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Paliperidone is the primary active metabolite of the older antipsychotic [[risperidone]].<ref>{{cite web|url=http://www.drugbank.ca/drugs/DB01267 | title = Paliperidone | work = The DrugBank database }}</ref> 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]]. 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.
Paliperidone is the primary active metabolite of the older antipsychotic [[risperidone]].<ref>{{cite web|url=http://www.drugbank.ca/drugs/DB01267 | title = Paliperidone | work = The DrugBank database }}</ref> 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. 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.
[[File:Risperidone and Paliperidone comparison.jpg | frameless|220x124px | right | risperidone and paliperidone in pharmacokinetics]]
[[File:Risperidone and Paliperidone comparison.jpg | frameless|220x124px | right | risperidone and paliperidone in pharmacokinetics]]
<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 }}</ref>
<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 }}</ref>

Revision as of 15:20, 16 November 2023

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 (OROS tablets), 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 Edit this at Wikidata
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 trade name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder.

It is marketed by Janssen Pharmaceuticals. An extended release formulation is available that uses the OROS extended release system to allow for once-daily dosing. Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.

It is on the World Health Organization's List of Essential Medicines.[4]

Medical use

It is used for the treatment of schizophrenia and schizoaffective disorder.[5]

Adverse effects

Sources:[6][7][8][9][10]

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.[11] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[12] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[12] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[12] Symptoms generally resolve after a short period of time.[12]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[13] It may also result in reoccurrence of the condition that is being treated.[14] Rarely tardive dyskinesia can occur when the medication is stopped.[12]

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.[15][16][17][18][19][20][21]

Pharmacology

Paliperidone[22]
Site Ki (nM)
5-HT1A 617
5-HT2A 1.1
5-HT2C 48
5-HT5A 278
5-HT6 2414
5-HT7 2.7
α1A 2.5
α2A 3.9
α2C 2.7
D1 41
D2 1.6
D3 3.5
D4 54[23]
D5 29
H1 19
H2 121
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.[22] 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. 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

[25]

The half-life is 23 hours.[25]

Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort[26][27]

Pharmacokinetics of long-acting injectable antipsychotics
Medication Brand name Class Vehicle Dosage Tmax t1/2 single t1/2 multiple logPc Ref
Aripiprazole lauroxil Aristada Atypical Watera 441–1064 mg/4–8 weeks 24–35 days ? 54–57 days 7.9–10.0
Aripiprazole monohydrate Abilify Maintena Atypical Watera 300–400 mg/4 weeks 7 days ? 30–47 days 4.9–5.2
Bromperidol decanoate Impromen Decanoas Typical Sesame oil 40–300 mg/4 weeks 3–9 days ? 21–25 days 7.9 [28]
Clopentixol decanoate Sordinol Depot Typical Viscoleob 50–600 mg/1–4 weeks 4–7 days ? 19 days 9.0 [29]
Flupentixol decanoate Depixol Typical Viscoleob 10–200 mg/2–4 weeks 4–10 days 8 days 17 days 7.2–9.2 [29][30]
Fluphenazine decanoate Prolixin Decanoate Typical Sesame oil 12.5–100 mg/2–5 weeks 1–2 days 1–10 days 14–100 days 7.2–9.0 [31][32][33]
Fluphenazine enanthate Prolixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks 2–3 days 4 days ? 6.4–7.4 [32]
Fluspirilene Imap, Redeptin Typical Watera 2–12 mg/1 week 1–8 days 7 days ? 5.2–5.8 [34]
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks 3–9 days 18–21 days 7.2–7.9 [35][36]
Olanzapine pamoate Zyprexa Relprevv Atypical Watera 150–405 mg/2–4 weeks 7 days ? 30 days –
Oxyprothepin decanoate Meclopin Typical ? ? ? ? ? 8.5–8.7
Paliperidone palmitate Invega Sustenna Atypical Watera 39–819 mg/4–12 weeks 13–33 days 25–139 days ? 8.1–10.1
Perphenazine decanoate Trilafon Dekanoat Typical Sesame oil 50–200 mg/2–4 weeks ? ? 27 days 8.9
Perphenazine enanthate Trilafon Enanthate Typical Sesame oil 25–200 mg/2 weeks 2–3 days ? 4–7 days 6.4–7.2 [37]
Pipotiazine palmitate Piportil Longum Typical Viscoleob 25–400 mg/4 weeks 9–10 days ? 14–21 days 8.5–11.6 [30]
Pipotiazine undecylenate Piportil Medium Typical Sesame oil 100–200 mg/2 weeks ? ? ? 8.4
Risperidone Risperdal Consta Atypical Microspheres 12.5–75 mg/2 weeks 21 days ? 3–6 days –
Zuclopentixol acetate Clopixol Acuphase Typical Viscoleob 50–200 mg/1–3 days 1–2 days 1–2 days 4.7–4.9
Zuclopentixol decanoate Clopixol Depot Typical Viscoleob 50–800 mg/2–4 weeks 4–9 days ? 11–21 days 7.5–9.0
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.[38]

Brand names

On May 18, 2015, a new formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[39] 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.[40] 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. ^ "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.
  2. ^ 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.
  3. ^ "Invega- paliperidone tablet, extended release". DailyMed. Retrieved August 19, 2020.
  4. ^ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
  5. ^ a b c d e 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.
  6. ^ "DrugPoint® System". Truven Health Analytics, Inc. Greenwood Village, CO: Thomsen Healthcare. 2013.
  7. ^ "INVEGA® PRODUCT INFORMATION". Janssen Pharmaceuticals. 2013.
  8. ^ 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.
  9. ^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  10. ^ "paliperidone (Rx) - Invega, Invega Sustenna". Medscape Reference.
  11. ^ 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.
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  34. ^ Janssen PA, Niemegeers CJ, Schellekens KH, Lenaerts FM, Verbruggen FJ, van Nueten JM, Marsboom RH, Hérin VV, Schaper WK (November 1970). "The pharmacology of fluspirilene (R 6218), a potent, long-acting and injectable neuroleptic drug". Arzneimittel-Forschung. 20 (11): 1689–98. PMID 4992598.
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  36. ^ 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.
  37. ^ 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.
  38. ^ "Procedural steps taken and scientific information after the authorisation" (PDF). EMA. July 16, 2015.
  39. ^ "Invega Trinza (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved December 10, 2015.
  40. ^ "Trevicta (previously Paliperidone Janssen)". Summary of the European public assessment report (EPAR) for Trevicta. EMC. September 17, 2018.
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