Fluphenazine

Last updated

Fluphenazine
Fluphenazine.svg
Fluphenazine-xtal-2012-ball-and-stick.png
Clinical data
Trade names Prolixin, Modecate, Moditen others
AHFS/Drugs.com Monograph
MedlinePlus a682172
License data
Pregnancy
category
  • AU:C
Routes of
administration
By mouth, Intramuscular injection, depot injection (fluphenazine decanoate)
Drug class Typical antipsychotic
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 2.7% (by mouth)
Metabolism unclear [2]
Elimination half-life IM 15 hours (HCL), 7–10 days (decanoate) [2]
Excretion Urine, feces
Identifiers
  • 2-[4-[3-[2-(trifluoromethyl)-10H-phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.639 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C22H26F3N3OS
Molar mass 437.53 g·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,3,8-15H2 Yes check.svgY
  • Key:PLDUPXSUYLZYBN-UHFFFAOYSA-N Yes check.svgY
   (verify)

Fluphenazine, sold under the brand name Prolixin among others, is a high-potency typical antipsychotic medication. [2] It is used in the treatment of chronic psychoses such as schizophrenia, [2] [3] and appears to be about equal in effectiveness to low-potency antipsychotics like chlorpromazine. [4] It is given by mouth, injection into a muscle, or 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]

Contents

Common side effects include movement problems, sleepiness, depression and increased weight. [2] Serious side effects may include neuroleptic malignant syndrome, low white blood cell levels, and the potentially permanent movement disorder tardive dyskinesia. [2] In older people with psychosis as a result of dementia it may increase the risk of dying. [2] It may also increase prolactin levels which may result in milk production, enlarged breasts in males, 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. [7] The injectable form is on the World Health Organization's List of Essential Medicines. [8] It is available as a 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

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]
SiteKi (nM)ActionRef
5-HT1A 145–2829ND [17]
5-HT1B 334ND [17]
5-HT1D 334ND [17]
5-HT1E 540ND [17]
5-HT2A 3.8–98ND [17]
5-HT2B NDND [17]
5-HT2C 174–2,570ND [17]
5-HT3 4,265– >10,000ND [17]
5-HT5A 145ND [17]
5-HT6 7.9–38ND [17]
5-HT7 8ND [17]
D1 14.45ND [17]
D2 0.89ND
D2L ND [17]
D3 1.412ND [17]
D4 89.12ND [17]
D5 95–2,590ND [17]
α1A 6.4–9ND [17]
α1B 13ND [17]
α2A 304–314ND [17]
α2B 181.6–320ND [17]
α2C 28.8–122ND [17]
β1 >10,000ND [17]
β2 >10,000ND [17]
H1 7.3–70ND [17]
H2 560ND [17]
H3 1,000ND [17]
H4 >10,000ND [17]
M1 1,095-3,235.93ND [17]
M2 2,187.76–7,163ND [17]
M3 1441–1445.4ND [17]
M4 5,321ND [17]
M5 357ND [17]
SERT Tooltip Serotonin transporterNDND [17]
NET Tooltip Norepinephrine transporterNDND [17]
DAT Tooltip Dopamine transporterNDND [17]
NMDA
(PCP)
NDND [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
MedicationBrand nameClassVehicleDosageTmaxt1/2 singlet1/2 multiplelogPcRef
Aripiprazole lauroxil Aristada Atypical Water a441–1064 mg/4–8 weeks24–35 days ?54–57 days7.9–10.0
Aripiprazole monohydrate Abilify Maintena Atypical Water a300–400 mg/4 weeks7 days ?30–47 days4.9–5.2
Bromperidol decanoate Impromen Decanoas Typical Sesame oil 40–300 mg/4 weeks3–9 days ?21–25 days7.9 [18]
Clopentixol decanoate Sordinol Depot Typical Viscoleo b50–600 mg/1–4 weeks4–7 days ?19 days9.0 [19]
Flupentixol decanoate Depixol Typical Viscoleo b10–200 mg/2–4 weeks4–10 days8 days17 days7.2–9.2 [19] [20]
Fluphenazine decanoateProlixin Decanoate Typical Sesame oil 12.5–100 mg/2–5 weeks1–2 days1–10 days14–100 days7.2–9.0 [21] [22] [23]
Fluphenazine enanthateProlixin Enanthate Typical Sesame oil 12.5–100 mg/1–4 weeks2–3 days4 days ?6.4–7.4 [22]
Fluspirilene Imap, Redeptin Typical Water a2–12 mg/1 week1–8 days7 days ?5.2–5.8 [24]
Haloperidol decanoate Haldol Decanoate Typical Sesame oil 20–400 mg/2–4 weeks3–9 days18–21 days7.2–7.9 [25] [26]
Olanzapine pamoate Zyprexa Relprevv Atypical Water a150–405 mg/2–4 weeks7 days ?30 days
Oxyprothepin decanoate Meclopin Typical  ? ? ? ? ?8.5–8.7
Paliperidone palmitate Invega Sustenna Atypical Water a39–819 mg/4–12 weeks13–33 days25–139 days ?8.1–10.1
Perphenazine decanoate Trilafon Dekanoat Typical Sesame oil 50–200 mg/2–4 weeks ? ?27 days8.9
Perphenazine enanthate Trilafon Enanthate Typical Sesame oil 25–200 mg/2 weeks2–3 days ?4–7 days6.4–7.2 [27]
Pipotiazine palmitate Piportil Longum Typical Viscoleo b25–400 mg/4 weeks9–10 days ?14–21 days8.5–11.6 [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 weeks21 days ?3–6 days
Zuclopentixol acetate Clopixol Acuphase Typical Viscoleo b50–200 mg/1–3 days1–2 days1–2 days4.7–4.9
Zuclopentixol decanoate Clopixol Depot Typical Viscoleo b50–800 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

Fluphenazine came into use in 1959. [7]

Availability

The injectable form is on the World Health Organization's List of Essential Medicines. [8] It is available as a 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]

Related Research Articles

<span class="mw-page-title-main">Antipsychotic</span> Class of medications

Antipsychotics, previously known as neuroleptics and major tranquilizers, are a class of psychotropic medication primarily used to manage psychosis, principally in schizophrenia but also in a range of other psychotic disorders. They are also the mainstay, together with mood stabilizers, in the treatment of bipolar disorder. Moreover, they are also used as adjuncts in the treatment of treatment-resistant major depressive disorder.

<span class="mw-page-title-main">Haloperidol</span> Typical antipsychotic medication

Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosis, and hallucinations from alcohol withdrawal. It may be used by mouth or injection into a muscle or a vein. Haloperidol typically works within 30 to 60 minutes. A long-acting formulation may be used as an injection every four weeks by people with schizophrenia or related illnesses, who either forget or refuse to take the medication by mouth.

<span class="mw-page-title-main">Typical antipsychotic</span> Class of drugs

Typical antipsychotics are a class of antipsychotic drugs first developed in the 1950s and used to treat psychosis. Typical antipsychotics may also be used for the treatment of acute mania, agitation, and other conditions. The first typical antipsychotics to come into medical use were the phenothiazines, namely chlorpromazine which was discovered serendipitously. Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second-generation antipsychotics, also known as atypical antipsychotics, have largely supplanted the use of typical antipsychotics as first-line agents due to the higher risk of movement disorders in the latter.

<span class="mw-page-title-main">Risperidone</span> Antipsychotic medication

Risperidone, sold under the brand name Risperdal among others, is an atypical antipsychotic used to treat schizophrenia and bipolar disorder. It is taken either by mouth or by injection. The injectable versions are long-acting and last for 2–4 weeks.

<span class="mw-page-title-main">Perphenazine</span> Antipsychotic medication

Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades.

<span class="mw-page-title-main">Aripiprazole</span> Atypical antipsychotic

Aripiprazole, sold under the brand names Abilify and Aristada, among others, is an atypical antipsychotic. It is primarily used in the treatment of schizophrenia and bipolar disorder; other uses include as an add-on treatment in major depressive disorder and obsessive compulsive disorder (OCD), tic disorders, and irritability associated with autism. Aripiprazole is taken by mouth or via injection into a muscle. A Cochrane review found low-quality evidence of effectiveness in treating schizophrenia.

<span class="mw-page-title-main">Haloperidol decanoate</span> Typical antipsychotic medication

Haloperidol decanoate, sold under the brand name Haldol Decanoate among others, is a typical antipsychotic which is used in the treatment of schizophrenia. It is administered by injection into muscle at a dose of 100 to 200 mg once every 4 weeks or monthly. The dorsogluteal site is recommended. A 3.75-cm (1.5-inch), 21-gauge needle is generally used, but obese individuals may require a 6.5-cm (2.5-inch) needle to ensure that the drug is indeed injected intramuscularly and not subcutaneously. Haloperidol decanoate is provided in the form of 50 or 100 mg/mL oil solution of sesame oil and benzyl alcohol in ampoules or pre-filled syringes. Its elimination half-life after multiple doses is 21 days. The medication is marketed in many countries throughout the world.

<span class="mw-page-title-main">Flupentixol</span> Typical antipsychotic drug of the thioxanthene class

Flupentixol (INN), also known as flupenthixol, marketed under brand names such as Depixol and Fluanxol is a typical antipsychotic drug of the thioxanthene class. It was introduced in 1965 by Lundbeck. In addition to single drug preparations, it is also available as flupentixol/melitracen—a combination product containing both melitracen and flupentixol . Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK, Australia, Canada, Russian Federation, South Africa, New Zealand, Philippines, Iran, Germany, and various other countries.

<span class="mw-page-title-main">Paliperidone</span> Antipsychotic medication

Paliperidone, sold under the brand name Invega among others, is an atypical antipsychotic. It is mainly used to treat schizophrenia and schizoaffective disorder. It is marketed by Janssen Pharmaceuticals.

<span class="mw-page-title-main">Fluspirilene</span> Typical antipsychotic medication

Fluspirilene is a diphenylbutylpiperidine typical antipsychotic drug, used for the treatment of schizophrenia. It is administered intramuscularly. It was discovered at Janssen Pharmaceutica in 1963. A 2007 systematic review investigated the efficacy of fluspirilene decanoate for people with schizophrenia:

<span class="mw-page-title-main">Bromperidol</span> Chemical compound

Bromperidol, sold under the brand names Bromidol and Impromen among others, is a typical antipsychotic of the butyrophenone group which is used in the treatment of schizophrenia. It was discovered at Janssen Pharmaceutica in 1966. An ester prodrug, bromperidol decanoate, is a long-acting form of bromperidol used as a depot injectable.

<span class="mw-page-title-main">Zuclopenthixol</span> Typical antipsychotic medication

Zuclopenthixol, also known as zuclopentixol, is a medication used to treat schizophrenia and other psychoses. It is classed, pharmacologically, as a typical antipsychotic. Chemically it is a thioxanthene. It is the cis-isomer of clopenthixol. Clopenthixol was introduced in 1961, while zuclopenthixol was introduced in 1978.

<span class="mw-page-title-main">Clopenthixol</span> Antipsychotic medication

Clopenthixol (Sordinol), also known as clopentixol, is a typical antipsychotic drug of the thioxanthene class. It was introduced by Lundbeck in 1961.

<span class="mw-page-title-main">Pipotiazine</span> Typical antipsychotic medication

Pipotiazine (Piportil), also known as pipothiazine, is a typical antipsychotic of the phenothiazine class used in the United Kingdom and other countries for the treatment of schizophrenia. Its properties are similar to those of chlorpromazine. A 2004 systematic review investigated its efficacy for people with schizophrenia:

<span class="mw-page-title-main">Aripiprazole lauroxil</span> Chemical compound

Aripiprazole lauroxil, sold under the brand name Aristada, is a long-acting injectable atypical antipsychotic that was developed by Alkermes. It is an N-acyloxymethyl prodrug of aripiprazole that is administered via intramuscular injection once every four to eight weeks for the treatment of schizophrenia. Aripiprazole lauroxil was approved by the U.S. Food and Drug Administration (FDA) on 5 October 2015.

Viscoleo is a thin or low-viscosity vegetable oil. It is specifically a proprietary form of fractionated coconut oil and a medium-chain triglyceride (MCT) oil. It is prepared from the dried, solid endosperm of the fruit Cocos nucifera via hydrolysis, fractionation, and purification. Viscoleo is composed of the medium-chain fatty acids caprylic acid (C8) (55–60%), capric acid (C10) (40%), lauric acid (C12) (1–5%), and caproic acid (C6) (0.5%). It is used as an oil vehicle for several depot antipsychotics including clopentixol decanoate, flupentixol decanoate, pipotiazine palmitate, zuclopentixol acetate, and zuclopentixol decanoate. Injectable antipsychotics using Viscoleo as a carrier may be absorbed more rapidly and have shorter durations than preparations using sesame oil.

<span class="mw-page-title-main">Bromperidol decanoate</span> Chemical compound

Bromperidol decanoate, sold under the brand names Bromidol Depot, Bromodol Decanoato, and Impromen Decanoas, is an antipsychotic which has been marketed in Europe and Latin America. It is an antipsychotic ester and long-acting prodrug of bromperidol which is administered by depot intramuscular injection once every 4 weeks.

<span class="mw-page-title-main">Perphenazine enanthate</span> Typical antipsychotic medication

Perphenazine enanthate, sold under the brand name Trilafon Enantat among others, is a typical antipsychotic and a depot antipsychotic ester which is used in the treatment of schizophrenia and has been marketed in Europe. It is formulated in sesame oil and administered by intramuscular injection and acts as a long-lasting prodrug of perphenazine. Perphenazine enanthate is used at a dose of 25 to 200 mg once every 2 weeks by injection, with a time to peak levels of 2 to 3 days and an elimination half-life of 4 to 7 days.

<span class="mw-page-title-main">Oxyprothepin decanoate</span> Antipsychotic medication

Oxyprothepin decanoate, sold under the brand name Meclopin, is a typical antipsychotic which was used in the treatment of schizophrenia in the Czech Republic but is no longer marketed. It is administered by depot injection into muscle. The medication has an approximate duration of 2 to 3 weeks. The history of oxyprothepin decanoate has been reviewed.

<span class="mw-page-title-main">Antipsychotic ester</span> Class of prodrugs

An antipsychotic ester is an ester of an antipsychotic. They are used clinically as prodrugs to increase fat solubility and thereby prolong duration when antipsychotics are used as depot injectables.

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