INVEGA- paliperidone tablet, extended release
Janssen Pharmaceuticals, Inc.
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. 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. INVEGA� (paliperidone) Extended-Release Tablets is not approved for the treatment of patients with dementia-related psychosis. [see Warnings and Precautions (5.1)]
1 INDICATIONS AND USAGE
INVEGA� (paliperidone) Extended-Release Tablets are indicated for the treatment of schizophrenia [see Clinical Studies (14.1)].
The efficacy of INVEGA� in schizophrenia was established in three 6-week trials in adults and one 6-week trial in adolescents, as well as one maintenance trial in adults.
1.2 Schizoaffective Disorder
INVEGA� (paliperidone) Extended-Release Tablets are indicated for the treatment of schizoaffective disorder as monotherapy and an adjunct to mood stabilizers and/or antidepressant therapy [see Clinical Studies (14.2)].
The efficacy of INVEGA� in schizoaffective disorder was established in two 6-week trials in adults.
2 DOSAGE AND ADMINISTRATION
The recommended dose of INVEGA� (paliperidone) Extended-Release Tablets for the treatment of schizophrenia in adults is 6 mg administered once daily. Initial dose titration is not required. Although it has not been systematically established that doses above 6 mg have additional benefit, there was a general trend for greater effects with higher doses. This must be weighed against the dose-related increase in adverse reactions. Thus, some patients may benefit from higher doses, up to 12 mg/day, and for some patients, a lower dose of 3 mg/day may be sufficient. Dose increases above 6 mg/day should be made only after clinical reassessment and generally should occur at intervals of more than 5 days. When dose increases are indicated, increments of 3 mg/day are recommended. The maximum recommended dose is 12 mg/day.
DOSAGE FORMS AND STRENGTHS
INVEGA� Extended-Release Tablets are available in the following strengths and colors: 1.5 mg (orange-brown), 3 mg (white), 6 mg (beige), and 9 mg (pink). All tablets are capsule shaped and are imprinted with either "PAL 1.5?, "PAL 3?, "PAL 6?, or "PAL 9?.
12.1 Mechanism of Action
Paliperidone is the major active metabolite of risperidone. The mechanism of action of paliperidone, as with other drugs having efficacy in schizophrenia, is unknown, but it has been proposed that the drug's therapeutic activity in schizophrenia is mediated through a combination of central dopamine Type 2 (D2 ) and serotonin Type 2 (5HT2A ) receptor antagonism.