Paliperidone

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Paliperidone
Paliperidone.svg
Clinical data
Trade names Invega, Xeplion, others
Synonyms 9-hydroxyrisperidone
AHFS/Drugs.com Monograph
MedlinePlus a607005
License data
Pregnancy
category
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
administration
Oral (OROS tablets), IM depot injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 28% (oral)
Biological half-life 23 hours (by mouth)
Excretion 1% unchanged in urine 18% unchanged in feces
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard 100.117.604
Chemical and physical data
Formula C23H27FN4O3
Molar mass 426.484 g/mol
3D model (JSmol)
 NYesY (what is this?)  (verify)

Paliperidone, sold under the trade name Invega among others, is a dopamine antagonist and 5-HT2A antagonist of the atypical antipsychotic class of medications. It is marketed 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 is a long-acting injectable formulation of paliperidone palmitoyl ester indicated for once-every 28 days injection after an initial titration period. Paliperidone is used to treat mania and at lower doses as maintenance for bipolar disorder. It is also indicated in the US by the FDA for schizophrenia and schizoaffective disorder.

Medical use[edit]

It is used for the treatment of schizophrenia and schizoaffective disorder. In a 2013 study in a comparison of 15 antipsychotic drugs in effectiveness in treating schizophrenic symptoms, paliperidone was ranked fifth, demonstrating standard-high effectiveness. 10-14% more effective than haloperidol, quetiapine, and aripiprazole, 11% less effective than risperidone (4th), and 43% less effective than clozapine (1st).[1]

Paliperidone palmitate long-acting injection compared to risperidone for schizophrenia[2]
When flexibly dosed every four weeks, paliperidone palmitate appears comparable in efficacy and tolerability to risperidone. In short-term studies, paliperidone palmitate - the longer-acting injection - has a similar adverse effect profile to related compounds such as risperidone by mouth. No difference was found in the high rate of reported adverse sexual outcomes and paliperidone palmitate is associated with an increase in serum prolactin.[2]

Adverse effects[edit]

Sources:[3][4][5][6]

Very Common (>10% incidence)
Common (1–10% incidence)

Deaths[edit]

In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone to date had died.[8][9][10][11][12][13][14]

Pharmacology[edit]

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.[15] 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.[16] 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.[17][18]

Food increases the absorption of Invega type ER OROS prolonged-release tablet. Food increased exposure of Paliperidone by up to 50-60%, however, half-life was not significantly affected. The effect was probably due to a delay in the transit of the ER OROS formulation in the upper part of the GI channel, resulting in increased absorption (uptake).[19]

The half life is 24 hours.[19]

History[edit]

Paliperidone (as Invega) was approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in 2006. Paliperidone was approved by the FDA for the treatment of schizoaffective disorder in 2009. 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 is the only available brand in Bangladesh under the brand name "Palimax ER" manufactured & marketed by ACI Pharmaceuticals.

It was initially approved in Europe in 2007 for schizophrenia, the extended release form and use for schizoaffective disorder were approved in Europe in 2010, and extension to use in adolescents older than 15 years old was approved in 2014.[20]

Brand names[edit]

On May 18, 2015, a new formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[21] A similar 3 -monthly injection of prolonged release suspension was approved in 2016 by the European Medicines Agency originally under the brand name Paliperidone Janssen, later renamed to Trevicta.[22]

Palimax ER - ACI Pharmaceuticals, Bangladesh

References[edit]

  1. ^ 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 (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". The Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. 
  2. ^ a b Nussbaum, A; Stroup, T (2012). "Paliperidone palmitate for schizophrenia". Cochrane Database of Systematic Reviews. 6: CD008296.pub2. doi:10.1002/14651858.CD008296.pub2. 
  3. ^ Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 30]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  4. ^ 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
  5. ^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  6. ^ paliperidone (Rx) - Invega, Invega Sustenna [Internet]. Medscape Reference. [cited 2013 Sep 30]. Available from: http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4
  7. ^ a b c d 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. PMID 23810019. doi:10.1016/S0140-6736(13)60733-3. 
  8. ^ 21 users of schizophrenia drug dead | The Japan Times
  9. ^ Schizophrénie: controverse autour d'un médicament au Japon | Médecine
  10. ^ 20 minutes - Un médicament anti-schizophrénie tue - Monde
  11. ^ Deaths reported after Xeplion injections - Life & Style - NZ Herald News
  12. ^ 17 deaths reported after schizophrenia drug injections | Japan Today: Japan News and Discussion
  13. ^ 21 Dead in Japan From New Johnson & Johnson Antipsychotic | Mad In America
  14. ^ Schizophrenia drug blamed for 17 deaths | Sky News Australia
  15. ^ "The DrugBank database". 
  16. ^ "Prescribing Reference: New Product Releases - INVEGA". Retrieved 2008-05-25. 
  17. ^ http://pdsp.med.unc.edu/pdsp.php?knowID=&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=2327&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query[full citation needed]
  18. ^ http://pdsp.med.unc.edu/pdsp.php?knowID=&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=2328&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query[full citation needed]
  19. ^ a b "Paliperidone extended release: Scientific Discussion" (PDF). EMA. 16 July 2007.  Linked from EMA main page on drug, in "Assessment History" tab.
  20. ^ "Procedural steps taken and scientific information after the authorisation" (PDF). EMA. 16 July 2015.  Linked from EMA main page on drug, in "Assessment History" tab.
  21. ^ "Invega Trinza™ (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved 10 December 2015. 
  22. ^ "Trevicta (previously Paliperidone Janssen) - summary of the European public assessment report (EPAR) for Trevicta". 

External links[edit]