Paliperidone
Clinical data
Trade namesInvega, Xeplion, Trevicta, others
Other names9-hydroxyrisperidone
AHFS/Drugs.comMonograph
MedlinePlusa607005
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, intramuscular
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
Chemical and physical data
FormulaC23H27FN4O3
Molar mass426.492 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 brand name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals. Paliperidone was approved by the FDA for the treatment of schizophrenia on December 20, 2006.[4] Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.

It is on the World Health Organization's List of Essential Medicines.[5]

Medical use

Paliperidone is used for the treatment of schizophrenia and schizoaffective disorder.[6]

Adverse effects

Sources:[7][8][9][10][11]

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

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[12] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[13] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[13] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[13] Symptoms generally resolve after a short period of time.[13]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[14] It may also result in reoccurrence of the condition that is being treated.[15] Rarely tardive dyskinesia can occur when the medication is stopped.[13]

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, out of 10,700 individuals prescribed the drug.[16][17][18][19][20][21][22]

Pharmacology

Paliperidone[23]
SiteKi (nM)
5-HT1A617
5-HT2A1.1
5-HT2C48
5-HT5A278
5-HT62414
5-HT72.7
α1A2.5
α2A3.9
α2C2.7
D141
D21.6
D33.5
D454[24]
D529
H119
H2121
mACh>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.[25] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.[23] Its efficacy is believed to result from central dopaminergic and serotonergic antagonism. Paliperidone is also active by acting as an antagonist of the alpha 1 and alpha 2 adrenergic receptors as well as the H1 histaminergic receptors.[26] Food is known to increase the absorption of Invega type ER OROS prolonged-release tablets. 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.

risperidone and paliperidone in pharmacokinetics
risperidone and paliperidone in pharmacokinetics

[27]

The half-life is 23 hours.[27]

Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort[28][29]

Pharmacokinetics of long-acting injectable antipsychotics
MedicationBrand nameClassVehicleDosageTmaxt1/2 singlet1/2 multiplelogPcRef
Aripiprazole lauroxilAristadaAtypicalWatera441–1064 mg/4–8 weeks24–35 days ?54–57 days7.9–10.0
Aripiprazole monohydrateAbilify MaintenaAtypicalWatera300–400 mg/4 weeks7 days ?30–47 days4.9–5.2
Bromperidol decanoateImpromen DecanoasTypicalSesame oil40–300 mg/4 weeks3–9 days ?21–25 days7.9[30]
Clopentixol decanoateSordinol DepotTypicalViscoleob50–600 mg/1–4 weeks4–7 days ?19 days9.0[31]
Flupentixol decanoateDepixolTypicalViscoleob10–200 mg/2–4 weeks4–10 days8 days17 days7.2–9.2[31][32]
Fluphenazine decanoateProlixin DecanoateTypicalSesame oil12.5–100 mg/2–5 weeks1–2 days1–10 days14–100 days7.2–9.0[33][34][35]
Fluphenazine enanthateProlixin EnanthateTypicalSesame oil12.5–100 mg/1–4 weeks2–3 days4 days ?6.4–7.4[34]
FluspirileneImap, RedeptinTypicalWatera2–12 mg/1 week1–8 days7 days ?5.2–5.8[36]
Haloperidol decanoateHaldol DecanoateTypicalSesame oil20–400 mg/2–4 weeks3–9 days18–21 days7.2–7.9[37][38]
Olanzapine pamoateZyprexa RelprevvAtypicalWatera150–405 mg/2–4 weeks7 days ?30 days–
Oxyprothepin decanoateMeclopinTypical ? ? ? ? ?8.5–8.7
Paliperidone palmitateInvega SustennaAtypicalWatera39–819 mg/4–12 weeks13–33 days25–139 days ?8.1–10.1
Perphenazine decanoateTrilafon DekanoatTypicalSesame oil50–200 mg/2–4 weeks ? ?27 days8.9
Perphenazine enanthateTrilafon EnanthateTypicalSesame oil25–200 mg/2 weeks2–3 days ?4–7 days6.4–7.2[39]
Pipotiazine palmitatePiportil LongumTypicalViscoleob25–400 mg/4 weeks9–10 days ?14–21 days8.5–11.6[32]
Pipotiazine undecylenatePiportil MediumTypicalSesame oil100–200 mg/2 weeks ? ? ?8.4
RisperidoneRisperdal ConstaAtypicalMicrospheres12.5–75 mg/2 weeks21 days ?3–6 days–
Zuclopentixol acetateClopixol AcuphaseTypicalViscoleob50–200 mg/1–3 days1–2 days1–2 days4.7–4.9
Zuclopentixol decanoateClopixol DepotTypicalViscoleob50–800 mg/2–4 weeks4–9 days ?11–21 days7.5–9.0
Note: All by intramuscular injection. Footnotes: a = Microcrystalline or nanocrystalline aqueous suspension. b = Low-viscosity vegetable oil (specifically fractionated coconut oil with medium-chain triglycerides). c = Predicted, from PubChem and DrugBank. Sources: Main: See template.

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.[40]

Brand names

In May 2015, a new formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[41] 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.[42] On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA which is available as an injection every six months.

References

  1. ↑ Anvisa (March 31, 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published April 4, 2023). Archived from the original on August 3, 2023. Retrieved August 16, 2023.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved October 22, 2023.
  3. ↑ "Invega- paliperidone tablet, extended release". DailyMed. Retrieved August 19, 2020.
  4. ↑ "Paliperidone".
  5. ↑ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  6. 1 2 3 4 5 Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. S2CID 32085212.
  7. ↑ "DrugPoint® System". Truven Health Analytics, Inc. Greenwood Village, CO: Thomsen Healthcare. 2013.
  8. ↑ "INVEGA® PRODUCT INFORMATION". Janssen Pharmaceuticals. 2013.
  9. ↑ Park YW, Kim Y, Lee JH (December 2012). "Antipsychotic-induced sexual dysfunction and its management". The World Journal of Men's Health. 30 (3): 153–159. doi:10.5534/wjmh.2012.30.3.153. PMC 3623530. PMID 23596605.
  10. ↑ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  11. ↑ "paliperidone (Rx) - Invega, Invega Sustenna". Medscape Reference.
  12. ↑ BMJ Joint Formulary Committee, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN 978-0-85369-845-6. Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
  13. 1 2 3 4 5 Haddad PM, Dursun S, Deakin B (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. pp. 207–216. ISBN 9780198527480.
  14. ↑ Moncrieff J (July 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica. 114 (1): 3–13. doi:10.1111/j.1600-0447.2006.00787.x. PMID 16774655. S2CID 6267180.
  15. ↑ Sacchetti E, Vita A, Siracusano A, Fleischhacker W (2013). Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. p. 85. ISBN 9788847026797.
  16. ↑ "21 users of schizophrenia drug dead". The Japan Times Online. The Japan Times. April 18, 2014.
  17. ↑ "Schizophrénie: controverse autour d'un médicament au Japon". Médecine. April 9, 2014.
  18. ↑ "20 minutes - Un médicament anti-schizophrénie tue". Monde. April 9, 2014.
  19. ↑ "Deaths reported after Xeplion injections". Life & Style. NZ Herald News. Archived from the original on March 4, 2016. Retrieved April 21, 2014.
  20. ↑ "17 deaths reported after schizophrenia drug injections". Japan Today: Japan News and Discussion. April 10, 2014.
  21. ↑ "21 Dead in Japan From New Johnson & Johnson Antipsychotic". Mad In America. April 18, 2014.
  22. ↑ "Schizophrenia drug blamed for 17 deaths". Sky News Australia. June 29, 2023.
  23. 1 2 Corena-McLeod M (June 2015). "Comparative Pharmacology of Risperidone and Paliperidone". Drugs in R&D. 15 (2): 163–174. doi:10.1007/s40268-015-0092-x. PMC 4488186. PMID 25943458.
  24. ↑ Gray JA, Roth BL (October 2007). "The pipeline and future of drug development in schizophrenia". Molecular Psychiatry. 12 (10): 904–922. doi:10.1038/sj.mp.4002062. PMID 17667958. S2CID 1672835.
  25. ↑ "Paliperidone". The DrugBank database.
  26. ↑ "Paliperidone". go.drugbank.com. Retrieved November 16, 2023.
  27. 1 2 "Paliperidone extended release: Scientific Discussion" (PDF). EMA. July 16, 2007. Archived from the original (PDF) on May 19, 2012. Retrieved May 8, 2017.
  28. ↑ Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL (December 2004). "The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein". The International Journal of Neuropsychopharmacology. 7 (4): 415–419. doi:10.1017/S1461145704004390. PMID 15683552.
  29. ↑ Gurley BJ, Swain A, Williams DK, Barone G, Battu SK (July 2008). "Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics". Molecular Nutrition & Food Research. 52 (7): 772–779. doi:10.1002/mnfr.200700081. PMC 2562898. PMID 18214850.
  30. ↑ Parent M, Toussaint C, Gilson H (1983). "Long-term treatment of chronic psychotics with bromperidol decanoate: clinical and pharmacokinetic evaluation". Current Therapeutic Research. 34 (1): 1–6.
  31. 1 2 Jørgensen A, Overø KF (1980). "Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. III. Serum levels". Acta Psychiatrica Scandinavica. Supplementum. 279: 41–54. doi:10.1111/j.1600-0447.1980.tb07082.x. PMID 6931472.
  32. 1 2 Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
  33. ↑ Ereshefsky L, Saklad SR, Jann MW, Davis CM, Richards A, Seidel DR (May 1984). "Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches". The Journal of Clinical Psychiatry. 45 (5 Pt 2): 50–9. PMID 6143748.
  34. 1 2 Curry SH, Whelpton R, de Schepper PJ, Vranckx S, Schiff AA (April 1979). "Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man". British Journal of Clinical Pharmacology. 7 (4): 325–31. doi:10.1111/j.1365-2125.1979.tb00941.x. PMC 1429660. PMID 444352.
  35. ↑ Young D, Ereshefsky L, Saklad SR, Jann MW, Garcia N (1984). Explaining the pharmacokinetics of fluphenazine through computer simulations. (Abstract.). 19th Annual Midyear Clinical Meeting of the American Society of Hospital Pharmacists. Dallas, Texas.
  36. ↑ Janssen PA, Niemegeers CJ, Schellekens KH, Lenaerts FM, Verbruggen FJ, van Nueten JM, et al. (November 1970). "The pharmacology of fluspirilene (R 6218), a potent, long-acting and injectable neuroleptic drug". Arzneimittel-Forschung. 20 (11): 1689–98. PMID 4992598.
  37. ↑ Beresford R, Ward A (January 1987). "Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis". Drugs. 33 (1): 31–49. doi:10.2165/00003495-198733010-00002. PMID 3545764.
  38. ↑ Reyntigens AJ, Heykants JJ, Woestenborghs RJ, Gelders YG, Aerts TJ (1982). "Pharmacokinetics of haloperidol decanoate. A 2-year follow-up". International Pharmacopsychiatry. 17 (4): 238–46. doi:10.1159/000468580. PMID 7185768.
  39. ↑ Larsson M, Axelsson R, Forsman A (1984). "On the pharmacokinetics of perphenazine: a clinical study of perphenazine enanthate and decanoate". Current Therapeutic Research. 36 (6): 1071–88.
  40. ↑ "Procedural steps taken and scientific information after the authorisation" (PDF). EMA. July 16, 2015. Archived from the original (PDF) on June 18, 2018. Retrieved May 8, 2017.
  41. ↑ "Invega Trinza (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved December 10, 2015.
  42. ↑ "Trevicta (previously Paliperidone Janssen)". Summary of the European public assessment report (EPAR) for Trevicta. EMC. September 17, 2018. Archived from the original on June 20, 2018. Retrieved January 17, 2017.
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