Iloperidone

The mechanism of action of iloperidone in schizophrenia and bipolar I disorder is unknown. However, the efficacy of iloperidone could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5-HT 2 ) antagonism.

• FANAPT ® is indicated for: Treatment of schizophrenia in adults [see Clinical Studies (14.1) ]. Acute treatment of manic or mixed episodes associated with bipolar I disorder in adults [see Clinical Studies (14.2) ] .ICD-10: F20.9, F31.9

• FANAPT is contraindicated in individuals with a known hypersensitivity reaction to the product. Anaphylaxis, angioedema, and other hypersensitivity reactions have been reported [see Adverse Reactions (6.2) ] .contraindicated

Administer FANAPT orally twice daily without regard to meals. ( 2.1 ) Titrate the dosage of FANAPT to avoid orthostatic hypotension. See Full Prescribing Information for titration schedule. ( 2.1 ) Recommended Dosage: Indication Starting Dosage Recommended Dosage Schizophrenia ( 2.1 ) 1 mg twice daily 6 mg to 12 mg twice daily Bipolar Mania ( 2.1 ) 1 mg twice daily 12 mg twice daily CYP2D6 Poor Metabolizers: See Full Prescribing Information for titration schedule and recommended dosage. ( 2.2 ) 2.1 Recommended Dosage Titrate FANAPT to avoid orthostatic hypotension [see Warnings and Precautions (5.7) ] . Administer FANAPT orally with or without food. Table 1 includes dosage recommendations for FANAPT for the treatment of schizophrenia and the acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia- Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). ( 5.2 ) QT prolongation: Prolongs QT interval and may be associated with arrhythmia and sudden death. Avoid use of FANAPT in combination with other drugs that are known to prolong QTc; use caution and consider dose modification when prescribing FANAPT with other drugs that inhibit FANAPT metabolism. Monitor serum potassium and magnesium in patients at risk for electrolyte disturbances. ( 1 , 5.3 , 7.1 , 7.2 , 12.3 ) Neuroleptic Malignant Syndrome (NMS): Manage with immediate discontinuation of drug and close monitoring. ( 5.4 ) Tardive dyskinesia: Discontinue if clinically appropriate. ( 5.5 ) Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia and weight gain. ( 5.6 ) Orthostatic hypotension and Syncope: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. ( 5.7 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold. ( 5.9 ) Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotics. Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia. Consider discontinuing FANAPT if clinically significant decline in WBC occurs in the absence of other causative factors.

The following adverse reactions are discussed in more detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.1) ] Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis [see Warnings and Precautions (5.2) ] QT Prolongation [see Warnings and Precautions (5.3) ] Neuroleptic Malignant Syndrome (NMS) [see Warnings and Precautions (5.4) ] Tardive Dyskinesia [see Warnings and Precautions (5.5) ] Metabolic Changes [see Warnings and Precautions (5.6) ] Orthostatic Hypotension and Syncope [see Warnings and Precautions (5.7) ] Falls [see Warnings and Precautions (5.8) ] Seizures [see Warnings and Precautions (5.9) ] Leukopenia, Neutropenia and Agranulocytosis [see Warnings and Precautions (5.10) ] Hyperprolactinemia [see Warnings and Precautions (5.11) ] Body Temperature Regulation [see Warnings and Precautions (5.12) ] Dysphagia [see Warnings and Precautions (5.13) ] Priapism [see Warnings and Precautions (5.14) ] Potential for Cognitive and Motor Impairment [see Warnings and Precautions (5.15) ] Intraoperative Floppy Iris Syndrome [see Warnings and Precautions (5.16) ] Commonly observed adverse reactions (incidence ≥5% and 2-fold greater than placebo) were ( 6.1 ): Schizophrenia: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased. Bipolar mania: tachycardia, dizziness, dry mouth, hepatic enzymes increased, nasal congestion, weight increased, hypotension, and somnolence.

Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) Lactation: Advise not to breast feed. ( 8.2 ) Pediatric Use: Safety and effectiveness not established in children and adolescents. ( 8.4 ) Hepatic Impairment: FANAPT is not recommended for patients with severe hepatic impairment. ( 2.3 , 8.6 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to FANAPT during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . Risk Summary Neonates whose mothers are exposed to antipsychotic drugs, including FANAPT, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery [see Clinical Considerations ] . The limited available data with FANAPT in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. Iloperidone was not teratogenic when administered orally to pregnant rats during organogenesis at doses up to 26 times the maximum recommended human dose of 24 mg/day on mg/m 2 basis.

Metabolism

The pharmacokinetics of iloperidone is more than dose proportional. Steady-state concentrations are attained within 3 to 4 days of dosing.

10.1 Human Experience In pre-marketing trials involving over 3,522 patients, accidental or intentional overdose of FANAPT was documented in 8 patients ranging from 48 mg to 576 mg taken at once and 292 mg taken over a 3-day period. No fatalities were reported from these cases. The largest confirmed single ingestion of FANAPT was 576 mg; no adverse physical effects were noted for this patient. The next largest confirmed ingestion of FANAPT was 438 mg over a 4-day period; extrapyramidal symptoms and a QTc interval of 507 msec were reported for this patient with no cardiac sequelae. This patient resumed FANAPT treatment for an additional 11 months. In general, reported signs and symptoms were those resulting from an exaggeration of the known pharmacological effects (e.g., drowsiness and sedation, tachycardia and hypotension) of FANAPT. 10.2 Management of Overdose There is no specific antidote for FANAPT. Therefore appropriate supportive measures should be instituted. In case of acute overdose, the healthcare provider should establish and maintain an airway and ensure adequate oxygenation and ventilation.

• May 6, 2009NDANDA022192Vanda Pharms Inc
• Nov 28, 2016ANDAANDA207231Inventia

1. 1Drug Ineffective1077.7%
2. 2Dizziness1007.2%
3. 3Insomnia836.0%
4. 4Weight Increased765.5%
5. 5Anxiety684.9%
6. 6Fatigue664.7%
7. 7Dyskinesia513.7%
8. 8Nausea503.6%
9. 9Suicidal Ideation483.5%
10. 10Dyspnoea473.4%
11. 11Somnolence473.4%
12. 12Aggression453.2%
13. 13Off Label Use443.2%
14. 14Speech Disorder402.9%
15. 15Vomiting402.9%

The 10 most recently updated of 32 ClinicalTrials.gov registrations naming Iloperidone as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Elpipodect (MK-8189) Multiple Dose Study in Healthy Volunteers and Schizophrenia Participants (MK-8189-003)
  Completed · Phase 1 · Interventional · 55 enrolled · Merck Sharp & Dohme LLC
  NCT02181803updated 2026-04-29
• Evaluation of Efficacy and Safety of Iloperidone for the Treatment of Participants With Uncontrolled Hypertension
  Recruiting · Phase 2 · Interventional · 240 enrolled · Vanda Pharmaceuticals
  NCT07090161updated 2026-02-27
• Randomized Withdrawal Study in Patients With Schizophrenia
  Recruiting · Phase 3 · Interventional · 400 enrolled · Vanda Pharmaceuticals
  NCT06961968updated 2026-01-12
• Pharmacokinetic Study of VHX-896 and Iloperidone Tablets Under Steady-State Conditions
  Completed · Phase 1 · Interventional · 26 enrolled · Vanda Pharmaceuticals
  NCT06494397updated 2025-09-19
• A Study to Assess Stroke Risk Among Users of Typical Versus Atypical Antipsychotics Stratified by Broad Age Group
  Completed · Observational · 1,234,412 enrolled · Janssen Research & Development, LLC
  NCT04002700updated 2025-06-25
• Safety and Tolerability of Open-Labeled Iloperidone in Adolescents
  Recruiting · Phase 4 · Interventional · 100 enrolled · Vanda Pharmaceuticals
  NCT05648591updated 2025-03-04
• Efficacy and Safety of Iloperidone Compared With Placebo and Active Control in Subjects With Acute Schizophrenia
  Completed · Phase 3 · Interventional · 593 enrolled · Vanda Pharmaceuticals
  NCT00254202updated 2024-12-13
• Evaluation of Efficacy and Safety of Iloperidone in the Acute Treatment of Manic or Mixed Episodes Associated With Bipolar I Disorder
  Completed · Phase 3 · Interventional · 417 enrolled · Vanda Pharmaceuticals
  NCT04819776updated 2024-04-18
• A Study to Evaluate Iloperidone for the Treatment of Parkinson's Disease Psychosis
  Withdrawn · Phase 2 · Interventional · 0 enrolled · Vanda Pharmaceuticals
  NCT05344365updated 2024-03-21
• Relapse Prevention Study in Patients With Schizophrenia
  Completed · Phase 3 · Interventional · 635 enrolled · Vanda Pharmaceuticals
  NCT01291511updated 2023-07-17

CPIC-curated drug–gene pairs for Iloperidone. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP2D6CPIC B/C (provisional)ClinPGx 3FDA label: Actionable PGx

Frequently asked questions

How does Iloperidone work?

The mechanism of action of iloperidone in schizophrenia and bipolar I disorder is unknown. However, the efficacy of iloperidone could be mediated through a combination of dopamine type 2 (D 2 ) and serotonin type 2 (5-HT 2 ) antagonism.

What is Iloperidone used for?

According to FDA labeling, Iloperidone carries indications including: FANAPT ® is indicated for: Treatment of schizophrenia in adults [see Clinical Studies (14.1) ]. Acute treatment of manic or mixed episodes associated with bipolar I disorder in adults [see Clinical Studies (14.2) ] .. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Iloperidone?

Iloperidone is classified as Other antipsychotics, Atypical Antipsychotic, Unknown Cellular or Molecular Interaction.

What are the brand names for Iloperidone?

Iloperidone is marketed under brand names including Fanapt.

What are the contraindications for Iloperidone?

Iloperidone labeling lists contraindications including: FANAPT is contraindicated in individuals with a known hypersensitivity reaction to the product. Anaphylaxis, angioedema, and other hypersensitivity reactions have been reported [see Adverse Reactions (6.2) ] .. Always consult the full prescribing information and a clinician.