Chemistry:Paliperidone
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| Trade names | Invega, Xeplion, Trevicta, others |
| Other names | 9-hydroxyrisperidone; PP; PP1M; PP3M; PP6M; JNS-010; RO-92670; RO92670 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a607005 |
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| Routes of administration | By mouth, intramuscular |
| Drug class | Atypical antipsychotic |
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| Pharmacokinetic data | |
| Bioavailability | 28% (oral) |
| Elimination half-life | 23 hours (by mouth) |
| Excretion | 1% unchanged in urine 18% unchanged in feces |
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| Formula | C23H27FN4O3 |
| Molar mass | 426.492 g·mol−1 |
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Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic.[10] It is mainly used to treat schizophrenia and schizoaffective disorder.[10] It is marketed by Janssen Pharmaceuticals.[1]
Paliperidone was approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia in December 2006.[1] Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.[10][11] It is on the World Health Organization's List of Essential Medicines.[12]
Medical use
Paliperidone is used for the treatment of schizophrenia and schizoaffective disorder.[13]
Adverse effects
Sources:[14][failed verification][15][16][17][18]
- Very Common (>10% incidence)
- Headache
- Tachycardia
- Somnolence (causes less sedation than most atypical antipsychotics)[13]
- Insomnia
- Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone)[13]
- Sexual Dysfunction
- Common (1–10% incidence)
- Cough
- 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)[13]
- Orthostatic hypotension
- Weight gain (tends to produce a moderate degree of weight gain, possibly related to its potent blockade of the 5-HT2C receptor)
- 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)[13]
- 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.[19] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[20] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[20] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[20] Symptoms generally resolve after a short period of time.[20]
There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[21] It may also result in reoccurrence of the condition that is being treated.[22] Rarely tardive dyskinesia can occur when the medication is stopped.[20]
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.[23][24][25][26][27][28][29]
Pharmacology
| 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[31] |
| 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.[32][unreliable medical source?] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.[30] 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.[32] 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.[33]
The half-life is 23 hours.[33]
Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort[34][35]
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,[3] and Xeplion in the EU,[9] 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.[36]
Society and culture
Brand names
In May 2015, a formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[37] [4] 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.[38] On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.[2]
References
- ↑ 1.0 1.1 1.2 "Invega- paliperidone tablet, extended release". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7b8e5b26-b9e4-4704-921b-3c3c0d159916.
- ↑ 2.0 2.1 "Invega Hafyera- paliperidone palmitate injection, suspension, extended release". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=6cd61892-d2cb-434d-83ed-5c1b2c4e7a0b.
- ↑ 3.0 3.1 "Invega Sustenna- paliperidone palmitate injection". January 31, 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1af14e42-951d-414d-8564-5d5fce138554.
- ↑ 4.0 4.1 "Invega Trinza- paliperidone palmitate injection, suspension, extended release". January 31, 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c39e65d7-fa44-4e4c-8b12-a654d3ed0eae.
- ↑ "Invega EPAR". June 25, 2007. https://www.ema.europa.eu/en/medicines/human/EPAR/invega.
- ↑ "Byannli EPAR". April 28, 2020. https://www.ema.europa.eu/en/medicines/human/EPAR/byannli-previously-paliperidone-janssen-cilag-international.
- ↑ "Byannli Product information". https://ec.europa.eu/health/documents/community-register/html/h1453.htm.
- ↑ "Trevicta EPAR". December 5, 2014. https://www.ema.europa.eu/en/medicines/human/EPAR/trevicta-previously-paliperidone-janssen.
- ↑ 9.0 9.1 "Xeplion EPAR". March 4, 2011. https://www.ema.europa.eu/en/medicines/human/EPAR/xeplion.
- ↑ 10.0 10.1 10.2 "A review of paliperidone palmitate". Expert Review of Neurotherapeutics 12 (12): 1383–1397. December 2012. doi:10.1586/ern.12.137. PMID 23237346.
- ↑ "Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review". Frontiers in Psychiatry 12: 699748. 2021. doi:10.3389/fpsyt.2021.699748. PMID 34621193.
- ↑ 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. 2023. WHO/MHP/HPS/EML/2023.02.
- ↑ 13.0 13.1 13.2 13.3 13.4 "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet 382 (9896): 951–962. September 2013. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019.
- ↑ "DrugPoint System". Truven Health Analytics, Inc.. Greenwood Village, CO: Thomsen Healthcare. 2013. http://truvenhealth.com/our-solutions/products/drugpoints.
- ↑ "Invega PRODUCT INFORMATION". Janssen Pharmaceuticals. 2013. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-01421-1.
- ↑ "Antipsychotic-induced sexual dysfunction and its management". The World Journal of Men's Health 30 (3): 153–159. December 2012. doi:10.5534/wjmh.2012.30.3.153. PMID 23596605.
- ↑ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
- ↑ "paliperidone (Rx) - Invega, Invega Sustenna". Medscape Reference. http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4.
- ↑ 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."
- ↑ 20.0 20.1 20.2 20.3 20.4 Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. 2004. pp. 207–216. ISBN 9780198527480. https://books.google.com/books?id=CWR7DwAAQBAJ&pg=PA207.
- ↑ "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica 114 (1): 3–13. July 2006. doi:10.1111/j.1600-0447.2006.00787.x. PMID 16774655.
- ↑ Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. 2013. p. 85. ISBN 9788847026797. https://books.google.com/books?id=odE-AgAAQBAJ&pg=PA85.
- ↑ "21 users of schizophrenia drug dead". The Japan Times Online (The Japan Times). April 18, 2014. http://www.japantimes.co.jp/news/2014/04/18/national/21-users-of-schizophrenia-drug-dead/#.U1U0EcfgVQY.
- ↑ "Schizophrénie: controverse autour d'un médicament au Japon". Médecine. April 9, 2014. http://www.lapresse.ca/sciences/medecine/201404/09/01-4755962-schizophrenie-controverse-autour-dun-medicament-au-japon.php.
- ↑ "20 minutes - Un médicament anti-schizophrénie tue". Monde. April 9, 2014. http://www.20min.ch/ro/news/monde/story/M-doc-anti-schizophr-nie-fait-17-morts-25477540.
- ↑ "Deaths reported after Xeplion injections". Life & Style. NZ Herald News. http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=11235899.
- ↑ "17 deaths reported after schizophrenia drug injections". Japan Today: Japan News and Discussion. April 10, 2014. http://www.japantoday.com/category/national/view/17-deaths-reported-after-schizophrenia-drug-injections.
- ↑ "21 Dead in Japan From New Johnson & Johnson Antipsychotic". Mad In America. April 18, 2014. https://www.madinamerica.com/2014/04/21-dead-japan-new-antipsychotic/.
- ↑ "Schizophrenia drug blamed for 17 deaths". Sky News Australia. June 29, 2023. http://www.skynews.com.au/health/article.aspx?id=966055.
- ↑ 30.0 30.1 "Comparative Pharmacology of Risperidone and Paliperidone". Drugs in R&D 15 (2): 163–174. June 2015. doi:10.1007/s40268-015-0092-x. PMID 25943458.
- ↑ "The pipeline and future of drug development in schizophrenia". Molecular Psychiatry 12 (10): 904–922. October 2007. doi:10.1038/sj.mp.4002062. PMID 17667958. http://www.escholarship.org/uc/item/9rq494d4.
- ↑ 32.0 32.1 "Paliperidone". DrugBank. http://www.drugbank.ca/drugs/DB01267.
- ↑ 33.0 33.1 "Paliperidone extended release: Scientific Discussion". EMA. July 16, 2007. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000746/WC500034928.pdf.
- ↑ "The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein". The International Journal of Neuropsychopharmacology 7 (4): 415–419. December 2004. doi:10.1017/S1461145704004390. PMID 15683552.
- ↑ "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. July 2008. doi:10.1002/mnfr.200700081. PMID 18214850.
- ↑ "Procedural steps taken and scientific information after the authorisation". EMA. July 16, 2015. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Procedural_steps_taken_and_scientific_information_after_authorisation/human/000746/WC500034930.pdf.
- ↑ "Invega Trinza (paliperidone palmitate) NDA approval letter". http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2015/207946Orig1s000ltr.pdf.
- ↑ "Trevicta (previously Paliperidone Janssen)". Summary of the European public assessment report (EPAR) for Trevicta. EMC. September 17, 2018. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/004066/human_med_001829.jsp&mid=WC0b01ac058001d124.
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