Paliperidone Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:461753832
Width:250
Tradename:Invega, Xeplion, Trevicta, others
Dailymedid:Paliperidone
Pregnancy Au:B3
Routes Of Administration:By mouth, intramuscular
Class:Atypical antipsychotic
Atc Prefix:N05
Atc Suffix:AX13
Legal Au:S4
Legal Br:C1
Legal Br Comment:[1]
Legal Ca:Rx-only
Legal Ca Comment:[2]
Legal Us:Rx-only
Legal Us Comment:[3]
Legal Eu:Rx-only
Legal Eu Comment:[4] [5] [6] [7] [8]
Bioavailability:28% (oral)
Elimination Half-Life:23 hours (by mouth)
Excretion:1% unchanged in urine 18% unchanged in feces
Index2 Label:as palmitate
Cas Number:144598-75-4
Cas Number2:199739-10-1
Pubchem:115237
Pubchem2:9852746
Drugbank:DB01267
Drugbank2:DBSALT001464
Chemspiderid:7978307
Chemspiderid2:8028457
Unii:838F01T721
Unii2:R8P8USM8FR
Kegg:D05339
Kegg2:D05340
Chebi:82978
Chebi2:83807
Chembl:1621
Chembl2:2107360
Synonyms:9-hydroxyrisperidone; PP; PP1M; PP3M; PP6M; JNS-010; RO-92670; RO92670
Iupac Name:(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
C:23
H:27
F:1
N:4
O:3
Smiles:O=C/1N5/C(=N\C(=C\1CCN4CCC(c3noc2cc(F)ccc23)CC4)C)[C@H](O)CCC5
Stdinchi: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
Stdinchi2:1S/C39H57FN4O4/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-18-36(45)47-34-17-16-24-44-38(34)41-29(2)32(39(44)46)23-27-43-25-21-30(22-26-43)37-33-20-19-31(40)28-35(33)48-42-37/h19-20,28,30,34H,3-18,21-27H2,1-2H3
Stdinchikey:PMXMIIMHBWHSKN-LJQANCHMSA-N
Stdinchikey2:VOMKSBFLAZZBOW-UHFFFAOYSA-N

Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic.[9] It is mainly used to treat schizophrenia and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals.

The most frequent side effects include headache, insomnia (difficulty sleeping), sleepiness, parkinsonism (effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement), dystonia (involuntary muscle contractions), tremor (shaking), dizziness, akathisia (restlessness), agitation, anxiety, depression, increased weight, nausea, vomiting, constipation, dyspepsia (heartburn), diarrhea, dry mouth, tiredness, toothache, muscle and bone pain, back pain, asthenia (weakness), tachycardia (increased heart rate), high blood pressure, prolonged QT interval (an alteration of the electrical activity of the heart), upper respiratory tract infection (nose and throat infections) and cough.

Paliperidone was approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia in December 2006, and in the European Union in June 2007. Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.[10] It is on the World Health Organization's List of Essential Medicines.[11] Paliperidone is available as a generic medication.[12]

Medical use

In the US, paliperidone is indicated for the treatment of schizophrenia and for the treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants.

In the EU, paliperidone is indicated for the treatment of schizophrenia in adults and in adolescents fifteen years of age and older and for the treatment of schizoaffective disorder in adults.

Paliperidone is used for the treatment of schizophrenia and schizoaffective disorder.[13]

Adverse effects

The most frequent side effects include headache, insomnia (difficulty sleeping), sleepiness, parkinsonism (effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement), dystonia (involuntary muscle contractions), tremor (shaking), dizziness, akathisia (restlessness), agitation, anxiety, depression, increased weight, nausea, vomiting, constipation, dyspepsia (heartburn), diarrhea, dry mouth, tiredness, toothache, muscle and bone pain, back pain, asthenia (weakness), tachycardia (increased heart rate), high blood pressure, prolonged QT interval (an alteration of the electrical activity of the heart), upper respiratory tract infection (nose and throat infections) and cough.

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[14] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[15] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[15] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[15] Symptoms generally resolve after a short period of time.[15]

Deaths

In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone palmitate had died, out of 10,700 individuals prescribed the drug.[16] [17] [18] [19] [20] [21] [22]

Pharmacology

Paliperidone
Site Ki (nM)
617
1.1
48
278
2414
2.7
2.5
3.9
2.7
D141
D21.6
D33.5
D454[23]
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.[24] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.[25] Its efficacy is believed to result from central dopaminergic and serotonergic antagonism except Paliperidone like its parent compound functions as an inverse agonist at 5-HT2A 15. 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. 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.[26]

The half-life is 23 hours.[26]

Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort[27] [28]

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 the US,[29] and Xeplion in the EU, was approved by the FDA in July 2009.

It was initially approved in the European Union in 2007, for schizophrenia, the extended release form and use for schizoaffective disorder were approved in the EU in 2010, and extension to use in adolescents older than 15 years old was approved in 2014.[30]

Society and culture

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[31] [32] A similar prolonged release suspension was approved in 2016 by the European Medicines Agency originally under the brand name Paliperidone Janssen, later renamed to Trevicta.[33] On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.[34]

External links

Notes and References

  1. Web site: Anvisa . Brazilian Health Regulatory Agency . 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. live . https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 . August 3, 2023 . August 16, 2023 . . pt-BR . April 4, 2023.
  2. Web site: Product monograph brand safety updates . . July 7, 2016 . April 3, 2024 . March 29, 2024 . https://web.archive.org/web/20240329200203/https://www.canada.ca/en/health-canada/services/drugs-health-products/drug-products/drug-product-database/label-safety-assessment-update/product-monograph-brand-safety-updates.html . live .
  3. Web site: Invega- paliperidone tablet, extended release . DailyMed . August 19, 2020 . January 24, 2016 . https://web.archive.org/web/20160124201027/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b8e5b26-b9e4-4704-921b-3c3c0d159916 . live .
  4. Web site: Invega EPAR . European Medicines Agency . June 25, 2007 . February 1, 2024 . January 9, 2021 . https://web.archive.org/web/20210109120220/https://www.ema.europa.eu/en/medicines/human/EPAR/invega . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. Web site: Byannli EPAR . European Medicines Agency . April 28, 2020 . March 4, 2023 . March 5, 2023 . https://web.archive.org/web/20230305063354/https://www.ema.europa.eu/en/medicines/human/EPAR/byannli-previously-paliperidone-janssen-cilag-international . live .
  6. Web site: Byannli Product information . Union Register of medicinal products . March 3, 2023 . March 5, 2023 . https://web.archive.org/web/20230305063541/https://ec.europa.eu/health/documents/community-register/html/h1453.htm . live .
  7. Web site: Trevicta EPAR . European Medicines Agency . December 5, 2014 . February 1, 2024 . February 1, 2024 . https://web.archive.org/web/20240201052325/https://www.ema.europa.eu/en/medicines/human/EPAR/trevicta-previously-paliperidone-janssen . live .
  8. Web site: Xeplion EPAR . European Medicines Agency . March 4, 2011 . February 1, 2024 . February 17, 2024 . https://web.archive.org/web/20240217190902/https://www.ema.europa.eu/en/medicines/human/EPAR/xeplion . live .
  9. Chue P, Chue J . A review of paliperidone palmitate . Expert Review of Neurotherapeutics . 12 . 12 . 1383–1397 . December 2012 . 23237346 . 10.1586/ern.12.137 . 36437470 .
  10. Edinoff AN, Doppalapudi PK, Orellana C, Ochoa C, Patti S, Ghaffar Y, Cornett EM, Kaye AJ, Viswanath O, Urits I, Kaye AM, Kaye AD . Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review . Frontiers in Psychiatry . 12 . 699748 . 2021 . 34621193 . 8490677 . 10.3389/fpsyt.2021.699748 . free .
  11. Book: ((World Health Organization)) . The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) . 2023 . 10665/371090 . World Health Organization . World Health Organization . Geneva . WHO/MHP/HPS/EML/2023.02 . free .
  12. Web site: Niapelf EPAR . European Medicines Agency (EMA) . March 21, 2024 . April 5, 2024 . February 17, 2024 . https://web.archive.org/web/20240217184908/https://www.ema.europa.eu/en/medicines/human/EPAR/niapelf . live .
  13. 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 . Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis . Lancet . 382 . 9896 . 951–962 . September 2013 . 23810019 . 10.1016/S0140-6736(13)60733-3 . 32085212 .
  14. Book: BMJ Joint Formulary Committee . British National Formulary . 57 . March 2009 . Royal Pharmaceutical Society of Great Britain . United Kingdom . 978-0-85369-845-6 . 192 . 4.2.1 . 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..
  15. Book: Haddad PM, Dursun S, Deakin B . Adverse Syndromes and Psychiatric Drugs: A Clinical Guide . 2004 . OUP Oxford . 9780198527480 . 207–216 . August 28, 2020 . January 10, 2023 . https://web.archive.org/web/20230110164012/https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 . live .
  16. News: 21 users of schizophrenia drug dead . The Japan Times . The Japan Times Online . April 18, 2014 . April 21, 2014 . July 3, 2021 . https://web.archive.org/web/20210703152415/https://www.japantimes.co.jp/news/2014/04/18/national/21-users-of-schizophrenia-drug-dead/#.U1U0EcfgVQY . live .
  17. News: Schizophrénie: controverse autour d'un médicament au Japon . Médecine . April 9, 2014 . April 21, 2014 . April 22, 2014 . https://web.archive.org/web/20140422232448/http://www.lapresse.ca/sciences/medecine/201404/09/01-4755962-schizophrenie-controverse-autour-dun-medicament-au-japon.php . live .
  18. Web site: 20 minutes - Un médicament anti-schizophrénie tue . Monde . April 9, 2014 . April 21, 2014 . April 23, 2014 . https://web.archive.org/web/20140423051757/http://www.20min.ch/ro/news/monde/story/M-doc-anti-schizophr-nie-fait-17-morts-25477540 . live .
  19. Web site: Deaths reported after Xeplion injections . Life & Style . NZ Herald News . April 21, 2014 . March 4, 2016 . https://web.archive.org/web/20160304003317/http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=11235899 . dead .
  20. Web site: 17 deaths reported after schizophrenia drug injections . Japan Today: Japan News and Discussion . April 10, 2014 . April 21, 2014 . April 23, 2014 . https://web.archive.org/web/20140423055204/http://www.japantoday.com/category/national/view/17-deaths-reported-after-schizophrenia-drug-injections . live .
  21. Web site: 21 Dead in Japan From New Johnson & Johnson Antipsychotic . Mad In America . April 18, 2014 . April 21, 2014 . April 22, 2014 . https://web.archive.org/web/20140422232117/https://www.madinamerica.com/2014/04/21-dead-japan-new-antipsychotic/ . live .
  22. Web site: Schizophrenia drug blamed for 17 deaths . Sky News Australia . June 29, 2023 . April 21, 2014 . April 13, 2014 . https://web.archive.org/web/20140413192428/http://www.skynews.com.au/health/article.aspx?id=966055 . live .
  23. Gray JA, Roth BL . The pipeline and future of drug development in schizophrenia . Molecular Psychiatry . 12 . 10 . 904–922 . October 2007 . 17667958 . 10.1038/sj.mp.4002062 . 1672835 . free . November 26, 2022 . January 23, 2023 . https://web.archive.org/web/20230123010809/https://escholarship.org/uc/item/9rq494d4 . live .
  24. Web site: Paliperidone . DrugBank . November 18, 2011 . November 17, 2011 . https://web.archive.org/web/20111117205610/http://www.drugbank.ca/drugs/DB01267 . live .
  25. Corena-McLeod M . Comparative Pharmacology of Risperidone and Paliperidone . Drugs in R&D . 15 . 2 . 163–174 . June 2015 . 25943458 . 4488186 . 10.1007/s40268-015-0092-x .
  26. Web site: Paliperidone extended release: Scientific Discussion . EMA . July 16, 2007 . May 8, 2017 . May 19, 2012 . https://web.archive.org/web/20120519124924/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000746/WC500034928.pdf . dead .
  27. Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL . The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein . The International Journal of Neuropsychopharmacology . 7 . 4 . 415–419 . December 2004 . 15683552 . 10.1017/S1461145704004390 .
  28. Gurley BJ, Swain A, Williams DK, Barone G, Battu SK . 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 . July 2008 . 18214850 . 2562898 . 10.1002/mnfr.200700081 .
  29. Web site: Invega Sustenna- paliperidone palmitate injection . DailyMed . January 31, 2019 . August 19, 2020 . May 13, 2021 . https://web.archive.org/web/20210513225814/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554 . live .
  30. Web site: Procedural steps taken and scientific information after the authorisation . EMA . July 16, 2015 . May 8, 2017 . June 18, 2018 . https://web.archive.org/web/20180618050405/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/000746/WC500034930.pdf . dead .
  31. Web site: Invega Trinza (paliperidone palmitate) NDA approval letter . U.S. Food and Drug Administration . December 10, 2015 . December 22, 2015 . https://web.archive.org/web/20151222170554/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/207946Orig1s000ltr.pdf . live .
  32. Web site: Invega Trinza- paliperidone palmitate injection, suspension, extended release . DailyMed . January 31, 2019 . August 19, 2020 . June 17, 2021 . https://web.archive.org/web/20210617113151/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c39e65d7-fa44-4e4c-8b12-a654d3ed0eae . live .
  33. Web site: Trevicta (previously Paliperidone Janssen) . Summary of the European public assessment report (EPAR) for Trevicta . EMC . September 17, 2018 . January 17, 2017 . June 20, 2018 . https://web.archive.org/web/20180620172955/http://www.ema.europa.eu/ema//index.jsp?curl=pages%2Fmedicines%2Fhuman%2Fmedicines%2F004066%2Fhuman_med_001829.jsp&mid=WC0b01ac058001d124 . dead .
  34. Web site: Invega Hafyera- paliperidone palmitate injection, suspension, extended release . DailyMed . October 31, 2021 . October 20, 2021 . https://web.archive.org/web/20211020045452/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6cd61892-d2cb-434d-83ed-5c1b2c4e7a0b . live .

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