Jump to content

Paliperidone

From Wikipedia, the free encyclopedia

This is an old revision of this page, as edited by CheMoBot (talk | contribs) at 20:31, 31 August 2016 (Updating {{infobox_drug}} (changes to verified and watched fields) per Chem/infobox_drug validation (report errors or bugs)). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

Paliperidone
Clinical data
Trade namesInvega
AHFS/Drugs.comMonograph
MedlinePlusa607005
License data
Pregnancy
category
  • AU: B3
Routes of
administration		Oral (OROS tablets), IM depot injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability28% (oral)
Elimination half-life23 hours (oral)
Identifiers
  • (RS)-3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.117.604 Edit this at Wikidata
Chemical and physical data
FormulaC23H27FN4O3
Molar mass426.484 g/mol g·mol−1
3D model (JSmol)
  • O=C/1N5/C(=N\C(=C\1CCN4CCC(c3noc2cc(F)ccc23)CC4)C)[C@H](O)CCC5
  • InChI=1S/C23H27FN4O3/c1-14-17(23(30)28-9-2-3-19(29)22(28)25-14)8-12-27-10-6-15(7-11-27)21-18-5-4-16(24)13-20(18)31-26-21/h4-5,13,15,19,29H,2-3,6-12H2,1H3/t19-/m1/s1 checkY
  • Key:PMXMIIMHBWHSKN-LJQANCHMSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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.[2] 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.[3]

Pharmacology

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.[4] 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.[5] 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.[6][7]

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.[8] 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.[9]

Effects

Comparison of paliperidone palmitate to risperidone long-acting injection for schizophrenia[10]
Measured outcome Findings in words Findings in numbers Quality of evidence
Recurrence of psychotic symptoms No more likely to have a recurrence of psychotic symptoms with paliperidone palmitate RR 1.23 CI 0.98 to 1.53 Moderate
Lack of efficacy People are 35% more likely to experience lack of efficacy with paliperidone palmitate RR 1.35 CI 1.06 to 1.71
Use of anticholinergic medications 30% less likely to use anticholinergic medications with paliperidone palmitate RR 0.67 CI 0.55 to 0.82

Adverse effects

Adverse effect incidences

Sources:[11][12][13][14]

Very Common (>10% incidence)
  • Headache
  • Tachycardia
  • Somnolence (causes less sedation than most atypical antipsychotics[15])
  • Insomnia
  • Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone[15])
Common (1–10% incidence)

Deaths

In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone to date had died.[16][17][18][19][20][21][22]

References

  1. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
  2. ^ "Invega Trinza™ (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved 10 December 2015.
  3. ^ "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.
  4. ^ "The DrugBank database".
  5. ^ "Prescribing Reference: New Product Releases - INVEGA". Retrieved 2008-05-25.
  6. ^ 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]
  7. ^ 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]
  8. ^ https://www.www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002105/human_med_001424.jsp&mid=WC0b01ac058001d124&murl=menus/medicines/medicines.jsp&jsenabled=true[full citation needed]
  9. ^ https://www.invegasustenna.com/invegasustenna/index.html[full citation needed]
  10. ^ 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.
  11. ^ Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 30]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  12. ^ 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
  13. ^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  14. ^ paliperidone (Rx) - Invega, Invega Sustenna [Internet]. Medscape Reference. [cited 2013 Sep 30]. Available from: http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4
  15. ^ 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. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019.
  16. ^ 21 users of schizophrenia drug dead | The Japan Times
  17. ^ Schizophrénie: controverse autour d'un médicament au Japon | Médecine
  18. ^ 20 minutes - Un médicament anti-schizophrénie tue - Monde
  19. ^ Deaths reported after Xeplion injections - Life & Style - NZ Herald News
  20. ^ 17 deaths reported after schizophrenia drug injections | Japan Today: Japan News and Discussion
  21. ^ 21 Dead in Japan From New Johnson & Johnson Antipsychotic | Mad In America
  22. ^ Schizophrenia drug blamed for 17 deaths | Sky News Australia
Retrieved from "https://en.wikipedia.org/w/index.php?title=Paliperidone&oldid=737109460"