Flupentixol

Flupentixol
Systematic (IUPAC) name
(EZ)-2-[4-[3-[2-(trifluoromethyl)thioxanthen-9-ylidene]propyl]piperazin-1-yl]ethanol
Clinical data
Trade names Depixol, Fluanxol
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
  • C
Routes of
administration		 Oral, IM (including a depot)
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)

  • Rx-only
Pharmacokinetic data
Bioavailability 40–55% (oral)[1]
Metabolism Gut wall, hepatic[2]
Biological half-life 35 hours[1]
Excretion Renal (negligible)[3]
Identifiers
CAS Number 2709-56-0 YesY
ATC code N05AF01 (WHO)
PubChem CID 5281881
IUPHAR/BPS 968
DrugBank DB00875 N
ChemSpider 4445173 YesY
UNII FA0UYH6QUO YesY
KEGG D01044 YesY
ChEMBL CHEMBL42055 N
Chemical data
Formula C23H25F3N2OS
Molar mass 434.5219 g/mol
 NYesY (what is this?)  (verify)

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.

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 however is little evidence to support its use for this indication.[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
- Muscle rigidity
- Hypokinesia
- Hyperkinesia
- Parkinsonism
- Tremor
- Akathisia
- Dystonia
- 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
Uncommon (0.1–1% incidence) adverse effects include
Rare (<0.1% incidence) adverse effects include
- 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
- 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

Interactions

It should be not 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]

Pharmacology

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.

References

  1. 1 2 3 4 5 "Depixol Tablets 3mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Lundbeck Ltd. 27 December 2012. Retrieved 20 October 2013.
  2. ↑ 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.
  3. ↑ "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.
  4. 1 2 3 4 5 6 7 Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
  5. 1 2 3 4 5 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
  6. ↑ "Fluanxol® (flupentixol) Tablets Registration Certificate". Russian State Register of Medicinal Products. Retrieved 29 July 2014.
  7. ↑ Shen, X; Xia, J; Adams, CE (Nov 14, 2012). Shen, Xiaohong, ed. "Flupenthixol versus placebo for schizophrenia". Cochrane database of systematic reviews (Online) 11: CD009777. doi:10.1002/14651858.CD009777.pub2. PMID 23152280.
  8. ↑ Robertson MM, Trimble MR (May 1981). "The antidepressant action of flupenthixol". The Practitioner 225 (1355): 761–3. PMID 7291129.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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.
  13. ↑ 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 : the Journal of Mental Science 140 (3): 287–91. doi:10.1192/bjp.140.3.287. PMID 7093597.
  14. ↑ 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.". The Cochrane database of systematic reviews 7: CD011777. PMID 26147958.
  15. ↑ Bostwick, JR; Guthrie, SK; Ellingrod, VL (January 2009). "ntipsychotic-induced hyperprolactinemia". Pharmacotherapy 29 (1): 64–73. doi:10.1592/phco.29.1.64. PMID 19113797.
  16. 1 2 3 4 5 6 "FLUANXOL® DEPOT FLUANXOL® CONCENTRATED DEPOT". TGA eBusiness Services. Lundbeck Australia Pty Ltd. 28 June 2013. Retrieved 20 October 2013.
  17. ↑ 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. Retrieved 20 October 2013.
  18. ↑ 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.
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