Paliperidone

Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic.^[13] It is used for the treatment of schizophrenia and schizoaffective disorder.^[13][14] It is marketed by Janssen Pharmaceuticals.^[3]

Paliperidone

Clinical data
Trade names	Invega, others
Other names	9-hydroxyrisperidone; PP; PP1M; PP3M; PP6M; JNS-010; RO-92670; RO92670
AHFS/Drugs.com	Monograph
MedlinePlus	a607005
License data	US DailyMed: Paliperidone
Pregnancy category	AU: B3
Routes of administration	By mouth, intramuscular
Drug class	Atypical antipsychotic
ATC code	N05AX13 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) BR: Class C1 (Other controlled substances)[1] CA: ℞-only[2] US: ℞-only[3][4][5][6] EU: Rx-only[7][8][9][10][11][12]
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 as palmitate: 199739-10-1
PubChem CID	115237 as palmitate: 9852746
DrugBank	DB01267 Y as palmitate: DBSALT001464
ChemSpider	7978307 Y as palmitate: 8028457
UNII	838F01T721 as palmitate: R8P8USM8FR
KEGG	D05339 Y as palmitate: D05340
ChEBI	CHEBI:82978 N as palmitate: CHEBI:83807
ChEMBL	ChEMBL1621 N as palmitate: ChEMBL2107360
ECHA InfoCard	100.117.604
Chemical and physical data
Formula	C23H27FN4O3
Molar mass	426.492 g·mol−1
3D model (JSmol)	Interactive image
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 as palmitate: InChI=1S/C39H57FN4O4/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-18-36(45)47-34-17-16-24-44-38(34)41-29(2)32(39(44)46)23-27-43-25-21-30(22-26-43)37-33-20-19-31(40)28-35(33)48-42-37/h19-20,28,30,34H,3-18,21-27H2,1-2H3 Key:VOMKSBFLAZZBOW-UHFFFAOYSA-N
NY (what is this?)  (verify)

Paliperidone was approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia in December 2006,^[3] and in the European Union in June 2007.^[7] Paliperidone palmitate is a long-acting injectable formulation of paliperidone palmitoyl ester.^[13][15] It is on the World Health Organization's List of Essential Medicines.^[16] Paliperidone is available as a generic medication.^[12]

Medical use

In the United States, paliperidone is indicated for the treatment of schizophrenia and for the treatment of schizoaffective disorder as monotherapy and as an adjunct to mood stabilizers and/or antidepressants.^[3]

In the European Union, paliperidone is indicated for the treatment of schizophrenia in adults and in adolescents fifteen years of age and older and for the treatment of schizoaffective disorder in adults.^[7]

Paliperidone is used for the treatment of schizophrenia and schizoaffective disorder.^[14]

Adverse effects

The most common side effects include headache, insomnia, sleepiness, parkinsonism (effects similar to Parkinson's disease such as shaking, muscle stiffness and slow movement), dystonia (involuntary muscle contractions), tremor (shaking), dizziness, akathisia (restlessness), agitation, anxiety, depression, increased weight, nausea, vomiting, constipation, dyspepsia (heartburn), diarrhea, dry mouth, tiredness, toothache, muscle and bone pain, back pain, asthenia (weakness), tachycardia (increased heart rate), high blood pressure, prolonged QT interval (an alteration of the electrical activity of the heart), upper respiratory tract infection (nose and throat infections) and cough.^[7]

A 2023 study found that paliperidone may worsen verbal learning and memory compared to placebo in the early months of psychosis treatment.^[17]

Other symptoms may include restlessness, increased sweating, and trouble sleeping.^[18] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.^[18]

Pharmacology

Paliperidone is the primary active metabolite of the older antipsychotic risperidone.^{[19][unreliable medical source?]} While its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways.^[20] Its efficacy is believed to result from central dopaminergic and serotonergic antagonism except paliperidone, like its parent compound risperidone, functions as an inverse agonist at 5-HT2A 15. Paliperidone also acts as an antagonist of alpha-1 and alpha-2 adrenergic receptors as well as H1 histaminergic receptors.^[19] 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 tract, resulting in increased absorption.^[21]

Risperidone and its metabolite paliperidone are reduced in efficacy by P-glycoprotein inducers such as St John's wort^[22][23]

• v
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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	[24]
Clopentixol decanoate	Sordinol Depot	Typical	Viscoleob	50–600 mg/1–4 weeks	4–7 days	?	19 days	9.0	[25]
Flupentixol decanoate	Depixol	Typical	Viscoleob	10–200 mg/2–4 weeks	4–10 days	8 days	17 days	7.2–9.2	[25][26]
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	[27][28][29]
Fluphenazine enanthate	Prolixin Enanthate	Typical	Sesame oil	12.5–100 mg/1–4 weeks	2–3 days	4 days	?	6.4–7.4	[28]
Fluspirilene	Imap, Redeptin	Typical	Watera	2–12 mg/1 week	1–8 days	7 days	?	5.2–5.8	[30]
Haloperidol decanoate	Haldol Decanoate	Typical	Sesame oil	20–400 mg/2–4 weeks	3–9 days	18–21 days		7.2–7.9	[31][32]
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	[33]
Pipotiazine palmitate	Piportil Longum	Typical	Viscoleob	25–400 mg/4 weeks	9–10 days	?	14–21 days	8.5–11.6	[26]
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.

Paliperidone^[20]

Site	Ki (nM)
5-HT1A	6.17
5-HT2A	1
5-HT2C	48
5-HT6	24
5-HT7	2.7
α1A	2.5
α2A	3.9
α2C	2.7
D1	41
D2	1.6
D3	3.5
D4	54[34]
D5	29
H1	19
H2	121
mACh	>10,000

Values are K_i (nM). The smaller the value, the more strongly the drug binds to the site.

History

Paliperidone (as Invega) was approved by the US 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 the US,^[5] and Xeplion in the EU,^[11] was approved by the FDA in July 2009.

It was initially approved in the European Union in 2007, for schizophrenia, the extended release form and use for schizoaffective disorder were approved in the EU in 2010, and extension to use in adolescents older than 15 years old was approved in 2014.^[35]

Society and culture

Deaths

In April 2014, it was reported that 21 Japanese people who had received shots of the long-acting injectable paliperidone palmitate had died, out of 10,700 individuals prescribed the drug.^{[36][37][38][39][40][41][42][excessive citations]}

Brand names

In May 2015, a formulation of paliperidone palmitate was approved by the US Food and Drug Administration under the brand name Invega Trinza.^[43][6] A similar prolonged release suspension was approved in 2016 by the European Medicines Agency originally under the brand name Paliperidone Janssen, later renamed to Trevicta.^[44] In September 2021, a newer formulation of paliperidone palmitate, Invega Hafyera, was approved by the US FDA.^[4]