FDA label 692f1569-a545-1b28-e053-2991aa0a8a90

WARNING: 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. Risperidone is not approved for the treatment of patients with dementia-related psychosis [See Warnings and Precautions (5.1) ]. 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. Risperidone is not approved for use in patients with dementia-related psychosis.( 5.1 )

5 WARNINGS AND PRECAUTIONS Cerebrovascular events, including stroke, in elderly patients with dementia-related psychosis: Risperidone is not approved for use in patients with dementia-related psychosis. ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of risperidone and close monitoring. ( 5.3 ) Tardive Dyskinesia: Consider discontinuing risperidone if clinically indicated. ( 5.4 ) Metabolic Changes: Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/ cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia and weight gain. ( 5.5 ) Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes. ( 5.5 ) Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. ( 5.5 ) Weight Gain: Significant weight gain has been reported. Monitor weight gain. ( 5.5 ) Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration. ( 5.6 ) Orthostatic hypotension: For patients at risk, consider a lower starting dose and slower titration. ( 5.7 ) Leukopenia, Neutropenia and Agranulocytosis: Perform complete blood counts in patients with a history of clinically significant low white blood cell count (WBC). Consider discontinuing risperidone if a clinically significant decline in WBC occurs in the absence of other causative factors. ( 5.8 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ( 5.9 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold. ( 5.10 )

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Increased Mortality in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning and Warnings and Precautions (5.1) ] Cerebrovascular adverse events, including stroke, in elderly patients with dementia-related psychosis [ see Warnings and Precautions (5.2) ] Neuroleptic malignant syndrome [ see Warnings and Precautions (5.3) ] Tardive dyskinesia [see Warnings and Precautions (5.4) ] Metabolic changes (Hyperglycemia and Diabetes Mellitus, Dyslipidemia and Weight Gain) [see Warnings and Precautions (5.5) ] Hyperprolactinemia [see Warnings and Precautions (5.6) ] Orthostatic hypotension [see Warnings and Precautions (5.7) ] Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions (5.8) ] Potential for cognitive and motor impairment [ see Warnings and Precautions (5.9) ] Seizures [see Warnings and Precautions (5.10) ] Dysphagia [see Warnings and Precautions (5.11) ] Priapism [see Warnings and Precautions (5.12) ] Disruption of Body Temperature Regulation [see Warnings and Precautions (5.13) ] The most common adverse reactions in clinical trials (> 5% and twice placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis and pharyngolaryngeal pain. The most common adverse reactions that were associated with discontinuation from clinical trials (causing discontinuation in > 1% of adults and/or > 2% of pediatrics) were nausea, somnolence, sedation, vomiting, dizziness and akathisia [see Adverse Reactions: Discontinuations due to Adverse Reactions (6.1) ] . The data described in this section are derived from a clinical trial database consisting of 9,803 adult and pediatric patients exposed to one or more doses of risperidone for the treatment of schizophrenia, bipolar mania, autistic disorder and other psychiatric disorders in pediatrics and elderly patients with dementia. Of these 9,803 patients, 2,687 were patients who received risperidone while participating in double-blind, placebo-controlled trials. The conditions and duration of treatment with risperidone varied greatly and included (in overlapping categories) double-blind, fixed- and flexible-dose, placebo- or active-controlled studies and open-label phases of studies, inpatients and outpatients, and short-term (up to 12 weeks) and longer term (up to 3 years) exposures. Safety was assessed by collecting adverse events and performing physical examinations, vital signs, body weights, laboratory analyses, and ECGs. The most common adverse reactions in clinical trials (>5% and twice placebo) were parkinsonism, akathisia, dystonia, tremor, sedation, dizziness, anxiety, blurred vision, nausea, vomiting, upper abdominal pain, stomach discomfort, dyspepsia, diarrhea, salivary hypersecretion, constipation, dry mouth, increased appetite, increased weight, fatigue, rash, nasal congestion, upper respiratory tract infection, nasopharyngitis, and pharyngolaryngeal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Caraco Pharmaceutical Laboratories, Ltd. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch