paliperidone paliperidone paliperidone, sold under the trade name invega among others, is an atypical antipsychotic. it is mainly used to treat schizophrenia and schizoaffective disorder. paliperidoneclinical datatrade namesinvega, xeplion, trevicta, othersother names9-hydroxyrisperidoneahfs/drugs.commonographmedlineplusa607005license data eu ema: by inn us fda: paliperidone pregnancycategory au: b3 routes ofadministrationby mouth (oros tablets), intramuscularatc coden05ax13 (who) legal statuslegal status au: s4 (prescription only) us: ℞-only eu: rx-only pharmacokinetic databioavailability28% (oral)elimination half-life23 hours (by mouth)excretion1% unchanged in urine 18% unchanged in fecesidentifiers iupac name (rs)-3-ethyl]-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyridopyrimidin-4-one cas number144598-75-4 ypubchem cid115237drugbankdb01267 ychemspider7978307 yunii838f01t721keggd05339 ychebichebi:82978 nchemblchembl1621 necha infocard100.117.604 chemical and physical dataformulac23h27fn4o3molar mass426.492 g·mol−13d model (jsmol)interactive image smiles o=c/1n5/c(=n\c(=c\1ccn4ccc(c3noc2cc(f)ccc23)cc4)c)(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 ykey:pmxmiimhbwhskn-ljqanchmsa-n y ny (what is this?) (verify) 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. medical use it is used for the treatment of schizophrenia and schizoaffective disorder. paliperidone palmitate long-acting injection compared to risperidone for schizophrenia 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. outcome findings in words findings in numbers quality of evidence global state: no clinically important change no 30% improvement on panss score.follow-up: 13-53 weeksthere is no clear difference between people given paliperidone palmitate and those receiving risperidone for this outcome. these findings are based on data of low quality. rr 1.03 (0.93 to 1.14)low relapse recurrence of psychotic symptoms.follow up: 13-53 weeksthere is no clear difference between people given paliperidone palmitate and those receiving risperidone for the outcome of 'relapse'. data supporting this finding are based on moderate quality evidence. rr 1.23 (0.98 to 1.53)moderate leaving the study early - for any reason.follow up: 13-53 weekspaliperidone palmitate causes little or no increase to the chance of leaving the study. rr 1.12 (1 to 1.25)high - because of lack of efficacy.follow up: 13-53 weekspaliperidone palmitate may increase the risk of finding treatment unacceptable or being withdrawn from treatment outcome for the reason of perceived lack of efficacy compared with risperidone. data are based on moderate quality evidence. rr 1.35 (1.06 to 1.71)moderate adverse event: death follow up: 13-53 weeksthere was no clear difference between people given paliperidone palmitate and those receiving risperidone for this rare outcome. these findings are based on data of low quality. rr 3.62 (0.6 to 21.89)low missing outcomes outcomes of 'cost' and 'quality of life' are not reported in the included randomized trials. adverse effects sources: very common (>10% incidence) headache tachycardia somnolence (causes less sedation than most atypical antipsychotics) insomnia hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone) 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) 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) nasopharyngitis anxiety indigestion constipation discontinuation the british national formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. other symptoms may include restlessness, increased sweating, and trouble sleeping. less commonly there may be a feeling of the world spinning, numbness, or muscle pains. symptoms generally resolve after a short period of time. there is tentative evidence that discontinuation of antipsychotics can result in psychosis. it may also result in reoccurrence of the condition that is being treated. rarely tardive dyskinesia can occur when the medication is stopped. 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. pharmacology paliperidone siteki (nm) 5-ht1a617 5-ht2a1.1 5-ht2c48 5-ht5a278 5-ht62414 5-ht72.7 α1a2.5 α2a3.9 α2c2.7 d141 d21.6 d33.5 d454 d529 h119 h2121 mach>10,000 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. while its specific mechanism of action is unknown, it is believed paliperidone and risperidone act via similar, if not identical, pathways. 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 the half-life is 23 hours. risperidone and its metabolite paliperidone are reduced in efficacy by p-glycoprotein inducers such as st john's wort pharmacokinetics of long-acting injectable antipsychotics medicationbrand nameclassvehicledosagetmaxt1/2 singlet1/2 multiplelogpcref aripiprazole lauroxilaristadaatypicalwatera441–1064 mg/4–8 weeks24–35 days ?54–57 days7.9–10.0 aripiprazole monohydrateabilify maintenaatypicalwatera300–400 mg/4 weeks7 days ?30–47 days4.9–5.2 bromperidol decanoateimpromen decanoastypicalsesame oil40–300 mg/4 weeks3–9 days ?21–25 days7.9 clopentixol decanoatesordinol depottypicalviscoleob50–600 mg/1–4 weeks4–7 days ?19 days9.0 flupentixol decanoatedepixoltypicalviscoleob10–200 mg/2–4 weeks4–10 days8 days17 days7.2–9.2 fluphenazine decanoateprolixin decanoatetypicalsesame oil12.5–100 mg/2–5 weeks1–2 days1–10 days14–100 days7.2–9.0 fluphenazine enanthateprolixin enanthatetypicalsesame oil12.5–100 mg/1–4 weeks2–3 days4 days ?6.4–7.4 fluspirileneimap, redeptintypicalwatera2–12 mg/1 week1–8 days7 days ?5.2–5.8 haloperidol decanoatehaldol decanoatetypicalsesame oil20–400 mg/2–4 weeks3–9 days18–21 days7.2–7.9 olanzapine pamoatezyprexa relprevvatypicalwatera150–405 mg/2–4 weeks7 days ?30 days– oxyprothepin decanoatemeclopintypical ? ? ? ? ?8.5–8.7 paliperidone palmitateinvega sustennaatypicalwatera39–819 mg/4–12 weeks13–33 days25–139 days ?8.1–10.1 perphenazine decanoatetrilafon dekanoattypicalsesame oil50–200 mg/2–4 weeks ? ?27 days8.9 perphenazine enanthatetrilafon enanthatetypicalsesame oil25–200 mg/2 weeks2–3 days ?4–7 days6.4–7.2 pipotiazine palmitatepiportil longumtypicalviscoleob25–400 mg/4 weeks9–10 days ?14–21 days8.5–11.6 pipotiazine undecylenatepiportil mediumtypicalsesame oil100–200 mg/2 weeks ? ? ?8.4 risperidonerisperdal constaatypicalmicrospheres12.5–75 mg/2 weeks21 days ?3–6 days– zuclopentixol acetateclopixol acuphasetypicalviscoleob50–200 mg/1–3 days1–2 days1–2 days4.7–4.9 zuclopentixol decanoateclopixol depottypicalviscoleob50–800 mg/2–4 weeks4–9 days ?11–21 days7.5–9.0 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. brand names on may 18, 2015, a new formulation of paliperidone palmitate was approved by the fda under the brand name invega trinza. 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. 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.