Paliperidone

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Paliperidone
Paliperidone.svg
Clinical data
Trade namesInvega, Xeplion, Trevicta, others
Other names9-hydroxyrisperidone
AHFS/Drugs.comMonograph
MedlinePlusa607005
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth (OROS tablets), intramuscular
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • US: ℞-only [1]
  • EU: Rx-only
Pharmacokinetic data
Bioavailability28% (oral)
Elimination half-life23 hours (by mouth)
Excretion1% 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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
ECHA InfoCard100.117.604 Edit this at Wikidata
Chemical and physical data
FormulaC23H27FN4O3
Molar mass426.492 g·mol−1
3D model (JSmol)
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 checkY
  • Key:PMXMIIMHBWHSKN-LJQANCHMSA-N checkY
 ☒NcheckY (what is this?)  

Paliperidone, sold under the trade name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder.

It is marketed by Janssen Pharmaceuticals. An extended release formulation is available that uses the OROS extended release system to allow for once-daily dosing. Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.

It is on the World Health Organization's List of Essential Medicines.[2]

Medical use[]

It is used for the treatment of schizophrenia and schizoaffective disorder.[3]

Paliperidone palmitate long-acting injection compared to risperidone for schizophrenia[4]
When flexibly dosed every four weeks, paliperidone palmitate appears comparable in efficacy and tolerability to risperidone. In short-term studies, paliperidone palmitate – the longer-acting injection – has a similar adverse effect profile to related compounds such as risperidone by mouth. No difference was found in the high rate of reported adverse sexual outcomes and paliperidone palmitate is associated with an increase in serum prolactin.[4]

Adverse effects[]

Sources:[5][6][7][8][9]

Very Common (>10% incidence)
  • Headache
  • Tachycardia
  • Somnolence (causes less sedation than most atypical antipsychotics)[3]
  • Insomnia
  • Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone)[3]
  • 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)[3]
  • 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)[3]
  • Nasopharyngitis
  • Anxiety
  • Indigestion
  • Constipation

Discontinuation[]

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[10] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[11] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[11] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[11] Symptoms generally resolve after a short period of time.[11]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[12] It may also result in reoccurrence of the condition that is being treated.[13] Rarely tardive dyskinesia can occur when the medication is stopped.[11]

Deaths[]

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.[14][15][16][17][18][19][20]

Pharmacology[]

Paliperidone[21]
Site Ki (nM)
5-HT1A 617
5-HT2A 1.1
5-HT2C 48
5-HT7 2.7
α1A 2.5
α2A 3.9
α2C 2.7
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.[22] While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.[21] Its efficacy is believed to result from central dopaminergic and serotonergic antagonism. 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.

risperidone and paliperidone in pharmacokinetics

[23]

The half-life is 23 hours.[23]

Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort[24][25]

  • v
  • t
Pharmacokinetics of long-acting injectable antipsychotics
Medication Brand name Class Vehicle Dosage Tmax t1/2 single t1/2 multiple logPc Ref
Aripiprazole lauroxil Aristada Atypical Watera 441–1064 mg/4–8 weeks 24–35 days ? 54–57 days 7.9–10.0
Aripiprazole monohydrate Abilify Maintena Atypical Watera 300–400 mg/4 weeks 7 days ? 30–47 days 4.9–5.2
Bromperidol decanoate Impromen Decanoas Typical Sesame oil 40–300 mg/4 weeks 3–9 days ? 21–25 days 7.9 [26]
Clopentixol decanoate Sordinol Depot Typical Viscoleob 50–600 mg/1–4 weeks 4–7 days ? 19 days 9.0 [27]
Flupentixol decanoate Depixol Typical Viscoleob 10–200 mg/2–4 weeks 4–10 days 8 days 17 days 7.2–9.2 [27][28]
Fluphenazine decanoate Prolixin Decanoate Typical Sesame oil 12.5–100 mg/2–5 weeks 1–2 days 1–10 days 14–100 days 7.2–9.0 [29][30][31]
Fluphenazine enanthate Prolixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks 2–3 days 4 days ? 6.4–7.4 [30]
Fluspirilene Imap, Redeptin Typical Watera 2–12 mg/1 week 1–8 days 7 days ? 5.2–5.8 [32]
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks 3–9 days 18–21 days 7.2–7.9 [33][34]
Olanzapine pamoate Zyprexa Relprevv Atypical Watera 150–405 mg/2–4 weeks 7 days ? 30 days –
Oxyprothepin decanoate Meclopin Typical ? ? ? ? ? 8.5–8.7
Paliperidone palmitate Invega Sustenna Atypical Watera 39–819 mg/4–12 weeks 13–33 days 25–139 days ? 8.1–10.1
Perphenazine decanoate Trilafon Dekanoat Typical Sesame oil 50–200 mg/2–4 weeks ? ? 27 days 8.9
Perphenazine enanthate Trilafon Enanthate Typical Sesame oil 25–200 mg/2 weeks 2–3 days ? 4–7 days 6.4–7.2 [35]
Pipotiazine palmitate Piportil Longum Typical Viscoleob 25–400 mg/4 weeks 9–10 days ? 14–21 days 8.5–11.6 [28]
Pipotiazine undecylenate Piportil Medium Typical Sesame oil 100–200 mg/2 weeks ? ? ? 8.4
Risperidone Risperdal Consta Atypical Microspheres 12.5–75 mg/2 weeks 21 days ? 3–6 days –
Zuclopentixol acetate Clopixol Acuphase Typical Viscoleob 50–200 mg/1–3 days 1–2 days 1–2 days 4.7–4.9
Zuclopentixol decanoate Clopixol Depot Typical Viscoleob 50–800 mg/2–4 weeks 4–9 days ? 11–21 days 7.5–9.0
Note: All by intramuscular injection. Footnotes: a = Microcrystalline or nanocrystalline aqueous suspension. b = Low-viscosity vegetable oil (specifically fractionated coconut oil with medium-chain triglycerides). c = Predicted, from PubChem and DrugBank. Sources: Main: See template.

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 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.[36]

Brand names[]

On May 18, 2015, a new formulation of paliperidone palmitate was approved by the FDA under the brand name Invega Trinza.[37] 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.[38] On September 1, 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA which is available as an injection every six months.

References[]

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  36. ^ "Procedural steps taken and scientific information after the authorisation" (PDF). EMA. July 16, 2015.
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