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Iloperidone (Fanapt)

Class

Second-generation (atypical) antipsychotic

Mechanism

Antagonist at dopamine D2 and serotonin 5-HT2A receptors, with additional antagonism at alpha-1 adrenergic receptors contributing to orthostatic hypotension risk; moderate affinity for histamine H1 and muscarinic receptors

FDA-Approved Use

Schizophrenia

Off-Label Use

Augmentation in bipolar disorder, management of psychosis in neuropsychiatric populations prioritizing metabolic tolerability

Formulation

Oral tablets

Titration

Start at 1 mg orally twice daily, titrated slowly over 4–7 days to minimize orthostatic hypotension risk

Dose Range

12–24 mg/day divided BID

Kinetics

Extensive hepatic metabolism via CYP2D6 and CYP3A4; half-life approximately 18 hours; steady state reached in 3–4 days

Common AEs

Dizziness, orthostatic hypotension, sedation, dry mouth, weight gain

Serious/Rare AEs

QT prolongation; caution in patients with cardiac risk factors

Monitoring

Baseline and periodic blood pressure monitoring to detect orthostatic hypotension; ECG recommended for patients with cardiac risk or symptoms; monitor weight and metabolic parameters periodically

Black Box Warning

Increased mortality in elderly patients with dementia-related psychosis

Considerations

Iloperidone may have a more favorable metabolic profile than other second generation (atypical) antipsychotic agents, but is limited by the need for slow titration and QT prolongation risk. Use caution in elderly patients, those with autonomic instability, and patients with poor adherence due to BID dosing requirements.