Chemical: Drug
flupenthixol

last updated 02/07/2014

1. DPWG Guideline for flupenthixol and CYP2D6

Summary

There are currently no dosing recommendations for flupenthixol based on CYP2D6 genotype.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for flupenthixol based on CYP2D6 genotype [Article:21412232]. They did not find evidence for a gene-drug interaction and therefore provide no dosing recommendations at this time.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
PM (2 inactive alleles) None. None. None.
IM (2 decreased activity alleles, or 1 active and 1 inactive allele, or 1 decreased activity and 1 inactive allele) None. None. None.
UM (gene duplication in absence of inactive or decreased activity alleles) None. None. None.
Allele Type Alleles
active *1, *2, *33, *35
decreased activity *9, *10, *17, *29, *36, *41
inactive *3-*8, *11-*16, *19-*21, *38, *40, *42

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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Overview

Generic Names
  • Flupenthixole
Trade Names
  • Depixol
  • Emergil
  • Fluanxol
  • Fluanxol Depot
  • Flupentixol
  • Flurentixol
  • Fluxanxol
  • Siplaril
  • Siplarol
Brand Mixture Names

PharmGKB Accession Id

PA10268

Type(s):

Drug

Description

Flupentixol is an antipsychotic neuroleptic drug. It is a thioxanthene, and therefore closely related to the phenothiazines. Its primary use is as a long acting injection given two or three weekly to people with schizophrenia who have a poor compliance with medication and suffer frequent relapses of illness. It is a D1 and D2 receptor antagonist.

Source: Drug Bank

Indication

For use in the treatment of schizophrenia and depression

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Flupenthixol is a thioxanthene antipsychotic. The mechanism of action of Flupenthixol is not completely understood. Flupenthixol is a powerful antagonist of both D1 and D2 dopamine receptors, and an alpha-adrenergic receptor antagonist. It's antipsychotic activity is thought to be related to blocks postsynaptic dopamine receptors in the CNS.

Source: Drug Bank

Pharmacology

Flupenthixol is an anxiolytic, antidepressive agent and a mood stabilizer. It inhibits the central monoamine receptors, particularly the dopamine D1 and D2 receptors. Therefore, it increases the amount of serotonin and noradrenaline that control mood and thinking, and improves mood.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Take with food to reduce irritation.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Mainly hepatic

Source: Drug Bank

Protein Binding

Highly bound to plasma proteins (>95%)

Source: Drug Bank

Absorption

Fairly slow and incomplete after oral administration

Source: Drug Bank

Half-Life

19 to 39 hours

Source: Drug Bank

Toxicity

LD 50=300 mk/kg (Oral in mice); LD 50=791 mg/kg (Oral in rats); LD 50=87 mk/kg (IV in mice); LD 50=37 mg/kg (IV in rats)

Source: Drug Bank

Chemical Properties

Chemical Formula

C23H27F3N2OS

Source: Drug Bank

Isomeric SMILES

C1CN(CCN1CC/C=C/2\C3=CC=CC=C3SC4=C2C=C(C=C4)C(F)(F)F)CCO

Source: Drug Bank

OCCN1CCN(CCC=C2C3=C(SC4=C2C=C(C=C4)C(F)(F)F)C=CC=C3)CC1

Source: Drug Bank

Canonical SMILES

[H]C(CCN1CCN(CCO)CC1)=C1C2C=C(C=CC2SC2=C1C=CC=C2)C(F)(F)F

Source: Drug Bank

Average Molecular Weight

436.533

Source: Drug Bank

Monoisotopic Molecular Weight

436.179618801

Source: Drug Bank

SMILES

[H]C(CCN1CCN(CCO)CC1)=C1C2C=C(C=CC2SC2=C1C=CC=C2)C(F)(F)F

Source: Drug Bank

InChI String

InChI=1S/C23H27F3N2OS/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/h1-2,4-8,16,20,22,29H,3,9-15H2/b18-5-

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
ABCB1 (source: Drug Bank)
ADRA1A (source: Drug Bank)
CALY (source: Drug Bank)
CHRM1 (source: Drug Bank)
DRD1 (source: Drug Bank)
DRD2 (source: Drug Bank)
HTR2A (source: Drug Bank)

Drug Interactions

Interaction Description
donepezil - flupenthixol Possible antagonism of action (source: Drug Bank)
donepezil - flupenthixol Possible antagonism of action (source: Drug Bank)
flupenthixol - donepezil Possible antagonism of action (source: Drug Bank)
flupenthixol - donepezil Possible antagonism of action (source: Drug Bank)
flupenthixol - galantamine Possible antagonism of action (source: Drug Bank)
flupenthixol - galantamine Possible antagonism of action (source: Drug Bank)
flupenthixol - rivastigmine Possible antagonism of action (source: Drug Bank)
flupenthixol - rivastigmine Possible antagonism of action (source: Drug Bank)
galantamine - flupenthixol Possible antagonism of action (source: Drug Bank)
galantamine - flupenthixol Possible antagonism of action (source: Drug Bank)
tacrine - flupenthixol The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Flupenthixol, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents. (source: Drug Bank)
tacrine - flupenthixol The therapeutic effects of the central acetylcholinesterase inhibitor (AChEI), Tacrine, and/or the anticholinergic/antipsychotic, Flupenthixol, may be reduced due to antagonism. This interaction may be beneficial when the anticholinergic action is a side effect. AChEIs may also augment the central neurotoxic effect of antipsychotics. Monitor for extrapyramidal symptoms and decreased efficacy of both agents. (source: Drug Bank)
tetrabenazine - flupenthixol May cause dopamine deficiency. Monitor for Tetrabenazine adverse effects. (source: Drug Bank)
thiothixene - flupenthixol May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
thiothixene - flupenthixol May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
toremifene - flupenthixol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration. (source: Drug Bank)
trimethobenzamide - flupenthixol Trimethobenzamide and Flupenthixol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
trimipramine - flupenthixol Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution. (source: Drug Bank)
triprolidine - flupenthixol Triprolidine and Flupenthixol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects. (source: Drug Bank)
triprolidine - flupenthixol Triprolidine and Flupenthixol, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects. (source: Drug Bank)
trospium - flupenthixol Trospium and Flupenthixol, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank)
voriconazole - flupenthixol Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)
vorinostat - flupenthixol Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)
ziprasidone - flupenthixol Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated. (source: Drug Bank)
zuclopenthixol - flupenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP). (source: Drug Bank)

Curated Information ?

EvidenceDisease
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Schizophrenia

Publications related to flupenthixol: 2

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Patterns of variation influencing antipsychotic treatment outcomes in South African first-episode schizophrenia patients. Pharmacogenomics. 2014. Drogemöller Britt I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00875
ChEBI:
5121
KEGG Drug:
D01044
PubChem Compound:
17012
Drugs Product Database (DPD):
2156016
Therapeutic Targets Database:
DAP000026

Clinical Trials

These are trials that mention flupenthixol and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.