IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR LATUDA

INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDAL THOUGHTS AND BEHAVIORS

Contraindications: LATUDA is contraindicated in the following:

• Known hypersensitivity to lurasidone HCl or any components in the formulation. Angioedema has been observed with lurasidone
• Strong CYP3A4 inhibitors (e.g., ketoconazole)
• Strong CYP3A4 inducers (e.g., rifampin)

Cerebrovascular Adverse Reactions, Including Stroke: In clinical trials, elderly subjects with dementia randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. LATUDA is not approved for the treatment of patients with dementia-related psychosis.

Neuroleptic Malignant Syndrome (NMS): NMS is a potentially fatal symptom complex reported with administration of antipsychotic drugs. Clinical signs of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. Manage NMS with immediate discontinuation of antipsychotic drugs, including LATUDA, intensive symptomatic treatment and monitoring.

Tardive Dyskinesia (TD): The risk of developing TD (a syndrome of abnormal involuntary movements) and the potential for it to become irreversible are believed to increase as the duration of treatment and total cumulative dose of antipsychotic increase. The syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment. The syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn.

Metabolic Changes: Atypical antipsychotic drugs have caused metabolic changes including:

Hyperglycemia and Diabetes Mellitus: Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics. Patients with diabetes should be regularly monitored for worsening of glucose control; those with risk factors for diabetes should undergo fasting blood glucose testing at the beginning of and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia, including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.

Dyslipidemia: Undesirable alterations in lipids have been observed in patients treated with atypical antipsychotics.

Weight Gain: Weight gain has been observed with atypical antipsychotic use. Clinical monitoring of weight is recommended.

Hyperprolactinemia: As with other drugs that antagonize dopamine D₂ receptors, LATUDA elevates prolactin levels. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds.

Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia/neutropenia has been reported with antipsychotics. Agranulocytosis (including fatal cases) has been reported with other agents in the class. Monitor complete blood count in patients with a pre-existing low white blood cell count (WBC)/absolute neutrophil count (ANC) or history of drug-induced leukopenia/neutropenia. Discontinue LATUDA at the first sign of a decline in WBC in the absence of other causative factors.

Orthostatic Hypotension and Syncope: Atypical antipsychotics cause orthostatic hypotension and syncope. Generally, the risk is greatest at the beginning of treatment and when increasing the dose. Monitor patients vulnerable to hypotension and those with cardiovascular and cerebrovascular disease.

Falls: Antipsychotics may cause somnolence, postural hypotension, or motor and sensory instability, which may lead to falls, causing fractures or other injuries. For patients with disease, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating treatment and recurrently during therapy.

Seizures: LATUDA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.

Potential for Cognitive and Motor Impairment: Patients should be cautioned about operating hazardous machinery, including motor vehicles, until they are reasonably certain that therapy with LATUDA does not affect them adversely.

Body Temperature Regulation: Use LATUDA with caution in patients who may experience conditions that increase body temperature (e.g., exercising strenuously, exposure to extreme heat, concomitant medication with anticholinergic activity, or being subject to dehydration).

Dysphagia: Antipsychotics, including LATUDA, have been associated with esophageal dysmotility and aspiration, and should be used with caution in patients at risk for aspiration pneumonia.

Most Commonly Observed Adverse Reactions: Commonly observed adverse reactions (≥5% incidence and at least twice the rate of placebo) for LATUDA:

• Adult patients with schizophrenia: somnolence, akathisia, extrapyramidal symptoms, and nausea
• Adolescent patients (13 to 17 years) with schizophrenia: somnolence, nausea, akathisia, extrapyramidal symptoms (non-akathisia), vomiting, and rhinorrhea/rhinitis
• Adult patients with bipolar depression: akathisia, extrapyramidal symptoms, and somnolence
• Pediatric patients (10 to 17 years) with bipolar depression: nausea, weight increase, and insomnia

To report SUSPECTED ADVERSE REACTIONS, contact Sunovion Pharmaceuticals Inc. at 877-737-7226 or FDA at 1-800-FDA-1088 (www.fda.gov/medwatch).

INDICATIONS

LATUDA is indicated for:

• Treatment of adult and adolescent patients (13 to 17 years) with schizophrenia
• Monotherapy treatment of adult and pediatric patients (10 to 17 years) with major depressive episode associated with bipolar I disorder (bipolar depression)
• Adjunctive treatment with lithium or valproate in adult patients with bipolar depression

Before prescribing LATUDA, please read the full Prescribing Information, including Boxed Warning.