Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Chlorhexidine: Difference between pages

{{Short description|Disinfectant and antiseptic}}

{{Use dmy dates|date=January 2024}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 464187733

| image = Chlorhexidin.svg

| width = 280

| alt =

| image2 = Chlorhexidine 3D spacefill.png

| alt2 =

<!-- Clinical data -->

| pronounce = klɔː(r)ˈhɛksɪdiːn

| tradename = Betasept, ChloraPrep, Chlorostat, others

| Drugs.com = {{drugs.com|monograph|chlorhexidine-gluconate-topical}}

| MedlinePlus =

| DailyMedID = Chlorhexidine

| pregnancy_AU = A

| pregnancy_AU_comment =

| pregnancy_category=

| routes_of_administration = [[Topical medication|Topical]]

| ATC_prefix = A01

| ATC_suffix = AB03

| ATC_supplemental = {{ATC|B05|CA02}}, {{ATC|D08|AC02}}, {{ATC|D09|AA12}} (dressing), {{ATC|R02|AA05}}, {{ATC|S01|AX09}}, {{ATC|S02|AA09}}, {{ATC|S03|AA04}}

<!-- Legal status -->

| legal_AU = S5, S6, S7

| legal_AU_comment =

| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F -->

| legal_BR_comment =

| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->

| legal_CA_comment =

| legal_DE = <!-- Anlage I, II, III or Unscheduled -->

| legal_DE_comment =

| legal_NZ = <!-- Class A, B, C -->

| legal_NZ_comment =

| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM / Class A, B, C -->

| legal_UK_comment =

| legal_US = OTC

| legal_US_comment = /&nbsp;Rx-only

| legal_EU =

| legal_EU_comment =

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

| legal_UN_comment =

| legal_status = <!-- For countries not listed above -->

<!-- Pharmacokinetic data -->

| bioavailability =

| protein_bound =

| metabolism =

| metabolites =

| onset =

| elimination_half-life =

| duration_of_action =

| excretion =

<!-- Identifiers -->

| CAS_supplemental =

| PubChem = 9552079

| IUPHAR_ligand =

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| NIAID_ChemDB =

| PDB_ligand =

| synonyms = CHX, CHG, 1,6-bis(4-chloro-phenylbiguanido)hexane

<!-- Chemical and physical data -->

| IUPAC_name = ''N'',''{{prime|N}}''{{prime}}{{prime}}{{prime}}<nowiki>1,6-Hexanediylbis[</nowiki>''{{prime|N}}''<nowiki>-(4-chlorophenyl)(imidodicarbonimidic diamide)]</nowiki>

| C=22 | H=30 | Cl=2 | N=10

| SMILES = Clc1ccc(NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)Nc2ccc(Cl)cc2)cc1

| StdInChI_comment =

| density =

| density_notes =

| melting_point = 134

| melting_high = 136

| melting_notes =

| boiling_point =

| boiling_notes =

| solubility = 0.8

| sol_units =

| specific_rotation =

<!-- Definition and medical uses -->

'''Chlorhexidine'''<ref>{{cite journal | vauthors = Varoni E, Tarce M, Lodi G, Carrassi A | title = Chlorhexidine (CHX) in dentistry: state of the art | journal = Minerva Stomatologica | volume = 61 | issue = 9 | pages = 399–419 | date = September 2012 | pmid = 22976567 | url = https://pubmed.ncbi.nlm.nih.gov/22976567/ | access-date = 30 September 2021 | archive-date = 30 September 2021 | archive-url = https://web.archive.org/web/20210930082631/https://pubmed.ncbi.nlm.nih.gov/22976567/ | url-status = live }}</ref> is a [[disinfectant]] and [[antiseptic]] with the [[Chemical formula#Molecular formula|molecular formula]] C₂₂H₃₀Cl₂N₁₀, which is used for [[skin disinfection]] before surgery and to sterilize [[surgical instruments]].<ref name="WHO2008">{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | pages = 321–22}}</ref> It is also used for cleaning [[wounds]], preventing [[dental plaque]], treating [[yeast infections of the mouth]], and to keep [[urinary catheters]] from blocking.<ref name="BNF69" /> It is used as a [[liquid]] or a powder.<ref name="WHO2008" /><ref name="BNF69" /> It is commonly used in [[Ionic compound|salt]] form, either the [[gluconate]]<ref name="PubChem CG">{{cite web|title=Chlorhexidine Gluconate|url=https://pubchem.ncbi.nlm.nih.gov/compound/Chlorhexidine-Gluconate|access-date=1 July 2023|website=PubChem}}</ref> or the [[acetate]].<ref name="PubChem CA">{{cite web|title=Chlorhexidine Acetate|url=https://pubchem.ncbi.nlm.nih.gov/compound/Chlorhexidine-Acetate|access-date=1 July 2023|website=PubChem}}</ref>

<!-- Side effects and mechanism -->

Side effects may include skin irritation, [[Human tooth|tooth]] discoloration, and [[allergic reactions]],<ref name="BNF69">{{cite book|title=British national formulary : BNF 69|date=2015|publisher=British Medical Association|isbn=9780857111562|pages=568, 791, 839|edition=69}}</ref> although apart from discoloration the risk appears to be the same as [[povidone-iodine]].<ref name=":1">{{cite journal | vauthors = Wade RG, Bourke G, Wormald JC, Totty JP, Stanley GH, Lewandowski A, Rakhra SS, Gardiner MD | title = Chlorhexidine versus povidone-iodine skin antisepsis before upper limb surgery (CIPHUR): an international multicentre prospective cohort study | journal = BJS Open | volume = 5 | issue = 6 | pages = zrab117 | date = November 2021 | pmid = 34915557 | pmc = 8677347 | doi = 10.1093/bjsopen/zrab117 }}</ref><ref name=":2">{{cite journal | vauthors = Wade RG, Burr NE, McCauley G, Bourke G, Efthimiou O | title = The Comparative Efficacy of Chlorhexidine Gluconate and Povidone-iodine Antiseptics for the Prevention of Infection in Clean Surgery: A Systematic Review and Network Meta-analysis | journal = Annals of Surgery | volume = 274 | issue = 6 | pages = e481–e488 | date = December 2021 | pmid = 32773627 | doi = 10.1097/SLA.0000000000004076 | s2cid = 225289226 | doi-access = free }}</ref> Chlorhexidine rinse is also known to have a bitter metallic aftertaste. Rinsing with water is not recommended as it is known to increase the bitterness.<ref>{{cite web |title=Chlorhexidine (Oral Route) Precautions - Mayo Clinic |url=https://www.mayoclinic.org/drugs-supplements/chlorhexidine-oral-route/precautions/drg-20068551 |access-date=27 June 2023 |website=www.mayoclinic.org}}</ref> It may cause eye problems if direct contact occurs.<ref name=AHFS2017>{{cite web|title=Chlorhexidine Gluconate topical|url=https://www.drugs.com/monograph/chlorhexidine-gluconate-topical.html|publisher=The American Society of Health-System Pharmacists|access-date=8 January 2017|url-status=live|archive-url=https://web.archive.org/web/20170113023435/https://www.drugs.com/monograph/chlorhexidine-gluconate-topical.html|archive-date=13 January 2017}}</ref><ref>{{cite journal | vauthors = Tabor E, Bostwick DC, Evans CC | title = Corneal damage due to eye contact with chlorhexidine gluconate | journal = JAMA | volume = 261 | issue = 4 | pages = 557–558 | date = January 1989 | pmid = 2909794 | doi = 10.1001/jama.1989.03420040091021 }}</ref> Use in [[pregnancy]] appears to be safe.<ref>{{cite book| vauthors = Briggs GG, Freeman RK, Yaffe SJ |title=Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk|date=2011|publisher=Lippincott Williams & Wilkins|isbn=9781608317080|page=252|url=https://books.google.com/books?id=OIgTE4aynrMC&pg=PA252|url-status=live|archive-url=https://web.archive.org/web/20170113121448/https://books.google.ca/books?id=OIgTE4aynrMC&pg=PA252|archive-date=13 January 2017}}</ref> Chlorhexidine may come mixed in [[ethanol|alcohol]],<ref>{{cite web | title=Prevantics Swab- chlorhexidine gluconate and isopropyl alcohol solution | website=DailyMed | date=26 October 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db61e7fd-c421-4e3c-bc88-0343230273de | access-date=24 January 2023 | archive-date=24 January 2023 | archive-url=https://web.archive.org/web/20230124030815/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=db61e7fd-c421-4e3c-bc88-0343230273de | url-status=live }}</ref><ref>{{cite web | title=Prevantics Swab- chlorhexidine gluconate and isopropyl alcohol solution | website=DailyMed | date=26 October 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ff999b50-0b6b-404e-b4f1-c6694fe47a9b | access-date=24 January 2023 | archive-date=24 January 2023 | archive-url=https://web.archive.org/web/20230124030813/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ff999b50-0b6b-404e-b4f1-c6694fe47a9b | url-status=live }}</ref><ref>{{cite web | title=Prevantics Maxi Swabstick- chlorhexidine gluconate and isopropyl alcohol solution | website=DailyMed | date=26 October 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=93ca3c07-40b4-3a91-e053-2995a90a0afd | access-date=24 January 2023 | archive-date=24 January 2023 | archive-url=https://web.archive.org/web/20230124030820/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=93ca3c07-40b4-3a91-e053-2995a90a0afd | url-status=live }}</ref> water, or [[surfactant solution]].<ref name=BNF69/> It is effective against a range of [[microorganisms]], but does not inactivate [[spores]].<ref name=WHO2008/>

<!-- Society and culture -->

Chlorhexidine came into medical use in the 1950s.<ref>{{cite book| vauthors = Schmalz G, Bindslev DA |title=Biocompatibility of Dental Materials|date=2008|publisher=Springer Science & Business Media|isbn=9783540777823|page=351|url=https://books.google.com/books?id=mrreTHuo54wC&pg=PA351|url-status=live|archive-url=https://web.archive.org/web/20170113080904/https://books.google.ca/books?id=mrreTHuo54wC&pg=PA351|archive-date=13 January 2017}}</ref> Chlorhexidine is available [[over the counter]] in the [[United States]].<ref name=AHFS2017 /> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref><ref name="WHO22nd">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 22nd list (2021) | year = 2021 | hdl = 10665/345533 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2021.02 | hdl-access=free }}</ref> In 2021, it was the 247th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2021 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=14 January 2024 | archive-date=15 January 2024 | archive-url=https://web.archive.org/web/20240115223848/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Chlorhexidine - Drug Usage Statistics | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Chlorhexidine | access-date = 14 January 2024}}</ref>

== Uses ==

Chlorhexidine is used in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eye drops, active substance in wound dressings and antiseptic mouthwashes).<ref name="guanidine">{{citation | vauthors = Güthner T, Mertschenk B, Schulz B | contribution=Guanidine and Derivatives | title=Ullman's Encyclopedia of Industrial Chemistry | edition=7th | publisher=Wiley | year=2007 | page=13 }}</ref> A 2019 [[Cochrane (organisation)|Cochrane review]] concluded that based on very low certainty evidence in those who are critically ill "it is not clear whether bathing with chlorhexidine reduces hospital-acquired infections, mortality, or length of stay in the [[intensive care unit]] (ICU), or whether the use of chlorhexidine results in more skin reactions."<ref>{{cite journal | vauthors = Lewis SR, Schofield-Robinson OJ, Rhodes S, Smith AF | title = Chlorhexidine bathing of the critically ill for the prevention of hospital-acquired infection | journal = The Cochrane Database of Systematic Reviews | volume = 8 | issue = 8 | pages = CD012248 | date = August 2019 | pmid = 31476022 | pmc = 6718196 | doi = 10.1002/14651858.CD012248.pub2 }}</ref>

In [[endodontics]], chlorhexidine has been used for root canal irrigation and as an intracanal dressing.<ref>{{cite journal | vauthors = Raab D | title = Preparation of contaminated root canal systems – the importance of antimicrobial irrigants. | journal = Dental Inc. | date = July–August 2008 | pages = 34–36 }}</ref><ref>{{cite journal | vauthors = Raab D | title = Die Bedeutung chemischer Spülungen in der Endodontie | journal = Endodontie Journal | date = 2010 | issue = 2 | pages = 22–23 | url = http://www.oemus.com/archiv/pub/sim/ej/2010/ej0210/ej0210_22_23_raab.pdf }}{{Dead link|date=April 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> It has however been replaced by the use of [[sodium hypochlorite]] [[bleach]] in much of the developed world.{{cn|date=June 2022}}

=== Antiseptic ===

Chlorhexidine is active against [[Gram-positive bacteria|Gram-positive]] and [[Gram-negative bacteria|Gram-negative]] organisms, [[facultative anaerobes]], [[aerobes]], and yeasts.<ref name="tox" /> It is particularly effective against Gram-positive bacteria (in concentrations ≥ 1&nbsp;μg/L). Significantly higher concentrations (10 to more than 73 μg/mL) are required for Gram-negative bacteria and fungi. Chlorhexidine is ineffective against [[polioviruses]] and [[adenoviruses]]. The effectiveness against herpes viruses has not yet been established unequivocally.<ref name="disinfectants">{{cite encyclopedia | vauthors= Harke HP | chapter = Disinfectants | encyclopedia=Ullman's Encyclopedia of Industrial Chemistry | edition=7th | publisher=Wiley | year=2007 | pages=10–11 }}</ref>

There is strong evidence that chlorhexidine is more effective than [[povidone-iodine]] for clean [[surgery]].<ref>{{cite journal | vauthors = Wade RG, Burr NE, McCauley G, Bourke G, Efthimiou O | title = The Comparative Efficacy of Chlorhexidine Gluconate and Povidone-iodine Antiseptics for the Prevention of Infection in Clean Surgery: A Systematic Review and Network Meta-analysis | journal = Annals of Surgery | volume = 274 | issue = 6 | pages = e481–e488 | date = December 2021 | pmid = 32773627 | doi = 10.1097/SLA.0000000000004076 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Dumville JC, McFarlane E, Edwards P, Lipp A, Holmes A, Liu Z | title = Preoperative skin antiseptics for preventing surgical wound infections after clean surgery | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 4 | pages = CD003949 | date = April 2015 | pmid = 25897764 | pmc = 6485388 | doi = 10.1002/14651858.CD003949.pub4 }}</ref> Evidence shows that it is an effective antiseptic for upper limb surgery.<ref name=":1" />

Meta-data spanning several decades shows that the efficacy of chlorhexidine (against organisms that cause surgical site infection) has not changed,<ref>{{cite journal | vauthors = Aftab R, Dodhia VH, Jeanes C, Wade RG | title = Bacterial sensitivity to chlorhexidine and povidone-iodine antiseptics over time: a systematic review and meta-analysis of human-derived data | journal = Scientific Reports | volume = 13 | issue = 1 | pages = 347 | date = January 2023 | pmid = 36611032 | pmc = 9825506 | doi = 10.1038/s41598-022-26658-1 | bibcode = 2023NatSR..13..347A }}</ref> dispelling concerns over emerging resistance.

=== Dental use ===

[[File:Perichlor, 0.12% chlorhexidine glucomate solution medication.jpg|thumb|Perichlor brand 0.12% chlorhexidine gluconate solution]]

Use of a chlorhexidine-based mouthwash in combination with normal tooth care can help reduce the build-up of plaque and improve mild [[gingivitis]].<ref name="coch2017">{{cite journal | vauthors = James P, Worthington HV, Parnell C, Harding M, Lamont T, Cheung A, Whelton H, Riley P | title = Chlorhexidine mouthrinse as an adjunctive treatment for gingival health | journal = The Cochrane Database of Systematic Reviews | volume = 3 | issue = 3 | pages = CD008676 | date = March 2017 | pmid = 28362061 | pmc = 6464488 | doi = 10.1002/14651858.CD008676.pub2 | doi-access = free }}</ref> There is not enough evidence to determine the effect in moderate to severe gingivitis.<ref name="coch2017" /> Its use as a mouthwash has a number of [[adverse effect]]s including damage to the mouth lining, tooth discoloration, [[Calculus (dental)|tartar]] build-up, and impaired taste.<ref name=coch2017/> Extrinsic tooth staining occurs when chlorhexidine rinse has been used for four weeks or longer.<ref name="coch2017" />

Mouthwashes containing chlorhexidine which stain teeth less than the classic solution have been developed, many of which contain [[chelation|chelated]] [[zinc]].<ref name="pmid16451475">{{cite journal | vauthors = Bernardi F, Pincelli MR, Carloni S, Gatto MR, Montebugnoli L | title = Chlorhexidine with an Anti Discoloration System. A comparative study | journal = International Journal of Dental Hygiene | volume = 2 | issue = 3 | pages = 122–126 | date = August 2004 | pmid = 16451475 | doi = 10.1111/j.1601-5037.2004.00083.x }}</ref><ref>{{cite journal | vauthors = Sanz M, Vallcorba N, Fabregues S, Müller I, Herkströter F | title = The effect of a dentifrice containing chlorhexidine and zinc on plaque, gingivitis, calculus and tooth staining | journal = Journal of Clinical Periodontology | volume = 21 | issue = 6 | pages = 431–437 | date = July 1994 | pmid = 8089246 | doi = 10.1111/j.1600-051X.1994.tb00741.x }}</ref><ref>{{cite journal | vauthors = Kumar S, Patel S, Tadakamadla J, Tibdewal H, Duraiswamy P, Kulkarni S | title = Effectiveness of a mouthrinse containing active ingredients in addition to chlorhexidine and triclosan compared with chlorhexidine and triclosan rinses on plaque, gingivitis, supragingival calculus and extrinsic staining | journal = International Journal of Dental Hygiene | volume = 11 | issue = 1 | pages = 35–40 | date = February 2013 | pmid = 22672130 | doi = 10.1111/j.1601-5037.2012.00560.x }}</ref>

Chlorhexidine is a [[cation]] which interacts with [[anionic]] components of [[toothpaste]], such as [[sodium lauryl sulfate]] and [[sodium monofluorophosphate]], and forms salts of low solubility and reduced antibacterial activity. Hence, to enhance the antiplaque effect of chlorhexidine, "it seems best that the interval between toothbrushing and rinsing with CHX [chlorhexidine] be more than 30 minutes, cautiously close to two hours after brushing".<ref>{{cite journal | vauthors = Kolahi J, Soolari A | title = Rinsing with chlorhexidine gluconate solution after brushing and flossing teeth: a systematic review of effectiveness | journal = Quintessence International | volume = 37 | issue = 8 | pages = 605–612 | date = September 2006 | pmid = 16922019 }}</ref>

=== Topical ===<!-- This section is redirected to from [[Septol]]. -->

Chlorhexidine gluconate is used as a skin cleanser for surgical scrubs, as a cleanser for skin wounds, for preoperative skin preparation, and for germicidal hand rinses.<ref name="tox" /> Chlorhexidine [[eye drop]]s have been used as a treatment for eyes affected by [[Acanthamoeba keratitis|''Acanthamoeba'' keratitis]].<ref name="Alkharashi">{{cite journal | vauthors = Alkharashi M, Lindsley K, Law HA, Sikder S | title = Medical interventions for acanthamoeba keratitis | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 2 | pages = CD010792 | date = February 2015 | pmid = 25710134 | pmc = 4730543 | doi = 10.1002/14651858.CD010792.pub2 }}</ref>

Chlorhexidine is a very effective antiseptic and its use is growing in the world for treating the umbilical cord. A 2015 [[Cochrane review]] has yielded high-quality evidence that within the community setting, chlorhexidine skin or cord care can reduce the incidence of [[omphalitis]] (inflammation of the [[umbilical cord]]) by 50% and neonatal mortality by 12%.<ref>{{cite journal | vauthors = Sinha A, Sazawal S, Pradhan A, Ramji S, Opiyo N | title = Chlorhexidine skin or cord care for prevention of mortality and infections in neonates | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 3 | pages = CD007835 | date = March 2015 | pmid = 25739381 | doi = 10.1002/14651858.CD007835.pub2 | s2cid = 16586836 | pmc = 10638659 }}</ref>

== Side effects ==

Side effects may include skin irritation, [[Human tooth|tooth]] discoloration, and [[allergic reactions]],<ref name="BNF69" /> although apart from discoloration the risk appears to be the same as [[povidone-iodine]].<ref name=":1" /><ref name=":2" />

Chlorhexidine is [[Ototoxicity|ototoxic]] (toxic to the inner ear). If put into a ruptured ear canal it may lead to deafness.<ref>{{cite journal | vauthors = Lai P, Coulson C, Pothier DD, Rutka J | title = Chlorhexidine ototoxicity in ear surgery, part 1: review of the literature | journal = Journal of Otolaryngology - Head & Neck Surgery | volume = 40 | issue = 6 | pages = 437–440 | date = December 2011 | pmid = 22420428 }}</ref>

Chlorhexidine does not meet European specifications for a hand disinfectant. Under the test conditions of the [[European Standard]] EN 1499, no significant difference in the efficacy was found between a 4% solution of chlorhexidine digluconate and soap.<ref name="disinfectants" /> In the US, between 2007 and 2009, [[Hunter Holmes McGuire Veterans Administration Medical Center]] conducted a cluster-randomized trial and concluded that daily bathing of patients in intensive care units with washcloths saturated with chlorhexidine gluconate reduced the risk of hospital-acquired infections.<ref>{{cite web |publisher=Agency for Healthcare Research and Quality |url=https://innovations.ahrq.gov/profiles/daily-bathing-antiseptic-agent-significantly-reduces-risk-hospital-acquired-infections |title=Daily Bathing With Antiseptic Agent Significantly Reduces Risk of Hospital-Acquired Infections in Intensive Care Unit Patients |date=23 April 2014 |access-date=29 April 2014 |url-status=live |archive-url=https://web.archive.org/web/20170113133136/https://innovations.ahrq.gov/profiles/daily-bathing-antiseptic-agent-significantly-reduces-risk-hospital-acquired-infections |archive-date=13 January 2017 }}</ref>

Whether prolonged exposure over many years may have carcinogenic potential is still not clear. The US [[Food and Drug Administration]] recommendation is to limit the use of a chlorhexidine gluconate mouthwash to a maximum of six months.<ref>{{cite journal | vauthors = Below H, Assadian O, Baguhl R, Hildebrandt U, Jäger B, Meissner K, Leaper DJ, Kramer A | title = Measurements of chlorhexidine, p-chloroaniline, and p-chloronitrobenzene in saliva after mouth wash before and after operation with 0.2% chlorhexidine digluconate in maxillofacial surgery: a randomised controlled trial | journal = The British Journal of Oral & Maxillofacial Surgery | volume = 55 | issue = 2 | pages = 150–155 | date = February 2017 | pmid = 27789177 | doi = 10.1016/j.bjoms.2016.10.007 }}</ref>

When ingested, chlorhexidine is poorly absorbed in the gastrointestinal tract and can cause stomach irritation or nausea.<ref>{{cite web|url=https://www.poison.org/articles/chlorhexidine-adverse-effects-172|title=Chlorhexidine Adverse Effects|website=www.poison.org|access-date=4 July 2018|archive-date=5 July 2018|archive-url=https://web.archive.org/web/20180705033148/https://www.poison.org/articles/chlorhexidine-adverse-effects-172|url-status=live}}</ref><ref name=":0">{{cite web|url=https://pubchem.ncbi.nlm.nih.gov/compound/chlorhexidine#section=Human-Toxicity-Excerpts|title=Chlorhexidine|work=Pubchem|publisher=U.S. National Library of Medicine|access-date=4 July 2018|archive-date=5 July 2018|archive-url=https://web.archive.org/web/20180705062731/https://pubchem.ncbi.nlm.nih.gov/compound/chlorhexidine#section=Human-Toxicity-Excerpts|url-status=live}}</ref> If aspirated into the lungs at high enough concentration, as reported in one case, it can be fatal due to the high risk of [[acute respiratory distress syndrome]].<ref name=":0" /><ref>{{cite journal | vauthors = Hirata K, Kurokawa A | title = Chlorhexidine gluconate ingestion resulting in fatal respiratory distress syndrome | journal = Veterinary and Human Toxicology | volume = 44 | issue = 2 | pages = 89–91 | date = April 2002 | pmid = 11931511 | quote = An 80-y-old woman with dementia accidentally ingested approximately 200 mL of Maskin (5% chlorhexidine) in a nursing home and then presumably aspirated gastric contents. }}</ref>

==Mechanism of action==

At physiologic [[pH]], chlorhexidine salts dissociate and release the positively charged chlorhexidine [[Ion#Anions and cations|cation]]. The bactericidal effect is a result of the binding of this cationic molecule to negatively charged bacterial cell walls. At low concentrations of chlorhexidine, this results in a [[Bacteriostatic agent|bacteriostatic]] effect; at high concentrations, membrane disruption results in cell death.<ref name="tox">{{cite book | veditors = Leikin JB, Paloucek FP | contribution=Chlorhexidine Gluconate | title=Poisoning and Toxicology Handbook | edition=4th | publisher=Informa | year=2008 | pages=183–84 }}</ref>

==Chemistry==

It is a cationic {{chem name|polybiguanide}} ([[bisbiguanide]]).<ref>{{cite journal | vauthors = Tanzer JM, Slee AM, Kamay BA | title = Structural requirements of guanide, biguanide, and bisbiguanide agents for antiplaque activity | journal = Antimicrobial Agents and Chemotherapy | volume = 12 | issue = 6 | pages = 721–729 | date = December 1977 | pmid = 931371 | pmc = 430011 | doi = 10.1128/aac.12.6.721 }}</ref>

== Deactivation ==

Chlorhexidine is deactivated by forming insoluble salts with [[anionic]] compounds, including the anionic [[surfactants]] commonly used as detergents in toothpastes and mouthwashes, anionic [[thickeners]] such as [[Polyacrylic acid|carbomer]], and anionic [[emulsifiers]] such as acrylates/C10-30 alkyl acrylate {{chem name|crosspolymer}}, among many others. For this reason, chlorhexidine mouth rinses should be used at least 30 minutes after other dental products.<ref name=Denton>{{cite book |vauthors=Denton GW |chapter=Chlorhexidine |chapter-url=https://books.google.com/books?id=3f-kPJ17_TYC&pg=PA321 |veditors=Block SS |year=2000 |title=Disinfection, Sterilization, and Preservation |edition=5th |publisher=[[Lippincott Williams & Wilkins]] |pages=321–36 |isbn=978-0-683-30740-5 |access-date=10 October 2016 |archive-date=12 January 2023 |archive-url=https://web.archive.org/web/20230112084021/https://books.google.com/books?id=3f-kPJ17_TYC&pg=PA321 |url-status=live }}</ref>

== Synthesis ==

The structure is based on two molecules of [[proguanil]], linked with a [[hexamethylenediamine]] [[Spacer (chemistry)|spacer]].

[[File:Chlorhexidine synthesis.png|center|700px|thumb|Two routes for chlorhexidine synthesis:<ref>{{cite journal | doi = 10.1039/JR9560004422| title = 850. Bisdiguanides having antibacterial activity| journal = Journal of the Chemical Society (Resumed)| year = 1956| vauthors = Rose FL, Swain G | pages = 4422–4425}}</ref> {{US patent|2684924}} (1954 to [[I.C.I.]]). The compounds designated (...)₂ are substituted hexanes.]]

== Society and culture ==

=== Brands ===

Chlorhexidine topical is sold as Betasept, Biopatch, Calgon Vesta, ChloraPrep One-Step, Dyna-Hex, Hibiclens, Hibistat Towelette, Scrub Care Exidine, Spectrum-4 among others.<ref>{{cite web |title=Hibiclens Uses, Side Effects & Warnings - Drugs.com |url=https://www.drugs.com/mtm/hibiclens.html |website=Drugs.com |access-date=4 August 2018 |archive-date=4 August 2018 |archive-url=https://web.archive.org/web/20180804231914/https://www.drugs.com/mtm/hibiclens.html |url-status=live }}</ref>

Chlorhexidine gluconate mouthwash is sold as Dentohexin, Paroex, Peridex, PerioChip, Corsodyl and Periogard, among others.<ref>{{cite web |title=Chlorhexidine gluconate Uses, Side Effects & Warnings - Drugs.com |url=https://www.drugs.com/mtm/chlorhexidine-gluconate-oral-rinse.html |website=Drugs.com |access-date=4 August 2018 |archive-date=28 August 2021 |archive-url=https://web.archive.org/web/20210828032628/https://www.drugs.com/mtm/chlorhexidine-gluconate-oral-rinse.html |url-status=live }}</ref>

==Veterinary medicine==

In animals, chlorhexidine is used for topical disinfection of wounds,<ref name="van Hengel">{{cite book| vauthors = van Hengel T, ter Haar G, Kirpensteijn J |chapter=Chapter 2. Wound management: a new protocol for dogs and cats. Chlorhexidine solution | veditors = Kirpensteijn J, ter Haar G |title=Reconstructive Surgery and Wound Management of the Dog and Cat|date=2013|publisher=CRC Press|isbn=9781482261455|page=<!-- no page numbers in e-book -->}}</ref> and to manage skin infections.<ref name=Maddison>{{cite book | veditors = Maddison JE, Page SW, Church DB |title=Small Animal Clinical Pharmacology|date=2008|publisher=Elsevier Health Sciences|isbn=978-0702028588|page=552|chapter=Antimicrobial agents. Chlorhexidine}}</ref> Chlorhexidine-based disinfectant products are used in the dairy farming industry.<ref name=Blowey>{{cite book | vauthors = Blowey RW, Edmondson P |title=Mastitis Control in Dairy Herds|date=2010|publisher=CABI|isbn=9781845937515|page=120}}</ref>

Post-surgical respiratory problems have been associated with the use of chlorhexidine products in cats.<ref>{{cite web| vauthors = Zeman D, Mosley J, Leslie-Steen P | date=Winter 1996| title=Post-Surgical Respiratory Distress in Cats Associated with Chlorhexidine Surgical Scrubs| url=http://www.addl.purdue.edu/newsletters/1996/winter/psrd.shtml| work=ADDL Newsletters| publisher=Indiana Animal Disease Diagnostic Laboratory| access-date=11 September 2011| url-status=live| archive-url=https://web.archive.org/web/20110927120035/http://www.addl.purdue.edu/newsletters/1996/winter/psrd.shtml| archive-date=27 September 2011}}</ref>

== References ==

{{reflist}}

{{Periodontology}}

{{Stomatological preparations}}

{{Antiseptics and disinfectants}}

{{Medicated dressings}}

{{Throat preparations}}

{{Otologicals}}

{{Portal bar|Medicine}}

[[Category:Antiseptics]]

[[Category:Biguanides]]

[[Category:Chloroarenes]]

[[Category:Disinfectants]]

[[Category:Oral hygiene]]

[[Category:Otologicals]]

[[Category:World Health Organization essential medicines]]

[[Category:Wikipedia medicine articles ready to translate]]