paliperidone

Initial Dose Recommended Dose Maximum Dose Schizophrenia - adults ( 2.1 ) 6 mg/day 3 mg/day to 12 mg/day 12 mg/day Schizophrenia-adolescents ( 2.1 ) Weight < 51 kg 3 mg/day 3 mg/day to 6 mg/day 6 mg/day Weight ≥ 51 kg 3 mg/day 3 mg/day to 12 mg/day 12 mg/day Schizoaffective disorder - adults ( 2.2 ) 6 mg/day 3 mg/day to 12 mg/day 12 mg/day Tablet should be swallowed whole and should not be chewed, divided, or crushed. ( 2.3 ) 2.1 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…

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 obstruction [see Warnings and Precautions (5.8)] Orthostatic hypotension and syncope [see Warnings and Precautions (5.9)] Falls [see Warnings and Precautions (5.10)] Leukopenia, neutropenia, and agranulocytosis [see Warnings and Precautions (5.11)] Potential for cognitive and motor impairment [see Warnings and Precautions (5.12)] Seizures [see Warnings and Precautions (5.13)] Dysphagia [see Warnings and Precautions (5.14)] Priapism [see Warnings and Precautions (5.1 5 )] Disruption of body temperature regulation [see Warnings and Precautions (5.1 7 )] Commonly observed adverse reactions (incidence ≥ 5% and at least twice that for placebo) were ( 6 ) Adults with schizophrenia: extrapyramidal symptoms,…

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 tablets 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. Known hypersensitivity to paliperidone, risperidone, or to any excipients in paliperidone extended-release tablets. ( 4 )

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 extended-release tablets 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. Torsade de pointes and ventricular fibrillation have been reported in a patient in the setting of overdose. Paliperidone is the major active metabolite of risperidone. Overdose experience reported with risperidone can be found in the OVERDOSAGE section of the risperidone package insert. 10.2 Management of Overdosage There is no specific antidote to paliperidone, therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers. Consideration should be given to the extended-release nature of the product when assessing treatment needs and recovery. Multiple drug involvement should also be considered. In case of acute overdose, establish and maintain an airway and ensure adequate oxygenation and ventilation. Administration of activated charcoal together with a laxative should be…

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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 extended-release tablets. ( 7.1 ) Strong CYP3A4/P-glycoprotein (P-gp) inducers: It may be necessary to increase the dose of paliperidone extended-release tablets 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 extended-release tablets. ( 7.2 ) Co-administration of divalproex sodium increased Cmax and AUC of paliperidone by approximately 50%. Adjust dose of paliperidone extended-release tablets if necessary based on clinical assessment. ( 7.2 ) 7.1 Potential for Paliperidone Extended-Release Tablets to Affect Other Drugs Given the primary CNS effects of paliperidone [see Adverse Reactions (6.1 , 6.2) ] , paliperidone extended-release tablets should be used with caution in combination with other centrally acting drugs and alcohol. Paliperidone may antagonize the effect of levodopa and other dopamine agonists. Because of its potential for inducing orthostatic hypotension, an additive effect may be observed when paliperidone extended-release tablets are administered with other therapeutic agents that have this potential [see Warnings and Precautions (5.9) ] . Paliperidone is not expected to cause clinically important pharmacokinetic interactions with drugs that are metabolized by cytochrome P450 isozymes. In vitro studies in human liver microsomes showed that paliperidone does not substantially inhibit the metabolism of drugs metabolized by cytochrome P450 isozymes, including CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, and CYP3A5. Therefore, paliperidone is not expected to inhibit clearance of drugs that are metabolized by these metabolic pathways in a clinically relevant manner. Paliperidone is also not expected to have enzyme inducing properties. Paliperidone is a weak inhibitor of P-glycoprotein (P-gp) at high concentrations. No in vivo data are available and the clinical relevance is unknown. Pharmacokinetic interaction between lithium and paliperidone extended-release tablets is unlikely. In a drug interaction study, co-administration of paliperidone extended-release tablets (12 mg once daily for 5 days) with divalproex sodium extended-release tablets (500 mg to 2,000 mg once daily) did not affect the steady-state pharmacokinetics (AUC 24h and C max,ss ) of valproate in 13 patients stabilized on valproate. In a clinical study, subjects on stable doses of valproate had comparable valproate average plasma concentrations when paliperidone extended-release tablets 3 mg/day to 15 mg/day were added to their existing valproate treatment. 7.2 Potential for Other Drugs to Affect Paliperidone Extended-Release Tablets Paliperidone is not a substrate of CYP1A2, CYP2A6, CYP2C9, and CYP2C19, so that an interaction with inhibitors or inducers of these isozymes is unlikely. While in vitro studies indicate that CYP2D6 and CYP3A4 may be minimally involved in paliperidone metabolism, in vivo studies do not show decreased elimination by these isozymes and they contribute to only a small fraction of total body clearance. In vitro studies have shown that paliperidone is a P-gp substrate. Co-administration of paliperidone extended-release tablets 6 mg once daily with carbamazepine, a strong inducer of both CYP3A4 and P-glycoprotein (P-gp), at 200 mg twice daily caused a decrease of approximately 37% in the mean steady-state C max and AUC of paliperidone. This decrease is caused, to a substantial degree, by a 35% increase in renal clearance of paliperidone. A minor decrease in the amount of drug excreted unchanged in the urine suggests that there was little effect on the CYP metabolism or bioavailability of paliperidone during carbamazepine co-administration. On initiation of carbamazepine, the dose of paliperidone extended-release tablets should be re-evaluated and increased if necessary. Conversely, on discontinuation of carbamazepine, the dose of paliperidone extended-release tablets should be re-evaluated and decreased if necessary. Paliperidone is metabolized to a limited extent by CYP2D6 [see Clinical Pharmacology (12.3) ] . In an interaction study in healthy subjects in which a single 3 mg dose of paliperidone extended-release tablets was administered concomitantly with 20 mg per day of paroxetine (a potent CYP2D6 inhibitor), paliperidone exposures were on average 16% (90% CI: 4, 30) higher in CYP2D6 extensive metabolizers. Higher doses of paroxetine have not been studied. The clinical relevance is unknown. Co-administration of a single dose of paliperidone extended-release tablets 12 mg with divalproex sodium extended-release tablets (two 500 mg tablets once daily) resulted in an increase of approximately 50% in the C max and AUC of paliperidone. Dosage reduction for paliperidone extended-release tablets should be considered when paliperidone extended-release tablets are co-administered with valproate after clinical assessment. Pharmacokinetic interaction between lithium and paliperidone extended-release tablets is unlikely.