Fluphenazine

Source: Wikipedia, the free encyclopedia.

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
Pharmacokinetic data
Bioavailability2.7% (by mouth)
Metabolismunclear[2]
Elimination half-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
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,3,8-15H2 checkY
  • Key:PLDUPXSUYLZYBN-UHFFFAOYSA-N checkY
  (verify)

Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical

just under the skin.[2] There is also a long acting injectable version that may last for up to four weeks.[2] Fluphenazine decanoate, the depot injection form of fluphenazine, should not be used by people with severe depression.[5]

Common side effects include

impotence, and the absence of menstrual periods.[2] It is unclear if it is safe for use in pregnancy.[2]

Fluphenazine is a typical antipsychotic of the phenothiazine class.[2] Its mechanism of action is not entirely clear but believed to be related to its ability to block 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.

generic medication.[2] It was discontinued in Australia in 2017.[9]

Medical use

A 2018 Cochrane review found that fluphenazine was an imperfect treatment and other inexpensive drugs less associated with side effects may be an equally effective choice for people with schizophrenia.[10]

Side effects

Discontinuation

The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse.[11] Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite.[12] Other symptoms may include restlessness, increased sweating, and trouble sleeping.[12] Less commonly there may be a feeling of the world spinning, numbness, or muscle pains.[12] Symptoms generally resolve after a short period of time.[12]

There is tentative evidence that discontinuation of antipsychotics can result in psychosis.[13] It may also result in reoccurrence of the condition that is being treated.[14] Rarely tardive dyskinesia can occur when the medication is stopped.[12]

Pharmacology

Pharmacodynamics

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

Fluphenazine acts primarily by blocking post-synaptic dopaminergic D2 receptors in the basal ganglia, cortical and limbic system. It also blocks α1 adrenergic receptors, muscarinic M1 receptors, and histaminergic H1 receptors.[15][16]

Fluphenazine[17]
Site Ki (nM) Action Ref
5-HT1A 145–2829 ND [17]
5-HT1B 334 ND [17]
5-HT1D 334 ND [17]
5-HT1E 540 ND [17]
5-HT2A 3.8–98 ND [17]
5-HT2B ND ND [17]
5-HT2C 174–2,570 ND [17]
5-HT3 4,265– >10,000 ND [17]
5-HT5A 145 ND [17]
5-HT6 7.9–38 ND [17]
5-HT7 8 ND [17]
D1
 14.45 ND [17]
D2
 0.89 ND
D2L
 ND [17]
D3
 1.412 ND [17]
D4
 89.12 ND [17]
D5
 95–2,590 ND [17]
α1A 6.4–9 ND [17]
α1B 13 ND [17]
α2A 304–314 ND [17]
α2B 181.6–320 ND [17]
α2C 28.8–122 ND [17]
β1 >10,000 ND [17]
β2 >10,000 ND [17]
H1
 7.3–70 ND [17]
H2
 560 ND [17]
H3
 1,000 ND [17]
H4
 >10,000 ND [17]
M1
 1,095-3,235.93 ND [17]
M2
 2,187.76–7,163 ND [17]
M3
 1441–1445.4 ND [17]
M4
 5,321 ND [17]
M5
 357 ND [17]
SERTTooltip Serotonin transporter ND ND [17]
NETTooltip Norepinephrine transporter ND ND [17]
DATTooltip Dopamine transporter ND ND [17]
NMDA
(PCP)		 ND ND [17]
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).[17]

Pharmacokinetics

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 [18]
Clopentixol decanoate
 Sordinol Depot Typical Viscoleob 50–600 mg/1–4 weeks 4–7 days ? 19 days 9.0 [19]
Flupentixol decanoate
 Depixol Typical Viscoleob 10–200 mg/2–4 weeks 4–10 days 8 days 17 days 7.2–9.2 [19][20]
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 [21][22][23]
Fluphenazine enanthate Prolixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks 2–3 days 4 days ? 6.4–7.4 [22]
Fluspirilene Imap, Redeptin Typical Watera 2–12 mg/1 week 1–8 days 7 days ? 5.2–5.8 [24]
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks 3–9 days 18–21 days 7.2–7.9 [25][26]
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 [27]
Pipotiazine palmitate
 Piportil Longum Typical Viscoleob 25–400 mg/4 weeks 9–10 days ? 14–21 days 8.5–11.6 [20]
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
fractionated coconut oil with medium-chain triglycerides). c = Predicted, from PubChem and DrugBank
. Sources: Main: See template.

History

Fluphenazine came into use in 1959.[7]

Availability

The injectable form is on the

generic medication.[2] It was discontinued in Australia in 2017.[9]

Veterinary

In horses, it is sometimes given by injection as an anxiety-relieving medication, though there are many negative common side effects and it is forbidden by many equestrian competition organizations.[28]

References

  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). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
  2. ^ a b c d e f g h i j k l m n o "fluphenazine decanoate". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 1 December 2015.
  3. ^ "Product Information: Modecate (Fluphenazine Decanoate Oily Injection )" (PDF). TGA eBusiness Services. Bristol-Myers Squibb Australia Pty Ltd. 1 November 2012. Archived from the original on 2 August 2017. Retrieved 9 December 2013.
  4. PMID 25087165
    .
  5. ^ "Modecate Injection 25mg/ml - Patient Information Leaflet (PIL) - (eMC)". www.medicines.org.uk. Archived from the original on 7 November 2017. Retrieved 6 November 2017.
  6. ^ "Fluphenazine". livertox.nih.gov. Retrieved 6 November 2017.
  7. ^
    ISBN 9780815518563
    .
  8. ^
    hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^ a b Rossi S, ed. (July 2017). "Fluphenazine - Australian Medicines Handbook". Australian Medicines Handbook. Adelaide, Australia: Australian Medicines Handbook Pty Ltd. Retrieved 8 August 2017.
  10. PMID 29893410
    .
  11. 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.
  12. ^
    ISBN 9780198527480
    .
  13. S2CID 6267180
    .
  14. ISBN 9788847026797
    .
  15. PMID 29083807
    .
  16. ^ "Fluphenazine". PubChem. U.S. National Library of Medicine. Retrieved 30 September 2019.
  17. ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  18. ^ 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.
  19. ^
    PMID 6931472
    .
  20. ^ a b Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
  21. PMID 6143748
    .
  22. ^
    PMID 444352
    .
  23. ^ 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.
  24. PMID 4992598
    .
  25. PMID 3545764
    .
  26. PMID 7185768
    .
  27. ^ 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.
  28. ^ Loving NS (31 March 2012). "Effects of Behavior-Modifying Drug Investigated (AAEP 2011)". The Horse Media Group. Archived from the original on 6 January 2017. Retrieved 13 December 2016.