Paliperidone

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Paliperidone
Paliperidone2DACS.svg
Systematic (IUPAC) name
(RS)-3-[2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-1-piperidyl]ethyl]-7-hydroxy-4-methyl-1,5-diazabicyclo[4.4.0]deca-3,5-dien-2-one
Clinical data
Trade names Invega
AHFS/Drugs.com monograph
MedlinePlus a607005
Licence data EMA:Link, US FDA:link
Pregnancy cat. B3 (AU) C (US)
Legal status Prescription Only (S4) (AU) -only (US)
Routes oral- extended release, long-acting, once-monthly IM injection
Pharmacokinetic data
Bioavailability 28% (oral)
Half-life 23 hours (oral)
Identifiers
CAS number 144598-75-4 YesY
ATC code N05AX13
PubChem CID 9802545
DrugBank DB01267
ChemSpider 7978307 YesY
UNII 838F01T721 YesY
KEGG D05339 YesY
ChEMBL CHEMBL1621 N
Chemical data
Formula C23H27FN4O3 
Mol. mass 426.484 g/mol
 N (what is this?)  (verify)

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 developed 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-monthly injection after an initial titration period. Paliperidone is used to treat mania and at lower doses as maintenance for bipolar disorder. It is also used for schizophrenia and schizoaffective disorder.

Pharmacology[edit]

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.[1] 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.[2] It does not bind to muscarinic acetylcholine receptors. In addition, it binds with dopamine and serotonin receptors.

Paliperidone has less affinity for D4 receptors than risperidone.[3][4]

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. Recently, 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.[5] In Europe the monthly (every 28 days) injection comes in 50 mg, 75 mg, 100 mg, and 150 mg of paliperidone without the 25 mg injection that is available in the U.S. A dose of 75 mg for a month in an injection is the equivalent of 6 mg per day of paliperidone oral. 6 mg of paliperidone oral (Invega) is equivalent to 2 to 3 mg of risperidone.[6]

Adverse effects[edit]

Adverse effect incidences[edit]

Sources:[7][8][9][10]

Very Common (>10% incidence)
  • Headache
  • Tachycardia
  • Somnolence (causes less sedation than most atypical antipsychotics[11])
  • Insomnia
  • Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone[11])
Common (1-10% incidence)
Rare/Uncommon (<1% incidence)
- Hyperthermia
- Muscle rigidity
- Autonomic dysregulation
- Mental status changes (e.g. confusion, agitation, etc.)
- Dysphagia
- Tremor
- Dyspnoea
- Elevated creatine kinase
  • Tardive dyskinesia, an often irreversible neurologic condition characterised by, frequently distressing, movement disorders.[13]
  • Dysphagia
  • Agranulocytosis, a potentially fatal drop in white blood cell count. More common in patients on clozapine than in those on paliperidone.
  • Leukopenia
  • Thrombocytopaenia
  • Pancreatitis
  • Atrial fibrilation
  • Dysgeusia
  • Mania
  • Diabetes mellitus
  • Diabetic ketoacidosis
  • Hypoglycaemia
  • Ileus
  • Jaundice
  • Angiooedema
  • Alopecia
  • Urinary retention
  • Hypothermia

Controversy[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]

  1. ^ "The DrugBank database". 
  2. ^ "Prescribing Reference: New Product Releases - INVEGA". Retrieved 2008-05-25. 
  3. ^ 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
  4. ^ 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
  5. ^ [1]
  6. ^ [2]
  7. ^ Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 30]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  8. ^ 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
  9. ^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  10. ^ paliperidone (Rx) - Invega, Invega Sustenna [Internet]. Medscape Reference. [cited 2013 Sep 30]. Available from: http://reference.medscape.com/drug/invega-sustenna-paliperidone-342992#4
  11. ^ a b c d Leucht S, Cipriani A, Spineli L, Mavridis D, Örey D, Richter F, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. The Lancet [Internet]. [cited 2013 Sep 30]; Available from: http://www.sciencedirect.com/science/article/pii/S0140673613607333
  12. ^ Tonkonogy J, Sholevar DP. Neuroleptic Malignant Syndrome. 2012 Jun 17 [cited 2013 Sep 30]; Available from: http://emedicine.medscape.com/article/288482-clinical
  13. ^ Brasic JR. Tardive Dyskinesia. 2012 Jun 17 [cited 2013 Sep 30]; Available from: http://emedicine.medscape.com/article/1151826-overview#aw2aab6b7
  14. ^ 21 users of schizophrenia drug dead | The Japan Times
  15. ^ Schizophrénie: controverse autour d'un médicament au Japon | Médecine
  16. ^ 20 minutes - Un médicament anti-schizophrénie tue - Monde
  17. ^ Deaths reported after Xeplion injections - Life & Style - NZ Herald News
  18. ^ 17 deaths reported after schizophrenia drug injections | Japan Today: Japan News and Discussion
  19. ^ 21 Dead in Japan From New Johnson & Johnson Antipsychotic | Mad In America
  20. ^ Schizophrenia drug blamed for 17 deaths | Sky News Australia

External links[edit]