Flupentixol

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Flupentixol
Flupentixol structure.svg
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
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)

  • Rx-only
Routes of
administration		 Oral, IM (including a depot)
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
Molecular mass 434.5219 g/mol
  • FC(F)(F)c2cc1C(\c3c(Sc1cc2)cccc3)=C/CCN4CCN(CCO)CC4
  • InChI=1S/C23H25F3N2OS/c24-23(25,26)17-7-8-22-20(16-17)18(19-4-1-2-6-21(19)30-22)5-3-9-27-10-12-28(13-11-27)14-15-29/h1-2,4-8,16,29H,3,9-15H2/b18-5- YesY
  • Key:NJMYODHXAKYRHW-DVZOWYKESA-N YesY
 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. 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 US. 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]

Adverse effects

Adverse effect incidence[1][4][5][14][15]

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
- 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
  • 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 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.[15][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][15] 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][15] It should be avoided in patients on CNS depressants such as opioids, alcohol and barbiturates.[15]

Contraindications

It should not be given in the following disease states:[1][4][5][15]

Pharmacology

Binding profile[16]

Protein cis-flupentixol trans-flupentixol
5-HT1A 8028 —
5-HT2A 87.5 (HFC) —
5-HT2C 102.2 (RC) —
mAChRs[17] 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

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  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ 15.0 15.1 15.2 15.3 15.4 15.5 Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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