CLOTRIMAZOLE

US Approved OTC

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H17ClN2
Molecular Weight	344.837
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=C(C=CC=C1)C(N2C=CN=C2)(C3=CC=CC=C3)C4=CC=CC=C4

InChI

InChIKey=VNFPBHJOKIVQEB-UHFFFAOYSA-N

InChI=1S/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H

HIDE SMILES / InChI

Molecular Formula	C22H17ClN2
Molecular Weight	344.837
Charge	0
Count

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

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018827s046lbl.pdf
Curator's Comment: description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018052Orig1s032lbl.pdf

Clotrimazole is an anti-fungal medicine indicated for the treatment of vaginal yeast infections and tinea. It can be used either in combination with other drugs (betamethasone dipropionate) or alone, in form of topical or vaginal cream. The drug exerts its action by inhibiting lanosterol demethylase thereby affecting the growth of fungi.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 51 28 Target ID: CHEMBL1780 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018827s046lbl.pdf	Inhibitor 8297		19.7 nM [Kd]

Conditions

Condition	Modality	Highest Phase	Product
Vaginal yeast infections 1 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018052Orig1s032lbl.pdf	Curative	Approved 8429	GYNE-LOTRIMIN Approved Use To treat vaginal yeast infections. Launch Date 1976
Tinea pedis 28 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018827s046lbl.pdf	Curative	Approved 8429	LOTRISONE Approved Use LOTRISONE cream contains a combination of clotrimazole, an azole antifungal, and betamethasone dipropionate, a corticosteroid, and is indicated for the topical treatment of symptomatic inflammatory tinea pedis, tinea cruris, and tinea corporis due to Epidermophyton floccosum, Trichophyton mentagrophytes, and Trichophyton rubrum in patients 17 years and older. Launch Date 1984
Tinea cruris 11 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018827s046lbl.pdf	Curative	Approved 8429	LOTRISONE Approved Use LOTRISONE cream contains a combination of clotrimazole, an azole antifungal, and betamethasone dipropionate, a corticosteroid, and is indicated for the topical treatment of symptomatic inflammatory tinea pedis, tinea cruris, and tinea corporis due to Epidermophyton floccosum, Trichophyton mentagrophytes, and Trichophyton rubrum in patients 17 years and older. Launch Date 1984
Tinea corporis 19 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/018827s046lbl.pdf	Curative	Approved 8429	LOTRISONE Approved Use LOTRISONE cream contains a combination of clotrimazole, an azole antifungal, and betamethasone dipropionate, a corticosteroid, and is indicated for the topical treatment of symptomatic inflammatory tinea pedis, tinea cruris, and tinea corporis due to Epidermophyton floccosum, Trichophyton mentagrophytes, and Trichophyton rubrum in patients 17 years and older. Launch Date 1984

C_max

Value	Dose	Co-administered	Analyte	Population
3.3 μM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7882513	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		CLOTRIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
12.59 μM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7882513	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		CLOTRIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
2.99 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/7882513	1 g single, oral dose: 1 g route of administration: Oral experiment type: SINGLE co-administered:		CLOTRIMAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

Doses

Dose	Population	Adverse events
10 mg 5 times / day multiple, oral Recommended Dose: 10 mg, 5 times / day Route: oral Route: multiple Dose: 10 mg, 5 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2073120	unhealthy, 33 years (range: 22 - 43 years) n = 20 Health Status: unhealthy Condition: Oral Candidiasis Age Group: 33 years (range: 22 - 43 years) Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2073120	Disc. AE: Nausea, Taste abnormality... AEs leading to discontinuation/dose reduction: Nausea (2 patients) Taste abnormality (2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/2073120
500 mg single, vaginal Highest studied dose Dose: 500 mg Route: vaginal Route: single Dose: 500 mg Co-administed with:: lactic acid Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf	unhealthy, adult n = 89 Health Status: unhealthy Age Group: adult Sex: F Population Size: 89 Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf	Disc. AE: Vulvovaginal burning sensation... AEs leading to discontinuation/dose reduction: Vulvovaginal burning sensation (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf
500 mg single, vaginal Highest studied dose Dose: 500 mg Route: vaginal Route: single Dose: 500 mg Co-administed with:: lactic acid Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf	Disc. AE: Vulvovaginal pruritus... AEs leading to discontinuation/dose reduction: Vulvovaginal pruritus (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf
50 mg 1 times / day multiple, vaginal Dose: 50 mg, 1 times / day Route: vaginal Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf Page: p. 5	unhealthy, adult n = 323 Health Status: unhealthy Age Group: adult Sex: F Population Size: 323 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf Page: p. 5	Disc. AE: Vaginal irritation, Spotting vaginal... AEs leading to discontinuation/dose reduction: Vaginal irritation (1 patient) Spotting vaginal (1 patient) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf Page: p. 5

AEs

AE	Significance	Dose	Population
Nausea	2 patients Disc. AE	10 mg 5 times / day multiple, oral Recommended Dose: 10 mg, 5 times / day Route: oral Route: multiple Dose: 10 mg, 5 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2073120	unhealthy, 33 years (range: 22 - 43 years) n = 20 Health Status: unhealthy Condition: Oral Candidiasis Age Group: 33 years (range: 22 - 43 years) Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2073120
Taste abnormality	2 patients Disc. AE	10 mg 5 times / day multiple, oral Recommended Dose: 10 mg, 5 times / day Route: oral Route: multiple Dose: 10 mg, 5 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2073120	unhealthy, 33 years (range: 22 - 43 years) n = 20 Health Status: unhealthy Condition: Oral Candidiasis Age Group: 33 years (range: 22 - 43 years) Sex: M+F Population Size: 20 Sources: https://pubmed.ncbi.nlm.nih.gov/2073120
Vulvovaginal burning sensation	1 patient Disc. AE	500 mg single, vaginal Highest studied dose Dose: 500 mg Route: vaginal Route: single Dose: 500 mg Co-administed with:: lactic acid Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf	unhealthy, adult n = 89 Health Status: unhealthy Age Group: adult Sex: F Population Size: 89 Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf
Vulvovaginal pruritus	1 patient Disc. AE	500 mg single, vaginal Highest studied dose Dose: 500 mg Route: vaginal Route: single Dose: 500 mg Co-administed with:: lactic acid Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf	unhealthy, adult Health Status: unhealthy Age Group: adult Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/4025444 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf
Spotting vaginal	1 patient Disc. AE	50 mg 1 times / day multiple, vaginal Dose: 50 mg, 1 times / day Route: vaginal Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf Page: p. 5	unhealthy, adult n = 323 Health Status: unhealthy Age Group: adult Sex: F Population Size: 323 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf Page: p. 5
Vaginal irritation	1 patient Disc. AE	50 mg 1 times / day multiple, vaginal Dose: 50 mg, 1 times / day Route: vaginal Route: multiple Dose: 50 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf Page: p. 5	unhealthy, adult n = 323 Health Status: unhealthy Age Group: adult Sex: F Population Size: 323 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21143_Trivagizole%203_medr.pdf Page: p. 5

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A1 1 CYP3A2 10 CYP2C11 4 CYP2B1/2 3 CYP1A 72 CYP2E1 882 UGT1A1 204 UGT1A3 84 UGT1A4 77 UGT1A6 108 UGT1A9 116 UGT2B7 146 UGT2B15 64 MRP1 106		CYP1A 56 P-gp 257

Drug as perpetrator

Target	Modality	Activity
CYP2E1 970	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/6/837.short Page: -	no
CYP3A2 13	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/6/837.short Page: -	yes [IC50 0.00315 uM]
CYP3A1 5	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/6/837.short Page: -	yes [IC50 0.00822 uM]
CYP2B1/2 4	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/6/837.short Page: -	yes [IC50 0.1 uM]
CYP2C11 15	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/6/837.short Page: -	yes [IC50 0.745 uM]
CYP1A 121	inhibitor 3277 Sources: https://dmd.aspetjournals.org/content/29/6/837.short Page: -	yes [IC50 2.3 uM]
UGT1A1 254	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0163725820302199 Page: -	yes [IC50 >10 uM]
UGT1A3 93	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0163725820302199 Page: -	yes [IC50 >10 uM]
UGT1A4 80	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0163725820302199 Page: -	yes [IC50 >10 uM]
UGT1A6 141	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0163725820302199 Page: -	yes [IC50 >10 uM]
UGT1A9 121	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0163725820302199 Page: -	yes [IC50 >10 uM]
UGT2B15 64	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0163725820302199 Page: -	yes [IC50 >10 uM]
UGT2B7 157	inhibitor 3277 Sources: https://www.sciencedirect.com/science/article/pii/S0163725820302199 Page: -	yes [IC50 >10 uM]
CYP1A 121	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S0024320504008598 Page: -	yes
MRP1 172	inhibitor 3277 Sources: https://febs.onlinelibrary.wiley.com/doi/full/10.1046/j.0014-2956.2001.02611.x Page: -	yes
P-gp 1650	inducer 1573 Sources: https://www.sciencedirect.com/science/article/pii/S1096495920301329 Page: -	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.sciencedirect.com/science/article/pii/S1056871905000523 Page: -

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3764	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3764
ChemicalBook	CB7404063	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB7404063
MolPort	MolPort-002-557-756	https://www.molport.com/shop/molecule-link/MolPort-002-557-756
Selleck Chemicals	Clotrimazole(Canesten)	http://www.selleckchem.com/products/Clotrimazole(Canesten).html
ZINC	ZINC000003807804	http://zinc15.docking.org/substances/ZINC000003807804
eMolecules	499093	https://www.emolecules.com/cgi-bin/more?vid=499093

PubMed

Title	Date	PubMed
Effects of clotrimazole on the growth, morphological characteristics, and cisplatin sensitivity of human glioblastoma cells in vitro.	1999 May	10223459
Synergy between 6-amino-2-n-pentylthiobenzothiazole and ergosterol biosynthesis-inhibiting antimycotics against Candida albicans in vitro.	2000 Jul	10854813
Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1: a potential immunosuppressant.	2000 Jul 5	10884437
Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands.	2000 May 19	10748001
Bactericidal and inhibitory effects of azole antifungal compounds on Mycobacterium smegmatis.	2000 Nov 15	11064188
A double-blind randomized comparative trial: eberconazole 1% cream versus clotrimazole 1% cream twice daily in Candida and dermatophyte skin infections.	2001	11486455
Clotrimazole increases tacrolimus blood levels: a drug interaction in kidney transplant patients.	2001 Apr	11264634
K+ channels and the microglial respiratory burst.	2001 Apr	11245596
A systematic review of the effectiveness of antifungal drugs for the prevention and treatment of oropharyngeal candidiasis in HIV-positive patients.	2001 Aug	11505264
Inhibition and stimulation of phospholipid scrambling activity. Consequences for lipid asymmetry, echinocytosis, and microvesiculation of erythrocytes.	2001 Aug 7	11478914
Toward a novel metal-based chemotherapy against tropical diseases. 6. Synthesis and characterization of new copper(II) and gold(I) clotrimazole and ketoconazole complexes and evaluation of their activity against Trypanosoma cruzi.	2001 Dec 31	11754267
Identification and expression of multidrug resistance-related ABC transporter genes in Candida krusei.	2001 Feb	11270397
Clotrimazole analogues: effective blockers of the slow afterhyperpolarization in cultured rat hippocampal pyramidal neurones.	2001 Feb	11181430
Expression and biological significance of Ca2+-activated ion channels in human keratinocytes.	2001 Jan	11149902
Insulin-induced relaxation of rat mesenteric artery is mediated by Ca(2+)-activated K(+) channels.	2001 Jan 5	11137870
Therapeutic strategies for prevention of sickle cell dehydration.	2001 Jan-Feb	11358364
Evaluation of two self-care treatments for prevention of vaginal candidiasis in women with HIV.	2001 Jul-Aug	11486720
In vitro activity of sertaconazole, fluconazole, ketoconazole, fenticonazole, clotrimazole and itraconazole against pathogenic vaginal yeast isolates.	2001 Mar	11484411
Optimization of the separation of a group of antifungals by capillary zone electrophoresis.	2001 May 11	11403486
Sertaconazole: in-vitro antifungal activity against vaginal and other superficial yeast isolates.	2001 Oct	11760221
Do azoles and chloroquine share similar mechanisms of antimalarial action?	2002 Apr	11998701
Cytochrome P450 3A conjugation to ubiquitin in a process distinct from classical ubiquitination pathway.	2002 Apr	11901229
Dehydration response of sickle cells to sickling-induced Ca(++) permeabilization.	2002 Apr 1	11895796
Translation initiation and its deregulation during tumorigenesis.	2002 Apr 8	11953842
Activation of ion secretion via proteinase-activated receptor-2 in human colon.	2002 Feb	11804840
Characterization of basolateral K+ channels underlying anion secretion in the human airway cell line Calu-3.	2002 Feb 1	11826162
Arginine supplementation of sickle transgenic mice reduces red cell density and Gardos channel activity.	2002 Feb 15	11830454
Influence of redox-active compounds and PXR-activators on human MRP1 and MRP2 gene expression.	2002 Feb 28	11836020
Topical antifungal drug products for over-the-counter human use; amendment of final monograph. Final rule.	2002 Feb 8	11837282
Development of a topical suspension containing three active ingredients.	2002 Jan	11858522
K+ currents generated by NMDA receptor activation in rat hippocampal pyramidal neurons.	2002 Jun	12037201
Involvement of nitric oxide and potassium channels in the bradykinin-induced vasodilatation in the rat kidney perfused ex situ.	2002 May 30	11959369

Patents

Sample Use Guides

In Vivo Use Guide

Vaginal 1% cream: insert an applicator full of cream into the vagina at bedtime for 7 days. External 1% cream for vaginal yeast infections: apply to the skin outside the vagina 2 times daily for up to 7 days. Topical 1% cream: apply a thin layer to the affected area twice daily for 2 weeks (tinea pedis) or 1 week (tinea cruris and tinea corporis).

Route of Administration: Topical

In Vitro Use Guide

In vitro antifungal activity indicated Clotrimazole (MIC 16 and 8 microg/ml) effective against 68 (70%) of Candida SPP.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:05:12 GMT 2023` Edited by `admin` on `Fri Dec 15 15:05:12 GMT 2023`
Record UNII	G07GZ97H65
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CLOTRIMAZOLE

Official Name

English

CLOTRIMAZOLE [GREEN BOOK]

Common Name

English

SVT-15652

Code

English

CLOTRIMAZOLE [ORANGE BOOK]

Common Name

English

GNF-PF-3499

Code

English

CLOTRIMAZOLE [USP IMPURITY]

Common Name

English

TRIVAGIZOLE

Brand Name

English

clotrimazole [INN]

Common Name

English

CLOTRIMAZOLE [MART.]

Common Name

English

CLOTRIMAZOLE [JAN]

Common Name

English

CLOTRIMAZOLE COMPONENT OF LOTRISONE

Common Name

English

Clotrimazole [WHO-DD]

Common Name

English

GYNIX

Brand Name

English

BAY-5097

Code

English

LOTRIMIN

Brand Name

English

LOTRISONE COMPONENT CLOTRIMAZOLE

Common Name

English

CLOTRIMAZOLE [MI]

Common Name

English

GYNE-LOTRIMIN

Brand Name

English

CLOTRIMAZOLE [EP IMPURITY]

Common Name

English

BAY 5097

Code

English

1-(2-CHLOROTRITYL)IMIDAZOLE

Systematic Name

English

CLOTRIMAZOLE [USP MONOGRAPH]

Common Name

English

MYCELEX

Brand Name

English

CLOTRIMAZOLE [EP MONOGRAPH]

Common Name

English

NSC-257473

Code

English

1-(O-CHLORO-.ALPHA.,.ALPHA.-DIPHENYLBENZYL)IMIDAZOLE

Common Name

English

CLOTRIMAZOLE [VANDF]

Common Name

English

1-((2-CHLOROPHENYL)DIPHENYLMETHYL)-1H-IMIDAZOLE

Systematic Name

English

CLOTRIMAZOLE [USAN]

Common Name

English

1H-IMIDAZOLE, 1-((2-CHLOROPHENYL)DIPHENYLMETHYL)-

Systematic Name

English

CLOTRIMAZOLE [USP-RS]

Common Name

English

Classification Tree Code System Code

CFR

21 CFR 524.1044G