|Oral (OROS tablets), IM depot injection|
|ATC code||N05AX13 (WHO)|
|Biological half-life||23 hours (oral)|
|Chemical and physical data|
|Molar mass||426.484 g/mol|
|3D model (Jmol)||Interactive image|
|(what is this?)|
Paliperidone (trade name Invega), also known as 9-hydroxyrisperidone, is a dopamine antagonist and 5-HT2A antagonist of the atypical antipsychotic class of medications. It is developed by Janssen Pharmaceutica. Invega is an extended release formulation of paliperidone that uses the OROS extended release system to allow for once-daily dosing.
Paliperidone palmitate (trade name Invega Sustenna, named Xeplion in Europe and other countries) is a long-acting injectable formulation of paliperidone palmitoyl ester indicated for once-monthly injection after an initial titration period. Paliperidone is used to treat mania and at lower doses as maintenance for bipolar disorder. It is also used for schizophrenia and schizoaffective disorder.
On May 18, 2015, a new formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza. It is a 3-month extended-release injectable suspension suitable for schizophrenic patients after they have been adequately treated with Invega Sustenna for at least four months.
Paliperidone is the primary active metabolite of the older antipsychotic risperidone. While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.
Paliperidone has antagonist effect at α1 and α2 adrenergic receptors and at H1 histamine receptors. It does not bind to muscarinic acetylcholine receptors. In addition, it blocks dopamine and serotonin receptors.
Paliperidone has less affinity for D4 receptors than risperidone.
Paliperidone (as Invega) was approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in 2006. It is marketed for the treatment of schizophrenia and schizoaffective disorder. Paliperidone was approved by the FDA for the treatment of schizoaffective disorder in 2009. It may also be used off-label for other conditions. The long-acting injectable form of paliperidone, marketed as Invega Sustenna in U.S. and Xeplion in Europe, was approved by the FDA on July 31, 2009. It was approved in Europe in 2011 for schizophrenia. In Europe the monthly (every 28 days) injection comes in 50 mg, 75 mg, 100 mg, and 150 mg of paliperidone without the 25 mg injection that is available in the U.S. A dose of 75 mg for a month in an injection is the equivalent of 6 mg per day of paliperidone oral. 6 mg of paliperidone oral (Invega) is equivalent to 2 to 3 mg of risperidone.
Adverse effect incidences
- Very Common (>10% incidence)
- Somnolence (causes less sedation than most atypical antipsychotics)
- Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone)
- Common (1–10% incidence)
- Extrapyramidal side effects (EPSE; e.g. dystonia, akathisia, muscle rigidity, parkinsonism. It appears to produce similar EPSE to risperidone, asenapine and ziprasidone and more EPSE than olanzapine, clozapine, aripiprazole, quetiapine, amisulpride and sertindole)
- Orthostatic hypotension
- Weight gain (tends to produce a moderate degree of weight gain, possibly related to its potent blockade of the 5-HT2C receptor)
- QT interval prolongation (tends to produce less QT interval prolongation than most other atypical antipsychotics and approximately as much QT interval prolongation as aripiprazole and lurasidone)
In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone to date had died.
- "Invega Trinza™ (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved 10 December 2015.
- "Invega Trinza™ (paliperidone palmitate) Extended-release Injectable Suspension, for Intramuscular Use. Full Prescribing Information" (PDF). Schizophrenia Treatment. INVEGA TRINZA® (paliperidone palmitate). Janssen Pharmaceuticals, Inc. Retrieved 10 December 2015.
- "The DrugBank database".
- "Prescribing Reference: New Product Releases - INVEGA". Retrieved 2008-05-25.
- Nussbaum, Abraham M; Stroup, T S; Nussbaum, Abraham M (2012). "Paliperidone palmitate for schizophrenia". The Cochrane Database of Systematic Reviews. 6: CD008296. doi:10.1002/14651858.CD008296.pub2. PMID 22696377.
- Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 30]. Greenwood Village, CO: Thomsen Healthcare; 2013.
- INVEGA® PRODUCT INFORMATION [Internet]. Janssen Pharmaceuticals; 2013 [cited 2013 Sep 30]. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-01421-1
- Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
- paliperidone (Rx) - Invega, Invega Sustenna [Internet]. Medscape Reference. [cited 2013 Sep 30]. Available from: http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4
- Leucht, Stefan; Cipriani, Andrea; Spineli, Loukia; Mavridis, Dimitris; Örey, Deniz; Richter, Franziska; Samara, Myrto; Barbui, Corrado; Engel, Rolf R; Geddes, John R; Kissling, Werner; Stapf, Marko Paul; Lässig, Bettina; Salanti, Georgia; Davis, John M (2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–62. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019.
- 21 users of schizophrenia drug dead | The Japan Times
- Schizophrénie: controverse autour d'un médicament au Japon | Médecine
- 20 minutes - Un médicament anti-schizophrénie tue - Monde
- Deaths reported after Xeplion injections - Life & Style - NZ Herald News
- 17 deaths reported after schizophrenia drug injections | Japan Today: Japan News and Discussion
- 21 Dead in Japan From New Johnson & Johnson Antipsychotic | Mad In America
- Schizophrenia drug blamed for 17 deaths | Sky News Australia