Misplaced Pages

Paliperidone

Article snapshot taken from Wikipedia with creative commons attribution-sharealike license. Give it a read and then ask your questions in the chat. We can research this topic together.
(Redirected from Xeplion) Antipsychotic medication

Pharmaceutical compound
Paliperidone
Clinical data
Trade namesInvega, Xeplion, Trevicta, others
Other names9-hydroxyrisperidone; PP; PP1M; PP3M; PP6M; JNS-010; RO-92670; RO92670
AHFS/Drugs.comMonograph
MedlinePlusa607005
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth, intramuscular
Drug classAtypical antipsychotic
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
IUPAC name
  • (RS)-3-ethyl]-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyridopyrimidin-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
3D model (JSmol)
SMILES
  • O=C/1N5/C(=N\C(=C\1CCN4CCC(c3noc2cc(F)ccc23)CC4)C)(O)CCC5
InChI
  • 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
  • Key:PMXMIIMHBWHSKN-LJQANCHMSA-N

  • as palmitate: InChI=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
  • Key:VOMKSBFLAZZBOW-UHFFFAOYSA-N
  (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 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. It is on the World Health Organization's List of Essential Medicines. Paliperidone is available as a generic medication.

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.

Adverse effects

The most frequent side effects include headache, insomnia, 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.

A 2023 study found that paliperidone may worsen verbal learning and memory compared to placebo in the early months of psychosis treatment.

Discontinuation

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

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.

Pharmacology

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

The half-life is 23 hours.

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

Pharmacokinetics of long-acting injectable antipsychotics
Medication Brand name Class Vehicle Dosage Tmax t1/2 single t1/2 multiple logP Ref
Aripiprazole lauroxil Aristada Atypical Water 441–1064 mg/4–8 weeks 24–35 days ? 54–57 days 7.9–10.0
Aripiprazole monohydrate Abilify Maintena Atypical Water 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
Clopentixol decanoate Sordinol Depot Typical Viscoleo 50–600 mg/1–4 weeks 4–7 days ? 19 days 9.0
Flupentixol decanoate Depixol Typical Viscoleo 10–200 mg/2–4 weeks 4–10 days 8 days 17 days 7.2–9.2
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
Fluphenazine enanthate Prolixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks 2–3 days 4 days ? 6.4–7.4
Fluspirilene Imap, Redeptin Typical Water 2–12 mg/1 week 1–8 days 7 days ? 5.2–5.8
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks 3–9 days 18–21 days 7.2–7.9
Olanzapine pamoate Zyprexa Relprevv Atypical Water 150–405 mg/2–4 weeks 7 days ? 30 days –
Oxyprothepin decanoate Meclopin Typical ? ? ? ? ? 8.5–8.7
Paliperidone palmitate Invega Sustenna Atypical Water 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
Pipotiazine palmitate Piportil Longum Typical Viscoleo 25–400 mg/4 weeks 9–10 days ? 14–21 days 8.5–11.6
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 Viscoleo 50–200 mg/1–3 days 1–2 days 1–2 days 4.7–4.9
Zuclopentixol decanoate Clopixol Depot Typical Viscoleo 50–800 mg/2–4 weeks 4–9 days ? 11–21 days 7.5–9.0
Note: All by intramuscular injection. Footnotes: = Microcrystalline or nanocrystalline aqueous suspension. = Low-viscosity vegetable oil (specifically fractionated coconut oil with medium-chain triglycerides). = Predicted, from PubChem and DrugBank. Sources: Main: See template.
Paliperidone
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
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.

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, 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.

Society and culture

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza. 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. On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.

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. "Product monograph brand safety updates". Health Canada. July 7, 2016. Archived from the original on March 29, 2024. Retrieved April 3, 2024.
  4. ^ "Invega- paliperidone tablet, extended release". DailyMed. Archived from the original on January 24, 2016. Retrieved August 19, 2020.
  5. ^ "Invega Hafyera- paliperidone palmitate injection, suspension, extended release". DailyMed. Archived from the original on October 20, 2021. Retrieved October 31, 2021.
  6. ^ "Invega Sustenna- paliperidone palmitate injection". DailyMed. January 31, 2019. Archived from the original on May 13, 2021. Retrieved August 19, 2020.
  7. ^ "Invega Trinza- paliperidone palmitate injection, suspension, extended release". DailyMed. January 31, 2019. Archived from the original on June 17, 2021. Retrieved August 19, 2020.
  8. ^ "Invega EPAR". European Medicines Agency. June 25, 2007. Archived from the original on January 9, 2021. Retrieved February 1, 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. "Byannli EPAR". European Medicines Agency. April 28, 2020. Archived from the original on March 5, 2023. Retrieved March 4, 2023.
  10. "Byannli Product information". Union Register of medicinal products. Archived from the original on March 5, 2023. Retrieved March 3, 2023.
  11. "Trevicta EPAR". European Medicines Agency. December 5, 2014. Archived from the original on February 1, 2024. Retrieved February 1, 2024.
  12. ^ "Xeplion EPAR". European Medicines Agency. March 4, 2011. Archived from the original on February 17, 2024. Retrieved February 1, 2024.
  13. ^ "Niapelf EPAR". European Medicines Agency (EMA). March 21, 2024. Archived from the original on February 17, 2024. Retrieved April 5, 2024.
  14. ^ Chue P, Chue J (December 2012). "A review of paliperidone palmitate". Expert Review of Neurotherapeutics. 12 (12): 1383–1397. doi:10.1586/ern.12.137. PMID 23237346. S2CID 36437470.
  15. Edinoff AN, Doppalapudi PK, Orellana C, Ochoa C, Patti S, Ghaffar Y, et al. (2021). "Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review". Frontiers in Psychiatry. 12: 699748. doi:10.3389/fpsyt.2021.699748. PMC 8490677. PMID 34621193.
  16. 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.
  17. 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.
  18. Allott K, Yuen HP, Baldwin L, O'Donoghue B, Fornito A, Chopra S, et al. (June 2023). "Effects of risperidone/paliperidone versus placebo on cognitive functioning over the first 6 months of treatment for psychotic disorder: secondary analysis of a triple-blind randomised clinical trial". Translational Psychiatry. 13 (1): 199. doi:10.1038/s41398-023-02501-7. PMC 10257667. PMID 37301832.
  19. 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.
  20. ^ Haddad PM, Dursun S, Deakin B (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. pp. 207–216. ISBN 9780198527480. Archived from the original on January 10, 2023. Retrieved August 28, 2020.
  21. "21 users of schizophrenia drug dead". The Japan Times Online. The Japan Times. April 18, 2014. Archived from the original on July 3, 2021. Retrieved April 21, 2014.
  22. "Schizophrénie: controverse autour d'un médicament au Japon". Médecine. April 9, 2014. Archived from the original on April 22, 2014. Retrieved April 21, 2014.
  23. "20 minutes - Un médicament anti-schizophrénie tue". Monde. April 9, 2014. Archived from the original on April 23, 2014. Retrieved April 21, 2014.
  24. "Deaths reported after Xeplion injections". Life & Style. NZ Herald News. Archived from the original on March 4, 2016. Retrieved April 21, 2014.
  25. "17 deaths reported after schizophrenia drug injections". Japan Today: Japan News and Discussion. April 10, 2014. Archived from the original on April 23, 2014. Retrieved April 21, 2014.
  26. "21 Dead in Japan From New Johnson & Johnson Antipsychotic". Mad In America. April 18, 2014. Archived from the original on April 22, 2014. Retrieved April 21, 2014.
  27. "Schizophrenia drug blamed for 17 deaths". Sky News Australia. June 29, 2023. Archived from the original on April 13, 2014. Retrieved April 21, 2014.
  28. ^ "Paliperidone". DrugBank. Archived from the original on November 17, 2011. Retrieved November 18, 2011.
  29. ^ 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.
  30. ^ "Paliperidone extended release: Scientific Discussion" (PDF). EMA. July 16, 2007. Archived from the original (PDF) on May 19, 2012. Retrieved May 8, 2017.
  31. 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.
  32. 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.
  33. 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.
  34. ^ 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.
  35. ^ Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
  36. 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.
  37. ^ 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.
  38. 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.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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. Archived from the original on January 23, 2023. Retrieved November 26, 2022.
  44. "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.
  45. "Invega Trinza (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Archived (PDF) from the original on December 22, 2015. Retrieved December 10, 2015.
  46. "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.

External links

Antipsychotics (N05A)
Typical
Disputed
Atypical
Others
Mood stabilizers
Anticonvulsants
Atypical antipsychotics
Others
Pharmacodynamics
Adrenergic receptor modulators
α1
Agonists
Antagonists
α2
Agonists
Antagonists
β
Agonists
Antagonists
Dopamine receptor modulators
D1-like
Agonists
PAMs
Antagonists
D2-like
Agonists
Antagonists
Histamine receptor modulators
H1
Agonists
Antagonists
H2
Agonists
Antagonists
H3
Agonists
Antagonists
H4
Agonists
Antagonists
See also
Receptor/signaling modulators
Monoamine metabolism modulators
Monoamine reuptake inhibitors
Serotonin receptor modulators
5-HT1
5-HT1A
5-HT1B
5-HT1D
5-HT1E
5-HT1F
5-HT2
5-HT2A
5-HT2B
5-HT2C
5-HT3–7
5-HT3
5-HT4
5-HT5A
5-HT6
5-HT7
Portal: Categories: