FANAPT® (iloperidone) tablet

Iloperidone is a white to off-white finely crystalline powder. It is practically insoluble in water, very slightly soluble in 0.1 N HCl and freely soluble in chloroform, ethanol, methanol, and acetonitrile.

FANAPT tablets are intended for oral administration only. Each round, uncoated tablet contains 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, or 12 mg of iloperidone. Inactive ingredients are: lactose monohydrate, microcrystalline cellulose, hydroxypropylmethylcellulose, crospovidone, magnesium stearate, colloidal silicon dioxide, and purified water (removed during processing). The tablets are white, round, flat, beveled-edged and identified with a logo “” debossed on one side and tablet strength “1”, “2”, “4”, “6”, “8”, “10”, or “12” debossed on the other side.

DRUG INTERACTIONS
The dose of FANAPT should be reduced in patients co-administered a strong CYP2D6 or CYP3A4 inhibitor.

USE IN SPECIFIC POPULATIONS
Pregnancy: No human or animal data. Use only if clearly needed.

Nursing Mothers: Should not breast feed.

Pediatric Use: Safety and effectiveness not established in children and adolescents.

Hepatic Impairment: Not recommended for patients with hepatic impairment.

The dose of FANAPT should be reduced in patients who are poor metabolizers of CYP2D6.

• Elderly patients with dementia-related psychosis who are treated with atypical antipsychotic drugs are at an increased risk of death and cerebrovascular-related adverse events, including stroke.
• QT prolongation: Prolongs QT interval and may be associated with arrhythmia and sudden death—consider using other antipsychotics first. 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: Manage with immediate discontinuation of drug and close monitoring.
• Tardive dyskinesia: Discontinue if clinically appropriate.
• Hyperglycemia and diabetes mellitus: Monitor glucose regularly in patients at risk for diabetes.
• Seizures: Use cautiously in patients with a history of seizures or with conditions that lower seizure threshold.
• Orthostatic hypotension: Dizziness, tachycardia, and syncope can occur with standing.
• Leukopenia, Neutropenia, and Agranulocytosis have been reported with antipsychotics. Patients with a pre-existing low white blood cell count (WBC) or a history of leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue FANAPT at the first sign of a decline in WBC in the absence of other causative factors.
• Suicide: Close supervision of high risk patients.
• Priapism: Cases have been reported in association with FANAPT treatment.
• Potential for cognitive and motor impairment: Use caution when operating machinery.
• See Full Prescribing Information for additional WARNINGS and PRECAUTIONS.

To report SUSPECTED ADVERSE REACTIONS, contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Usual Dose
FANAPT must be titrated slowly from a low starting dose to avoid orthostatic hypotension due to its alpha-adrenergic blocking properties. The recommended starting dose for FANAPT tablets is 1 mg twice daily. Increases to reach the target dose range of 6-12 mg twice daily may be made with daily dosage adjustments to 2 mg twice daily, 4 mg twice daily, 6 mg twice daily, 8 mg twice daily, 10 mg twice daily, and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7, respectively. Efficacy was demonstrated with FANAPT in a dose range of 6 to 12 mg twice daily. Prescribers should be mindful of the fact that patients need to be titrated to an effective dose of FANAPT. Thus, control of symptoms may be delayed during the first 1 to 2 weeks of treatment compared to some other antipsychotic drugs that do not require similar titration. Prescribers should also be aware that some adverse effects associated with FANAPT use are dose related.

The maximum recommended dose is 12 mg twice daily (24 mg/day); FANAPT doses above 24 mg/day have not been systematically evaluated in the clinical trials.

FANAPT can be administered without regard to meals.

Dosage in Special Populations
Dosage adjustments are not routinely indicated on the basis of age, gender, race, or renal impairment status.

Dosage adjustment for patients taking FANAPT concomitantly with potential CYP2D6 inhibitors: FANAPT dose should be reduced by one-half when administered concomitantly with strong CYP2D6 inhibitors such as fluoxetine or paroxetine. When the CYP2D6 inhibitor is withdrawn from the combination therapy, FANAPT dose should then be increased to where it was before.

Dosage adjustment for patients taking FANAPT concomitantly with potential CYP3A4 inhibitors: FANAPT dose should be reduced by one-half when administered concomitantly with strong CYP3A4 inhibitors such as ketoconazole or clarithromycin. When the CYP3A4 inhibitor is withdrawn from the combination therapy, FANAPT dose should be increased to where it was before.

Dosage adjustment for patients taking FANAPT who are poor metabolizers of CYP2D6: FANAPT dose should be reduced by one-half for poor metabolizers of CYP2D6.

Hepatic Impairment: FANAPT is not recommended for patients with hepatic impairment.

Maintenance Treatment
Although there is no body of evidence available to answer the question of how long the patient treated with FANAPT should be maintained, it is generally recommended that responding patients be continued beyond the acute response. Patients should be periodically reassessed to determine the need for maintenance treatment.

Reinitiation of Treatment in Patients Previously Discontinued
Although there are no data to specifically address re-initiation of treatment, it is recommended that the initiation titration schedule be followed whenever patients have had an interval off FANAPT of more than 3 days.

Switching from Other Antipsychotics
There are no specific data to address how patients with schizophrenia can be switched from other antipsychotics to FANAPT or how FANAPT can be used concomitantly with other antipsychotics. Although immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized.

Storage
Store FANAPT tablets at controlled room temperature, 25°C (77°F); excursions permitted to 15° - 30 °C (59° - 86°F) [See USP Controlled Room Temperature]. Protect FANAPT tablets from exposure to light and moisture.

Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, NJ 07936
T2011-110