What is Fanapt (Iloperidone) Used For?
Fanapt (iloperidone) is FDA-approved specifically for the treatment of schizophrenia in adults. 1
Primary Indication
Iloperidone is indicated for the acute treatment of schizophrenia in adults, functioning as a second-generation atypical antipsychotic with mixed serotonin (5-HT2A) and dopamine D2 receptor antagonist properties. 1, 2
The drug has demonstrated efficacy in reducing both positive symptoms (hallucinations, delusions, disorganized behavior) and negative symptoms (social withdrawal, apathy, flat affect) of schizophrenia. 3
Evidence of Efficacy
In Phase III trials, iloperidone at doses of 12-24 mg/day significantly reduced Positive and Negative Syndrome Scale (PANSS) total scores compared to placebo, with the 12 mg/day dose showing a reduction of -9.9 versus -4.6 for placebo (P = 0.047). 3, 2
Post-hoc analysis demonstrated comparable efficacy to haloperidol and risperidone when patients received active treatment for at least 2 weeks, particularly at the 20-24 mg/day dosing range. 3
Long-term maintenance efficacy (52 weeks) showed no significant difference in time to relapse when compared to haloperidol as an active control. 2
Key Clinical Characteristics
Iloperidone requires slow titration starting at 1 mg twice daily, increasing over 7 days to reach the target dose of 12-24 mg/day to minimize orthostatic hypotension and dizziness. 1, 2
The drug demonstrates a favorable extrapyramidal symptom profile with lower risk of motor-related adverse events (akathisia, extrapyramidal symptoms) compared to haloperidol and risperidone, generally similar to placebo. 3, 4
Most common adverse events are dizziness (5.1%-23.2%), dry mouth (5.2%-10.4%), somnolence (4%-13%), and dyspepsia (4.8%-7.8%), which appear dose-related. 2
Important Safety Considerations
Iloperidone carries a black box warning for increased mortality in elderly patients with dementia-related psychosis and is NOT approved for this population. 1
QTc prolongation is a concern, comparable to haloperidol and ziprasidone, requiring baseline ECG assessment in patients with cardiac risk factors. 4
Dose reduction by one-half is required for CYP2D6 poor metabolizers and when co-administered with strong CYP2D6 or CYP3A4 inhibitors (such as fluoxetine, paroxetine, ketoconazole, or clarithromycin). 1
Place in Therapy
Iloperidone represents an additional treatment option for patients with schizophrenia who have not adequately responded to or tolerated other antipsychotic agents, particularly those experiencing problematic extrapyramidal symptoms with other medications. 5, 6
The twice-daily dosing requirement and mandatory slow titration period may be disadvantages compared to other atypical antipsychotics, but the favorable motor side effect profile may offset these limitations in selected patients. 2