Paliperidone

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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
  • (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
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

  • 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
 ☒NcheckY (what is this?)  (verify)

Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic.[12] It is mainly used to treat schizophrenia and schizoaffective disorder.[12] It is marketed by Janssen Pharmaceuticals.[3]

Paliperidone was approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia in December 2006.[3] Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.[12][13] It is on the World Health Organization's List of Essential Medicines.[14]

Medical use

Paliperidone is used for the treatment of schizophrenia and schizoaffective disorder.[15]

Adverse effects

Sources:[16][failed verification][17][18][19][20]

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.[21] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[22] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[22] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[22] Symptoms generally resolve after a short period of time.[22]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[23] It may also result in reoccurrence of the condition that is being treated.[24] Rarely tardive dyskinesia can occur when the medication is stopped.[22]

Deaths

In April 2014, it was reported that 21

paliperidone palmitate to date had died, out of 10,700 individuals prescribed the drug.[25][26][27][28][29][30][31]

Pharmacology

Paliperidone[32]
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[33]
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.[34][unreliable medical source?] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.[32] 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.[34] 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.[35]

The half-life is 23 hours.[35]

St John's wort[36][37]

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 [38]
Clopentixol decanoate
Sordinol Depot Typical Viscoleob 50–600 mg/1–4 weeks 4–7 days ? 19 days 9.0 [39]
Flupentixol decanoate
Depixol Typical Viscoleob 10–200 mg/2–4 weeks 4–10 days 8 days 17 days 7.2–9.2 [39][40]
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 [41][42][43]
Fluphenazine enanthate
Prolixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks 2–3 days 4 days ? 6.4–7.4 [42]
Fluspirilene Imap, Redeptin Typical Watera 2–12 mg/1 week 1–8 days 7 days ? 5.2–5.8 [44]
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks 3–9 days 18–21 days 7.2–7.9 [45][46]
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 [47]
Pipotiazine palmitate
Piportil Longum Typical Viscoleob 25–400 mg/4 weeks 9–10 days ? 14–21 days 8.5–11.6 [40]
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
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 the US,[5] and Xeplion in the EU,[11] 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.[48]

Society and culture

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[49] [6] 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.[50] On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.[4]

References

  1. 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. ^ a b c "Invega- paliperidone tablet, extended release". DailyMed. Retrieved August 19, 2020.
  4. ^ a b "Invega Hafyera- paliperidone palmitate injection, suspension, extended release". DailyMed. Retrieved October 31, 2021.
  5. ^ a b "Invega Sustenna- paliperidone palmitate injection". DailyMed. January 31, 2019. Retrieved August 19, 2020.
  6. ^ a b "Invega Trinza- paliperidone palmitate injection, suspension, extended release". DailyMed. January 31, 2019. Retrieved August 19, 2020.
  7. ^ "Invega EPAR". European Medicines Agency. June 25, 2007. Retrieved February 1, 2024.
  8. ^ "Byannli EPAR". European Medicines Agency. April 28, 2020. Retrieved March 4, 2023.
  9. ^ "Byannli Product information". Union Register of medicinal products. Retrieved March 3, 2023.
  10. ^ "Trevicta EPAR". European Medicines Agency. December 5, 2014. Retrieved February 1, 2024.
  11. ^ a b "Xeplion EPAR". European Medicines Agency. March 4, 2011. Retrieved February 1, 2024.
  12. ^
    S2CID 36437470
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  14. . WHO/MHP/HPS/EML/2023.02.
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  16. ^ "DrugPoint System". Truven Health Analytics, Inc. Greenwood Village, CO: Thomsen Healthcare. 2013.
  17. ^ "Invega PRODUCT INFORMATION". Janssen Pharmaceuticals. 2013.
  18. PMID 23596605
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  19. ^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  20. ^ "paliperidone (Rx) - Invega, Invega Sustenna". Medscape Reference.
  21. . 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.
  22. ^ .
  23. .
  24. .
  25. ^ "21 users of schizophrenia drug dead". The Japan Times Online. The Japan Times. April 18, 2014.
  26. ^ "Schizophrénie: controverse autour d'un médicament au Japon". Médecine. April 9, 2014.
  27. ^ "20 minutes - Un médicament anti-schizophrénie tue". Monde. April 9, 2014.
  28. ^ "Deaths reported after Xeplion injections". Life & Style. NZ Herald News. Archived from the original on March 4, 2016. Retrieved April 21, 2014.
  29. ^ "17 deaths reported after schizophrenia drug injections". Japan Today: Japan News and Discussion. April 10, 2014.
  30. ^ "21 Dead in Japan From New Johnson & Johnson Antipsychotic". Mad In America. April 18, 2014.
  31. ^ "Schizophrenia drug blamed for 17 deaths". Sky News Australia. June 29, 2023.
  32. ^
    PMID 25943458
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  34. ^ a b "Paliperidone". DrugBank.
  35. ^ a b "Paliperidone extended release: Scientific Discussion" (PDF). EMA. July 16, 2007. Archived from the original (PDF) on May 19, 2012. Retrieved May 8, 2017.
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  38. ^ 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.
  39. ^
    PMID 6931472
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  40. ^ a b Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
  41. PMID 6143748
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  43. ^ 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.
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  47. ^ 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.
  48. ^ "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.
  49. ^ "Invega Trinza (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved December 10, 2015.
  50. ^ "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