Chemical: Drug
darifenacin

PharmGKB contains no prescribing info for this . Contact us to report known genotype-based dosing guidelines, or if you are interested in developing guidelines.

Annotated Labels

  1. Annotation of FDA Label for darifenacin and CYP2D6
  2. Annotation of EMA Label for darifenacin and CYP2D6
  3. Annotation of HCSC Label for darifenacin and CYP2D6
last updated 03/15/2017

1. Annotation of FDA Label for darifenacin and CYP2D6

On FDA Biomarker List
Actionable PGx

Summary

The FDA-approved drug label for darifenacin (Enablex) notes that CYP2D6 poor metabolizers may have increased maximum plasma concentrations of darifenacin, as compared to CYP2D6 extensive metabolizers. However, the label does not comment on the clinical significance of these increased concentrations.

There's more of this label. Read more.

last updated 08/07/2014

2. Annotation of EMA Label for darifenacin and CYP2D6

Actionable PGx

Summary

The EMA European Public Assessment Report (EPAR) for darifenacin (Emselex) contains information regarding differences in exposure to drug in patients who are CYP2D6 poor metabolizers compared to extensive metabolizers. Darifenacin is primarily metabolized by CYP3A4 in CYP2D6 poor metabolizers, therefore exposure to darifenacin may be greater in CYP2D6 poor metabolizers when CYP3A4 inhibitors are taken concomitantly.

There's more of this label. Read more.

3. Annotation of HCSC Label for darifenacin and CYP2D6

Actionable PGx

Summary

The product monograph for darifenacin notes that CYP2D6 poor metabolizers may have higher levels of the drug as compared to extensive metabolizers. However, it also notes that there are no special dosing requirements for poor metabolizers.

There's more of this label. Read more.

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.

? = Mouse-over for quick help
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • darifenacin
Trade Names
  • Emselex
  • Enablex
Brand Mixture Names

PharmGKB Accession Id

PA164774901

Type(s):

Drug

Description

Darifenacin (Enablex®, Novartis) is a medication used to treat urinary incontinence. Darifenacin works by blocking the M3 muscarinic acetylcholine receptor, which is primarily responsible for bladder muscle contractions. It thereby decreases the urgency to urinate. It should not be used in people with urinary retention. It is not known whether this selectivity for the M3 receptor translates into any clinical advantage when treating symptoms of overactive bladder syndrome.

Source: Drug Bank

Indication

For the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency and frequency.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Darifenacin selectively antagonizes the muscarinic M3 receptor. M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function.

Source: Drug Bank

Pharmacology

Darifenacin is a competitive muscarinic receptor antagonist. _In vitro_ studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9 and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of the urinary bladder smooth muscle and stimulation of salivary secretion. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs.

Source: Drug Bank

Food Interaction

Take without regard to meals.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. Primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4.

Source: Drug Bank

Protein Binding

Darifenacin is approximately 98% bound to plasma proteins (primarily to alpha-1-acid-glycoprotein).

Source: Drug Bank

Absorption

The mean oral bioavailability at steady state is estimated to be 15% and 19% for 7.5 mg and 15 mg tablets, respectively.

Source: Drug Bank

Half-Life

The elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours.

Source: Drug Bank

Toxicity

Overdosage can potentially result in severe central anticholinergic effects.

Source: Drug Bank

Clearance

* 40 L/h [extensive metabolizers] * 32 L/h [poor metabolizers]

Source: Drug Bank

Volume of Distribution

* 163 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C28H30N2O2

Source: Drug Bank

Isomeric SMILES

C1CN(C[C@@H]1C(C2=CC=CC=C2)(C3=CC=CC=C3)C(=O)N)CCC4=CC5=C(C=C4)OCC5

Source: Drug Bank

NC(=O)C([C@@H]1CCN(CCC2=CC3=C(OCC3)C=C2)C1)(C1=CC=CC=C1)C1=CC=CC=C1

Source: Drug Bank

Canonical SMILES

NC(=O)C([C@@H]1CCN(CCC2=CC3=C(OCC3)C=C2)C1)(C1=CC=CC=C1)C1=CC=CC=C1

Source: Drug Bank

Average Molecular Weight

426.55

Source: Drug Bank

Monoisotopic Molecular Weight

426.230728214

Source: Drug Bank

SMILES

NC(=O)C([C@@H]1CCN(CCC2=CC3=C(OCC3)C=C2)C1)(C1=CC=CC=C1)C1=CC=CC=C1

Source: Drug Bank

InChI String

InChI=1S/C28H30N2O2/c29-27(31)28(23-7-3-1-4-8-23,24-9-5-2-6-10-24)25-14-17-30(20-25)16-13-21-11-12-26-22(19-21)15-18-32-26/h1-12,19,25H,13-18,20H2,(H2,29,31)/t25-/m1/s1

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 ?

EvidenceGene
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP2D6
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4

Drug Targets

Gene Description
CHRM1 (source: Drug Bank )
CHRM2 (source: Drug Bank )
CHRM3 (source: Drug Bank )
CHRM4 (source: Drug Bank )
CHRM5 (source: Drug Bank )

Drug Interactions

Interaction Description
clarithromycin - darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - clarithromycin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - clarithromycin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - donepezil Possible antagonism of action (source: Drug Bank )
darifenacin - donepezil Possible antagonism of action (source: Drug Bank )
darifenacin - galantamine Possible antagonism of action (source: Drug Bank )
darifenacin - galantamine Possible antagonism of action (source: Drug Bank )
darifenacin - itraconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - itraconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - ketoconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - ketoconazole This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - nefazodone This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - nefazodone This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - nelfinavir This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - nelfinavir This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - ritonavir This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - ritonavir This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
darifenacin - rivastigmine Possible antagonism of action (source: Drug Bank )
darifenacin - rivastigmine Possible antagonism of action (source: Drug Bank )
donepezil - darifenacin Possible antagonism of action (source: Drug Bank )
galantamine - darifenacin Possible antagonism of action (source: Drug Bank )
itraconazole - darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
ketoconazole - darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
ketoconazole - darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
nefazodone - darifenacin This potent CYP3A4 inhibitor slows darifenacin/solifenacin metabolism (source: Drug Bank )
nelfinavir - darifenacin This potent CYP3A4 inhibitor slows darifenacin / solifenacin metabolism (source: Drug Bank )
tacrine - darifenacin The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Darifenacin, 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 )
tamoxifen - darifenacin Darifenacin may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank )
tamoxifen - darifenacin Darifenacin may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy. (source: Drug Bank )
tamsulosin - darifenacin Darifenacin, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Darifenacin is initiated, discontinued, or dose changed. (source: Drug Bank )
tamsulosin - darifenacin Darifenacin, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Darifenacin is initiated, discontinued, or dose changed. (source: Drug Bank )
telithromycin - darifenacin Telithromycin may reduce clearance of Darifenacin. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Darifenacin if Telithromycin is initiated, discontinued or dose changed. (source: Drug Bank )
tramadol - darifenacin Darifenacin may decrease the effect of Tramadol by decreasing active metabolite production. (source: Drug Bank )
triprolidine - darifenacin Triprolidine and Darifenacin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank )
triprolidine - darifenacin Triprolidine and Darifenacin, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank )
trospium - darifenacin Trospium and Darifenacin, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects. (source: Drug Bank )
voriconazole - darifenacin Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of darifenacin by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of darifenacin if voriconazole is initiated, discontinued or dose changed. (source: Drug Bank )
No related diseases are available

Publications related to darifenacin: 1

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
EMA Initiatives and Perspectives on Pharmacogenomics. British journal of clinical pharmacology. 2014. Ehmann Falk, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0078-0419-15
DrugBank:
DB00496
ChEBI:
391960
KEGG Drug:
D01699
PubChem Compound:
444031
PubChem Substance:
46508104
7979027
IUPHAR Ligand:
319
321
BindingDB:
50109647
ChemSpider:
392054
Therapeutic Targets Database:
DAP001131
FDA Drug Label at DailyMed:
cdf1487b-9f1d-42c6-9184-0015fff0b48f

Clinical Trials

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

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Sources for PharmGKB drug information: DrugBank, PubChem.