Paliperidone
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This article may be unbalanced towards certain viewpoints. (September 2014) |
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| Clinical data | |
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| Trade names | Invega |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a607005 |
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| Routes of administration |
Oral (OROS tablets), IM depot injection |
| ATC code | N05AX13 (WHO) |
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| Pharmacokinetic data | |
| Bioavailability | 28% (oral) |
| Biological half-life | 23 hours (oral) |
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| CAS Number | 144598-75-4  |
| PubChem (CID) | 115237 |
| DrugBank | DB01267 |
| ChemSpider | 7978307 |
| UNII | 838F01T721 |
| KEGG | D05339 |
| ChEBI | CHEBI:82978  |
| ChEMBL | CHEMBL1621 |
| ECHA InfoCard | 100.117.604 |
| Chemical and physical data | |
| Formula | C23H27FN4O3 |
| Molar mass | 426.484 g/mol |
| 3D model (Jmol) | Interactive image |
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Paliperidone (trade name Invega), also known as 9-hydroxyrisperidone, is a dopamine antagonist and 5-HT2A antagonist of the atypical antipsychotic class of medications. It is marketed by Janssen Pharmaceutica. Invega is an extended release formulation of paliperidone that uses the OROS extended release system to allow for once-daily dosing.
Paliperidone palmitate (trade name Invega Sustenna, named Xeplion in Europe and other countries) is a long-acting injectable formulation of paliperidone palmitoyl ester indicated for once-every 28 days injection after an initial titration period. Paliperidone is used to treat mania and at lower doses as maintenance for bipolar disorder. It is also indicated in the US by the FDA for schizophrenia and schizoaffective disorder.
On May 18, 2015, a new formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[1] 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.[2]
Contents
Pharmacology[edit]
Paliperidone is the primary active metabolite of the older antipsychotic risperidone.[3] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.
Paliperidone has antagonist effect at α1 and α2 adrenergic receptors and at H1 histamine receptors.[4] It does not bind to muscarinic acetylcholine receptors. In addition, it blocks dopamine and serotonin receptors.
Paliperidone has less affinity for D4 receptors than risperidone.[5][6]
Paliperidone (as Invega) was approved by the Food and Drug Administration (FDA) for the treatment of schizophrenia in 2006. It is marketed for the treatment of schizophrenia and schizoaffective disorder. Paliperidone was approved by the FDA for the treatment of schizoaffective disorder in 2009. It may also be used off-label for other conditions. 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 was approved in Europe in 2011 for schizophrenia.[7]
Effects[edit]
| Measured outcome | Findings in words | Findings in numbers | Quality of evidence |
|---|---|---|---|
| Recurrence of psychotic symptoms | No more likely to have a recurrence of psychotic symptoms with paliperidone palmitate | RR 1.23 CI 0.98 to 1.53 | Moderate |
| Lack of efficacy | People are 35% more likely to experience lack of efficacy with paliperidone palmitate | RR 1.35 CI 1.06 to 1.71 | |
| Use of anticholinergic medications | 30% less likely to use anticholinergic medications with paliperidone palmitate | RR 0.67 CI 0.55 to 0.82 |
Adverse effects[edit]
Adverse effect incidences[edit]
- 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])
- 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
Deaths[edit]
In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone to date had died.[14][15][16][17][18][19][20]
References[edit]
- ^ "Invega Trinza™ (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved 10 December 2015.
- ^ "Trevicta (previously Paliperidone Janssen) - summary of the European public assessment report (EPAR) for Trevicta".
- ^ "The DrugBank database".
- ^ "Prescribing Reference: New Product Releases - INVEGA". Retrieved 2008-05-25.
- ^ http://pdsp.med.unc.edu/pdsp.php?knowID=&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=2327&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query[full citation needed]
- ^ http://pdsp.med.unc.edu/pdsp.php?knowID=&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testDDRadio=testDDRadio&testLigandDD=2328&testLigand=&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query[full citation needed]
- ^ https://www.www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002105/human_med_001424.jsp&mid=WC0b01ac058001d124&murl=menus/medicines/medicines.jsp&jsenabled=true[full citation needed]
- ^ Nussbaum, Abraham M; Stroup, T S; Nussbaum, Abraham M (2012). "Paliperidone palmitate for schizophrenia". The Cochrane Database of Systematic Reviews. 6: CD008296. doi:10.1002/14651858.CD008296.pub2. PMID 22696377.
- ^ Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 30]. Greenwood Village, CO: Thomsen Healthcare; 2013.
- ^ INVEGA® PRODUCT INFORMATION [Internet]. Janssen Pharmaceuticals; 2013 [cited 2013 Sep 30]. Available from: https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2013-PI-01421-1
- ^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
- ^ paliperidone (Rx) - Invega, Invega Sustenna [Internet]. Medscape Reference. [cited 2013 Sep 30]. Available from: http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4
- ^ a b c d Leucht, Stefan; Cipriani, Andrea; Spineli, Loukia; Mavridis, Dimitris; Örey, Deniz; Richter, Franziska; Samara, Myrto; Barbui, Corrado; Engel, Rolf R; Geddes, John R; Kissling, Werner; Stapf, Marko Paul; Lässig, Bettina; Salanti, Georgia; Davis, John M (2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–62. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019.
- ^ 21 users of schizophrenia drug dead | The Japan Times
- ^ Schizophrénie: controverse autour d'un médicament au Japon | Médecine
- ^ 20 minutes - Un médicament anti-schizophrénie tue - Monde
- ^ Deaths reported after Xeplion injections - Life & Style - NZ Herald News
- ^ 17 deaths reported after schizophrenia drug injections | Japan Today: Japan News and Discussion
- ^ 21 Dead in Japan From New Johnson & Johnson Antipsychotic | Mad In America
- ^ Schizophrenia drug blamed for 17 deaths | Sky News Australia
