Paliperidone

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Paliperidone
Clinical data
Trade namesInvega, 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)
SMILES
  • 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.[13] It is used for the treatment of schizophrenia and schizoaffective disorder.[13][14] It is marketed by Janssen Pharmaceuticals.[3]

Paliperidone was approved by the US

generic medication.[12]

Medical use

In the United States, 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.[3]

In the European Union, 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.[7]

Paliperidone is used for the treatment of schizophrenia and schizoaffective disorder.[14]

Adverse effects

The most common 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, weight gain, 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.[7]

A 2023 study found that paliperidone may worsen verbal learning and memory compared to placebo in the early months of psychosis treatment.[17]

Other symptoms may include restlessness, increased sweating, and trouble sleeping.[18] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[18]

Pharmacology

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.[19][unreliable medical source?] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.[20] Its efficacy is believed to result from central dopaminergic and serotonergic antagonism except paliperidone, like its parent compound risperidone, functions as an inverse agonist at 5-HT2A 15. Paliperidone also acts as an antagonist of alpha-1 and alpha-2 adrenergic receptors as well as H1 histaminergic receptors.[19] 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 tract, resulting in increased absorption.[21]

St John's wort[22][23]

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 [24]
Clopentixol decanoate
 Sordinol Depot Typical Viscoleob 50–600 mg/1–4 weeks 4–7 days ? 19 days 9.0 [25]
Flupentixol decanoate
 Depixol Typical Viscoleob 10–200 mg/2–4 weeks 4–10 days 8 days 17 days 7.2–9.2 [25][26]
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 [27][28][29]
Fluphenazine enanthate
 Prolixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks 2–3 days 4 days ? 6.4–7.4 [28]
Fluspirilene Imap, Redeptin Typical Watera 2–12 mg/1 week 1–8 days 7 days ? 5.2–5.8 [30]
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks 3–9 days 18–21 days 7.2–7.9 [31][32]
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 [33]
Pipotiazine palmitate
 Piportil Longum Typical Viscoleob 25–400 mg/4 weeks 9–10 days ? 14–21 days 8.5–11.6 [26]
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.
Paliperidone[20]
Site Ki (nM)
5-HT1A 6.17
5-HT2A 1
5-HT2C 48
5-HT6 24
5-HT7 2.7
α1A 2.5
α2A 3.9
α2C 2.7
D1 41
D2 1.6
D3 3.5
D4 54[34]
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 US 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.[35]

Society and culture

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.[36][37][38][39][40][41][42][excessive citations
]

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the US Food and Drug Administration under the brand name Invega Trinza.[43][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.[44] In September 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.[4]

References

  1. ^ 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.
  2. ^ "Product monograph brand safety updates". Health Canada. July 7, 2016. Archived from the original on March 29, 2024. Retrieved April 3, 2024.
  3. ^ a b c d "Invega- paliperidone tablet, extended release". DailyMed. Archived from the original on January 24, 2016. Retrieved August 19, 2020.
  4. ^ a b "Invega Hafyera- paliperidone palmitate injection, suspension, extended release". DailyMed. Archived from the original on October 20, 2021. Retrieved October 31, 2021.
  5. ^ a b "Invega Sustenna- paliperidone palmitate injection". DailyMed. January 31, 2019. Archived from the original on May 13, 2021. Retrieved August 19, 2020.
  6. ^ a b "Invega Trinza- paliperidone palmitate injection, suspension, extended release". DailyMed. January 31, 2019. Archived from the original on June 17, 2021. Retrieved August 19, 2020.
  7. ^ a b c d "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.
  8. ^ "Byannli EPAR". European Medicines Agency. April 28, 2020. Archived from the original on March 5, 2023. Retrieved March 4, 2023.
  9. ^ "Byannli Product information". Union Register of medicinal products. Archived from the original on March 5, 2023. Retrieved March 3, 2023.
  10. ^ "Trevicta EPAR". European Medicines Agency. December 5, 2014. Archived from the original on February 1, 2024. Retrieved February 1, 2024.
  11. ^ a b "Xeplion EPAR". European Medicines Agency. March 4, 2011. Archived from the original on February 17, 2024. Retrieved February 1, 2024.
  12. ^ a b "Niapelf EPAR". European Medicines Agency (EMA). March 21, 2024. Archived from the original on February 17, 2024. Retrieved April 5, 2024.
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    S2CID 36437470
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    ISBN 9780198527480. Archived
    from the original on January 10, 2023. Retrieved August 28, 2020.
  19. ^ a b "Paliperidone". DrugBank. Archived from the original on November 17, 2011. Retrieved November 18, 2011.
  20. ^
    PMID 25943458
    .
  21. ^ "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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    .
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  24. ^ 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.
  25. ^
    PMID 6931472
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  26. ^ a b Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
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  29. ^ 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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  33. ^ 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.
  34. S2CID 1672835. Archived
    from the original on January 23, 2023. Retrieved November 26, 2022.
  35. ^ "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.
  36. ^ "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.
  37. ^ "Schizophrénie: controverse autour d'un médicament au Japon". Médecine. April 9, 2014. Archived from the original on April 22, 2014. Retrieved April 21, 2014.
  38. ^ "20 minutes - Un médicament anti-schizophrénie tue". Monde. April 9, 2014. Archived from the original on April 23, 2014. Retrieved April 21, 2014.
  39. ^ "Deaths reported after Xeplion injections". Life & Style. NZ Herald News. Archived from the original on March 4, 2016. Retrieved April 21, 2014.
  40. ^ "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.
  41. ^ "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.
  42. ^ "Schizophrenia drug blamed for 17 deaths". Sky News Australia. June 29, 2023. Archived from the original on April 13, 2014. Retrieved April 21, 2014.
  43. ^ "Invega Trinza (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Archived from the original (PDF) on December 22, 2015. Retrieved December 10, 2015.
  44. ^ "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.