TERBINAFINE HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H25N.ClH
Molecular Weight	327.891
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CN(C\C=C\C#CC(C)(C)C)CC1=CC=CC2=CC=CC=C12

InChI

InChIKey=BWMISRWJRUSYEX-SZKNIZGXSA-N

InChI=1S/C21H25N.ClH/c1-21(2,3)15-8-5-9-16-22(4)17-19-13-10-12-18-11-6-7-14-20(18)19;/h5-7,9-14H,16-17H2,1-4H3;1H/b9-5+;

HIDE SMILES / InChI

Molecular Formula	C21H25N
Molecular Weight	291.4299
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf

Terbinafine (brand name Lamisil, Terbisil, Terboderm and others) is an antifungal medication used to treat ringworm and fungal nail infections. Terbinafine inhibits ergosterol synthesis by inhibiting squalene epoxidase, an enzyme that is part of the fungal cell membrane synthesis pathway. Because terbinafine prevents the conversion of squalene to lanosterol, ergosterol cannot be synthesized. This is thought to change cell membrane permeability, causing fungal cell lysis. Many side effects and adverse drug reactions have been reported with oral terbinafine hydrochloride possibly due to its extensive biodistribution and the often extended durations involved in antifungal treatment (longer than two months).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Squalene monooxygenase 10 Target ID: CHEMBL1888 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21229992	Inhibitor 8146		30.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Onychomycosis 18 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf	Curative		Approved 8307	LAMISIL Approved Use Uses cures most athlete’s foot (tinea pedis) between the toes.Effectiveness on the bottom or sides of foot is unknown. cures most jock itch (tinea cruris) and ringworm (tinea corporis) relieves itching, burning, cracking and scaling which accompany these conditions Launch Date 8.9380802E11

C_max

Value	Dose	Analyte	Population
1.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8593011/	250 mg 1 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TERBINAFINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.34 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8593011/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	TERBINAFINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	TERBINAFINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
10.48 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8593011/	250 mg 1 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:	TERBINAFINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.74 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8593011/	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	TERBINAFINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.56 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:	TERBINAFINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
16.5 day EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8593011/	250 mg 1 times / day multiple, oral dose: 250 mg route of administration: Oral experiment type: MULTIPLE co-administered:		TERBINAFINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
36 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		TERBINAFINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020539s021lbl.pdf	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		TERBINAFINE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
500 mg 2 times / day multiple, oral Highest studied dose Dose: 500 mg, 2 times / day Route: oral Route: multiple Dose: 500 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16445509 Page: p.155	unhealthy, 31 n = 27 Health Status: unhealthy Condition: Eumycetoma Age Group: 31 Sex: M+F Population Size: 27 Sources: https://pubmed.ncbi.nlm.nih.gov/16445509 Page: p.155	Disc. AE: Neutropenia, Neutropenia... AEs leading to discontinuation/dose reduction: Neutropenia (7.4%) Neutropenia (3.7%) Glutamic-oxaloacetic transaminase increased (3.7%) Serum glutamic-pyruvic transaminase increased (3.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/16445509 Page: p.155
5 g single, oral Overdose Dose: 5 g Route: oral Route: single Dose: 5 g Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.6	unhealthy Health Status: unhealthy Condition: Fingernail onychomycosis\|Toenail onychomycosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.6	Other AEs: Nausea, Vomiting... Other AEs: Nausea Vomiting Abdominal pain Dizziness Rash Urination frequency of Headache Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.6
1 % 1 times / day multiple, topical Recommended Dose: 1 %, 1 times / day Route: topical Route: multiple Dose: 1 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20846s001lbl.pdf Page: p.8	unhealthy Health Status: unhealthy Condition: Tinea\|tinea pedis\|tinea corporis\|tinea cruris Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20846s001lbl.pdf Page: p.8	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20846s001lbl.pdf Page: p.8
250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.3	unhealthy n = 465 Health Status: unhealthy Condition: Fingernail onychomycosis\|Toenail onychomycosis Population Size: 465 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.3	Disc. AE: Headache... AEs leading to discontinuation/dose reduction: Headache (0.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.3
250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.4	unhealthy n = 465 Health Status: unhealthy Condition: Fingernail onychomycosis\|Toenail onychomycosis Population Size: 465 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.4	Disc. AE: Diarrhea, Dyspepsia... AEs leading to discontinuation/dose reduction: Diarrhea (0.6%) Dyspepsia (0.4%) Abdominal pain (0.4%) Nausea (0.2%) Rash (0.9%) Pruritus (0.2%) Liver enzyme abnormal (0.2%) Taste disturbance (0.2%) Visual disturbance (0.9%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.4
250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Fingernail onychomycosis\|Toenail onychomycosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.1	Disc. AE: Liver failure, Taste disturbance... AEs leading to discontinuation/dose reduction: Liver failure Taste disturbance (severe) Smell alteration Depressive symptom Neutropenia (severe) Stevens-Johnson syndrome Toxic epidermal necrolysis Erythema multiforme Exfoliative dermatitis Bullous dermatitis Drug reaction with eosinophilia and systemic symptoms Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.1
250 mg 1 times / day multiple, oral Recommended Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.3	unhealthy Health Status: unhealthy Condition: Fingernail onychomycosis\|Toenail onychomycosis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.3	Disc. AE: Lupus erythematosus, Thrombotic microangiopathy... AEs leading to discontinuation/dose reduction: Lupus erythematosus Thrombotic microangiopathy Thrombotic thrombocytopenic purpura Hemolytic uremic syndrome Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020539s029,022071s013lbl.pdf Page: p.3

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1670	substrate 985	inhibitor 1789	inhibitor 1570

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP1A2 1013 CYP2C8 670 CYP2C19 955 CYP2B6 648

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2D6 1826	inhibitor 3185 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes [Ki 0.03 uM]		yes (co-administration study) Comment: In studies in healthy subjects characterized as extensive metabolizers of dextromethorphan (antitussive drug and CYP2D6 probe substrate), terbinafine increases the dextromethorphan/ dextrorphan metabolite ratio in urine by 16- to 97-fold on average Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes
CYP1A2 1013	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes	Hydroxyterbinafine 4
CYP2B6 648	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes	Hydroxyterbinafine 4
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes
CYP2C19 955	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes	Hydroxyterbinafine 4
CYP2C8 670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes
CYP2C8 670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes	Hydroxyterbinafine 4
CYP2C9 985	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes	Hydroxyterbinafine 4
CYP3A4 1670	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes	Hydroxyterbinafine 4
CYP2C9 985	substrate 3264 Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -	yes		yes (co-administration study) Comment: Coadministration of a single dose of fluconazole (100 mg) with a single dose of terbinafine resulted in a 52% and 69% increase in terbinafine Cmax and AUC, respectively. Fluconazole is an inhibitor of CYP2C9 and CYP3A enzymes. Based on this finding, it is likely that other inhibitors of both CYP2C9 and CYP3A4 (e.g., ketoconazole, amiodarone) may also lead to a substantial increase in the systemic exposure (Cmax and AUC) of terbinafine when concomitantly administered. Sources: https://pubmed.ncbi.nlm.nih.gov/10460803/ Page: -
CYP3A4 1670	substrate 3264 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020539s033lbl.pdf#page=5 Page: 5.0	yes		yes (co-administration study) Comment: Coadministration of a single dose of fluconazole (100 mg) with a single dose of terbinafine resulted in a 52% and 69% increase in terbinafine Cmax and AUC, respectively. Fluconazole is an inhibitor of CYP2C9 and CYP3A enzymes. Based on this finding, it is likely that other inhibitors of both CYP2C9 and CYP3A4 (e.g., ketoconazole, amiodarone) may also lead to a substantial increase in the systemic exposure (Cmax and AUC) of terbinafine when concomitantly administered. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020539s033lbl.pdf#page=5 Page: 5.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1603	inhibitor 1584 Sources: https://pubmed.ncbi.nlm.nih.gov/12729675/ Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:9448	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:9448
MolPort	MolPort-002-507-761	https://www.molport.com/shop/molecule-link/MolPort-002-507-761
Selleck Chemicals	Terbinafine(Lamisil)	http://www.selleckchem.com/products/Terbinafine(Lamisil).html
ZINC	ZINC000001530981	http://zinc15.docking.org/substances/ZINC000001530981
eMolecules	902552	https://www.emolecules.com/cgi-bin/more?vid=902552

PubMed

Title	Date	PubMed
Terbinafine: mode of action and properties of the squalene epoxidase inhibition.	1992 Feb	1543672
Synthesis and structure-activity relationships of phenyl-substituted benzylamine antimycotics: a novel benzylbenzylamine antifungal agent for systemic treatment.	1993 Jul 23	8340915
[Ageusia caused by terbinafine].	1995 Sep 9	7475473
Terbinafine-induced prolonged cholestasis with reduction of interlobular bile ducts.	1997 Jul	9246051
Effects of sterol inhibitors on the ATP content of Pneumocystis carinii.	1999 Sep-Oct	10519292
In vitro activities of terbinafine against Aspergillus species in comparison with those of itraconazole and amphotericin B.	2001 Jun	11353643
Terbinafine: a review of its use in onychomycosis in adults.	2003	12477372
Safety and tolerability of oral antifungal agents in the treatment of fungal nail disease: a proven reality.	2005 Dec	18360572
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
N- and S-alpha-l-arabinopyranosyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. First synthesis and biological evaluation.	2007 Sep	17408811
Terbinafine hydrochloride oral granules versus oral griseofulvin suspension in children with tinea capitis: results of two randomized, investigator-blinded, multicenter, international, controlled trials.	2008 Jul	18378354
Isavuconazole: a comprehensive review of spectrum of activity of a new triazole.	2010 Nov	20524153
Synthesis and in-vitro antimicrobial activity of secondary and tertiary amines containing 2-chloro-6-methylquinoline moiety.	2011 Jul	21618272
Assessment of phytochemicals, antimicrobial and cytotoxic activities of extract and fractions from Fagonia olivieri (Zygophyllaceae).	2013 Jul 10	23842440
Synthesis, antifungal activities and molecular docking studies of novel 2-(2,4-difluorophenyl)-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propyl dithiocarbamates.	2014 Mar 3	24487187
Arachidonic acid affects biofilm formation and PGE2 level in Candida albicans and non-albicans species in presence of subinhibitory concentration of fluconazole and terbinafine.	2014 May-Jun	24389279

Patents

Sample Use Guides

In Vivo Use Guide

Prior to administering, evaluate patients for evidence of chronic or active liver disease. Fingernail onychomycosis: One 250 mg tablet, once daily for 6 weeks. Toenail onychomycosis: One 250 mg tablet, once daily for 12 weeks.

Route of Administration: Oral

In Vitro Use Guide

TRB (Terbinafine) were diluted 100-fold in dimethyl sulfoxide to obtain stock solutions that were kept at -20ºC. The antifungals were diluted in RPMI-1640 medium (Sigma Chemical Co, Missouri, USA) at pH 7.0 buffered with 0.16 M morpholinepropanesulfonic acid to obtain final concentrations ranging from 0.03-16 μg/mL for TRB. The diluted antifungal suspensions were then added to 96-well microtitre trays. Next, each fungal suspension was inoculated into the appropriate well at final concentrations ranging from 0.5 x 10^3-2.5 x 10^3 CFU/mL. The minimum inhibitory concentration (MIC) of each antifungal was determined by spectrophotometric reading at 492 nm following incubation at 35ºC for 72 h.

Substance Class	Chemical Created by `admin` on `Fri Dec 16 17:02:25 UTC 2022` Edited by `admin` on `Fri Dec 16 17:02:25 UTC 2022`
Record UNII	012C11ZU6G
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TERBINAFINE HYDROCHLORIDE

Common Name

English

LAMISIL

Brand Name

English

TERBINAFINE (AS HYDROCHLORIDE)

Common Name

English

TERBINAFINE HYDROCHLORIDE [EP MONOGRAPH]

Common Name

English

NSC-759113

Code

English

TERBINAFINE HYDROCHLORIDE [USP MONOGRAPH]

Common Name

English

TERBINAFINE HYDROCHLORIDE [VANDF]

Common Name

English

BRAMIZIL

Brand Name

English

(E)-N-(6,6-Dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethylamine, hydrochloride

Systematic Name

English

TERBINA

Brand Name

English

TERBINAFINE HYDROCHLORIDE [MI]

Common Name

English

TERBINE

Brand Name

English

BRAMAZIL

Brand Name

English

MUZONAL

Brand Name

English

TERBINAFINE HCL

Common Name

English

(2E)-N,6,6-TRIMETHYL-N-(NAPHTHALEN-1-YLMETHYL)HEPT-2-EN-4-YN-1-AMINE HYDROCHLORIDE

Systematic Name

English

TERBINAFINE HYDROCHLORIDE [USP-RS]

Common Name

English

Terbinafine hydrochloride [WHO-DD]

Common Name

English

TERBINAFINE HYDROCHLORIDE [MART.]

Common Name

English

TERBINAFINE HYDROCHLORIDE [JAN]

Common Name

English

1-NAPHTHALENEMETHANAMINE, N-(6,6-DIMETHYL-2-HEPTEN-4-YNYL)-N-METHYL-, (E)-, HYDROCHLORIDE

Common Name

English

TERBINAFINE HYDROCHLORIDE [ORANGE BOOK]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C514