Wikipedia

Fluphenazine

Fluphenazine,sold under the brand nameProlixinamong others, is a high-potency typicalantipsychoticmedication.[2]It is used in the treatment of chronicpsychosessuch asschizophrenia,[2][3]and appears to be about equal in effectiveness to low-potencyantipsychoticslikechlorpromazine.[4]It is givenby mouth,injection into a muscle,orjust under the skin.[2]There is also a long acting injectable version that may last for up to four weeks.[2]Fluphenazine decanoate, thedepot injectionform of fluphenazine, should not be used by people with severe depression.[5]

Fluphenazine
Clinical data
Trade namesProlixin, Modecate, Moditen others
AHFS/Drugs.comMonograph
MedlinePlusa682172
License data
Pregnancy
category
  • AU:C
Routes of
administration		By mouth,Intramuscular injection,depot injection (fluphenazine decanoate)
Drug classTypical antipsychotic
ATC code
Legal status
Legal status
Pharmacokineticdata
Bioavailability2.7% (by mouth)
Metabolismunclear[2]
Eliminationhalf-lifeIM 15 hours (HCl), 7–10 days (decanoate)[2]
ExcretionUrine, feces
Identifiers
  • 2-[4-[3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol
CAS Number
PubChemCID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard(EPA)
ECHA InfoCard100.000.639Edit this at Wikidata
Chemical and physical data
FormulaC22H26F3N3OS
Molar mass437.53g·mol−1
3D model (JSmol)
  • FC(F)(F)c2cc1N(c3c(Sc1cc2)cccc3)CCCN4CCN(CCO)CC4
  • InChI=1S/C22H26F3N3OS/c23-22(24,25)17-6-7-21-19(16-17)28(18-4-1-2-5-20(18)30-21)9-3-8-26-10-12-27(13-11-26)14-15-29/h1-2,4-7,16,29H,3,8-15H2checkY
  • Key:PLDUPXSUYLZYBN-UHFFFAOYSA-NcheckY
(verify)

Common side effects includemovement problems,sleepiness,depressionandincreased weight.[2]Serious side effects may includeneuroleptic malignant syndrome,low white blood cell levels,and the potentially permanent movement disordertardive dyskinesia.[2]In older people with psychosis as a result ofdementiait may increase the risk of dying.[2]It may also increaseprolactinlevels which may result inmilk production,enlarged breasts in males,impotence,andthe absence of menstrual periods.[2]It is unclear if it is safe for use inpregnancy.[2]

Fluphenazine is atypical antipsychoticof thephenothiazineclass.[2]Its mechanism of action is not entirely clear but believed to be related to its ability toblock dopamine receptors.[2]In up to 40% of those on long term phenothiazines, liver function tests become mildly abnormal.[6]

Fluphenazine came into use in 1959.[7]The injectable form is on theWorld Health Organization's List of Essential Medicines.[8]It is available as ageneric medication.[2]It was discontinued in Australia in 2017.[9]

Medical use

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A 2018Cochranereview found that fluphenazine was an imperfect treatment and other inexpensive drugs less associated with side effects may be an equally effective choice for people withschizophrenia.[10]Another 2018 Cochrane review found that there was limited evidence that neweratypical antipsychoticswere more tolerable than fluphenazine.[11]Intramusculardepot injectionforms are available as both thedecanoateandenanthateesters.[12]

Side effects

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Discontinuation

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TheBritish National Formularyrecommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[13]Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[14]Other symptoms may include restlessness, increased sweating, and trouble sleeping.[14]Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[14]Symptoms generally resolve after a short period of time.[14]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[15]It may also result in reoccurrence of the condition that is being treated.[16]Rarely tardive dyskinesia can occur when the medication is stopped.[14]

Pharmacology

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Pharmacodynamics

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See also:Antipsychotic § Pharmacodynamics,andAntipsychotic § Comparison of medications

Fluphenazine acts primarily by blocking post-synaptic dopaminergic D2receptors in the basal ganglia, cortical and limbic system. It also blocks α1adrenergic receptors, muscarinic M1receptors, and histaminergic H1receptors.[17][18]

Fluphenazine[19]
Site Ki(nM) Action Ref
5-HT1A 145–2829 ND [19]
5-HT1B 334 ND [19]
5-HT1D 334 ND [19]
5-HT1E 540 ND [19]
5-HT2A 3.8–98 ND [19]
5-HT2B ND ND [19]
5-HT2C 174–2,570 ND [19]
5-HT3 4,265– >10,000 ND [19]
5-HT5A 145 ND [19]
5-HT6 7.9–38 ND [19]
5-HT7 8 ND [19]
D1 14.45 ND [19]
D2 0.89 ND
D2L ND [19]
D3 1.412 ND [19]
D4 89.12 ND [19]
D5 95–2,590 ND [19]
α1A 6.4–9 ND [19]
α1B 13 ND [19]
α2A 304–314 ND [19]
α2B 181.6–320 ND [19]
α2C 28.8–122 ND [19]
β1 >10,000 ND [19]
β2 >10,000 ND [19]
H1 7.3–70 ND [19]
H2 560 ND [19]
H3 1,000 ND [19]
H4 >10,000 ND [19]
M1 1,095-3,235.93 ND [19]
M2 2,187.76–7,163 ND [19]
M3 1441–1445.4 ND [19]
M4 5,321 ND [19]
M5 357 ND [19]
SERTTooltip Serotonin transporter ND ND [19]
NETTooltip Norepinephrine transporter ND ND [19]
DATTooltip Dopamine transporter ND ND [19]
NMDA
(PCP)		 ND ND [19]
Values are Ki(nM). The smaller the value, the more strongly the drug binds to the site. All data are for human cloned proteins, except 5-HT3(rat), D4(human/rat), H3(guinea pig), and NMDA/PCP (rat).[19]

Pharmacokinetics

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Pharmacokinetics of long-acting injectable antipsychotics
Medication Brand name Class Vehicle Dosage Tmax t1/2single t1/2multiple 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 [20]
Clopentixol decanoate Sordinol Depot Typical Viscoleob 50–600 mg/1–4 weeks 4–7 days ? 19 days 9.0 [21]
Flupentixol decanoate Depixol Typical Viscoleob 10–200 mg/2–4 weeks 4–10 days 8 days 17 days 7.2–9.2 [21][22]
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 [23][24][25]
Fluphenazine enanthate Prolixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks 2–3 days 4 days ? 6.4–7.4 [24]
Fluspirilene Imap, Redeptin Typical Watera 2–12 mg/1 week 1–8 days 7 days ? 5.2–5.8 [26]
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks 3–9 days 18–21 days 7.2–7.9 [27][28]
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 [29]
Pipotiazine palmitate Piportil Longum Typical Viscoleob 25–400 mg/4 weeks 9–10 days ? 14–21 days 8.5–11.6 [22]
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 byintramuscular injection.Footnotes:a=Microcrystallineornanocrystallineaqueous suspension.b= Low-viscosityvegetable oil(specificallyfractionated coconut oilwithmedium-chain triglycerides).c= Predicted, fromPubChemandDrugBank.Sources:Main:See template.

History

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Fluphenazine came into use in 1959.[7]

Availability

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The injectable form is on theWorld Health Organization's List of Essential Medicines.[8]It is available as ageneric medication.[2]It was discontinued in Australia in 2017.[9]

Veterinary

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In horses, it is sometimes given by injection as ananxiety-relieving medication,though there are many negative common side effects and it is forbidden by many equestrian competition organizations.[30]

References

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  1. ^Anvisa(31 March 2023)."RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial"[Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese).Diário Oficial da União(published 4 April 2023).Archivedfrom the original on 3 August 2023.Retrieved16 August2023.
  2. ^abcdefghijklmno"fluphenazine decanoate".The American Society of Health-System Pharmacists.Archivedfrom the original on 8 December 2015.Retrieved1 December2015.
  3. ^"Product Information: Modecate (Fluphenazine Decanoate Oily Injection )"(PDF).TGA eBusiness Services.Bristol-Myers Squibb Australia Pty Ltd. 1 November 2012.Archivedfrom the original on 2 August 2017.Retrieved9 December2013.
  4. ^Tardy M, Huhn M, Engel RR, Leucht S (August 2014)."Fluphenazine versus low-potency first-generation antipsychotic drugs for schizophrenia".The Cochrane Database of Systematic Reviews.2014(8): CD009230.doi:10.1002/14651858.CD009230.pub2.PMC10898219.PMID25087165.
  5. ^"Modecate Injection 25mg/ml - Patient Information Leaflet (PIL) - (eMC)".www.medicines.org.uk.Archived fromthe originalon 7 November 2017.Retrieved6 November2017.
  6. ^"Fluphenazine".livertox.nih.gov.2012.PMID31643176.Retrieved6 November2017.
  7. ^abMcPherson EM (2007).Pharmaceutical Manufacturing Encyclopedia(3rd ed.). Burlington: Elsevier. p. 1680.ISBN9780815518563.
  8. ^abWorld Health Organization(2019).World Health Organization model list of essential medicines: 21st list 2019.Geneva: World Health Organization.hdl:10665/325771.WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^abRossi S, ed. (July 2017)."Fluphenazine - Australian Medicines Handbook".Australian Medicines Handbook.Adelaide, Australia: Australian Medicines Handbook Pty Ltd.Retrieved8 August2017.
  10. ^Matar HE, Almerie MQ, Sampson SJ (June 2018)."Fluphenazine (oral) versus placebo for schizophrenia".The Cochrane Database of Systematic Reviews.6(6): CD006352.doi:10.1002/14651858.CD006352.pub3.PMC6513420.PMID29893410.
  11. ^Sampford JR, Sampson S, Li BG, Zhao S, Xia J, Furtado VA (July 2016)."Fluphenazine (oral) versus atypical antipsychotics for schizophrenia".The Cochrane Database of Systematic Reviews.7(7): CD010832.doi:10.1002/14651858.CD010832.pub2.PMC6474115.PMID27370402.
  12. ^Maayan N, Quraishi SN, David A, Jayaswal A, Eisenbruch M, Rathbone J, et al. (February 2015)."Fluphenazine decanoate (depot) and enanthate for schizophrenia".The Cochrane Database of Systematic Reviews.2015(2): CD000307.doi:10.1002/14651858.CD000307.pub2.PMC10388394.PMID25654768.
  13. ^Joint Formulary Committee B, ed. (March 2009). "4.2.1".British National Formulary(57 ed.). United Kingdom: Royal Pharmaceutical Society of Great Britain. p. 192.ISBN978-0-85369-845-6.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.
  14. ^abcdeHaddad P, Haddad PM, Dursun S, Deakin B (2004).Adverse Syndromes and Psychiatric Drugs: A Clinical Guide.OUP Oxford. pp.207–216.ISBN9780198527480.
  15. ^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.PMID16774655.S2CID6267180.
  16. ^Sacchetti E, Vita A, Siracusano A, Fleischhacker W (2013).Adherence to Antipsychotics in Schizophrenia.Springer Science & Business Media. p. 85.ISBN9788847026797.
  17. ^Siragusa S, Saadabadi A (2020)."Fluphenazine".StatPearls.PMID29083807.
  18. ^"Fluphenazine".PubChem.U.S. National Library of Medicine.Retrieved30 September2019.
  19. ^abcdefghijklmnopqrstuvwxyzaaabacadaeafagahaiajakalRoth BL,Driscol J."PDSP KiDatabase ".Psychoactive Drug Screening Program (PDSP).University of North Carolina at Chapel Hill and the United States National Institute of Mental Health.Retrieved14 August2017.
  20. ^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.
  21. ^abJørgensen 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.PMID6931472.
  22. ^abReynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.".Martindale: The Extra Pharmacopoeia(30th ed.). London: Pharmaceutical Press. pp.364–623.
  23. ^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.PMID6143748.
  24. ^abCurry 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.PMC1429660.PMID444352.
  25. ^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.
  26. ^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.PMID4992598.
  27. ^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.PMID3545764.
  28. ^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.PMID7185768.
  29. ^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.
  30. ^Loving NS (31 March 2012)."Effects of Behavior-Modifying Drug Investigated (AAEP 2011)".The Horse Media Group.Archivedfrom the original on 6 January 2017.Retrieved13 December2016.
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