関: flupenthixol

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/05/19 23:16:02」(JST)

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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
Hyperprolactinaemia and its complications such as: (acutely)

- Sexual dysfunction

- Amenorrhoea — cessation of menstrual cycles

- Gynaecomastia — enlargement of breast tissue in males

- Galactorrhoea — the expulsion of breast milk that's not related to breastfeeding or pregnancy

and if the hyperprolactinaemia 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

- Neutropaenia — 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, diarrhoea, 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
Hyperglycaemia — high blood glucose (sugar) levels
Abnormal glucose tolerance
Pruritus — itchiness
Rash
Dermatitis
Photosensitivity — sensitivity to light
Oculogyration
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]

Phaeochromocytoma
Prolactin-dependent tumours 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

Binding profile^[16]

Protein	cis-flupentixol	trans-flupentixol
5-HT_1A	8028	-
5-HT_2A	87.5 (HFC)	-
5-HT_2C	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-HT_2A antagonism, whereas its antidepressant effects at lower doses may be mediated by preferential D₂/D₃ autoreceptor blockade, resulting in increased postsynaptic activation.

Society and culture

The combination of flupenthixol and melitracen is banned by Indian regulatory body.^[18]

References

^ ^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.
^ 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.
^ "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.
^ ^a ^b ^c ^d ^e ^f ^g Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
^ ^a ^b ^c ^d ^e 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 (Online) 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 : the Journal of Mental Science 140 (3): 287–91. doi:10.1192/bjp.140.3.287. PMID 7093597.
^ 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.
^ ^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.
^ Roth, BL; Driscol, J (12 January 2011). "PDSP K_i 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.
^ 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.
^ "Central Government prohibits combination of Flupenthixol and Melitracen". PharmaTutor. 24 July 2014. Retrieved 12 August 2014.

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「フルペンチキソール」

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;
Legal status	AU: Prescription Only (S4); CA: ℞-only; UK: Prescription-only (POM); ; Rx-only;
Routes of; administration	Oral, IM (including a depot)
Pharmacokinetic data
Bioavailability	40-55% (Oral)
Metabolism	Gut wall, hepatic
Half-life	35 hours
Excretion	Renal (negligible)
Identifiers
CAS Registry Number	2709-56-0
ATC code	N05AF01
PubChem	CID 5281881
IUPHAR ligand	968
DrugBank	DB00875
ChemSpider	4445173
UNII	FA0UYH6QUO
KEGG	D01044
ChEMBL	CHEMBL42055
Chemical data
Formula	C23H25F3N2OS
Molecular mass	434.5219 g/mol
	SMILES FC(F)(F)c2cc1C(\c3c(Sc1cc2)cccc3)=C/CCN4CCN(CCO)CC4;
	InChI 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- ; Key:NJMYODHXAKYRHW-DVZOWYKESA-N ;
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英: flupentixol、flupenthixol
関: フルペンチクソール

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英: flupentixol
関: フルペンチキソール

「flupenthixol」

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フルペンチキソール

関: flupentixol

[EMC-1] "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.

[BNF-4] ^ ^a ^b ^c ^d ^e ^f ^g Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.

[AMH-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.

[pmid7291129-8] Robertson MM, Trimble MR (May 1981). "The antidepressant action of flupenthixol". The Practitioner 225 (1355): 761–3. PMID 7291129.

[pmid6674820-9] 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.

[pmid369298-10] 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.

[pmid773506-11] 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.

[pmid961463-12] 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.

[pmid7093597-13] 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] 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.

[FLUANXOL-15] ^ ^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.

[16] Roth, BL; Driscol, J (12 January 2011). "PDSP K_i 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.

[pmid7052344-17] 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.

[18] "Central Government prohibits combination of Flupenthixol and Melitracen". PharmaTutor. 24 July 2014. Retrieved 12 August 2014.

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