CHLORHEXIDINE

First approved in 1959

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H30Cl2N10
Molecular Weight	505.447
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC=C(NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC2=CC=C(Cl)C=C2)C=C1

InChI

InChIKey=GHXZTYHSJHQHIJ-UHFFFAOYSA-N

InChI=1S/C22H30Cl2N10/c23-15-5-9-17(10-6-15)31-21(27)33-19(25)29-13-3-1-2-4-14-30-20(26)34-22(28)32-18-11-7-16(24)8-12-18/h5-12H,1-4,13-14H2,(H5,25,27,29,31,33)(H5,26,28,30,32,34)

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019028s022lbl.pdf
Curator's Comment: Description was created based on several sources, including: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019028s022lbl.pdf http://www.drugbank.ca/drugs/DB00878 http://www.wikidoc.org/index.php/Chlorhexidine_gluconate

Chlorhexidine is a broad-spectrum biocide effective against Gram-positive bacteria, Gram-negative bacteria and fungi. It is used primarily as its salts (e.g., the dihydrochloride, diacetate, and digluconate). Chlorhexidine inactivates microorganisms with a broader spectrum than other antimicrobials (e.g. antibiotics) and has a quicker kill rate than other antimicrobials (e.g. povidone-iodine). It has both bacteriostatic (inhibits bacterial growth) and bactericidal (kills bacteria) mechanisms of action, depending on its concentration. Chlorhexidine kills by disrupting the cell membrane. The most common side effects associated with chlorhexidine gluconate oral rinses are: 1) an increase in staining of teeth and other oral surfaces; 2) an increase in calculus formation; and 3) an alteration in taste perception; 4) toothache; 5) upper respiratory tract infection; and 6) headache.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
bacterial cell wall 7 Target ID: bacterial cell wall Sources: http://chlorhexidinefacts.com/mechanism-of-action.html	Binding Agent 1064

Conditions

Condition	Modality	Targets	Highest Phase	Product
Gingivitis 44 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019028s022lbl.pdf	Curative		Approved 8429	HIBICLENS Approved Use Use for the preparation of the patient's skin prior to surgery. Helps to reduce bacteria that potentially can cause skin infection. Launch Date 1976

C_max

Value	Dose	Co-administered	Analyte	Population
2007 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9869352	2.5 mg single, dental dose: 2.5 mg route of administration: Dental experiment type: SINGLE co-administered:		CHLORHEXIDINE inflammatory exudate	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.206 μg/g DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019028s022lbl.pdf	300 mg single, oral dose: 300 mg route of administration: Oral experiment type: SINGLE co-administered:		CHLORHEXIDINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
187083.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9869352	2.5 mg single, dental dose: 2.5 mg route of administration: Dental experiment type: SINGLE co-administered:	CHLORHEXIDINE inflammatory exudate	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
148287.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26271869	0.2 % single, dental dose: 0.2 % route of administration: Dental experiment type: SINGLE co-administered:	CHLORHEXIDINE saliva	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
180892.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26271869	0.2 % 1 times / day multiple, dental dose: 0.2 % route of administration: Dental experiment type: MULTIPLE co-administered:	CHLORHEXIDINE saliva	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
17% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4269593			CHLORHEXIDINE serum	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN
73% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4269593/			CHLORHEXIDINE saliva	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2 % 1 times / day single, topical Recommended Dose: 2 %, 1 times / day Route: topical Route: single Dose: 2 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83	healthy, 18-64 years n = 36 Health Status: healthy Age Group: 18-64 years Sex: M+F Population Size: 36 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83	Other AEs: Redness... Other AEs: Redness (grade 2) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83
3 % 1 times / day multiple, topical (mean) Recommended Dose: 3 %, 1 times / day Route: topical Route: multiple Dose: 3 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83	healthy, 18-79 years n = 204 Health Status: healthy Age Group: 18-79 years Sex: M+F Population Size: 204 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83	Disc. AE: Papule, Erythema... AEs leading to discontinuation/dose reduction: Papule Erythema (grade 2) Edema (grade 1) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83
3 % 1 times / day multiple, topical (mean) Recommended Dose: 3 %, 1 times / day Route: topical Route: multiple Dose: 3 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83	healthy, 22-60 years n = 23 Health Status: healthy Age Group: 22-60 years Sex: M+F Population Size: 23 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83	Disc. AE: Burning sensation, Petechial rash... AEs leading to discontinuation/dose reduction: Burning sensation (grade 1) Petechial rash (grade 1) Scab Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21669s000_MedR.pdf Page: nda/2005/21669s000_MedR.pdf - p.83
1.5 oz 1 times / day single, oral (mean) Studied dose Dose: 1.5 oz, 1 times / day Route: oral Route: single Dose: 1.5 oz, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019028s022lbl.pdf	healthy, child n = 1 Health Status: healthy Age Group: child Population Size: 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019028s022lbl.pdf	Other AEs: Distress epigastric, Nausea... Other AEs: Distress epigastric Nausea Alcohol intoxication Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019028s022lbl.pdf
2.5 mg 3 times / month multiple, subgingival Recommended Dose: 2.5 mg, 3 times / month Route: subgingival Route: multiple Dose: 2.5 mg, 3 times / month Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20774lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20774-ltr-lab-mr.pdf https://pubmed.ncbi.nlm.nih.gov/9776027/	unhealthy, mean age 47 years n = 225 Health Status: unhealthy Condition: periodontitis Age Group: mean age 47 years Sex: M+F Population Size: 225 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20774lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20774-ltr-lab-mr.pdf https://pubmed.ncbi.nlm.nih.gov/9776027/	Other AEs: Toothache, Upper respiratory tract infection... Other AEs: Toothache (50.7%) Upper respiratory tract infection (28.4%) Headache (27.1%) Sinusitis (13.8%) Influenza-like symptoms (7.6%) Back pain (6.7%) Tooth disorder (6.2%) Bronchitis (6.2%) Abscess (5.8%) Pain (4.9%) Allergy (4%) Myalgia (4%) Gum hyperplasia (3.6%) Pharyngitis (3.6%) Arthralgia (3.1%) Dysmenorrhea (3.1%) Dyspepsia (3.1%) Rhinitis (2.7%) Coughing (2.7%) Arthrosis (2.7%) Hypertension (2.2%) Stomatitis ulcerative (2.2%) Tendinitis (2.2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20774lbl.pdf https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20774-ltr-lab-mr.pdf https://pubmed.ncbi.nlm.nih.gov/9776027/

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:3614	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:3614
ChemicalBook	CB2771984	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2771984
ChemicalBook	CB4732251	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4732251
MolPort	MolPort-002-541-741	https://www.molport.com/shop/molecule-link/MolPort-002-541-741
MolPort	MolPort-006-167-649	https://www.molport.com/shop/molecule-link/MolPort-006-167-649
ZINC	ZINC000014768621	http://zinc15.docking.org/substances/ZINC000014768621
eMolecules	491622	https://www.emolecules.com/cgi-bin/more?vid=491622

PubMed

Title	Date	PubMed
The effect of chlorhexidine irrigation of the bladder in the rat.	1975 Oct	1191923
Nephrotoxic and hepatotoxic effects of triclosan and chlorhexidine in rats.	1977 Oct	145039
Combined effects of Zn(2+)-chlorhexidine and Zn(2+)-cetylpyridinium chloride on caries incidence in partially desalivated rats.	1991 Aug	1771376
The effectiveness and side effects of 0.1% and 0.2% chlorhexidine mouthrinses: a clinical study.	1998 Jul	9759061
6-month use of 0.2% delmopinol hydrochloride in comparison with 0.2% chlorhexidine digluconate and placebo. (I). Effect on plaque formation and gingivitis.	1998 Sep	9763330
Developing a dynamic pharmacophore model for HIV-1 integrase.	2000 Jun 1	10841789
Chlorhexidine and taste. Influence of mouthwashes concentration and of rinsing time.	2000 May	11068420
Probing depth changes following 2 years of periodontal maintenance therapy including adjunctive controlled release of chlorhexidine.	2003 Apr	12747445
Chlorhexidine induces DNA damage in rat peripheral leukocytes and oral mucosal cells.	2004 Oct	15324357
Chlorhexidine in urethral gel: does it cause pain at flexible cystoscopy?	2006 Apr	16566965
Chemoenzymatic synthesis and antimicrobial and haemolytic activities of amphiphilic bis(phenylacetylarginine) derivatives.	2006 Oct	16972292
Adverse events associated with chlorhexidine use: results from the Department of Veterans Affairs Dental Diabetes Study.	2008 Feb	18245686
[Ultrastructure study of pathogen of acanthamoeba keratitis].	2008 Nov	19176099

Patents

Sample Use Guides

In Vivo Use Guide

Recommended use is twice daily oral rinsing for 30 seconds, morning and evening after tooth brushing. Usual dosage is 15 ml (1 tablespoon) of undiluted Chlorhexidine gluconate oral rinse. Prophylaxis intervals - no longer than six months.

Route of Administration: Topical

In Vitro Use Guide

Minimum bactericidal concentrations are different for different bacterial strains (3.9-83.3 mg/l).

Name

Type

Language

CHLORHEXIDINE

Official Name

English

Chlorhexidine [WHO-DD]

Common Name

English

CHLORHEXIDINE [INCI]

Common Name

English

MERFEN-INCOLORE

Brand Name

English

CHLORHEXIDINE [HSDB]

Common Name

English

CHLORHEXIDINE [VANDF]

Common Name

English

CHLORHEXADINE

Common Name

English

CHLORHEXIDINE [MI]

Common Name

English

DENTISEPT

Brand Name

English

CHLORHEXIDINE [USP-RS]

Common Name

English

CHLORHEXIDINE [MART.]

Common Name

English

chlorhexidine [INN]

Common Name

English

Classification Tree Code System Code

WHO-ATC

D08AC02