Fluphenazine
Fluphenazine, sold under the brand names Prolixin among others, is an antipsychotic medication.[1] It is used in the treatment of chronic psychoses such as schizophrenia,[1][2] and appears to be about equal in effectiveness to low-potency antipsychotics like chlorpromazine.[3] It is given by mouth, injection into a muscle, or just under the skin.[1] There is also a long acting injectable version that may last for up to four weeks.[1] Fluphenazine decanoate, the depot injection form of fluphenazine, should not be used by people with severe depression.[4]
Clinical data | |
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Trade names | Prolixin, Modecate, Moditen others |
AHFS/Drugs.com | Monograph |
MedlinePlus | a682172 |
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Routes of administration | by mouth, IM, depot injection (fluphenazine decanoate) |
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Pharmacokinetic data | |
Bioavailability | 2.7% (by mouth) |
Metabolism | unclear[1] |
Elimination half-life | IM 15 hours (HCL), 7-10 days (decanoate)[1] |
Excretion | Urine, faeces |
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ECHA InfoCard | 100.000.639 |
Chemical and physical data | |
Formula | C22H26F3N3OS |
Molar mass | 437.523 g/mol g·mol−1 |
3D model (JSmol) | |
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Common side effects include movement problems, sleepiness, depression and increased weight.[1] Serious side effects may include neuroleptic malignant syndrome, low white blood cell levels, and the potentially permanent movement disorder tardive dyskinesia.[1] In older people with psychosis as a result of dementia it may increase the risk of dying.[1] It may also increase prolactin levels which may result in milk production, enlarged breasts in males, impotence, and the absence of menstrual periods.[1] It is unclear if it is safe for use in pregnancy.[1] Fluphenazine is a typical antipsychotic of the phenothiazine class.[1] Its mechanism of action is not entirely clear but believed to be related to its ability to block dopamine receptors.[1] In up to 40% of those on long term phenothiazines, liver function tests become mildly abnormal.[5]
Fluphenazine came into use in 1959.[6] The injectable form is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[7] It is available as a generic medication.[1] In the United States the tablets costs between $0.22 and $0.42 per day for a typical dose.[1] The wholesale cost in the developing world of the long acting form is between US$0.20 and US$6.20 per injection as of 2014.[8] It was discontinued in Australia around mid 2017.[9]
Medical use
A 2018 Cochrane review found that fluphenazine's was an imperfect treatment and other inexpensive drugs less associated with side effects may be an just as good in 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 felling 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]
Mechanism of action
The drug acts primarily by blocking post-synaptic D2 receptors in the basal ganglia, cortical and limbic system. It also blocks alpha-1 adrenergic receptors, muscarinic-1 receptors, and histamine-1 receptors.[15][16]
Pharmacology
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] |
SERT | ND | ND | [17] |
NET | ND | ND | [17] |
DAT | 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] |
History
Fluphenazine came into use in 1959.[6]
Availability
The injectable form is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.[7] It is available as a generic medication.[1] In the United States the tablets costs between 0.22 and 0.42 USD per day for a typical dose.[1] The wholesale cost in the developing world of the long acting form is between 0.20 and 6.20 USD per injection as of 2014.[8] It was discontinued in Australia around mid 2017.[9]
Other animals
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.[18]
See also
- Phenothiazine
References
- "fluphenazine decanoate". The American Society of Health-System Pharmacists. Archived from the original on 8 December 2015. Retrieved 1 December 2015.
- "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.
- 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. 8 (8): CD009230. doi:10.1002/14651858.CD009230.pub2. PMID 25087165.
- "Modecate Injection 25mg/ml - Patient Information Leaflet (PIL) - (eMC)". www.medicines.org.uk. Retrieved 6 November 2017.
- "Fluphenazine". livertox.nih.gov. Retrieved 6 November 2017.
- McPherson EM (2007). Pharmaceutical Manufacturing Encyclopedia (3rd ed.). Burlington: Elsevier. p. 1680. ISBN 9780815518563.
- World 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.
- "Fluphenazine Decanoate". International Drug Price Indicator Guide. Archived from the original on 2 August 2017. Retrieved 2 December 2015.
- Rossi S, ed. (July 2017). "Fluphenazine - Australian Medicines Handbook". Australian Medicines Handbook. Adelaide, Australia: Australian Medicines Handbook Pty Ltd. Retrieved 8 August 2017.
- Matar, Hosam E.; Almerie, Muhammad Qutayba; Sampson, Stephanie J. (12 June 2018). "Fluphenazine (oral) versus placebo for schizophrenia". The Cochrane Database of Systematic Reviews. 6: CD006352. doi:10.1002/14651858.CD006352.pub3. ISSN 1469-493X. PMC 6513420. PMID 29893410.
- Joint Formulary Committee, BMJ, 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, Peter; Haddad, Peter M.; Dursun, Serdar; Deakin, Bill (2004). Adverse Syndromes and Psychiatric Drugs: A Clinical Guide. OUP Oxford. p. 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.
- Sacchetti, Emilio; Vita, Antonio; Siracusano, Alberto; Fleischhacker, Wolfgang (2013). Adherence to Antipsychotics in Schizophrenia. Springer Science & Business Media. p. 85. ISBN 9788847026797.
- Siragusa S, Saadabadi A. "Fluphenazine". StatPearls. PMID 29083807.
- PubChem. "Fluphenazine". pubchem.ncbi.nlm.nih.gov. Retrieved 30 September 2019.
- 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.
- 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.