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[C@@H](N1CCC(=C)CC1)[C@](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.

Associated Conditions
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
AgmatineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Agmatine.Experimental, Investigational
AmiodaroneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Amiodarone.Approved, Investigational
AmlodipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Efinaconazole.Approved, Investigational
AmrinoneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Amrinone.Approved
AranidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Aranidipine.Approved, Investigational
AtorvastatinThe risk or severity of myopathy can be increased when Efinaconazole is combined with Atorvastatin.Approved
AzelnidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Azelnidipine.Approved, Investigational
AzimilideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Azimilide.Investigational
BarnidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Barnidipine.Approved
BencyclaneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Bencyclane.Experimental
BenidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Benidipine.Approved, Investigational
BepridilThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Bepridil.Approved, Withdrawn
BioallethrinThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Bioallethrin.Approved, Experimental
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 therapeutic efficacy of Efinaconazole can be increased when used in combination with Carboxyamidotriazole.Investigational
CaroverineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Caroverine.Experimental
CilnidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Cilnidipine.Approved, Investigational
CinnarizineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Cinnarizine.Approved, Investigational
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Efinaconazole.Approved, Investigational, Withdrawn
ClevidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Clevidipine.Approved, Investigational
CyclandelateThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Cyclandelate.Approved
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Efinaconazole.Approved, Investigational, Vet Approved
DarodipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination 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 therapeutic efficacy of Efinaconazole can be increased when used in combination with Diltiazem.Approved, Investigational
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Efinaconazole.Approved, Investigational
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Efinaconazole.Approved, Investigational
DotarizineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Dotarizine.Investigational
EfonidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Efonidipine.Approved, Investigational
EperisoneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Eperisone.Approved, Investigational
EthosuximideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Ethosuximide.Approved
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Efinaconazole.Approved
FelodipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Felodipine.Approved, Investigational
FendilineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Fendiline.Withdrawn
Fish oilThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Fish oil.Approved, Nutraceutical
FlunarizineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Flunarizine.Approved
FluspirileneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Fluspirilene.Approved, Investigational
FosphenytoinThe serum concentration of Efinaconazole can be decreased when it is combined with Fosphenytoin.Approved, Investigational
GabapentinThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Gabapentin.Approved, Investigational
GallopamilThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Gallopamil.Investigational
IsradipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Isradipine.Approved, Investigational
LacidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Lacidipine.Approved, Investigational
LamotrigineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Lamotrigine.Approved, Investigational
LercanidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Lercanidipine.Approved, Investigational
LevetiracetamThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Levetiracetam.Approved, Investigational
LidoflazineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Lidoflazine.Experimental
LoperamideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Loperamide.Approved
LosartanThe metabolism of Losartan can be decreased when combined with Efinaconazole.Approved
Magnesium sulfateThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Magnesium sulfate.Approved, Investigational, Vet Approved
ManidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Manidipine.Approved, Investigational
MentholThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Menthol.Approved
MethsuximideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Methsuximide.Approved
MibefradilThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Mibefradil.Investigational, Withdrawn
NaftopidilThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Naftopidil.Investigational
NicardipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nicardipine.Approved, Investigational
NifedipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nifedipine.Approved
NiguldipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Niguldipine.Experimental
NiludipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Niludipine.Experimental
NilvadipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nilvadipine.Approved, Investigational
NimesulideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nimesulide.Approved, Investigational, Withdrawn
NimodipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nimodipine.Approved, Investigational
NisoldipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nisoldipine.Approved
NitrendipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nitrendipine.Approved, Investigational
NylidrinThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Nylidrin.Approved
OtiloniumThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Otilonium.Experimental, Investigational
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Efinaconazole.Approved, Vet Approved
PinaveriumThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Pinaverium.Approved
PrenylamineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Prenylamine.Withdrawn
ProgesteroneThe absorption of Progesterone can be decreased when combined with Efinaconazole.Approved, Vet Approved
QuinidineThe serum concentration of Quinidine can be increased when it is combined with Efinaconazole.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Efinaconazole.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Efinaconazole.Approved, Investigational
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, Investigational
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Efinaconazole.Approved, Investigational
SeletracetamThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Seletracetam.Investigational
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 therapeutic efficacy of Efinaconazole can be increased when used in combination with Terodiline.Experimental
TetrahydropalmatineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Tetrahydropalmatine.Investigational
Tolfenamic AcidThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Tolfenamic Acid.Approved, Investigational
TranilastThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Tranilast.Approved, Investigational
TrimebutineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Trimebutine.Approved
TrimethadioneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Trimethadione.Approved
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Efinaconazole.Approved
VerapamilThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Verapamil.Approved
VinpocetineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Vinpocetine.Investigational
WIN 55212-2The therapeutic efficacy of Efinaconazole can be increased when used in combination with WIN 55212-2.Experimental
ZiconotideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Efinaconazole.Approved
ZonisamideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Zonisamide.Approved, Investigational
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
4Active Not RecruitingTreatmentDermatophytosis / Onychomycosis1
4Active Not RecruitingTreatmentOnychomycosis1
4Active Not RecruitingTreatmentOnychomycosis of Toenail1
4RecruitingTreatmentMild to Moderate Onychomycosis Due to Dermatophyte1
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
US9861698No2010-07-082030-07-08Us
US9877955No2008-01-032028-01-03Us

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 July 13, 2018 01:11