|Trade names||Invega, Xeplion, Trevicta, others|
|By mouth (OROS tablets), intramuscular|
|Elimination half-life||23 hours (by mouth)|
|Excretion||1% unchanged in urine 18% unchanged in feces|
|Chemical and physical data|
|Molar mass||426.492 g·mol−1|
|3D model (JSmol)|
|(what is this?)|
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.
|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.|
- Very Common (>10% incidence)
- Somnolence (causes less sedation than most atypical antipsychotics)
- Hyperprolactinaemia (seems to cause comparable prolactin elevation to its parent drug, risperidone)
- Sexual Dysfunction
- Common (1–10% incidence)
- 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)
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.
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.
|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.
The half-life is 23 hours.
|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|||
|Clopentixol decanoate||Sordinol Depot||Typical||Viscoleob||50–600 mg/1–4 weeks||4–7 days||?||19 days||9.0|||
|Flupentixol decanoate||Depixol||Typical||Viscoleob||10–200 mg/2–4 weeks||4–10 days||8 days||17 days||7.2–9.2|||
|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|||
|Fluphenazine enanthate||Prolixin Enanthate||Typical||Sesame oil||12.5–100 mg/1–4 weeks||2–3 days||4 days||?||6.4–7.4|||
|Fluspirilene||Imap, Redeptin||Typical||Watera||2–12 mg/1 week||1–8 days||7 days||?||5.2–5.8|||
|Haloperidol decanoate||Haldol Decanoate||Typical||Sesame oil||20–400 mg/2–4 weeks||3–9 days||18–21 days||7.2–7.9|||
|Olanzapine pamoate||Zyprexa Relprevv||Atypical||Watera||150–405 mg/2–4 weeks||7 days||?||30 days||–|
|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|||
|Pipotiazine palmitate||Piportil Longum||Typical||Viscoleob||25–400 mg/4 weeks||9–10 days||?||14–21 days||8.5–11.6|||
|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 (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.
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.
- "Invega- paliperidone tablet, extended release". DailyMed. Retrieved August 19, 2020.
- World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
- Leucht S, Cipriani A, Spineli L, Mavridis D, Orey D, Richter F, et al. (September 2013). "Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis". Lancet. 382 (9896): 951–962. doi:10.1016/S0140-6736(13)60733-3. PMID 23810019. S2CID 32085212.
- Nussbaum AM, Stroup TS (June 2012). "Paliperidone palmitate for schizophrenia". The Cochrane Database of Systematic Reviews. 6 (6): CD008296. doi:10.1002/14651858.CD008296.pub2. PMC 3494051. PMID 22696377.
- "DrugPoint® System". Truven Health Analytics, Inc. Greenwood Village, CO: Thomsen Healthcare. 2013.
- "INVEGA® PRODUCT INFORMATION". Janssen Pharmaceuticals. 2013.
- Park YW, Kim Y, Lee JH (December 2012). "Antipsychotic-induced sexual dysfunction and its management". The World Journal of Men's Health. 30 (3): 153–159. doi:10.5534/wjmh.2012.30.3.153. PMC 3623530. PMID 23596605.
- Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
- "paliperidone (Rx) - Invega, Invega Sustenna". Medscape Reference.
- BMJ Joint Formulary Committee, ed. (March 2009). "4.2.1". British National Formulary (57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192. ISBN 978-0-85369-845-6.
Withdrawal of antipsychotic drugs after long-term therapy should always be gradual and closely monitored to avoid the risk of acute withdrawal syndromes or rapid relapse.
- Haddad PM, Dursun S, Deakin B (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. pp. 207–216. ISBN 9780198527480.
- Moncrieff J (July 2006). "Does antipsychotic withdrawal provoke psychosis? Review of the literature on rapid onset psychosis (supersensitivity psychosis) and withdrawal-related relapse". Acta Psychiatrica Scandinavica. 114 (1): 3–13. doi:10.1111/j.1600-0447.2006.00787.x. PMID 16774655. S2CID 6267180.
- Sacchetti E, Vita A, Siracusano A, Fleischhacker W (2013). Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. p. 85. ISBN 9788847026797.
- "21 users of schizophrenia drug dead". The Japan Times Online. The Japan Times. April 18, 2014.
- "Schizophrénie: controverse autour d'un médicament au Japon". Médecine. April 9, 2014.
- "20 minutes - Un médicament anti-schizophrénie tue". Monde. April 9, 2014.
- "Deaths reported after Xeplion injections". Life & Style. NZ Herald News.
- "17 deaths reported after schizophrenia drug injections". Japan Today: Japan News and Discussion.
- "21 Dead in Japan From New Johnson & Johnson Antipsychotic". Mad In America. April 18, 2014.
- "Schizophrenia drug blamed for 17 deaths". Sky News Australia.
- Corena-McLeod M (June 2015). "Comparative Pharmacology of Risperidone and Paliperidone". Drugs in R&D. 15 (2): 163–174. doi:10.1007/s40268-015-0092-x. PMC 4488186. PMID 25943458.
- Gray JA, Roth BL (October 2007). "The pipeline and future of drug development in schizophrenia". Molecular Psychiatry. 12 (10): 904–922. doi:10.1038/sj.mp.4002062. PMID 17667958. S2CID 1672835.
- "Paliperidone". The DrugBank database.
- "Paliperidone extended release: Scientific Discussion" (PDF). EMA. July 16, 2007.
- Wang JS, Ruan Y, Taylor RM, Donovan JL, Markowitz JS, DeVane CL (December 2004). "The brain entry of risperidone and 9-hydroxyrisperidone is greatly limited by P-glycoprotein". The International Journal of Neuropsychopharmacology. 7 (4): 415–419. doi:10.1017/S1461145704004390. PMID 15683552.
- Gurley BJ, Swain A, Williams DK, Barone G, Battu SK (July 2008). "Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics". Molecular Nutrition & Food Research. 52 (7): 772–779. doi:10.1002/mnfr.200700081. PMC 2562898. PMID 18214850.
- Parent M, Toussaint C, Gilson H (1983). "Long-term treatment of chronic psychotics with bromperidol decanoate: clinical and pharmacokinetic evaluation". Current Therapeutic Research. 34 (1): 1–6.
- Jørgensen A, Overø KF (1980). "Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. III. Serum levels". Acta Psychiatrica Scandinavica. Supplementum. 279: 41–54. doi:10.1111/j.1600-0447.1980.tb07082.x. PMID 6931472.
- Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
- Ereshefsky L, Saklad SR, Jann MW, Davis CM, Richards A, Seidel DR (May 1984). "Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches". The Journal of Clinical Psychiatry. 45 (5 Pt 2): 50–9. PMID 6143748.
- Curry SH, Whelpton R, de Schepper PJ, Vranckx S, Schiff AA (April 1979). "Kinetics of fluphenazine after fluphenazine dihydrochloride, enanthate and decanoate administration to man". British Journal of Clinical Pharmacology. 7 (4): 325–31. doi:10.1111/j.1365-2125.1979.tb00941.x. PMC 1429660. PMID 444352.
- Young D, Ereshefsky L, Saklad SR, Jann MW, Garcia N (1984). Explaining the pharmacokinetics of fluphenazine through computer simulations. (Abstract.). 19th Annual Midyear Clinical Meeting of the American Society of Hospital Pharmacists. Dallas, Texas.
- Janssen PA, Niemegeers CJ, Schellekens KH, Lenaerts FM, Verbruggen FJ, van Nueten JM, et al. (November 1970). "The pharmacology of fluspirilene (R 6218), a potent, long-acting and injectable neuroleptic drug". Arzneimittel-Forschung. 20 (11): 1689–98. PMID 4992598.
- Beresford R, Ward A (January 1987). "Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis". Drugs. 33 (1): 31–49. doi:10.2165/00003495-198733010-00002. PMID 3545764.
- Reyntigens AJ, Heykants JJ, Woestenborghs RJ, Gelders YG, Aerts TJ (1982). "Pharmacokinetics of haloperidol decanoate. A 2-year follow-up". International Pharmacopsychiatry. 17 (4): 238–46. doi:10.1159/000468580. PMID 7185768.
- Larsson M, Axelsson R, Forsman A (1984). "On the pharmacokinetics of perphenazine: a clinical study of perphenazine enanthate and decanoate". Current Therapeutic Research. 36 (6): 1071–88.
- "Procedural steps taken and scientific information after the authorisation" (PDF). EMA. July 16, 2015.
- "Invega Trinza (paliperidone palmitate) NDA approval letter" (PDF). U.S. Food and Drug Administration. Retrieved December 10, 2015.
- "Trevicta (previously Paliperidone Janssen)". Summary of the European public assessment report (EPAR) for Trevicta. EMC. September 17, 2018.