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Paliperidone

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Paliperidone
Clinical data
Trade namesInvega, Xeplion, others
Other names9-hydroxyrisperidone
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 (by mouth)
Excretion1% unchanged in urine 18% unchanged in feces
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, 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 is mainly used to treat schizophrenia and schizoaffective disorder. It is also used to treat mania and at lower doses as maintenance for bipolar disorder.

Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester indicated for once-every 28 days injection after an initial titration period.

Medical use

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 and demonstrated 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).[2]

Paliperidone palmitate long-acting injection compared to risperidone for schizophrenia[3]
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.[3]

Adverse effects

Sources:[4][5][6][7][8]

Very Common (>10% incidence)
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.[9][10][11][12][13][14][15]

Pharmacology

Paliperidone[16]
Site Ki (nM)
5-HT1A 617
5-HT2A 1.1
5-HT2C 48
5-HT6 2414
5-HT7 2.7
α1A 2.5
α2A 3.9
α2B 4.0
α2C 2.7
D2 1.6
D2L 6.6
D3 3.5
H1 19
mAChTooltip Muscarinic acetylcholine receptor >10,000
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.[17] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.[18] Blocks dopamine and serotonin. 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

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

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]

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. ^ a b c d e Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, Samara M, Barbui C, Engel RR, Geddes JR, Kissling W, Stapf MP, Lässig B, Salanti G, Davis JM (September 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.
  3. ^ a b Nussbaum AM, Stroup TS (June 2012). "Paliperidone palmitate for schizophrenia". The Cochrane Database of Systematic Reviews. 6 (6): CD008296. doi:10.1002/14651858.CD008296.pub2. PMC 3494051. PMID 22696377.
  4. ^ "DrugPoint® System". Truven Health Analytics, Inc. Greenwood Village, CO: Thomsen Healthcare. 2013.
  5. ^ "INVEGA® PRODUCT INFORMATION". Janssen Pharmaceuticals. 2013.
  6. ^ Park YW, Kim Y, Lee JH (December 2012). "Antipsychotic-induced sexual dysfunction and its management". The World Journal of Men's Health. 30 (3): 153–9. doi:10.5534/wjmh.2012.30.3.153. PMC 3623530. PMID 23596605.
  7. ^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  8. ^ "paliperidone (Rx) - Invega, Invega Sustenna". Medscape Reference.
  9. ^ "21 users of schizophrenia drug dead". The Japan Times.
  10. ^ "Schizophrénie: controverse autour d'un médicament au Japon". Médecine.
  11. ^ "20 minutes - Un médicament anti-schizophrénie tue". Monde.
  12. ^ "Deaths reported after Xeplion injections". Life & Style. NZ Herald News.
  13. ^ "17 deaths reported after schizophrenia drug injections". Japan Today: Japan News and Discussion.
  14. ^ "21 Dead in Japan From New Johnson & Johnson Antipsychotic". Mad In America.
  15. ^ "Schizophrenia drug blamed for 17 deaths". Sky News Australia.
  16. ^ Corena-McLeod M (June 2015). "Comparative Pharmacology of Risperidone and Paliperidone - Table 1". Drugs in R&D. 15 (2): 163–74. doi:10.1007/s40268-015-0092-x. PMC 4488186.
  17. ^ "Paliperidone". The DrugBank database.
  18. ^ Corena-McLeod M (2015). "Comparative Pharmacology of Risperidone and Paliperidone". Drugs in R&D. 15 (2): 163–74. doi:10.1007/s40268-015-0092-x. PMC 4488186. PMID 25943458.
  19. ^ a b "Paliperidone extended release: Scientific Discussion" (PDF). EMA. 16 July 2007.
  20. ^ "Procedural steps taken and scientific information after the authorisation" (PDF). EMA. 16 July 2015.
  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. EMC.
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