Company:

Janssen

Antipsychotic (benzisoxazole)

Paliperidone 3mg, 6mg, 9mg; ext-rel tabs.

Schizophrenia.

Paliperidone is the major active metabolite of risperidone. Although the mechanism of action of this atypical antipsychotic is unknown, the therapeutic effect may be due to a combination of central dopamine Type 2 (D₂) and serotonin Type 2 (5HT_2a) receptor antagonism. Paliperidone also antagonizes at α₁ and α₂ adrenergic receptors and H1 histaminergic receptors.

Invega tablets use osmotic pressure to deliver paliperidone at a controlled rate. Peak plasma concentrations occur approximately 24 hrs after dosing; steady state concentrations are attained within 4–5 days.

Since paliperidone is the major active metabolite of risperidone, consideration should be given to the additive paliperidone exposure if risperidone is coadministered with paliperidone.

The short-term efficacy of paliperidone was determined in three placebo-controlled and active-controlled (olanzapine), 6-week, fixed-dose trials involving 1665 patients who met DSM-IV criteria for schizophrenia. The doses studied among these three trials included 3, 6, 9, 12, and 15mg/day. Efficacy was evaluated using the Positive and Negative Syndrome scale (PANSS) and the Personal and Social Performance scale (PSP). In all three studies, paliperidone was superior to placebo on the PANSS at all doses. Paliperidone was also superior to placebo on the PSP in these trials.

The efficacy of paliperidone has not been evaluated in placebo-controlled trials for longer than six weeks. Therefore, patients who are taking paliperidone for extended periods should be reevaluated periodically.

Swallow whole. ≥18yrs: 6mg once daily in AM; may increase in increments of 3mg/day at intervals of >5 days if needed. Max 12mg/day. Renal impairment: CrCl ≥50–80mL/min: max 6mg/day; CrCl 10–< 50mL/min: max 3mg/day.

<18yrs: not recommended.

Avoid in congenital long QT syndrome, cardiac arrhythmias. Diabetes risk factors (obtain baseline fasting blood sugar). Monitor for hyperglycemia. Pre-existing severe GI narrowing: not recommended. Cardio- or cerebrovascular disease. Orthostatic hypotension. History of seizures. Patients at risk for aspiration pneumonia. Renal insufficiency. Severe hepatic impairment. Exposure to extreme temperatures. May have antiemetic effect. Suicidal patients. Reevaluate periodically. Elderly (not for dementia-related psychosis); consider monitoring renal function and for orthostatic effects. Pregnancy (Cat.C). Nursing mothers: not recommended.

Avoid alcohol, drugs that prolong QT interval (eg, Class 1A and Class III antiarrhythmics). Caution with other CNS drugs. May antagonize levodopa, other dopamine agonists.

Tachycardia, extrapyramidal effects, akathisia, dizziness, anxiety, somnolence, headache, GI upset; may cause neuroleptic malignant syndrome, tardive dyskinesia, QT prolongation, hyperglycemia, orthostatic hypotension, syncope, hyperprolactinemia, priapism.

Tabs—30, 350

1/31/07