PALIPERIDONE

Following a single dose, the plasma concentrations of paliperidone gradually rise to reach peak plasma concentration (C max ) approximately 24 hours after dosing. The pharmacokinetics of paliperidone following paliperidone administration are dose-proportional within the available dose range. The terminal elimination half-life of paliperidone is approximately 23 hours. Steady-state concentrations of paliperidone are attained within 4 to 5 days of dosing with paliperidone in most subjects. The mea...

14.1 Schizophrenia Adults The acute efficacy of paliperidone (3 mg to 15 mg once daily) was established in three placebo-controlled and active-controlled (olanzapine), 6-week, fixed-dose trials in non-elderly adult subjects (mean age of 37) who met DSM-IV criteria for schizophrenia. Studies were carried out in North America, Eastern Europe, Western Europe, and Asia. The doses studied among these three trials included 3 mg/day, 6 mg/day, 9 mg/day, 12 mg/day, and 15 mg/day. Dosing was in the morning without regard to meals. Efficacy was evaluated using the Positive and Negative Syndrome Scale (P...

The following adverse reactions 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 reactions, including stroke, in elderly patients with dementia-related psychosis [see Warnings and Precautions (5.2) ] Neuroleptic malignant syndrome [see Warnings and Precautions (5.3) ] QT prolongation [see Warnings and Precautions (5.4) ] Tardive dy...

Paliperidone extended-release tablets are contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the paliperidone extended-release tablet formulation. Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been reported in patients treated with risperidone and in patients treated with paliperidone. ...

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. (5.2) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation of drug and close monitoring. (5.3) QT Prolongation: Increase in QT interval, avoid use with drugs that also increase QT interval and in patients with risk facto...

7 DRUG INTERACTIONS Centrally-acting drugs: Due to CNS effects, use caution in combination. Avoid alcohol. (7.1) Drugs that may cause orthostatic hypotension: An additive effect may be observed when co-administered with paliperidone. (7.1) Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of paliperidone when a strong inducer of both CYP3A4 and P-gp (e.g., carb...