Paliperidone - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions: An increased incidence of cerebrovascular adverse reactions (e.g. stroke, transient ischemic attack, including fatalities) has been seen in elderly patients with dementia-related psychoses treated with atypical antipsychotics.

Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of drug and close monitoring.

QT Prolongation: Increase in QT interval, avoid use with drugs that also increase QT interval and in patients with risk factors for prolonged QT interval.

Tardive Dyskinesia: Discontinue drug if clinically appropriate.

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.

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.

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

Weight Gain: Significant weight gain has been reported.

Hyperprolactinemia: Prolactin elevations occur and persist during chronic administration.

Gastrointestinal Narrowing: Obstructive symptoms may result in patients with gastrointestinal disease.

Orthostatic Hypotension and Syncope: Use with caution in patients with known cardiovascular or cerebrovascular disease and patients predisposed to hypotension.

Leukopenia, Neutropenia, and Agranulocytosis: has been reported with antipsychotics, including Paliperidone Extended-Release Tablets.

Patients with a history of a clinically significant low white blood cell count (WBC) or a drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and discontinuation of Paliperidone Extended-Release Tablets should be considered at the first sign of a clinically significant decline in WBC in the absence of other causative factors.

Potential for Cognitive and Motor Impairment: Use caution when operating machinery.

Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.

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

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.

Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality.

The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

Paliperidone Extended-Release Tablets are not approved for the treatment of dementia-related psychosis [see Boxed Warning ].

5.2 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks) including fatalities compared to placebo-treated subjects.