not recommended for use in patients with severe hepatic impairment. The wholesale acquisition cost (WAC) for a 30-day supply of Fanapt at the recommended target dosage is about $3525.5

CONCLUSION ― In one 4-week trial, the oral secondgeneration antipsychotic drug iloperidone (Fanapt) reduced symptoms of mania associated with bipolar I disorder in adults. Antipsychotic drugs that are available generically and have a longer record of efficacy for acute treatment of manic or mixed episodes are preferred.


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