Fanapt

Generic Name: iloperidone
Date of Approval: May 6, 2009
Company: Vanda Pharmaceuticals Inc.

Treatment for: Schizophrenia

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FDA Approves Fanapt

The U.S. Food and Drug Administration has approved Fanapt tablets (iloperidone) to treat adults with schizophrenia, a chronic, severe and disabling brain disorder.

Fanapt is included in the atypical antipsychotic class of drugs. All atypical antipsychotics contain a boxed warning, the FDA’s strongest warning. The warning alerts prescribers to an increased risk of death associated with off-label use of these drugs to treat behavioral problems in older people with dementia-related psychosis. Fanapt is not approved for patients with dementia-related psychosis.

Fanapt demonstrated efficacy in two placebo-controlled short-term clinical trials. In both, Fanapt was superior to placebo (sugar pill) in reducing the symptoms of schizophrenia.

The most common adverse reactions reported by patients using Fanapt in clinical trials were dizziness, dry mouth, fatigue, nasal congestion, sudden fall in blood pressure causing light-headedness upon standing (orthostatic hypotension), drowsiness, rapid heart rate (tachycardia) and weight increase.

Highlights of Fanapt Prescribing Information

These highlights do not include all the information needed to use Fanapt safely and effectively. See full prescribing information for Fanapt.

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS

See full prescribing information for complete boxed warning.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Fanapt is not approved for use in patients with dementia-related psychosis.

Indications and Usage

Fanapt is an atypical antipsychotic agent indicated for the acute treatment of schizophrenia in adults. In choosing among treatments, prescribers should consider the ability of Fanapt to prolong the QT interval and the use of other drugs first. Prescribers should also consider the need to titrate Fanapt slowly to avoid orthostatic hypotension, which may lead to delayed effectiveness compared to some other drugs that do not require similar titration.

Dosage and Administration

The recommended target dosage of Fanapt tablets is 12 to 24 mg/day administered twice daily. This target dosage range is achieved by daily dosage adjustments, alerting patients to symptoms of orthostatic hypotension, starting at a dose of 1 mg twice daily, then moving to 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, and 12 mg twice daily on days 2, 3, 4, 5, 6, and 7 respectively, to reach the 12 mg/day to 24 mg/day dose range. Fanapt can be administered without regard to meals.

Dosage Forms and Strengths

1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg and 12 mg tablets.

Contraindications

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

Warnings and Precautions

• 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 PREACUTIONS.

Fanapt Side Effects

Commonly observed adverse reactions (incidence =5% and two-fold greater than placebo) were: dizziness, dry mouth, fatigue, nasal congestion, orthostatic hypotension, somnolence, tachycardia, and weight increased.

To report SUSPECTED ADVERSE REACTIONS, contact Vanda Pharmaceuticals at 1-888-49VANDA (1-888-498-2632) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

Patient Counseling Information for Fanapt

Physicians are advised to discuss the following issues with patients for whom they prescribe Fanapt:

• QT Interval Prolongation Patients should be advised to consult their physician immediately if they feel faint, lose consciousness or have heart palpitations. Patients should be counseled not to take Fanapt with other drugs that cause QT interval prolongation. Patients should be told to inform physicians that they are taking Fanapt before any new drug is taken.
• Neuroleptic Malignant Syndrome Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia).
• Orthostatic Hypotension Patients should be advised of the risk of orthostatic hypotension, particularly at the time of initiating treatment, re-initiating treatment, or increasing the dose.
• Interference with Cognitive and Motor Performance Because Fanapt may have the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Fanapt therapy does not affect them adversely.
• Pregnancy Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with Fanapt.
• Nursing Patients should be advised not to breast-feed an infant if they are taking Fanapt.
• Concomitant Medication Patients should be advised to inform their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs, since there is a potential for interactions.
• Alcohol Patients should be advised to avoid alcohol while taking Fanapt.
• Heat Exposure and Dehydration Patients should be advised regarding appropriate care in avoiding overheating and dehydration.