Iloperidone

Iloperidone is an atypical antipsychotic indicated for:

• Treatment of schizophrenia in adults.
• Acute treatment of manic or mixed episodes associated with bipolar I disorder in adults.

Iloperidone shows high affinity and maximal receptor occupancy for dopamine D2 receptors in the caudate nucleus and putamen of the brains of schizophrenic patients. The improvement in cognition is attributed to iloperidone's high affinity for α adrenergic receptors. Iloperidone also binds with high affinity to serotonin 5-HT2a and dopamine 3 receptors. Iloperidone binds with moderate affinity to dopamine D4, serotonin 5-HT6 and 5-HT7, and norepinephrine NEα1 receptors. Furthermore, iloperidone binds with weak affinity to serotonin 5-HT1A, dopamine D1, and histamine H1 receptors.

This drug must be titrated slowly to avoid orthostatic hypotension; because of the need to titrate slowly, control of symptoms may be delayed during the first 1 to 2 weeks of treatment.

Administer Iloperidone orally twice daily without regard to meals. Titrate the dosage of Iloperidone to avoid orthostatic hypotension. Recommended Dosage:

Schizophrenia-

• Starting Dosage: 1 mg twice daily
• Recommended Dosage: 6 mg to 12 mg twice daily.

Bipolar Mania-

• Starting Dosage: 1 mg twice daily 
• Recommended Dosage: 12 mg twice daily.

Pediatric Use: Safety and effectiveness not established in children and adolescents.
Hepatic Impairment: Iloperidone is not recommended for patients with severe hepatic impairment.

There are no known drug interactions and none well documented.

Known hypersensitivity to Iloperidone or to any components in the formulation.

Commonly observed adverse reactions (incidence ≥5% and 2-fold greater than placebo) were:

• 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.

Lactation: There is no information regarding the presence of iloperidone or its metabolites in human milk, the effects of iloperidone on a breastfed child, nor the effects of iloperidone on human milk production. Iloperidone is present in rat milk

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis: Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack).

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.

Neuroleptic Malignant Syndrome (NMS): Manage with immediate discontinuation of drug and close monitoring.

Tardive dyskinesia: Discontinue if clinically appropriate.

Metabolic Changes: Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. 

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.

Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold.

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.

Priapism: Cases have been reported in association with FANAPT treatment. Severe priapism may require surgical intervention.

Potential for cognitive and motor impairment: Use caution when operating machinery.

Intraoperative Floppy Iris Syndrome (IFIS): IFIS during cataract surgery may require modifications to the surgical technique.

Piperidinyl-benzisoxazole derivative

Store Iloperidone tablets at controlled room temperature, 25°C; excursions permitted to 15° to 30°C.