Paliperidone

Paliperidone extended-release tablets are an atypical antipsychotic agent indicated for Treatment of schizophrenia (1.1) Adults: Efficacy was established in three 6-week trials and one maintenance trial. (14.1) Adolescents (ages 12 to 17): Efficacy was established in one 6-week trial. (14.1) Treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants. (1.2) Efficacy was established in two 6-week trials in adult patients. (14.2) 1.1 Schizophrenia Paliperidone extended-release tablets are indicated for the treatment of schizophrenia [see Clinical Studies (14.1) ]. …

• Initial Dose Recommended Dose Maximum Dose Schizophrenia - adults 6 mg/day 3 to 12 mg/day 12 mg/day Schizophrenia-adolescents Weight < 51 kg 3 mg/day 3 to 6 mg/day 6 mg/day Weight ≥ 51 kg 3 mg/day 3 to 12 mg/day 12 mg/day Schizoaffective disorder - adults 6 mg/day 3 to 12 mg/day 12 mg/day Tablet should be swallowed whole and should not be chewed, divided, or crushed
• Schizophrenia
• Adults The recommended dose of 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
• In a longer-term study, paliperidone extended-release tablets have been shown to be effective in delaying time to relapse in patients with schizophrenia who were stabilized on paliperidone extended-release tablets for 6 weeks [see Clinical Studies ]. …

Paliperidone extended-release tablets are available in the following strengths and colors: 1.5 mg: brown, round, biconvex tablets, debossed “AN” over “80” on one side and plain on the other side. 3 mg: white, round, biconvex tablets, debossed “AN” over “81” on one side and plain on the other side. …

• Safety and effectiveness of paliperidone in the treatment of schizophrenia were evaluated in 150 adolescent subjects 12 to 17 years of age with schizophrenia who received paliperidone in the dose range of 1.5 mg to 12 mg/day in a 6-week, double-blind, placebo-controlled trial
• Safety and effectiveness of paliperidone
• For the treatment of schizophrenia in patients < 12 years of age have not been established
• Safety and effectiveness of paliperidone
• For the treatment of schizoaffective disorder in patients < 18 years of age have not been studied. …

The safety, tolerability, and efficacy of paliperidone were evaluated in a 6-week placebo-controlled study of 114 elderly subjects with schizophrenia (65 years of age and older, of whom 21 were 75 years of age and older). In this study, subjects received flexible doses of paliperidone (3 mg to 12 mg once daily). …

• Physicians are advised to discuss the following issues with patients for whom they prescribe paliperidone
• Neuroleptic Malignant Syndrome (NMS) Counsel patients about a potentially fatal adverse reaction, Neuroleptic Malignant Syndrome (NMS), that has been reported in association with administration of antipsychotic drugs
• Advise patients, family members, or caregivers to contact their healthcare provider or report to the emergency room if they experience signs and symptoms of NMS, including hyperpyrexia, muscle rigidity, altered mental status including delirium, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see …

• 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
• Paliperidone is a metabolite of risperidone. …

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., carbamazepine) is co-administered. Conversely, on discontinuation of the strong inducer, it may be necessary to decrease the dose of paliperidone. (7.2) Co-administration of divalproex sodium increased C max and AUC of paliperidone by approximately 50%. …

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 factors for prolonged QT interval. (5.4) Tardive Dyskinesia: Discontinue drug if clinically appropriate. …

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 dyskinesia [see Warnings and Precautions (5.5) ] Metabolic changes [see Warnings and Precautions (5.6) ] Hyperprolactinemia [see Warnings and Precautions (5.7) ] Potential for gastrointestinal obstructi …

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including paliperidone, during pregnancy. Healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/ . …

10.1 Human Experience While experience with paliperidone overdose is limited, among the few cases of overdose reported in pre-marketing trials, the highest estimated ingestion of paliperidone was 405 mg. Observed signs and symptoms included extrapyramidal symptoms and gait unsteadiness. Other potential signs and symptoms include those resulting from an exaggeration of paliperidone’s known pharmacological effects, i.e., drowsiness and somnolence, tachycardia and hypotension, and QT prolongation. …

9.1 Controlled Substance Paliperidone is not a controlled substance. 9.2 Abuse Paliperidone has not been systematically studied in animals or humans for its potential for abuse. It is not possible to predict the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.