Paliperidone

Clinical data
Trade names	Invega, Xeplion, others
Synonyms	9-hydroxyrisperidone
AHFS/Drugs.com	Monograph
MedlinePlus	a607005
License data	EU EMA: by INN US FDA: Paliperidone
Pregnancy category	AU: B3 US: C (Risk not ruled out)
Routes of administration	Oral (OROS tablets), IM depot injection
ATC code	N05AX13 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	28% (oral)
Elimination half-life	23 hours (by mouth)
Excretion	1% unchanged in urine 18% unchanged in feces
Identifiers
IUPAC name (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
CAS Number	144598-75-4 Y
PubChem CID	115237
DrugBank	DB01267 Y
ChemSpider	7978307 Y
UNII	838F01T721
KEGG	D05339 Y
ChEBI	CHEBI:82978 N
ChEMBL	ChEMBL1621 N
ECHA InfoCard	100.117.604
Chemical and physical data
Formula	C23H27FN4O3
Molar mass	426.484 g/mol
3D model (JSmol)	Interactive image
SMILES O=C/1N5/C(=NC(=C1CCN4CCC(c3noc2cc(F)ccc23)CC4)C)[C@H](O)CCC5
InChI 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 Y Key:PMXMIIMHBWHSKN-LJQANCHMSA-N Y
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Paliperidone, sold under the trade name Invega among others, is a dopamine antagonist and 5-HT_2A 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 is mainly used to treat schizophrenia and schizoaffective disorder. It is also used to treat mania and at lower doses as maintenance for bipolar disorder.

Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester indicated for once-every 28 days injection after an initial titration period.

Medical use[edit]

It is used for the treatment of schizophrenia and schizoaffective disorder. In a 2013 study in a comparison of 15 antipsychotic drugs in effectiveness in treating schizophrenic symptoms, paliperidone was ranked fifth and demonstrated standard-high effectiveness. 10-14% more effective than haloperidol, quetiapine, and aripiprazole, 11% less effective than risperidone (4th), and 43% less effective than clozapine (1st).^[1]

Adverse effects[edit]

Sources:^{[3][4][5][6][7]}

Very Common (>10% incidence)

• Headache


• Tachycardia


• 
  Somnolence (causes less sedation than most atypical antipsychotics)^[1]
  


• Insomnia


• 
  Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone)^[1]
  


• 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)^[1]
  


• Orthostatic hypotension


• Weight gain (tends to produce a moderate degree of weight gain, possibly related to its potent blockade of the 5-HT_2C 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)^[1]
  


• 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, out of 10,700 individuals prescribed the drug.^{[8][9][10][11][12][13][14]}

Pharmacology[edit]

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.^[16] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.^[17]
Blocks dopamine and serotonin.
Food increases the absorption of Invega type ER OROS prolonged-release tablet. 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 (uptake).^[18]

The half life is 24 hours.^[18]

History[edit]

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 U.S. and Xeplion in Europe, was approved by the FDA on July 31, 2009. It is the only available brand in Bangladesh under the brand name "Palimax ER" manufactured & marketed by ACI Pharmaceuticals.

It was initially approved in Europe in 2007 for schizophrenia, the extended release form and use for schizoaffective disorder were approved in Europe in 2010, and extension to use in adolescents older than 15 years old was approved in 2014.^[19]

Brand names[edit]

On May 18, 2015, a new formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.^[20] 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.^[21]

References[edit]

External links[edit]

• Invega Official website


• Invega Sustenna Official website


• Invega Trinza Official website