CHLORHEXIDINE DIGLUCONATE

CAS No.: 18472-51-0
EC No.: 242-354-0

Synonyms:
CHLORHEXIDINE DIGLUCONATE; Chlorhexidine digluconate; CHLORHEXIDINE DIGLUCONATE; 18472-51-0; Chlorhexidine gluconate; Unisept; Chlorhexidine D-digluconate; Peridex; UNII-MOR84MUD8E; Chlorhexidine di-D-gluconate; Periogard; MOR84MUD8E; Exidine; 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide), digluconate; Kleersight; Fight bac; Chlorhexidin glukonatu; MFCD00083599; Prevacare; pHiso-Med; Chlorhexidine digluconate solution; Hibitane gluconate; Hibiclens (TN); Periogard (TN); Peridex (TN); Chlohexidine gluconate; Chlorhexidine gluconate [USAN:USP:JAN]; EC 242-354-0; SCHEMBL34468; CHEMBL4297088; DTXSID5034519; CHEBI:28312; Chx plus concentrate premium chlorhexidine teat dip concentrate; Chlorhexidine gluconate (JP17/USP); AKOS015896303; AKOS025310696; D-Gluconic acid, compd. with N1,N14-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1); M166; C08038; D00858; Chlorhexidine digluconate solution, 20% in H2O; J-011837; Chlorhexidine digluconate, Pharmaceutical Secondary Standard; Certified Reference Material; 1,6-Bis(N5-[p-chlorophenyl]-N1-biguanido)hexane; 1,1'-Hexamethylenebis(5-[p-chlorophenyl]biguanide); 1-(4-chlorophenyl)-3-[N-[6-[[N-[N-(4-chlorophenyl)carbamimidoyl]carbamimidoyl]amino]hexyl]carbamimidoyl]guanidine; (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanoic acid; 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-, digluconate; D-Gluconic acid, compd with N,N''-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1); Gluconic acid, compd. with 1,1'-hexamethylene bis(5-(p-chlorophenyl)biguanide) (2:1), D- (8CI); N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]--D-gluconic acid (1/2); 1,6-Bis(N5-[p-chlorophenyl]-N1-biguanido)hexane; 1,1′-Hexamethylenebis(5-[p-chlorophenyl]biguanide); chlorhexidine; 55-56-1; Rotersept; Tubulicid; Fimeil; Hexadol; Soretol; Chlorhexidin; Chlorhexidinum; Chlorohexidine; Sterilon; Nolvasan; Cloresidina [DCIT]; Chlorhexidin [Czech]; Chlorhexidinum [INN-Latin]; Clorhexidina [INN-Spanish]; Hibistat; 1,6-Bis(p-chlorophenyldiguanido)hexane; 1,6-Di(4'-chlorophenyldiguanido)hexane; UNII-R4KO0DY52L; 1,6-Bis(5-(p-chlorophenyl)biguandino)hexane; 1,1'-Hexamethylenebis(5-(p-chlorophenyl)biguanide); 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide); 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-; CHEMBL790; R4KO0DY52L; MLS001332388; CHEBI:3614; Cloresidina; Clorhexidina; Exidine; Biguanide, 1,1'-hexamethylenebis(5-(p-chlorophenyl)-; Chlorhexidine, 98%; 56-95-1; CAS-55-56-1; NCGC00016246-03; SMR000857146; Sterido; Savlon babycare; N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]; DSSTox_CID_13314; DSSTox_RID_79062; N,N'-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide; DSSTox_GSID_33314; Chlorhexidine [INN:BAN]; Chlorhexidine dihydrochloride; MLS001304094; 1-(4-chlorophenyl)-3-[N-[6-[[N-[N-(4-chlorophenyl)carbamimidoyl]carbamimidoyl]amino]hexyl]carbamimidoyl]guanidine; N-(4-chlorophenyl)-1-3-(6-{N-[3-(4-chlorophenyl)carbamimidamidomethanimidoyl]amino}hexyl)carbamimidamidomethanimidamide; CCRIS 9230; Chlorhexidine (INN); C22H30Cl2N10; HSDB 7196; Merfen-incolore (TN); SR-01000799135; Nolvasan (*Diacetate*); 1,1'-Hexamethylenebis(5-[p-chlorophenyl]biguanide); SMR000718621; EINECS 200-238-7; Lisium (*Dihydrochloride*); BRN 2826432; 1,6-Di(N-p-chlorophenyldiguanido)hexane; Hibisol; Dentisept [veterinary] (TN); 1,6-Bis(N5-[p-chlorophenyl]-N1-biguanido)hexane; Prestwick_53; Chlorhexidine (1); Hibidil (Salt/Mix); Hibisol (Salt/Mix); Chlorhexidine diacetate salt hydrate; Hibitane (Salt/Mix); Hibiscrub (Salt/Mix); Hibispray (Salt/Mix); NSC526936; Spectrum_000237; Savloclens (Salt/Mix); 3697-42-5; Prestwick0_000143; Prestwick1_000143; Prestwick2_000143; Prestwick3_000143; Spectrum2_000135; Spectrum3_000339; Spectrum4_000277; Spectrum5_001322; chlorhexidine diacetate salt; EC 200-238-7; SCHEMBL3984; Chlorhexidine, >=99.5%; BSPBio_000246; BSPBio_001977; KBioGR_000774 ;KBioSS_000717; 4-12-00-01201 (Beilstein Handbook Reference); MLS001332387; MLS002154209; DivK1c_000761; SPBio_000210; SPBio_002185; BPBio1_000272; DTXSID2033314; BDBM51937; BDBM64773; cid_9552079; KBio1_000761; KBio2_000717; KBio2_003285; KBio2_005853; KBio3_001197; 2,4,11,13-Tetraazatetradecanediimidamide, N1,N14-bis(4-chlorophenyl)-3,12-diimino-; cid_12303047; NINDS_000761; REGID_for_CID_9552079; BDBM152706; HMS1568M08; HMS2095M08; HMS2233B16; HMS3712M08; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine; HY-B1248; Tox21_110325; Tox21_201404; Tox21_303445; BDBM50170723; s5397; SBB057564; STK089248; AKOS005394319; Tox21_110325_1; CCG-220143; CS-4958; DB00878; EBD2224760; MCULE-4644073142; 2,4,11,13-Tetraazatetradecanediimidamide, N,N'-bis(4-chlorophenyl)-3,12-diimino-; IDI1_000761; N,N''''-hexane-1,6-diylbis[N'-(4-chlorophenyl)(imidodicarbonimidic diamide)]; N,N'-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradeca- nediimidamide; QTL1_000020; NCGC00016246-01; NCGC00016246-02; NCGC00016246-04; NCGC00016246-05; NCGC00016246-06; NCGC00016246-07; NCGC00016246-09; NCGC00016246-13; NCGC00091025-01; NCGC00091025-02; NCGC00091025-04; NCGC00247766-01; NCGC00257242-01; NCGC00258955-01; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylene]amino]methylene]amino]hexyl]-1-[amino-(4-chloroanilino)methylene]guanidine; AS-12648; SC-17656; Chlorhexidine, purum, >=99.0% (HPLC); SBI-0051301.P003; AB00053427; C06902; D07668; AB00053427-24; AB00053427-28; AB00053427_29; 009C673; Q-200828; SR-01000799135-5; 1,1''-Hexamethylene bis(5-(p-chlorophenyl)biguanide); BRD-K52256627-300-03-3; BRD-K52256627-300-05-8; SR-01000799135-10; SR-01000799135-11; Chlorhexidine, European Pharmacopoeia (EP) Reference Standard; 1,1'-(Hexane-1,6-diyl)bis[5-(4-chlorophenyl)biguanide] diacetate; Chlorhexidine, United States Pharmacopeia (USP) Reference Standard; Chlorhexidine, Pharmaceutical Secondary Standard; Certified Reference Material; N'',N''''''''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]; N,N''-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylene]amino]methylene]amino]hexyl]-1-[amino-(4-chloroanilino)methylene]guanidine;hydrochloride; (1E)-2-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexyl]-1-[amino-(4-chloroanilino)methylidene]guanidine;hydrochloride; (1E)-2-[6-[[azanyl-[(E)-[azanyl-[(4-chlorophenyl)amino]methylidene]amino]methylidene]amino]hexyl]-1-[azanyl-[(4-chlorophenyl)amino]methylidene]guanidine; (1E)-2-[6-[[azanyl-[(E)-[azanyl-[(4-chlorophenyl)amino]methylidene]amino]methylidene]amino]hexyl]-1-[azanyl-[(4-chlorophenyl)amino]methylidene]guanidine;hydrochloride; {[(4-chlorophenyl)amino]iminomethyl}{[(6-{[({[(4-chlorophenyl)amino]iminomethy l}amino)iminomethyl]amino}hexyl)amino]iminomethyl}amine; 2-[amino-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexylimino]methyl]-1-(4-chlorophenyl)guanidine; 2-[amino-[6-[[amino-[(E)-[amino-(4-chloroanilino)methylidene]amino]methylidene]amino]hexylimino]methyl]-1-(4-chlorophenyl)guanidine;hydrochloride; 

CHLORHEXIDINE DIGLUCONATE

Chlorhexidine digluconate solution is a bis(biguanide) family cationic broad spectrum antibiotic. Studies indicate that Chlorhexidine digluconate solution functions, via destabilization of the outer bacterial membrane, which resulted in the release of periplasmic enzymes in gram negative bacteria. In addition, Chlorhexidine digluconate solution inhibits oxygen utilization which leads to a reduction in bacterial ATP. These studies also indicate that the inner membrane in gram negative bacteria was not affected by the solution, however there was inhibition of active transport for small molecules entering the cell. Furthermore, Chlorhexidine digluconate solution is very effective against bacteria such as Propionibacterium, Selenomonas, and cocci resembling Veillonella.

Chlorhexidine digluconate
Chlorhexidine digluconate (commonly known by the salt forms Chlorhexidine digluconate gluconate and Chlorhexidine digluconate (CHG) or Chlorhexidine digluconate acetate), is a disinfectant and antiseptic that is used for skin disinfection before surgery and to sterilize surgical instruments.It may be used both to disinfect the skin of the patient and the hands of the healthcare providers.It is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and to keep urinary catheters from blocking.It is used as a liquid or powder.

Side effects may include skin irritation, teeth discoloration, and allergic reactions.It may cause eye problems if direct contact occurs.Use in pregnancy appears to be safe.Chlorhexidine digluconate may come mixed in alcohol, water, or surfactant solution.It is effective against a range of microorganisms, but does not inactivate spores.

Chlorhexidine digluconate came into medical use in the 1950s.Chlorhexidine digluconate is available over the counter (OTC) in the United States.It is on the World Health Organization's List of Essential Medicines.In 2017, it was the 286th most commonly prescribed medication in the United States, with more than one million prescriptions.

Uses
Chlorhexidine digluconate 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).A 2019 Cochrane review concluded that based on very low certainty evidence in those who are critically ill "it is not clear whether bathing with Chlorhexidine digluconate reduces hospital‐acquired infections, mortality, or length of stay in the ICU, or whether the use of Chlorhexidine digluconate results in more skin 

In endodontics, Chlorhexidine digluconate is used for root canal irrigation and as an intracanal dressing,but has been replaced by the use of sodium hypochlorite bleach in much of the developed world.

Antiseptic
There is strong evidence that it is more effective than povidone-iodine and is it proved to kill 99.9% of germs in 30 sec.

CHG is active against Gram-positive and Gram-negative organisms, facultative anaerobes, aerobes, and yeasts.It is particularly effective against Gram-positive bacteria (in concentrations ≥ 1 μg/l). Significantly higher concentrations (10 to more than 73 μg/ml) are required for Gram-negative bacteria and fungi. Chlorhexidine digluconate is ineffective against polioviruses. The effectiveness against Covid-19 viruses has been established. The effectiveness against herpes viruses has not yet been established unequivocally.

Chlorhexidine digluconate, like other cation-active compounds, remains on the skin. It is frequently combined with alcohols (ethanol and isopropyl alcohol).

Dental use

Perichlor brand 0.12% Chlorhexidine digluconate gluconate solution
Use of a CHG-based mouthwash in combination with normal tooth care can help reduce the build-up of plaque and improve mild gingivitis.There is not enough evidence to determine the effect in moderate to severe gingivitis.About 20 mL twice a day of concentrations of 0.1% to 0.2% is recommended for mouth-rinse solutions with a duration of at least 30 seconds.Such mouthwash also has a number of adverse effects including damage to the mouth lining, tooth discoloration, tartar build-up, and impaired taste.Extrinsic tooth staining occurs when Chlorhexidine digluconate rinse has been used for 4 weeks or longer.

Mouthwashes containing Chlorhexidine digluconate which stain teeth less than the classic solution have been developed, many of which contain chelated zinc.
Using Chlorhexidine digluconate as a supplement to everyday mechanical oral hygiene procedures for 4 to 6 weeks and 6 months leads to a moderate reduction in gingivitis compared to placebo, control or mechanical oral hygiene alone.

Chlorhexidine digluconate 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 antibacterial activity. Hence, to enhance the antiplaque effect of Chlorhexidine digluconate, "it seems best that the interval between toothbrushing and rinsing with CHX [Chlorhexidine digluconate] be more than 30 minutes, cautiously close to 2 hours after brushing.".

Topical
Nepal was the first country in the world to use Chlorhexidine digluconate to treat the umbilical cord of newborn babies, and received a USAID Pioneers Prize for reducing the neonatal death rate.Chlorhexidine digluconate is very effective for poor countries like Nepal 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 digluconate skin or cord care can reduce the incidence of omphalitis (inflammation of the umbilical cord) by 50% and also neonatal mortality by 12%.Chlorhexidine digluconate 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.Chlorhexidine digluconate eye drops have been used as a treatment for eyes affected by Acanthamoeba keratitis.

Side effects
CHG is ototoxic; if put into an ear canal which has a ruptured eardrum, it can lead to deafness.

CHG does not meet current 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.In the U.S., 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 digluconate gluconate reduced the risk of hospital-acquired infections.

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 digluconate gluconate mouthwash to a maximum of six months.

When ingested, CHG is poorly absorbed in the gastrointestinal tract and can cause stomach irritation or nausea. 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.

Mechanism of action
At physiologic pH, Chlorhexidine digluconate salts dissociate and release the positively charged Chlorhexidine digluconate 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 digluconate, this results in a bacteriostatic effect; at high concentrations, membrane disruption results in cell death.

Chemistry
It is a cationic polybiguanide (bisbiguanide).It is used primarily as its salts (e.g., the dihydrochloride, diacetate, and digluconate).

Deactivation
Chlorhexidine digluconate 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 carbomer, and anionic emulsifiers such as acrylates/C10-30 alkyl acrylate crosspolymer, among many others. For this reason, Chlorhexidine digluconate mouth rinses should be used at least 30 minutes after other dental products.For best effectiveness, food, drink, smoking, and mouth rinses should be avoided for at least one hour after use. Many topical skin products, cleansers, and hand sanitizers should also be avoided to prevent deactivation when Chlorhexidine digluconate (as a topical by itself or as a residue from a cleanser) is meant to remain on the skin.

Synthesis
The structure is based on two molecules of proguanil, linked with a hexamethylenediamine spacer.

Two routes for Chlorhexidine digluconate synthesis:U.S. Patent 2,684,924 (1954 to I.C.I.). The compounds designated (...)2 are substituted hexanes.
Brands
Chlorhexidine digluconate topical is sold as Betasept, Biopatch, Calgon Vesta, ChloraPrep One-Step, Dyna-Hex, Hibiclens, Hibistat Towelette, Scrub Care Exidine, Spectrum-4 among others.

Chlorhexidine digluconate gluconate mouthwash is sold as Dentohexinm, Paroex, Peridex, PerioChip, Corsodyl and Periogard, among others.

Hexoralettene N contains benzocaine, menthol and Chlorhexidine digluconate hydrochloride. It is used as oral antiseptic candies.

Terminology
The name "Chlorhexidine digluconate" breaks down as chlor(o) + hex(ane) + id(e) + (am)ine), is a cationic polybiguanide. It is used primarily as its gluconate salt.

Veterinary medicine
In animals, Chlorhexidine digluconate is used for topical disinfection of wounds,and to manage skin infections.Chlorhexidine digluconate-based disinfectant products are used within the dairy farming industry.

Post-surgical respiratory problems have been associated with the use of Chlorhexidine digluconate products in cats.

FACTS ABOUT CHLORHEXIDINE IN ORAL CARE

Chlorhexidine digluconate is an antiseptic and antimicrobial often used as an active ingredient in oral rinse.
It provides protection against a wide range of bacteria. It kills bacteria by binding to bacteria cell walls.
The FDA approved chlorhexidine 0.12% in August 1986 as ANDA 19-028
Chlorhexidine digluconate, to date is the most potent anti-plaque agent. It is considered gold standard anti plaque agent, against which efficacy of other anti-plaque and anti -gingivitis agents is measured. Its efficacy can be attributed to:
Immediate bactericidal action
Prolonged bacteriostatic action.
The antimicrobial properties of Chlorhexidine digluconate are attributed to its bi-cationic molecule.
FOR WHICH INDICATION CAN WE USE CHLORHEXIDINE?

Gingivitis which causes redness, swelling, and bleeding of the gums.  Chlorhexidine digluconate gluconate has a positive chemical charge; it is attracted to the negative charge on certain bacteria in the mouth. This attraction affects the bacterial cell membrane and causes increased permeability for immediate antimicrobial activity. Chlorhexidine digluconate gluconate is also attracted to negatively charged surfaces on oral tissue. This additional attraction gives chlorhexidine gluconate a sustained action that can help prevent the formation of plaque
Periodontitis disease occurs when inflammation or infection of the gums (gingivitis) is allowed to progress without treatment. Chip impregnated with chlorhexidine are used to reduce or eliminate the sub-gingival microorganisms associated with periodontal diseases.
Prevention of Early Childhood Caries. Dental plaque is the main source for dental caries and there is no proper vaccine that can affect dental plaques. Studies have demonstrated that chlorhexidine was superior to other indicated products in its ability to maintain low plaque scores
Dental traumas, such as subluxation, intrusion associated with pulp exposure are treated with  mechanical decontamination and intracanal medication composed by 2% of chlorhexidine gel.
Wisdom tooth extraction. Use of Chlorhexidine digluconate (CHX)-based mouthwash immediately before third molar extraction reduces bacteria levels in patients’ blood after the procedure.
Ventilator-associated pneumonia (VAP) is the most common nosocomial infection among ventilated patients and is associated with increased mortality and morbidity. Oral chlorhexidine has been used to decontaminate the airway in critically ill patients, as studies suggest a risk reduction in VAP

The Advantages and Disadvantages of Chlorhexidine digluconate Mouthwash
Side effects
Warnings
Takeaway
What is it?

Chlorhexidine digluconate  is a prescription germicidal mouthwash that decreases bacteria in your mouth.

A 2017 studyTrusted Source suggests chlorhexidine is the most effective antiseptic mouthwash to date. Dentists primarily prescribe it to treat the inflammation, swelling, and bleeding that comes with gingivitis.

Chlorhexidine digluconate is available in the United States under the brand names:

Paroex (GUM)
Peridex (3M)
PerioGard (Colgate)
Chlorhexidine digluconate mouthwash side effects
There are three side effects of using chlorhexidine to consider before using it:

Staining. Chlorhexidine digluconate might cause staining of tooth surfaces, restorations, and the tongue. Often, a thorough cleaning can remove any stains. But if you have a lot of anterior white fillings, your dentist might not prescribe chlorhexidine.
Alteration in taste. Come people experience an alteration in taste during treatment. In rare instances, permanent taste alteration is experienced after the treatment has run its course.
Tartar formation. You may have an increase in tartar formation.
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Chlorhexidine digluconate warnings
If your dentist prescribes chlorhexidine, review how to use it thoroughly with them. Talk to your dentist about the following:

Allergic reactions. If you’re allergic to chlorhexidine, don’t use it. There’s a possibility of serious allergic reaction.
Dosage. Carefully follow your dentist’s instructions. The usual dosage is 0.5 fluid ounces undiluted), twice daily for 30 seconds.
Ingestion. After rinsing, spit it out. Don’t swallow it.
Timing. Chlorhexidine digluconate should be used after brushing. Don’t brush your teeth, rinse with water, or eat immediately after use.
Periodontitis. Some people have periodontitis along with gingivitis. Chlorhexidine digluconate treats gingivitis, not periodontitis. You’ll need separate treatment for periodontitis. Chlorhexidine digluconate might even make gum problems like periodontitis worse.
Pregnancy. Tell your dentist if you’re pregnant or planning on becoming pregnant. It hasn’t been determined whether or not chlorhexidine is safe for a fetus.
Breastfeeding. Tell your dentist if you’re breastfeeding. It hasn’t been determined whether chlorhexidine is passed to the baby in breastmilk or if it could affect the baby.
Follow up. Re-evaluate with your dentist whether the treatment is working at consistent intervals, waiting no longer than six months to check in.
Dental hygiene. The use of chlorhexidine isn’t a replacement for brushing your teeth, using dental floss, or regular visits to your dentist.
Children. Chlorhexidine digluconate isn’t approved for use by children under the age of 18.
Takeaway
Primary advantage
Chlorhexidine digluconate can kill the bacteria in your mouth that cause gum disease. This makes it an effective antiseptic mouthwash. Your dentist can prescribe it to treat the inflammation, swelling, and bleeding of gingivitis.

Primary disadvantages
Chlorhexidine digluconate may cause staining, alter your taste perception, and cause an increase in tartar.

When you hear the word chlorhexidine, these things probably come to mind:

“It stains.”
“A great killer of bacteria.”
“Has poor patient compliance.”
“Works well … but causes calculus.”
“Tastes terrible.”
“Adds a lot more work.”
Given these characteristics, it’s no surprise clinicians generally fall into two camps on chlorhexidine. There are those who hate it and refuse to use it, and there are those who use it and choose to overlook the side effects. For the clinicians who use it, if we asked why, they probably wouldn’t say, “Because I love it!” Instead, they’d likely say things such as “There’s no alternative” or “I use it because it’s what I learned in school.” Yet, there is an alternative to chlorhexidine and, as most of us know, doing something just because you learned it in school isn’t always good enough. 

For us to understand this controversial chemical’s place in dentistry, as well as possible alternatives, let’s take a hard look at chlorhexidine—the good, the bad, and the ugly.

The good: When used as designed
Chlorhexidine digluconate was introduced into dentistry in 1954 as a broad-spectrum biocide effective against gram-positive and gram-negative bacteria.1 It was designed to be used temporarily to help patients reverse gingivitis.

Chlorhexidine digluconate is a great bacterial killer. There is no need to debate this, as study after study has confirmed it. However, it requires an incredibly high concentration to achieve positive results: 1,200 parts per million.2 This is one of the reasons why chlorhexidine is not intended to be used longer than two weeks.

Even though chlorhexidine has many side effects, it can be safely used to treat gingivitis. However, many dental professionals use chlorhexidine off-label, and this is where the contraindications and safety concerns come into play.

The bad: Side effects
The main reason many clinicians dislike chlorhexidine is because of its side effects. We all know chlorhexidine stains teeth, and another common side effect is calculus buildup. Neither side effect is something you’d logically want for patients after their scalings, prophies, or surgeries.

Patients struggle to stay compliant with chlorhexidine because of the taste. They can’t rinse with water afterward because it renders the chlorhexidine ineffective. In fact, water actually increases the bitterness!3 After using, patients may complain of a “metallic” aftertaste that sticks around for several hours.4 Some patients even experience an alteration in taste.4 In rare instances, permanent taste alteration is experienced after the treatment has run its course.5

The ugly: Things you might not know
Side effects such as staining and calculus aren’t ideal, but they aren’t dangerous. Clinicians may be willing to compromise in an effort to get better treatment results. However, studies and real-world cases show us we may want to reconsider.

Even with the treatment of gingivitis, there are unrealistic instructions and expectations for patients to follow. Because chlorhexidine is easily inactivated, it should be used 30 minutes after other dental products. It is deactivated by anionic compounds, including the anionic surfactants used in toothpaste.6 So patients should not rinse immediately after brushing.6 Furthermore, they must then avoid drinking, eating, and smoking for at least one hour after use. 

There is also information that states saliva and blood inactivate chlorhexidine.7,8 How do we avoid saliva in the mouth? We can’t. So does it really even make sense to use chlorhexidine at all?

The serious side effects of chlorhexidine also include its impact on fibroblast formation in the periodontal pocket. The most alarming findings date back to 1991, when Charles D. Alleyn, DDS, studied the reestablishment of lost connective tissue attachment to the root surface following periodontal therapy. Chlorhexidine digluconate was found to damage the fibroblasts, which are essential factors in reattachment,9 which is the purpose of scaling and root planing. Chlorhexidine digluconate disrupted the healing process, causing the healing phase to take longer and decreasing the likelihood of a favorable outcome with therapy. 

Another study published in 2006 discussed the cytotoxic effect of chlorhexidine on cells and cautioned against using it following scaling and root-planing procedures (such as irrigation) due to its damaging cells that aid in the healing process (such as fibroblasts).10 A different study stated that the higher concentration (≥ 0.04%) of chlorhexidine inhibits cell proliferation and, to a certain extent, affects cell morphology. The study concluded that “the application of CHX in the post-surgical antiseptic treatment of the oral cavity should be limited.”11 (However, it should be noted in chlorhexidine’s defense that it was never meant to be used that way.)

Off-label uses of chlorhexidine are where many of the serious issues originate. It was not created to be used with implants, periodontal therapy, or oral surgery. The Food and Drug Administration has reported more than 52 cases of anaphylaxis between 1998 and 2010, and this number has been increasing.5 The serious cases involving allergic reactions reported outcomes that required emergency department visits or hospitalizations to receive drug and other medical treatments. Two of these cases actually resulted in death. In both scenarios, each patient had left the dental office after an extraction with instructions to use chlorhexidine rinse at home. As previously mentioned, it takes 1,200 ppm of chlorhexidine to achieve results.2 For this reason, it should not be used with open wounds. In the cases in which patients died, both had open wounds and the uptake of the active ingredient was too high, inducing severe allergic reactions.5

An alternative
Many dental professionals feel “the bad” and “the ugly” of chlorhexidine outweigh “the good,” leaving them in search of an alternative. More than 10 years ago, a group of dentists sharing this feeling decided to develop an alternative. After years of research and development, they came up with OraCare.

The active ingredient in OraCare, activated chlorine dioxide, kills the same bacteria as chlorhexidine but with only 44 ppm.2 Chlorine dioxide is a gas, so it dissipates through the tissues quickly and without lingering side effects. Taken together, these features make it safe for everyday use. In addition, activated chlorine dioxide has been shown to effectively remove biofilm, neutralize volatile sulfur compounds, and kill fungi and viruses.2 

OraCare differentiates itself in that it leaves no stains, does not cause additional calculus buildup, and has no negative impact on fibroblasts. The most common uses for OraCare are for bleeding gums, periodontitis, implant maintenance, dry mouth, bad breath, and mouth sores.

Summary
While chlorhexidine is an effective killer of bacteria, its side effects and dangerous off-label usage open the door to safer and equally effective alternatives. If you are ready to make the switch, an alternative to chlorhexidine can help you provide “the good” and avoid “the bad” and “the ugly.”