Iloperidone - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS 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. ( 1 , 5.3 , 7.1 , 7.2 , 12.3 ) 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.

5.1 Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death.

Analyses of 17 dementia-related psychosis placebo-controlled trials (modal duration of 10 weeks) largely in patients taking atypical antipsychotic drugs, revealed a risk of death in the drug-treated patients of between 1.6 to 1.7 times that in placebo-treated patients.

Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in placebo-treated patients.

Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.

FANAPT is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions ] .

5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke.

FANAPT is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions ] .

5.3 QT Prolongation In an open-label QTc study in patients with schizophrenia or schizoaffective disorder (n=160), FANAPT was associated with QTc prolongation of 9 msec at an iloperidone dose of 12 mg twice daily.

The effect of FANAPT on the QT interval was augmented by the presence of CYP450 2D6 or 3A4 metabolic inhibition (paroxetine 20 mg once daily and ketoconazole 200 mg twice daily, respectively).

Under conditions of metabolic inhibition for both 2D6 and 3A4, FANAPT 12 mg twice daily was associated with a mean QTcF increase from baseline of about 19 msec.