Identification

Name
Efinaconazole
Accession Number
DB09040
Type
Small Molecule
Groups
Approved
Description

Efinaconazole is a 14 alpha-demethylase inhibitor indicated in the treatment of fungal infection of the nail, known as onychomycosis. It was approved for use in Canada and the USA in 2014 and is marketed by Valeant Pharmaceuticals North America LLC under the name Jublia.

Structure
Thumb
Synonyms
  • (2R,3R)-2-(2,4-Difluorophenyl)-3-(4-methylene-1-piperidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
External IDs
IDP 108 / IDP-108 / IDP108 / KP 103 / KP-103
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
JubliaSolution10 %TopicalValeant Canada Lp Valeant Canada S.E.C.2014-07-21Not applicableCanada
JubliaSolution100 mg/mLTopicalValeant Pharmaceuticals North America2014-06-06Not applicableUs
Categories
UNII
J82SB7FXWB
CAS number
164650-44-6
Weight
Average: 348.398
Monoisotopic: 348.17616767
Chemical Formula
C18H22F2N4O
InChI Key
NFEZZTICAUWDHU-RDTXWAMCSA-N
InChI
InChI=1S/C18H22F2N4O/c1-13-5-7-23(8-6-13)14(2)18(25,10-24-12-21-11-22-24)16-4-3-15(19)9-17(16)20/h3-4,9,11-12,14,25H,1,5-8,10H2,2H3/t14-,18-/m1/s1
IUPAC Name
(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
SMILES
C[[email protected]@H](N1CCC(=C)CC1)[[email protected]](O)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1

Pharmacology

Indication

Indicated in the treatment of fungal infection of the nail, known as onychomycosis.

Structured Indications
Pharmacodynamics

mean ± SD plasma Cmax on Day 28 of treatment: 0.67 ± 0.37 ng/mL. mean ± SD AUC was 12.15 ± 6.91 ng*h/mL.

Mechanism of action

Efinaconazole is an azole antifungal. Efinaconazole inhibits fungal lanosterol 14α-demethylase involved in the biosynthesis of ergosterol, a constituent of fungal cell membranes.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Yeast
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

29.9 hours in healthy patients.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Candida albicans and other yeasts
  • Yeast and other Trichophyton or Microsporum fungi
  • Dermatophytic fungi including Trichophyton, Microsporum and Epidermophyton
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmlodipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Efinaconazole.Approved, Investigational
AmrinoneThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Amrinone.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Atorvastatin.Approved
AzelnidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Azelnidipine.Approved, Investigational
AzimilideThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Azimilide.Investigational
BarnidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Barnidipine.Approved
BencyclaneThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Bencyclane.Experimental
BenidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Benidipine.Approved, Investigational
BepridilThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Bepridil.Approved, Withdrawn
BuspironeThe metabolism of Buspirone can be decreased when combined with Efinaconazole.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Efinaconazole.Approved, Investigational
CarboxyamidotriazoleThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Carboxyamidotriazole.Investigational
CaroverineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Caroverine.Experimental
CerivastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Cerivastatin.Withdrawn
CilnidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Cilnidipine.Approved, Investigational
CinnarizineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Efinaconazole.Approved, Investigational, Withdrawn
ClevidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Clevidipine.Approved
ConivaptanThe metabolism of Conivaptan can be decreased when combined with Efinaconazole.Approved, Investigational
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Efinaconazole.Approved, Investigational, Vet Approved
DarodipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Darodipine.Experimental
DidanosineDidanosine can cause a decrease in the absorption of Efinaconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Diltiazem.Approved
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Efinaconazole.Approved, Investigational
DofetilideThe metabolism of Dofetilide can be decreased when combined with Efinaconazole.Approved
DotarizineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Dotarizine.Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Efonidipine.Approved, Investigational
EperisoneThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Eperisone.Approved, Investigational
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Efinaconazole.Approved
FelodipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Felodipine.Approved, Investigational
FendilineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Fendiline.Withdrawn
FlunarizineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Flunarizine.Approved
FluvastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Fluvastatin.Approved
FosphenytoinThe serum concentration of Efinaconazole can be decreased when it is combined with Fosphenytoin.Approved
GabapentinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Gabapentin.Approved, Investigational
GallopamilThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Gallopamil.Investigational
IsradipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Isradipine.Approved
LacidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Lacidipine.Approved, Investigational
LamotrigineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Lamotrigine.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Lercanidipine.Approved, Investigational
LidoflazineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Lidoflazine.Experimental
LosartanThe metabolism of Losartan can be decreased when combined with Efinaconazole.Approved
LovastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Lovastatin.Approved, Investigational
Magnesium SulfateThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Magnesium Sulfate.Approved, Vet Approved
ManidipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Manidipine.Approved, Investigational
MevastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Mevastatin.Experimental
MibefradilThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Mibefradil.Investigational, Withdrawn
NaftopidilThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Naftopidil.Investigational
NicardipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Nicardipine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Nifedipine.Approved
NiguldipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Niguldipine.Experimental
NiludipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Niludipine.Experimental
NilvadipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Nilvadipine.Approved, Investigational
NimesulideThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Nimodipine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Nisoldipine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Nitrendipine.Approved, Investigational
OtiloniumThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Otilonium.Experimental, Investigational
PerhexilineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Perhexiline.Approved, Investigational
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Efinaconazole.Approved, Vet Approved
PimozideEfinaconazole may increase the arrhythmogenic activities of Pimozide.Approved
PinaveriumThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Pinaverium.Approved
PitavastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Pitavastatin.Approved
PravastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Pravastatin.Approved
PregabalinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Pregabalin.Approved, Illicit, Investigational
PrenylamineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Prenylamine.Withdrawn
ProgesteroneThe therapeutic efficacy of Progesterone can be decreased when used in combination with Efinaconazole.Approved, Vet Approved
QuinidineThe metabolism of Quinidine can be decreased when combined with Efinaconazole.Approved
RanolazineThe metabolism of Ranolazine can be decreased when combined with Efinaconazole.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Efinaconazole.Approved
RifampicinThe serum concentration of Rifampicin can be increased when it is combined with Efinaconazole.Approved
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Efinaconazole.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Efinaconazole.Approved, Investigational
RisedronateThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Risedronate.Approved, Investigational
RosuvastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Rosuvastatin.Approved
SimvastatinThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Simvastatin.Approved
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Efinaconazole.Approved
SucralfateSucralfate can cause a decrease in the absorption of Efinaconazole resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Efinaconazole.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Efinaconazole.Approved, Investigational
TerodilineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Terodiline.Experimental
TetrahydropalmatineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Tetrahydropalmatine.Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Tolfenamic Acid.Approved
TranilastThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Tranilast.Approved, Investigational
UbidecarenoneThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Ubidecarenone.Approved, Investigational, Nutraceutical
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Efinaconazole.Approved
VerapamilThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Verapamil.Approved
VinpocetineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Vinpocetine.Investigational
XylometazolineThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Xylometazoline.Approved
ZiconotideThe risk or severity of adverse effects can be increased when Efinaconazole is combined with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Efinaconazole.Approved
Food Interactions
Not Available

References

General References
  1. Patel T, Dhillon S: Efinaconazole: first global approval. Drugs. 2013 Nov;73(17):1977-83. doi: 10.1007/s40265-013-0152-x. [PubMed:24249649]
External Links
KEGG Drug
D10021
PubChem Compound
489181
PubChem Substance
310264988
ChemSpider
428538
ChEBI
82718
ChEMBL
CHEMBL2103877
Drugs.com
Drugs.com Drug Page
Wikipedia
Efinaconazole
ATC Codes
D01AC19 — Efinaconazole
AHFS Codes
  • 84:04.08.08 — Azoles
FDA label
Download (330 KB)
MSDS
Download (226 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentOnychomycosis2
4Not Yet RecruitingTreatmentMild to Moderate Onychomycosis Due to Dermatophyte1
4RecruitingTreatmentOnychomycosis1
Not AvailableRecruitingNot AvailableDistal Lateral Subungual Onychomycosis (DLSO)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionTopical10 %
SolutionTopical100 mg/mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7214506No2001-10-052021-10-05Us
US8039494No2010-07-082030-07-08Us
US8486978No2010-10-242030-10-24Us
US9302009No2010-10-242030-10-24Us
US9662394No2014-10-022034-10-02Us
US9566272No2008-01-032028-01-03Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.61 mg/mLALOGPS
logP1.49ALOGPS
logP2.24ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)12.7ChemAxon
pKa (Strongest Basic)7.45ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.18 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity103.94 m3·mol-1ChemAxon
Polarizability34.48 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenethylamines
Direct Parent
Amphetamines and derivatives
Alternative Parents
Phenylpropanes / Fluorobenzenes / Aralkylamines / Piperidines / Aryl fluorides / Triazoles / Tertiary alcohols / Heteroaromatic compounds / Trialkylamines / 1,2-aminoalcohols
show 5 more
Substituents
Amphetamine or derivatives / Phenylpropane / Fluorobenzene / Halobenzene / Aralkylamine / Aryl fluoride / Aryl halide / Piperidine / Azole / Heteroaromatic compound
show 19 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, organofluorine compound, tertiary alcohol, tertiary amino compound, triazole antifungal drug, conazole antifungal drug, olefinic compound (CHEBI:82718)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity).
Gene Name
ERG11
Uniprot ID
P50859
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
61304.95 Da
References
  1. Patel T, Dhillon S: Efinaconazole: first global approval. Drugs. 2013 Nov;73(17):1977-83. doi: 10.1007/s40265-013-0152-x. [PubMed:24249649]

Drug created on April 21, 2015 10:37 / Updated on December 11, 2017 13:01