Flupentixol
Flupentixol (INN), also known as flupenthixol (former BAN), 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 (a tricyclic antidepressant) and flupentixol. Flupentixol is not approved for use in the United States. It is, however, approved for use in the UK,[4] Australia,[5] Canada, Russian Federation,[6] South Africa, New Zealand, Philippines and various other countries.
 | |
| Clinical data | |
|---|---|
| Trade names | Depixol, Fluanxol |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
| Pregnancy category |
|
| Routes of administration | Oral, IM (including a depot) |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 40–55% (oral)[1] |
| Metabolism | Gut wall, hepatic[2] |
| Elimination half-life | 35 hours[1] |
| Excretion | Renal (negligible)[3] |
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| IUPHAR/BPS | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.053.397 100.018.459, 100.053.397  |
| Chemical and physical data | |
| Formula | C23H25F3N2OS |
| Molar mass | 434.52 g·mol−1 |
| 3D model (JSmol) | |
| |
| |
  (what is this?) (verify) | |
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 suffer 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.[4][7]
Flupentixol is also used in low doses as an antidepressant.[4][8][9][10][11][12][13] There is tentative evidence that it reduces the rate of deliberate self-harm, among those who self-harm repeatedly.[14]
Adverse effects
Adverse effect incidence[1][4][5][15][16]
- 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)
- - Muscle rigidity
- - Hypokinesia
- - Hyperkinesia
- - Parkinsonism
- - Tremor
- - Akathisia
- - Dystonia
- Dry mouth
- Constipation
- Hypersalivation – excessive salivation
- Blurred vision
- Diaphoresis – excessive sweating
- Nausea
- Dizziness
- Somnolence
- Restlessness
- Insomnia
- Overactivity
- Headache
- Nervousness
- Fatigue
- Myalgia
- Hyperprolactinemia and 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
- - Neutropenia – a drop in the number of 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
- Neuroleptic malignant syndrome – a potentially fatal condition that appear to result from central D2 receptor blockade. 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
- Tardive dyskinesia – an often incurable movement disorder that usually results from years of continuous treatment with antipsychotic drugs, especially typical antipsychotics like 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
- QTc interval prolongation – an abnormality in the electrical activity of the heart that can lead to potentially fatal changes in heart rhythm
- 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. 5-HT3 antagonists, tricyclic antidepressants, citalopram, etc.) as this may lead to an increased risk of QTc interval prolongation.[16][1] Neither should it be given concurrently with lithium (medication) as it may increase the risk of lithium toxicity and neuroleptic malignant syndrome.[4][5][16] It should not be given concurrently with other antipsychotics due to the potential for this to increase the risk of side effects, especially neurological side effects such as neuroleptic malignant syndrome.[4][5][16] It should be avoided in patients on CNS depressants such as opioids, alcohol and barbiturates.[16]
Contraindications
It should not be given in the following disease states:[1][4][5][16]
- 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[17]
| Protein | cis-flupentixol | trans-flupentixol |
|---|---|---|
| 5-HT1A | 8028 | — |
| 5-HT2A | 87.5 (HFC) | — |
| 5-HT2C | 102.2 (RC) | — |
| mAChRs[18] | 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
Its antipsychotic effects are likely caused by D2 and/or 5-HT2A antagonism, whereas its antidepressant effects at lower doses may be mediated by preferential D2/D3 autoreceptor blockade, resulting in increased postsynaptic activation.
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 | [19] |
| Clopentixol decanoate | Sordinol Depot | Typical | Viscoleob | 50–600 mg/1–4 weeks | 4–7 days | ? | 19 days | 9.0 | [20] |
| Flupentixol decanoate | Depixol | Typical | Viscoleob | 10–200 mg/2–4 weeks | 4–10 days | 8 days | 17 days | 7.2–9.2 | [20][21] |
| 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 | [22][23][24] |
| Fluphenazine enanthate | Prolixin Enanthate | Typical | Sesame oil | 12.5–100 mg/1–4 weeks | 2–3 days | 4 days | ? | 6.4–7.4 | [23] |
| Fluspirilene | Imap, Redeptin | Typical | Watera | 2–12 mg/1 week | 1–8 days | 7 days | ? | 5.2–5.8 | [25] |
| Haloperidol decanoate | Haldol Decanoate | Typical | Sesame oil | 20–400 mg/2–4 weeks | 3–9 days | 18–21 days | 7.2–7.9 | [26][27] | |
| 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 | [28] |
| Pipotiazine palmitate | Piportil Longum | Typical | Viscoleob | 25–400 mg/4 weeks | 9–10 days | ? | 14–21 days | 8.5–11.6 | [21] |
| 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 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. | |||||||||
References
- "Depixol Tablets 3mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Lundbeck Ltd. 27 December 2012. Retrieved 20 October 2013.
- Jann, MW; Ereshefsky, L; Saklad, SR (July–August 1985). "Clinical pharmacokinetics of the depot antipsychotics". Clinical Pharmacokinetics. 10 (4): 315–333. doi:10.2165/00003088-198510040-00003. PMID 2864156.
- Balant-Gorgia, A. E.; Balant, L. (Aug 1987). "Antipsychotic drugs: clinical pharmacokinetics of potential candidates for plasma concentration monitoring". Clinical Pharmacokinetics. 13 (2): 65–90. doi:10.2165/00003088-198713020-00001. PMID 2887326.
- Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
- Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
- "Fluanxol® (flupentixol) Tablets Registration Certificate". Russian State Register of Medicinal Products. Retrieved 29 July 2014.
- Shen, X; Xia, J; Adams, CE (Nov 14, 2012). Shen, Xiaohong (ed.). "Flupenthixol versus placebo for schizophrenia". Cochrane Database of Systematic Reviews. 11: CD009777. doi:10.1002/14651858.CD009777.pub2. PMID 23152280.
- Robertson MM, Trimble MR (May 1981). "The antidepressant action of flupenthixol". The Practitioner. 225 (1355): 761–3. PMID 7291129.
- Pöldinger W, Sieberns S (1983). "Depression-inducing and antidepressive effects of neuroleptics. Experiences with flupenthixol and flupenthixol decanoate". Neuropsychobiology. 10 (2–3): 131–6. doi:10.1159/000117999. PMID 6674820.
- Johnson DA (January 1979). "A double-blind comparison of flupenthixol, nortriptyline and diazepam in neurotic depression". Acta Psychiatrica Scandinavica. 59 (1): 1–8. doi:10.1111/j.1600-0447.1979.tb06940.x. PMID 369298.
- Young JP, Hughes WC, Lader MH (May 1976). "A controlled comparison of flupenthixol and amitriptyline in depressed outpatients". British Medical Journal. 1 (6018): 1116–8. doi:10.1136/bmj.1.6018.1116. PMC 1639983. PMID 773506.
- Fujiwara J, Ishino H, Baba O, Hanaoka M, Sasaki K (August 1976). "Effect of flupenthixol on depression with special reference to combination use with tricyclic antidepressants. An uncontrolled pilot study with 45 patients". Acta Psychiatrica Scandinavica. 54 (2): 99–105. doi:10.1111/j.1600-0447.1976.tb00101.x. PMID 961463.
- Tam W, Young JP, John G, Lader MH (March 1982). "A controlled comparison of flupenthixol decanoate injections and oral amitriptyline in depressed out-patients". The British Journal of Psychiatry. 140 (3): 287–91. doi:10.1192/bjp.140.3.287. PMID 7093597.
- Hawton, K; Witt, KG; Taylor Salisbury, TL; Arensman, E; Gunnell, D; Hazell, P; Townsend, E; van Heeringen, K (6 July 2015). "Pharmacological interventions for self-harm in adults" (PDF). The Cochrane Database of Systematic Reviews. 7 (7): CD011777. doi:10.1002/14651858.CD011777. hdl:10536/DRO/DU:30080508. PMID 26147958.
- Bostwick, JR; Guthrie, SK; Ellingrod, VL (January 2009). "ntipsychotic-induced hyperprolactinemia" (PDF). Pharmacotherapy. 29 (1): 64–73. doi:10.1592/phco.29.1.64. hdl:2027.42/90238. PMID 19113797.
- "FLUANXOL® DEPOT FLUANXOL® CONCENTRATED DEPOT". TGA eBusiness Services. Lundbeck Australia Pty Ltd. 28 June 2013. Retrieved 20 October 2013.
- 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.
- Golds PR, Przyslo FR, Strange PG (March 1980). "The binding of some antidepressant drugs to brain muscarinic acetylcholine receptors". British Journal of Pharmacology. 68 (3): 541–9. doi:10.1111/j.1476-5381.1980.tb14570.x. PMC 2044199. PMID 7052344.
- 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.
- Jørgensen 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. PMID 6931472.
- Reynolds JE (1993). "Anxiolytic sedatives, hypnotics and neuroleptics.". Martindale: The Extra Pharmacopoeia (30th ed.). London: Pharmaceutical Press. pp. 364–623.
- 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. PMID 6143748.
- Curry 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. PMC 1429660. 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.
- 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. PMID 4992598.
- 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. PMID 3545764.
- 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. PMID 7185768.
- 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.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.