Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Paliperidone: Difference between pages

{{Short description|Antipsychotic medication}}

{{Use mdy dates|date=April 2024}}

{{cs1 config |name-list-style=vanc |display-authors=6}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 461753832

| image = Paliperidone2DACS.svg

| width = 250

| alt =

| caption =

<!-- Clinical data -->

| pronounce =

| tradename = Invega, Xeplion, Trevicta, others

| DailyMedID = Paliperidone

| pregnancy_AU = B3

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = [[Oral administration|By mouth]], [[Intramuscular injection|intramuscular]]

| class = [[Atypical antipsychotic]]

| ATC_prefix = N05

| ATC_suffix = AX13

| ATC_supplemental =

<!-- Legal status -->

| legal_AU = S4

| legal_AU_comment =

| legal_BR = C1

| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=March 31, 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=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 |archive-date=August 3, 2023 |access-date=August 16, 2023 |publisher=[[Diário Oficial da União]] |language=pt-BR |publication-date=April 4, 2023}}</ref>

| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web | title=Product monograph brand safety updates | website=[[Health Canada]] | date=July 7, 2016 | url=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 | access-date=April 3, 2024 | archive-date=March 29, 2024 | archive-url=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 | url-status=live }}</ref>

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = Rx-only

| legal_US_comment = <ref name="Invega FDA label">{{cite web | title=Invega- paliperidone tablet, extended release | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b8e5b26-b9e4-4704-921b-3c3c0d159916 | access-date=August 19, 2020 | archive-date=January 24, 2016 | archive-url=https://web.archive.org/web/20160124201027/http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b8e5b26-b9e4-4704-921b-3c3c0d159916 | url-status=live }}</ref><ref name="Invega Hafyera FDA label" /><ref name="Invega Sustenna FDA label" /><ref name="Invega Trinza FDA label" />

| legal_EU = Rx-only

| legal_EU_comment = <ref name="Invega EPAR">{{cite web | title=Invega EPAR | website=European Medicines Agency | date=June 25, 2007 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/invega | access-date=February 1, 2024 | archive-date=January 9, 2021 | archive-url=https://web.archive.org/web/20210109120220/https://www.ema.europa.eu/en/medicines/human/EPAR/invega | url-status=live }}</ref><ref name="Byannli EPAR">{{cite web | title=Byannli EPAR | website=European Medicines Agency | date=April 28, 2020 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/byannli-previously-paliperidone-janssen-cilag-international | access-date=March 4, 2023 | archive-date=March 5, 2023 | archive-url=https://web.archive.org/web/20230305063354/https://www.ema.europa.eu/en/medicines/human/EPAR/byannli-previously-paliperidone-janssen-cilag-international | url-status=live }}</ref><ref>{{cite web | title=Byannli Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1453.htm | access-date=March 3, 2023 | archive-date=March 5, 2023 | archive-url=https://web.archive.org/web/20230305063541/https://ec.europa.eu/health/documents/community-register/html/h1453.htm | url-status=live }}</ref><ref>{{cite web | title=Trevicta EPAR | website=European Medicines Agency | date=December 5, 2014 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/trevicta-previously-paliperidone-janssen | access-date=February 1, 2024 | archive-date=February 1, 2024 | archive-url=https://web.archive.org/web/20240201052325/https://www.ema.europa.eu/en/medicines/human/EPAR/trevicta-previously-paliperidone-janssen | url-status=live }}</ref><ref name="Xeplion EPAR">{{cite web | title=Xeplion EPAR | website=European Medicines Agency | date=March 4, 2011 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/xeplion | access-date=February 1, 2024 | archive-date=February 17, 2024 | archive-url=https://web.archive.org/web/20240217190902/https://www.ema.europa.eu/en/medicines/human/EPAR/xeplion | url-status=live }}</ref><ref name="Niapelf EPAR" />

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life = 23 hours (by mouth)

| duration_of_action =

| excretion = 1% unchanged in urine 18% unchanged in feces

<!-- Identifiers -->

| index2_label = as palmitate

| CAS_number2 = 199739-10-1

| CAS_supplemental =

| PubChem = 115237

| PubChem2 = 9852746

| IUPHAR_ligand =

| DrugBank2 = DBSALT001464

| ChemSpiderID2 = 8028457

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII2 = R8P8USM8FR

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG2 = D05340

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 82978

| ChEBI2 = 83807

| ChEMBL = 1621

| ChEMBL2 = 2107360

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = 9-hydroxyrisperidone; PP; PP1M; PP3M; PP6M; JNS-010; RO-92670; RO92670

<!-- Chemical and physical data -->

| 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

| SMILES = O=C/1N5/C(=N\C(=C\1CCN4CCC(c3noc2cc(F)ccc23)CC4)C)[C@H](O)CCC5

| 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

| StdInChI_comment =

| StdInChIKey2 = VOMKSBFLAZZBOW-UHFFFAOYSA-N

| density =

| density_notes =

| melting_point =

| melting_high =

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility =

| sol_units =

| specific_rotation =

'''Paliperidone''', sold under the brand name '''Invega''' among others, is an [[atypical antipsychotic]].<ref name="pmid23237346">{{cite journal | vauthors = Chue P, Chue J | title = A review of paliperidone palmitate | journal = Expert Review of Neurotherapeutics | volume = 12 | issue = 12 | pages = 1383–1397 | date = December 2012 | pmid = 23237346 | doi = 10.1586/ern.12.137 | s2cid = 36437470 }}</ref> It is mainly used to treat [[schizophrenia]] and [[schizoaffective disorder]].<ref name="pmid23237346" /> It is marketed by [[Janssen Pharmaceuticals]].<ref name="Invega FDA label" />

Paliperidone was approved by the US [[Food and Drug Administration]] (FDA) for the treatment of schizophrenia in December 2006,<ref name="Invega FDA label" /> and in the European Union in June 2007.<ref name="Invega EPAR" /> Paliperidone palmitate is a long-acting injectable formulation of paliperidone [[palmitic acid|palmitoyl]] [[ester]].<ref name="pmid23237346" /><ref name="pmid34621193">{{cite journal | vauthors = Edinoff AN, Doppalapudi PK, Orellana C, Ochoa C, Patti S, Ghaffar Y, Cornett EM, Kaye AJ, Viswanath O, Urits I, Kaye AM, Kaye AD | title = Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review | journal = Frontiers in Psychiatry | volume = 12 | issue = | pages = 699748 | date = 2021 | pmid = 34621193 | pmc = 8490677 | doi = 10.3389/fpsyt.2021.699748 | doi-access = free }}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> Paliperidone is available as a [[generic medication]].<ref name="Niapelf EPAR">{{cite web | title=Niapelf EPAR | website=[[European Medicines Agency]] (EMA) | date=March 21, 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/niapelf | access-date=April 5, 2024 | archive-date=February 17, 2024 | archive-url=https://web.archive.org/web/20240217184908/https://www.ema.europa.eu/en/medicines/human/EPAR/niapelf | url-status=live }}</ref>

==Medical use==

Paliperidone is used for the treatment of [[schizophrenia]] and [[schizoaffective disorder]].<ref name = "Leucht_2013">{{cite journal | vauthors = 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 | title = Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis | journal = Lancet | volume = 382 | issue = 9896 | pages = 951–962 | date = September 2013 | pmid = 23810019 | doi = 10.1016/S0140-6736(13)60733-3 | s2cid = 32085212 }}</ref>

==Adverse effects==

Sources:<ref name = "DrugPoint">{{cite web | publisher = Thomsen Healthcare | work = Truven Health Analytics, Inc. | title = DrugPoint System | url = http://truvenhealth.com/our-solutions/products/drugpoints | location = Greenwood Village, CO | year = 2013 | access-date = January 26, 2018 | archive-date = January 27, 2018 | archive-url = https://web.archive.org/web/20180127004613/http://truvenhealth.com/our-solutions/products/drugpoints | url-status = live }}</ref>{{Failed verification|date=February 2024}}<ref name = "TGA">{{cite web | title = Invega PRODUCT INFORMATION | publisher = Janssen Pharmaceuticals | date = 2013 | url = https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-01421-1 | access-date = September 30, 2013 | archive-date = December 15, 2018 | archive-url = https://web.archive.org/web/20181215123341/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-01421-1 | url-status = live }}</ref><ref name="Prolactin SD">{{cite journal | vauthors = Park YW, Kim Y, Lee JH | title = Antipsychotic-induced sexual dysfunction and its management | journal = The World Journal of Men's Health | volume = 30 | issue = 3 | pages = 153–159 | date = December 2012 | pmid = 23596605 | pmc = 3623530 | doi = 10.5534/wjmh.2012.30.3.153 }}</ref><ref name = "BNF">Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.</ref><ref name = "Medscape">{{cite web | title = paliperidone (Rx) - Invega, Invega Sustenna | work = Medscape Reference | url = http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4 | access-date = September 30, 2013 | archive-date = May 12, 2015 | archive-url = https://web.archive.org/web/20150512045236/http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4 | url-status = live }}</ref>

;Very Common (>10% incidence)

* Headache

* [[Tachycardia]]

* [[Somnolence]] (causes less sedation than most atypical antipsychotics)<ref name = "Leucht_2013" />

* Insomnia

* [[Hyperprolactinaemia]] (seems to cause comparable prolactin elevation to its parent drug, [[risperidone]])<ref name = "Leucht_2013" />

* [[Sexual Dysfunction]]

;Common (1–10% incidence)

* Cough

* [[Extrapyramidal symptoms|Extrapyramidal side effects]] (EPSE; e.g. [[dystonia]], [[akathisia]], muscle rigidity, [[parkinsonism]]. It appears to produce similar EPSE to [[risperidone]], [[asenapine]] and [[ziprasidone]] and more EPSE than [[olanzapine]], [[clozapine]], [[aripiprazole]], [[quetiapine]], [[amisulpride]] and [[sertindole]])<ref name = "Leucht_2013" />

* [[Orthostatic hypotension]]

* Weight gain (tends to produce a moderate degree of weight gain, possibly related to its potent blockade of the 5-HT_2C receptor)

* [[Long QT syndrome|QT interval prolongation]] (tends to produce less [[QT interval]] prolongation than most other atypical antipsychotics and approximately as much QT interval prolongation as [[aripiprazole]] and [[lurasidone]])<ref name = "Leucht_2013" />

* [[Common cold|Nasopharyngitis]]

* [[Anxiety]]

* Indigestion

* Constipation

* [[Infertility]]

===Discontinuation===

The [[British National Formulary]] recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.<ref name="Group 2009 192">{{cite book | editor = BMJ Joint Formulary Committee | title = British National Formulary | edition = 57 | date = March 2009 |publisher=Royal Pharmaceutical Society of Great Britain |location=United Kingdom |isbn=978-0-85369-845-6 |page=192 |chapter=4.2.1 |quote=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.}}</ref> Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.<ref name=Had2004>{{cite book |vauthors=Haddad PM, Dursun S, Deakin B |title=Adverse Syndromes and Psychiatric Drugs: A Clinical Guide |date=2004 |publisher=OUP Oxford |isbn=9780198527480 |pages=207–216 |url=https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |access-date=August 28, 2020 |archive-date=January 10, 2023 |archive-url=https://web.archive.org/web/20230110164012/https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207 |url-status=live }}</ref> Other symptoms may include restlessness, increased sweating, and trouble sleeping.<ref name=Had2004/> Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.<ref name=Had2004/> Symptoms generally resolve after a short period of time.<ref name=Had2004/>

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.<ref>{{cite journal | vauthors = Moncrieff J | title = Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse | journal = Acta Psychiatrica Scandinavica | volume = 114 | issue = 1 | pages = 3–13 | date = July 2006 | pmid = 16774655 | doi = 10.1111/j.1600-0447.2006.00787.x | s2cid = 6267180 }}</ref> It may also result in reoccurrence of the condition that is being treated.<ref>{{cite book |vauthors=Sacchetti E, Vita A, Siracusano A, Fleischhacker W |title=Adherence to Antipsychotics in Schizophrenia |date=2013 |publisher=Springer Science & Business Media |isbn=9788847026797 |page=85 |url=https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |access-date=August 28, 2020 |archive-date=January 10, 2023 |archive-url=https://web.archive.org/web/20230110164029/https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85 |url-status=live }}</ref> Rarely tardive dyskinesia can occur when the medication is stopped.<ref name=Had2004/>

===Deaths===

In April 2014, it was reported that 21 [[Japan]]ese people who had received shots of the long-acting injectable [[paliperidone palmitate]] to date had died, out of 10,700 individuals prescribed the drug.<ref>{{cite news | url = http://www.japantimes.co.jp/news/2014/04/18/national/21-users-of-schizophrenia-drug-dead/#.U1U0EcfgVQY | title = 21 users of schizophrenia drug dead | publisher = The Japan Times | newspaper = The Japan Times Online | date = April 18, 2014 | access-date = April 21, 2014 | archive-date = July 3, 2021 | archive-url = https://web.archive.org/web/20210703152415/https://www.japantimes.co.jp/news/2014/04/18/national/21-users-of-schizophrenia-drug-dead/#.U1U0EcfgVQY | url-status = live }}</ref><ref>{{cite news | url = http://www.lapresse.ca/sciences/medecine/201404/09/01-4755962-schizophrenie-controverse-autour-dun-medicament-au-japon.php | title = Schizophrénie: controverse autour d'un médicament au Japon | work = Médecine | date = April 9, 2014 | access-date = April 21, 2014 | archive-date = April 22, 2014 | archive-url = https://web.archive.org/web/20140422232448/http://www.lapresse.ca/sciences/medecine/201404/09/01-4755962-schizophrenie-controverse-autour-dun-medicament-au-japon.php | url-status = live }}</ref><ref>{{cite web | url = http://www.20min.ch/ro/news/monde/story/M-doc-anti-schizophr-nie-fait-17-morts-25477540 | title = 20 minutes - Un médicament anti-schizophrénie tue | work = Monde | date = April 9, 2014 | access-date = April 21, 2014 | archive-date = April 23, 2014 | archive-url = https://web.archive.org/web/20140423051757/http://www.20min.ch/ro/news/monde/story/M-doc-anti-schizophr-nie-fait-17-morts-25477540 | url-status = live }}</ref><ref>{{cite web | url = http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=11235899 | title = Deaths reported after Xeplion injections | work = Life & Style | publisher = NZ Herald News | access-date = April 21, 2014 | archive-date = March 4, 2016 | archive-url = https://web.archive.org/web/20160304003317/http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=11235899 | url-status = dead }}</ref><ref>{{cite web | url = http://www.japantoday.com/category/national/view/17-deaths-reported-after-schizophrenia-drug-injections | title = 17 deaths reported after schizophrenia drug injections | work = Japan Today: Japan News and Discussion | date = April 10, 2014 | access-date = April 21, 2014 | archive-date = April 23, 2014 | archive-url = https://web.archive.org/web/20140423055204/http://www.japantoday.com/category/national/view/17-deaths-reported-after-schizophrenia-drug-injections | url-status = live }}</ref><ref>{{cite web | url = https://www.madinamerica.com/2014/04/21-dead-japan-new-antipsychotic/ | title = 21 Dead in Japan From New Johnson & Johnson Antipsychotic | work = Mad In America | date = April 18, 2014 | access-date = April 21, 2014 | archive-date = April 22, 2014 | archive-url = https://web.archive.org/web/20140422232117/https://www.madinamerica.com/2014/04/21-dead-japan-new-antipsychotic/ | url-status = live }}</ref><ref>{{cite web | url = http://www.skynews.com.au/health/article.aspx?id=966055 | title = Schizophrenia drug blamed for 17 deaths | work = Sky News Australia | date = June 29, 2023 | access-date = April 21, 2014 | archive-date = April 13, 2014 | archive-url = https://web.archive.org/web/20140413192428/http://www.skynews.com.au/health/article.aspx?id=966055 | url-status = live }}</ref>

==Pharmacology==

{| class="wikitable floatright" style="font-size:small;"

|+ Paliperidone<ref name="Corena-McLeod_2015" />

|-

! Site !! K_i (nM)

|-

| [[5-HT1A receptor|5-HT_1A]] || 617

|-

| [[5-HT2A receptor|5-HT_2A]] || 1.1

|-

| [[5-HT2C receptor|5-HT_2C]] || 48

|-

| [[5-HT5A receptor|5-HT_5A]] || 278

|-

| [[5-HT6 receptor|5-HT₆]] || 2414

|-

| [[5-HT7 receptor|5-HT₇]] || 2.7

|-

| [[Alpha-1A adrenergic receptor|α_1A]] || 2.5

|-

| [[Alpha-2A adrenergic receptor|α_2A]] || 3.9

|-

| [[Alpha-2C adrenergic receptor|α_2C]] || 2.7

|-

| [[Dopamine receptor D1|D₁]]|| 41

|-

| [[Dopamine receptor D2|D₂]]|| 1.6

|-

| [[Dopamine receptor D3|D₃]]|| 3.5

|-

| [[Dopamine receptor D4|D₄]]|| 54<ref>{{cite journal | vauthors = Gray JA, Roth BL | title = The pipeline and future of drug development in schizophrenia | journal = Molecular Psychiatry | volume = 12 | issue = 10 | pages = 904–922 | date = October 2007 | pmid = 17667958 | doi = 10.1038/sj.mp.4002062 | s2cid = 1672835 | url = http://www.escholarship.org/uc/item/9rq494d4 | doi-access = free | access-date = November 26, 2022 | archive-date = January 23, 2023 | archive-url = https://web.archive.org/web/20230123010809/https://escholarship.org/uc/item/9rq494d4 | url-status = live }}</ref>

|-

| [[Dopamine receptor D5|D₅]]|| 29

|-

| [[Histamine H1 receptor|H₁]]|| 19

|-

| [[Histamine H2 receptor|H₂]]|| 121

|-

| [[Muscarinic acetylcholine receptor|mACh]]|| >10,000

|-

| Values are K_i (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]].<ref name="DrugBank">{{cite web | url = http://www.drugbank.ca/drugs/DB01267 | title = Paliperidone | work = DrugBank | access-date = November 18, 2011 | archive-date = November 17, 2011 | archive-url = https://web.archive.org/web/20111117205610/http://www.drugbank.ca/drugs/DB01267 | url-status = live }}</ref>{{Unreliable medical source|date=February 2024}} While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.<ref name="Corena-McLeod_2015">{{cite journal | vauthors = Corena-McLeod M | title = Comparative Pharmacology of Risperidone and Paliperidone | journal = Drugs in R&D | volume = 15 | issue = 2 | pages = 163–174 | date = June 2015 | pmid = 25943458 | pmc = 4488186 | doi = 10.1007/s40268-015-0092-x }}</ref> Its efficacy is believed to result from central [[dopamine antagonist|dopaminergic]] and [[5-HT2A receptor|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.<ref name="DrugBank" /> 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.<ref name=EMA-InvegaOriginalSA>{{cite web | title = Paliperidone extended release: Scientific Discussion | url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000746/WC500034928.pdf | publisher = EMA | date = July 16, 2007 | access-date = May 8, 2017 | archive-date = May 19, 2012 | archive-url = https://web.archive.org/web/20120519124924/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000746/WC500034928.pdf | url-status = dead }}</ref>

The half-life is 23 hours.<ref name=EMA-InvegaOriginalSA/>

[[Risperidone]] and its metabolite paliperidone are reduced in efficacy by [[P-glycoprotein]] [[Enzyme induction and inhibition|inducers]] such as [[St John's wort]]<ref>{{cite journal | vauthors = Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL | title = The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein | journal = The International Journal of Neuropsychopharmacology | volume = 7 | issue = 4 | pages = 415–419 | date = December 2004 | pmid = 15683552 | doi = 10.1017/S1461145704004390 | doi-access = }}</ref><ref>{{cite journal | vauthors = Gurley BJ, Swain A, Williams DK, Barone G, Battu SK | title = 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 | journal = Molecular Nutrition & Food Research | volume = 52 | issue = 7 | pages = 772–779 | date = July 2008 | pmid = 18214850 | pmc = 2562898 | doi = 10.1002/mnfr.200700081 }}</ref>

{{Pharmacokinetics of long-acting injectable antipsychotics}}

==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,<ref name="Invega Sustenna FDA label">{{cite web | title=Invega Sustenna- paliperidone palmitate injection | website=DailyMed | date=January 31, 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554 | access-date=August 19, 2020 | archive-date=May 13, 2021 | archive-url=https://web.archive.org/web/20210513225814/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554 | url-status=live }}</ref> and Xeplion in the EU,<ref name="Xeplion EPAR" /> 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.<ref name=EMAhistory>{{cite web | title = Procedural steps taken and scientific information after the authorisation | url = http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/000746/WC500034930.pdf | publisher = EMA | date = July 16, 2015 | access-date = May 8, 2017 | archive-date = June 18, 2018 | archive-url = 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 | url-status = dead }}</ref>

== Society and culture ==

=== Brand names ===

In May 2015, a formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.<ref>{{cite web | title = Invega Trinza (paliperidone palmitate) NDA approval letter | url = http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/207946Orig1s000ltr.pdf | website = U.S. Food and Drug Administration | access-date = December 10, 2015 | archive-date = December 22, 2015 | archive-url = https://web.archive.org/web/20151222170554/http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/207946Orig1s000ltr.pdf | url-status = live }}</ref><ref name="Invega Trinza FDA label">{{cite web | title=Invega Trinza- paliperidone palmitate injection, suspension, extended release | website=DailyMed | date=January 31, 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c39e65d7-fa44-4e4c-8b12-a654d3ed0eae | access-date=August 19, 2020 | archive-date=June 17, 2021 | archive-url=https://web.archive.org/web/20210617113151/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c39e65d7-fa44-4e4c-8b12-a654d3ed0eae | url-status=live }}</ref> 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.<ref>{{cite web | url = http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004066/human_med_001829.jsp&mid=WC0b01ac058001d124 | title = Trevicta (previously Paliperidone Janssen) | work = Summary of the European public assessment report (EPAR) for Trevicta | publisher = EMC | date = September 17, 2018 | access-date = January 17, 2017 | archive-date = June 20, 2018 | archive-url = 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 | url-status = dead }}</ref> On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.<ref name="Invega Hafyera FDA label">{{cite web | title=Invega Hafyera- paliperidone palmitate injection, suspension, extended release | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6cd61892-d2cb-434d-83ed-5c1b2c4e7a0b | access-date=October 31, 2021 | archive-date=October 20, 2021 | archive-url=https://web.archive.org/web/20211020045452/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6cd61892-d2cb-434d-83ed-5c1b2c4e7a0b | url-status=live }}</ref>

== References ==

{{reflist}}

== External links ==

* {{cite web | title=Paliperidone Injection | website=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a615032.html }}

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