New drugs: asenapine, iloperidone, and bepotastine besilate.

Antipsychotic agents Asenapine (Saphris—Schering) and iloperidone (Fanapt—Vanda) are new atypical antipsychotic agents that join an already large class of these drugs that includes aripiprazole (Abilify), clozapine (e.g., Clozaril), olanzapine (Zyprexa), quetiapine (Seroquel), ziprasidone (Geodon), and risperidone (e.g., Risperdal) and its active metabolite paliperidone (Invega). Both new drugs have been approved for the acute treatment of schizophrenia in adults, and asenapine has also been approved for the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. The labeled indications for asenapine and iloperidone are more limited than those of their predecessors, with which long-term experience and additional studies have resulted in an extension of the indications for which they were initially approved. Although much remains to be learned regarding the mechanisms through which the antipsychotic agents provide benefit in the treatment of schizophrenia, it is thought that their efficacy is mediated through a combination of antagonist activity at dopamine type 2 and serotonin type 2 receptors. Most of the warnings and precautions associated with using asenapine and iloperidone are similar to those of the other atypical antipsychotic agents. The labeling for all of these agents includes a boxed warning regarding increased mortality in elderly patients with dementia-related psychosis, as well as the statement that these agents have not been approved for treating patients with dementia-related psychosis. Other shared warnings and precautions include the potential for cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia/diabetes, weight gain, orthostatic hypotension/syncope, hyperprolactinemia, seizures, cognitive and motor impairment, dysphagia, problems associated with body temperature regulation, and leukopenia, neutropenia, and agranulocytosis. The possibility of suicide is inherent in psychiatric illness, and these drugs should be prescribed in the smallest quantities consistent with good patient management to reduce the possibility of overdosage. The labeling for both asenapine and iloperidone, as well as that for selected other atypical antipsychotic agents (e.g., paliperidone, ziprasidone), includes a warning regarding prolongation of the QT interval and the associated risk of cardiac dysrhythmias. Accordingly, the use of these agents should be avoided in patients with congenital long QT syndrome, hypokalemia and/or hypomagnesemia, or a history of cardiac dysrhythmias, as well as in patients being treated with other medications that are known to cause QT prolongation, including Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antidysrhythmic agents, antipsychotic agents (e.g., chlorpromazine, thioridazine, ziprasidone), and antimicrobial agents (e.g., moxifloxacin [Avelox]). Both asenapine and iloperidone are classified in Pregnancy Category C and should only be used during pregnancy if the anticipated benefit outweighs the risk to the fetus. Although it is not known whether the new drugs or their metabolites are excreted in human milk, it is recommended that women treated with either of these agents should not breast feed. The effectiveness and safety of asenapine and iloperidone in patients younger than 18 years of age have not been established. Asenapine and iloperidone are considered on an individual basis below.