Paliperidone

Paliperidone

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 Y
ATC code	N05AX13
PubChem	CID 9802545
DrugBank	DB01267
ChemSpider	7978307 Y
UNII	838F01T721 Y
KEGG	D05339 Y
ChEMBL	CHEMBL1621 N
Chemical data
Formula	C23H27FN4O3
Mol. mass	426.484 g/mol
SMILES O=C/1N5/C(=N\C(=C\1CCN4CCC(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
N (what is this?)  (verify)

Paliperidone (trade name Invega), also known as 9-hydroxyrisperidone, is a dopamine 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) 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

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 for D4 receptors than risperidone^[3][4]

Paliperidone (as Invega) was approved by the 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

Adverse Effect Incidences

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)

• 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^[11])
• 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 as aripiprazole and lurasidone^[11])
• Nasopharyngitis
• Anxiety
• Indigestion
• Constipation

Rare/Uncommon (<1% incidence)

• Sialorrhoea
• Priapism
• Neuroleptic malignant syndrome which is a potentially life-threatening condition characterised by:^[12]

- 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.
• Leukopaenia
• Thrombocytopaenia
• Pancreatitis
• Atrial fibrilation
• Dysgeusia
• Mania
• Diabetes mellitus
• Diabetic ketoacidosis
• Hypoglycaemia
• Ileus
• Jaundice
• Angiooedema
• Alopecia
• Urinary retention
• Hypothermia

Dosing

1.5 mg to 12 mg.^{[citation needed]} Injection 25 mg to 150 mg monthly.^{[citation needed]}

References

External links

• INVEGA Web site
• INVEGA Sustenna (paliperidone palmitate Extended Release Injectable Suspension) Web site

v t e Palm oil Oil palms Attalea A. maripa Elaeis E. guineesis E. oleifera Diseases and pests Basal stem rot (Ganoderma orbiforme) Cadang-cadang disease Little leaf syndrome Oryctes rhinoceros Rhynchophorus palmarum Oil palm bunch moth Tirathaba mundella Tirathaba rufivena Red ring disease (Bursaphelenchus cocophilus) Components Mesocarp Palm kernel oil lauric acid Palm oil stearin stearic acid linoleic acid myristic acid oleic acid palmitic acid Processes Fractionation Hydrolysis Milling Refining Saponification Transesterification Products Biodiesel by region NExBTL Bioplastics Cellulosic ethanol Girl Scout Cookies Napalm Oleochemicals Paliperidone (antipsychotic) Sunlight (soap) Vegetable oil cooking fuel Organizations AAK Bumitama Agri Cargill FELDA GreenPalm Indonesia Commodity and Derivatives Exchange IOI Group Journal of Oil Palm Research Kuala Lumpur Kepong Berhad Malaysia Derivatives Exchange Malaysian Palm Oil Board Neste Oil Roundtable on Sustainable Palm Oil Sime Darby The Forest Trust Unilever Wilmar International Policies, impacts and debates Biodiesel impacts Biofuel policy (Malaysia) Biofuels issues Certified sustainable palm oil Deforestation haze Food vs. fuel Social and environmental impacts Vegetable oil economy By country Indonesia Malaysia Portals: Agriculture Energy Food Forestry Category by country Commons