indication

For the treatment of schizophrenia.

pharmacology

Paliperidone is an atypical antipsychotic developed by Janssen Pharmaceutica. Chemically, paliperidone is primary active metabolite of the older antipsychotic risperidone (paliperidone is 9-hydroxyrisperidone). While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not the same, pathways.

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.

toxicity

The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.

biotransformation

Although in vitro studies suggested a role for CYP2D6 and CYP3A4 in the metabolism of paliperidone, in vivo results indicate that these isozymes play a limited role in the overall elimination of paliperidone. Four primary metabolic pathways have been identified in vivo, none of which could be shown to account for more than 10% of the dose: dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission. Paliperidone does not undergo extensive metabolism and a significant portion of its metabolism occurs in the kidneys.

absorption

The absolute oral bioavailability of paliperidone following paliperidone administration is 28%.

half life

The terminal elimination half-life of paliperidone is approximately 23 hours.

route of elimination

One week following administration of a single oral dose of 1 mg immediate-release 14C-paliperidone to 5 healthy volunteers, 59% (range 51% – 67%) of the dose was excreted unchanged into urine, 32% (26% – 41%) of the dose was recovered as metabolites, and 6% – 12% of the dose was not recovered.

drug interactions

Amantadine: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, amantadine. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Apomorphine: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, apomorphine. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Bromocriptine: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, bromocriptine. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Levodopa: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, levodopa. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Methotrimeprazine: The CNS depressant agents, paliperidone and methotrimeprazine, may cause additive CNS depressant effects. Monitor for increased CNS depressant effects during concomitant therapy.

Metoclopramide: Metoclopramide may increase the risk of extrapyramidal side effects of paliperidone. Concomitant therapy should be avoided.

Pramipexole: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, pramipexole. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Risperidone: Paliperidone is the active metabolite of risperidone, 9-OH-risperidone. Concomitant therapy may increase the adverse effects of paliperidone due to additive paliperidone exposure. Consider alternate therapy.

Ropinirole: The atypical antipsychotic agent, paliperidone, may decrease the therapeutic effect of the anti-Parkinson's agent, ropinirole. This interaction may be due to the dopamine antagonist properties of paliperidone. Consider an alternate antipsychotic in those with Parkinson's disease or consider using clozapine or quetiapine if an atypical antipsychotic is necessary.

Tacrine: Tacrine, a central acetylcholinesterase inhibitor, may augment the central neurotoxic effect of antipsychotics such as Paliperidone. Monitor for extrapyramidal symptoms.

Tetrabenazine: May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects.

Triprolidine: The CNS depressants, Triprolidine and Paliperidone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.