Flupentixol
Clinical data | |
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Trade names | Depixol, Fluanxol |
AHFS/Drugs.com | Micromedex Detailed Consumer Information |
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IM (including a depot) | |
Drug class | Typical antipsychotic |
ATC code | |
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Renal (negligible)[3] | |
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Flupentixol (
Medical uses
Flupentixol's main use is as a long-acting injection given once in every two or three weeks to individuals with schizophrenia who have poor compliance with medication and have frequent relapses of illness, though it is also commonly given as a tablet. There is little formal evidence to support its use for this indication but it has been in use for over fifty years.[5][8]
Flupentixol is also used in low doses as an antidepressant.[5][9][10][11][12][13][14] There is tentative evidence that it reduces the rate of deliberate self-harm, among those who self-harm repeatedly.[15]
Adverse effects
Adverse effect incidence[2][5][6][16][17]
- Common (>1% incidence) adverse effects include
- Extrapyramidal side effects such as: (which usually become apparent soon after therapy is begun or soon after an increase in dose is made)
- Dry mouth
- Constipation
- Hypersalivation – excessive salivation
- Blurred vision
- Diaphoresis – excessive sweating
- Nausea
- Dizziness
- Somnolence
- Restlessness
- Insomnia
- Overactivity
- Headache
- Nervousness
- Fatigue
- Myalgia
- Hyperprolactinemiaand its complications such as: (acutely)
- Sexual dysfunction
- Amenorrhea – cessation of menstrual cycles
- Gynecomastia – enlargement of breast tissue in males
- Galactorrhea – the expulsion of breast milk that's not related to breastfeeding or pregnancy
- and if the hyperprolactinemia persists chronically, the following adverse effects may be seen:
- Reduced bone mineral density leading to osteoporosis (brittle bones)
- Infertility
- Dyspepsia – indigestion
- Abdominal pain
- Flatulence
- Nasal congestion
- Polyuria – passing more urine than usual
- Uncommon (0.1–1% incidence) adverse effects include
- Fainting
- Palpitations
- Rare (<0.1% incidence) adverse effects include
- Blood dyscrasias (abnormalities in the cell composition of blood), such as:
- Agranulocytosis – a drop in white blood cell counts that leaves one open to potentially life-threatening infections
- neutrophils(white blood cells that specifically fight bacteria) in one's blood
- Leucopenia– a less severe drop in white blood cell counts than agranulocytosis
- Thrombocytopenia – a drop in the number of platelets in the blood. Platelets are responsible for blood clotting and hence this leads to an increased risk of bruising and other bleeds
- D2 receptorblockade. The symptoms include:
- Hyperthermia
- Muscle rigidity
- Rhabdomyolysis
- Autonomic instability (e.g., tachycardia, diarrhea, diaphoresis, etc.)
- Mental status changes (e.g., coma, agitation, anxiety, confusion, etc.)
- Unknown incidence adverse effects include
- Jaundice
- Abnormal liver function test results
- typical antipsychoticslike flupenthixol. It presents with repetitive, involuntary, purposeless and slow movements; TD can be triggered by a fast dose reduction in any antipsychotic.
- Hypotension
- Confusional state
- Seizures
- Mania
- Hypomania
- Depression
- Hot flush
- Anergia
- Appetite changes
- Weight changes
- Hyperglycemia – high blood glucose (sugar) levels
- Abnormal glucose tolerance
- Pruritus – itchiness
- Rash
- Dermatitis
- Photosensitivity – sensitivity to light
- Oculogyric crisis
- Accommodation disorder
- Sleep disorder
- Impaired concentration
- Tachycardia
- Torsades de pointes
- Miosis – constriction of the pupil of the eye
- Paralytic ileus – paralysis of the bowel muscles leading to severe constipation, inability to pass wind, etc.
- Mydriasis
- Glaucoma
Interactions
It should not be used concomitantly with medications known to prolong the QTc interval (e.g.,
Contraindications
It should not be given in the following disease states:[2][5][6][17]
- Pheochromocytoma
- Prolactin-dependent tumors such as pituitary prolactinomas and breast cancer
- Long QT syndrome
- Coma
- Circulatory collapse
- Subcortical brain damage
- Blood dyscrasia
- Parkinson's disease
- Dementia with Lewy bodies
Pharmacology
Pharmacodynamics
Binding profile[20]
Protein | cis-flupentixol | trans-flupentixol |
---|---|---|
5-HT1A | 8028 | — |
5-HT2A | 87.5 (HFC) | — |
5-HT2C | 102.2 (RC) | — |
mAChRs[21] | Neg. | Neg. |
D1 |
3.5 | 474 (MB) |
D2 |
0.35 | 120 |
D3 |
1.75 | 162.5 |
D4 |
66.3 | >1000 |
H1 | 0.86 | 5.73 |
Acronyms used:
HFC – Human frontal cortex receptor
MB – Mouse brain receptor
RC – Cloned rat receptor
A study measuring the in vivo receptor occupancies of 13 schizophrenic patients treated with 5.7 ± 1.4 mg/day of flupentixol found 50-70% receptor occupancy for D2, 20 ± 5% for D1, and 20 ± 10% for 5-HT2A.[22]
Its antipsychotic effects are predominantly a function of D2 antagonism.
Its antidepressant effects at lower doses are not well understood; however, it may be mediated by functional selectivity and/or preferentially binding to D2 autoreceptors at low doses, resulting in increased postsynaptic activation via higher dopamine levels. Flupentixol's demonstrated ability to raise dopamine levels in mice[23] and flies[24] lends credibility to the supposition of autoreceptor bias. Functional selectivity may be responsible through causing preferential autoreceptor binding or other means. The effective dosage guideline for an antipsychotic is very closely related to its receptor residency time (i.e., where drugs like aripiprazole take several minutes or more to disassociate from a receptor while drugs like quetiapine and clozapine—with guideline dosages in the hundreds of milligrams—take under 30s)[25][26][27] and long receptor residency time is strongly correlated with likehood of pronounced functional selectivity;[28] thus, with a maximum guideline dose of only 18 mg/day for schizophrenia, there is a significant possibility of this drug possessing unique signalling characteristics that permit counterintuitive dopaminergic action at low doses.
Pharmacokinetics
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 | [29] |
Clopentixol decanoate |
Sordinol Depot | Typical | Viscoleob | 50–600 mg/1–4 weeks | 4–7 days | ? | 19 days | 9.0 | [30] |
Flupentixol decanoate | Depixol | Typical | Viscoleob | 10–200 mg/2–4 weeks | 4–10 days | 8 days | 17 days | 7.2–9.2 | [30][31] |
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 | [32][33][34] |
Fluphenazine enanthate |
Prolixin Enanthate | Typical | Sesame oil | 12.5–100 mg/1–4 weeks | 2–3 days | 4 days | ? | 6.4–7.4 | [33] |
Fluspirilene | Imap, Redeptin | Typical | Watera | 2–12 mg/1 week | 1–8 days | 7 days | ? | 5.2–5.8 | [35] |
Haloperidol decanoate | Haldol Decanoate | Typical | Sesame oil | 20–400 mg/2–4 weeks | 3–9 days | 18–21 days | 7.2–7.9 | [36][37] | |
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 | [38] |
Pipotiazine palmitate |
Piportil Longum | Typical | Viscoleob | 25–400 mg/4 weeks | 9–10 days | ? | 14–21 days | 8.5–11.6 | [31] |
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 . Sources: Main: See template. |
History
In March 1963 the Danish pharmaceutical company Lundbeck began research into further agents for schizophrenia, having already developed the thioxanthene derivatives clopenthixol and chlorprothixene. By 1965 the promising agent flupenthixol had been developed and trialled in two hospitals in Vienna by Austrian psychiatrist Heinrich Gross.[39] The long- acting decanoate preparation was synthesised in 1967 and introduced into hospital practice in Sweden in 1968, with a reduction in relapses among patients who were put on the depot.[40]
References
- ^ Anvisa (2023-03-31). "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 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
- ^ a b c d e "Depixol Tablets 3mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Lundbeck Ltd. 27 December 2012. Retrieved 20 October 2013.
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- ^ ISBN 978-0-85711-084-8.
- ^ ISBN 978-0-9805790-9-3.
- ^ "Fluanxol® (flupentixol) Tablets Registration Certificate". Russian State Register of Medicinal Products. Retrieved 29 July 2014.
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- ^ a b c d e f "FLUANXOL® DEPOT FLUANXOL® CONCENTRATED DEPOT". TGA eBusiness Services. Lundbeck Australia Pty Ltd. 28 June 2013. Retrieved 20 October 2013.
- ^ "Guidelines for the Management of QTc Prolongation in Adults Prescribed Antipsychotics" (PDF). nhs.uk.
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- ^ Roth, BL, Driscol, J (12 January 2011). "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Archived from the original on 8 November 2013. Retrieved 20 October 2013.
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- ^ 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.
- ^ PMID 6931472.
- ^ a b Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
- PMID 6143748.
- ^ 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.
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- ^ 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.
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