PRODUCTS

CHLORHEXIDINE GLUCONATE

Chlorhexidine (commonly known by the salt forms Chlorhexidine gluconate (CHG) or Chlorhexidine 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. Chlorhexidine gluconate is also used for cleaning wounds, preventing dental plaque, treating yeast infections of the mouth, and to keep urinary catheters from blocking. Chlorhexidine gluconate 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 gluconate may come mixed in alcohol, water, or surfactant solution.It is effective against a range of microorganisms, but does not inactivate spores.

CAS No. : 55-56-1
EC No. : 242-354-0

Synonyms:
Chlorhexidine; chlorhexidine gluconate (CHG); chlorhexidine acetate; Betasept; ChloraPrep; Chlorostat; 1,6-bis(4-chloro-phenylbiguanido)hexane; Polyaminopropyl biguanide; Polyhexanide; Triclosan; CHLORHEXIDINE DIGLUCONATE; 18472-51-0; Chlorhexidine gluconate; Unisept; Chlorhexidine D-digluconate; Peridex; UNII-MOR84MUD8E; Chlorhexidine di-D-gluconate; Periogard; kloroheksin glukonat; Exidine; 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide), digluconate; Kleersight; Fight bac; Chlorhexidin glukonatu; 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; Chx plus concentrate premium chlorhexidine teat dip concentrate; Chlorhexidine gluconate (JP17/USP); D-Gluconic acid, compd. with N1,N14-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide (2:1); 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; Chlorhexidine Gluconate; 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); chlorhexidine; 55-56-1; Rotersept; Tubulicid; Fimeil; Hexadol; Soretol; Chlorhexidin; Chlorhexidinum; Sterilon; Nolvasan; Cloresidina [DCIT]; Chlorhexidin [Czech]; Chlorohexidine; Chlorhexidinum [INN-Latin]; Clorhexidina [INN-Spanish]; Hibistat; Chlorhexidine [INN:BAN]; 1,6-Bis(p-chlorophenyldiguanido)hexane; 1,6-Di(4'-chlorophenyldiguanido)hexane; UNII-R4KO0DY52L; 1,6-Bis(5-(p-chlorophenyl)biguandino)hexane; CCRIS 9230; C22H30Cl2N10; 1,1'-Hexamethylenebis(5-(p-chlorophenyl)biguanide); 1,1'-Hexamethylene bis(5-(p-chlorophenyl)biguanide); HSDB 7196; 2,4,11,13-Tetraazatetradecanediimidamide, N,N''-bis(4-chlorophenyl)-3,12-diimino-; 1,6-Di(N-p-chlorophenyldiguanido)hexane; CHEBI:3614; Cloresidina; Clorhexidina; Exidine; Biguanide, 1,1'-hexamethylenebis(5-(p-chlorophenyl)-; Chlorhexidine, 98%; CAS-55-56-1; Novalsan; Chlorhexidine Gluconate; Sterido; Savlon babycare; Sebidin A; N',N'''''-hexane-1,6-diylbis[N-(4-chlorophenyl)(imidodicarbonimidic diamide)]; N,N'-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide; DSSTox_GSID_33314; Chlorhexidine dihydrochloride; MLS001304094; 2,4,11,13-Tetraazatetradecanediimidamide, N,N'-bis(4-chlorophenyl)-3,12-diimino-; N,N'-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradeca- nediimidamide; 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; Chlorhexidine (INN); Merfen-incolore (TN); MK-412A; SR-01000799135; Nolvasan (*Diacetate*); 1,1'-Hexamethylenebis(5- [p-chlorophenyl]biguanide); Lisium (*Dihydrochloride*); 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); Savloclens (Salt/Mix); chlorhexidine diacetate salt; Chlorhexidine Gluconate; Chlorohexidine 55-56-1; Chlorhexidine, >=99.5%; 4-12-00-01201 (Beilstein Handbook Reference); 2,4,11,13-Tetraazatetradecanediimidamide, N1,N14-bis(4-chlorophenyl)-3,12-diimino-e; Chlorhexidine, purum, >=99.0% (HPLC); 1,1''-Hexamethylene bis(5-(p-chlorophenyl)biguanide); 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''-Bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide; (1E)-2-[6- [[amino-[(E)-[amino- (4-chloroanilino)methylidene]amino]methylidene]amino]hexyl] -1-[amino-(4-chloroanilino)methylidene]guanidine; hydrochloride

Chlorhexidine Gluconate

Uses of Chlorhexidine gluconate
Chlorhexidine gluconate 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 gluconate reduces hospital‐acquired infections, mortality, or length of stay in the ICU, or whether the use of Chlorhexidine gluconate results in more skin reactions."
In endodontics, Chlorhexidine gluconate 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.
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 gluconate is ineffective against polioviruses and adenoviruses. The effectiveness against herpes viruses has not yet been established unequivocally.
Chlorhexidine gluconate, 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 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 gluconate rinse has been used for 4 weeks or longer.
Mouthwashes containing Chlorhexidine gluconate which stain teeth less than the classic solution have been developed, many of which contain chelated zinc.
Using Chlorhexidine gluconate 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 gluconate 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 gluconate, "it seems best that the interval between toothbrushing and rinsing with CHX [Chlorhexidine gluconate] be more than 30 minutes, cautiously close to 2 hours after brushing.".

Topical
Nepal was the first country in the world to use Chlorhexidine gluconate to treat the umbilical cord of newborn babies, and received a USAID Pioneers Prize for reducing the neonatal death rate. Chlorhexidine gluconate 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 gluconate skin or cord care can reduce the incidence of omphalitis (inflammation of the umbilical cord) by 50% and also neonatal mortality by 12%.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.Chlorhexidine gluconate 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 gluconate 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 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 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 gluconate salts dissociate and release the positively charged Chlorhexidine gluconate 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 gluconate, this results in a bacteriostatic effect; at high concentrations, membrane disruption results in cell death.
It is a cationic polybiguanide (bisbiguanide).It is used primarily as its salts (e.g., the dihydrochloride, diacetate, and digluconate).

Deactivation
Chlorhexidine gluconate 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 gluconate 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 gluconate (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.
Brands
Chlorhexidine gluconate topical is sold as Betasept, Biopatch, Calgon Vesta, ChloraPrep One-Step, Dyna-Hex, Hibiclens, Hibistat Towelette, Scrub Care Exidine, Spectrum-4 among others.
Chlorhexidine gluconate mouthwash is sold as Dentohexinm, Paroex, Peridex, PerioChip, Corsodyl and Periogard, among others.
Hexoralettene N contains benzocaine, menthol and Chlorhexidine gluconate hydrochloride. It is used as oral antiseptic candies.

Terminology
The name "Chlorhexidine gluconate" 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 gluconate is used for topical disinfection of wounds,and to manage skin infections.Chlorhexidine gluconate-based disinfectant products are used within the dairy farming industry.
Post-surgical respiratory problems have been associated with the use of Chlorhexidine gluconate products in cats.

What is chlorhexidine gluconate?
Chlorhexidine gluconate is a germicidal mouthwash that reduces bacteria in the mouth.
Chlorhexidine gluconate oral rinse is used to treat gingivitis (swelling, redness, bleeding gums). Chlorhexidine gluconate is usually prescribed by a dentist.
Chlorhexidine gluconate oral rinse is not for treating all types of gingivitis. Use the medication only to treat the condition your dentist prescribed it for. Do not share this medication with another person, even if they have the same gum symptoms you have.
Chlorhexidine gluconate may also be used for purposes not listed in this medication guide.

Important Information
Chlorhexidine gluconate can cause a rare but serious allergic reaction that may be life-threatening. Get emergency medical help if you have: hives, severe skin rash; wheezing, difficult breathing; cold sweats, feeling light-headed; swelling of your face, lips, tongue, or throat.
Do not give this medication to a child or teenager without a doctor's advice. chlorhexidine gluconate may cause severe irritation or chemical burns in young children.

Before taking this medicine
You should not use this medication if you are allergic to chlorhexidine gluconate.
If you have periodontal disease, you may need special treatments while you are using chlorhexidine gluconate.
Do not give this medication to a child or teenager without a doctor's advice. This medicine may cause severe irritation or chemical burns in young children. Chlorhexidine gluconate is not approved for use by anyone younger than 18 years old.
It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.
It is not known whether chlorhexidine gluconate passes into breast milk or if it could affect the nursing baby. Tell your doctor if you are breast-feeding.

How should I use chlorhexidine gluconate?
Follow all directions on your prescription label. Do not use chlorhexidine gluconate in larger or smaller amounts or for longer than recommended.
Rinse your mouth with chlorhexidine gluconate twice daily after brushing your teeth.
Measure your dose using the cup provided with the medication. Swish the medicine in your mouth for at least 30 seconds, then spit it out. Do not swallow the mouthwash.
Do not add water to the oral rinse. Do not rinse your mouth with water or other mouthwashes right after using chlorhexidine gluconate.
Chlorhexidine gluconate may leave an unpleasant taste in your mouth. Do not rinse your mouth to remove this taste after using the medication. You may rinse the medicine away and reduce its effectiveness.
Use this medication for the full prescribed length of time. Your symptoms may improve before your gingivitis is completely cleared. Chlorhexidine gluconate will not treat a viral or fungal infection such as cold sores, canker sores, or oral thrush (yeast infection).
Visit your dentist at least every 6 months for preventive tooth and gum care.
Store chlorhexidine gluconate at room temperature away from moisture and heat.

What happens if I miss a dose?
Use the missed dose as soon as you remember, but brush your teeth first. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?
Seek emergency medical attention or call the Poison Help line at 1-800-222-1222, especially if a child has swallowed 4 or more ounces of chlorhexidine gluconate.
An overdose of chlorhexidine would occur only if the medicine were swallowed. Overdose symptoms may include nausea, stomach pain, or the appearance of being drunk.

What should I avoid while taking chlorhexidine gluconate?
Chlorhexidine gluconate can stain teeth, dentures, tooth restorations, your tongue, or the inside of your mouth. Talk with your dentist about ways to remove staining from these surfaces. Stains may be harder to remove from false teeth that have scratches in their surfaces.
Avoid eating, drinking, or brushing your teeth just after using this medication.
Do not use any other mouthwash unless your doctor has told you to.

Chlorhexidine gluconate side effects
Chlorhexidine gluconate can cause a rare but serious allergic reaction that may be life-threatening. Get emergency medical help if you have any of these signs of an allergic reaction: hives, severe skin rash; wheezing, difficult breathing; cold sweats, feeling light-headed; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:
white patches or sores inside your mouth or on your lips; mouth ulcers; or swelling of your salivary glands (underneath your jaws).
Common side effects may include:
mouth irritation; tooth staining; dry mouth; unusual or unpleasant taste in your mouth; or decreased taste sensation.

How to use Chlorhexidine Gluconate Mouthwash
Rinse your mouth with the solution after brushing your teeth, usually twice daily (after breakfast and at bedtime) or as directed by your doctor.
Measure 1/2 ounce (15 milliliters) of the solution using the supplied measuring cup. Swish the solution in your mouth for 30 seconds, and then spit it out.
Do not swallow the solution or mix it with any other substance. After using chlorhexidine, wait at least 30 minutes before rinsing your mouth with water or mouthwash, brushing your teeth, eating, or drinking.
Dosage is based on your medical condition and response to treatment.
Use Chlorhexidine gluconate regularly to get the most benefit from it. To help you remember, use it at the same times each day. It may take up to 6 weeks to see the full benefits of using Chlorhexidine gluconate.
Tell your doctor if your condition persists or worsens.

Chlorhexidine Gluconate is the gluconate salt form of chlorhexidine, a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine gluconate is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, chlorhexidine gluconate penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.
For external use only: For external use only. Keep out of eyes, ears, and mouth. Chlorhexidine gluconate should not be used as a preoperative skin preparation of the face or head. Misuse of products containing chlorhexidine gluconate has been reported to cause serious and permanent eye injury when it has been permitted to enter and remain in the eye during surgical procedures. If chlohexidine gluconate should contact these areas, rinse out promptly and thoroughly with cold water. Avoid contact with neninges. Do not use in genital area. /Chlorhexidine gluconate-topical/
Sensitivity: Chlorhexidine gluconate should not be used by persons who have a sensitivity to it or its components.
Deafness: Chlorhexidine gluconate has been reported to cause deafness when instilled in the middle ear through perforate ear drums. /Chlorhexidine gluconate-topical/

To determine if Chlorhexidine gluconate can be used as an intervention to prolong the time to relapse of oral candidiasis. SUBJECTS AND METHODS: A double-blinded randomized clinical trial was performed in 75 HIV/AIDS subjects with oral candidiasis. Clotrimazole troche was prescribed, and the subjects were re-examined every 2 weeks until the lesions were completely eradicated. The subjects were then randomly divided into two groups; 0.12% Chlorhexidine gluconate (n = 37, aged 22-52 years, mean 34 years) and 0.9% normal saline (n = 38, aged 22-55 years, mean 38 years). They were re-examined every 2 weeks until the next episode was observed. RESULTS: The time to recurrence of oral candidiasis between the Chlorhexidine gluconate and the saline group was not statistically significant (P > 0.05). The following variables were significantly associated with the time of recurrence; frequency of antifungal therapy (P = 0.011), total lymphocyte (P = 0.017), alcohol consumption (P = 0.043), and candidiasis on gingiva (P = 0.048). The subjects with lower lymphocyte showed shorter oral candidiasis-free periods (P = 0.034). CONCLUSIONS: Chlorhexidine gluconate showed a small but not statistically significant effect in maintenance of oral candidiasis-free period. This lack of significance may be due to the small sample size. Further study should be performed to better assess the size of the effect, or to confirm our findings.

Hypersensitivity reactions: Irritation, sensitization, and generalized allergic reactions have been reported with Chlorhexidine gluconate-containing products, especially in the genital areas. If adverse reactions occur and last more than 72 hr, discontinue use immediately and, if severe, contact a health care provider.
Chlorhexidine gluconate is a broad-spectrum antimicrobial with demonstrated activity against both gram-positive and gram-negative bacteria, yeasts, and viruses.[A190417] Antimicrobial activity is dose-dependent - Chlorhexidine gluconate is bacteriostatic at lower concentrations (0.02%-0.06%) and bactericidal at higher concentrations (>0.12%).[A190417] Pharmacokinetic studies of oral Chlorhexidine gluconate rinses indicate that approximately 30% of the active ingredient is retained in the mouth following rinsing, which is subsequently slowly released into oral fluids.[L11512] This ability to adsorb to dentine, shared with tetracycline antibiotics such as [doxycycline], is known as "substantivity" and is the result of Chlorhexidine gluconate's positive charge - it is likely that this substantivity plays at least some role in Chlorhexidine gluconate's antimicrobial activity, as its persistence on surfaces such as dentine prevent microbial colonization.[A190453] Dental Chlorhexidine gluconate rinses may result in staining of oral surfaces, such as teeth. This effect is not ubiquitous and appears to be more significant with extended therapy (i.e. up to 6 months) - nevertheless, patients for whom oral staining is unacceptable should use Chlorhexidine gluconate rinse with caution and for the shortest effective interval.[L11512] Allergic reactions to Chlorhexidine gluconate have been associated with the development of anaphylaxis.

Chlorhexidine gluconate is a biguanide compound used as an antiseptic agent with topical antibacterial activity. Chlorhexidine gluconate is positively charged and reacts with the negatively charged microbial cell surface, thereby destroying the integrity of the cell membrane. Subsequently, Chlorhexidine gluconate penetrates into the cell and causes leakage of intracellular components leading to cell death. Since gram positive bacteria are more negatively charged, they are more sensitive to this agent.
Topically, Chlorhexidine gluconate is unlikely to undergo any degree of systemic absorption. Orally administered Chlorhexidine gluconate, such as that found in oral rinses for dental purposes, is very poorly absorbed from the gastrointestinal tract - the Cmax in human subjects following an oral dose of 300mg was 0.206 µg/g and occurred approximately 30 minutes after ingestion (Tmax).[L11512] Following the insertion of 4 PerioChips in 18 adult patients, no detectable plasma or urine Chlorhexidine gluconate levels were observed.

Percutaneous absorption of the antimicrobial agent Chlorhexidine gluconate (labelled with carbon-14) was studied in rats. Less than 5% of the topically applied Chlorhexidine gluconate was absorbed during a 5-day period. Excretion of absorbed radioactivity occurred mainly in the feces.
The percutaneous absorption of Chlorhexidine gluconate (Chlorhexidine gluconate digluconate; Hibitane) through hairless rat skin with or without stratum corneum was studied. For tests carried out on whole skin, storage in cutaneous structures after 48 hr was more important than diffusion; the reverse was observed for stripped skin. When the skin was stripped, the amount absorbed was multiplied by approximately 100, and the amount stored in skin by approximately 10. The difference in Chlorhexidine gluconate diffusion observed between whole and stripped skin was related to the physicochemical characteristics of Chlorhexidine gluconate.

To evaluate the elimination kinetics of Chlorhexidine gluconate in milk when used as an intramammary infusion to stop lactation in cows. ... The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with Chlorhexidine gluconate suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine gluconate was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. In phases I and II, there was no quantifiable transference of Chlorhexidine gluconate to milk in untreated mammary gland quarters. Measurable Chlorhexidine gluconate residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for Chlorhexidine gluconate in milk was 11.5 days.

Chlorhexidine gluconate’s broad-spectrum antimicrobial effects are due to its ability to disrupt microbial cell membranes. The positively charged Chlorhexidine gluconate molecule reacts with negatively charged phosphate groups on microbial cell surfaces - this reaction both destroys the integrity of the cell, allowing leakage of intracellular material, and allows Chlorhexidine gluconate to enter the cell, causing precipitation of cytoplasmic components and ultimately cell death.[L11536,A190453] The specific means of cell death is dependent on the concentration of Chlorhexidine gluconate - lower concentrations are bacteriostatic and result in leakage of intracellular substances such as potassium and phosphorous, whereas higher concentrations are bactericidal and cause cytoplasmic precipitation.

Chlorhexidine gluconate is a solid crystal. It will not volatilize and is slightly soluble in water. Salts of Chlorhexidine gluconate are solid powders. They will not volatilize and are soluble in water. USE: Salts of Chlorhexidine gluconate are used as disinfectants. Chlorhexidine gluconate salts are used in skin and hand disinfectants, skin creams, toothpaste, and deodorants. They are also used as a preservative in eyedrops, wound dressings and antiseptic mouthwashes. Water-based solutions of the salts, Chlorhexidine gluconate diacetate and Chlorhexidine gluconate digluconate, are used to control bacteria and viruses on farms, egg handling and packaging equipment, meat and poultry processing plants, and in certain veterinary settings. The Chlorhexidine gluconate part of these salts is the active antimicrobial ingredient. EXPOSURE: People may be exposed to Chlorhexidine gluconate by dermal contact or ingestion of antimicrobial products containing salts of this compound. The U.S. EPA requires workers to wear protective clothing and gloves when they are using solutions of Chlorhexidine gluconate salts to disinfect surfaces. If these solutions are applied as a mist, workers must also wear protective respirators. Dietary exposure to Chlorhexidine gluconate salts is not expected in the U.S., because workers using the salts to disinfect surfaces in food processing plants are directed to rinse the surfaces with water after treatment. Chlorhexidine gluconate is used commercially as its salts which are soluble in water. This reaction can then release Chlorhexidine gluconate to the environment through direct discharge or discharge to waste water treatment plants. If released to the air, Chlorhexidine gluconate may be broken down by sunlight. It is not likely to move through soil. Chlorhexidine gluconate may not volatilize from soil or water. It is not broken down by microorganisms and is not expected to build up in aquatic organisms. RISK: Direct contact with solutions of Chlorhexidine gluconate salts can be damaging to eyes and skin. Repeated exposure of the skin of laboratory animals to high doses of solutions of Chlorhexidine gluconate diacetate salt produced skin damage and liver effects in some animals. Animals given high doses of Chlorhexidine gluconate diacetate by mouth during pregnancy had decreased body weight gain, but no abortions or birth defects were found. The potential for Chlorhexidine gluconate salts to produce cancer in laboratory animals has not been tested. The potential for Chlorhexidine gluconate or its salts to cause cancer in humans has not been assessed by the U.S. EPA IRIS program, the International Agency for Research on Cancer, or the U.S. National Toxicology Program 13th Report on Carcinogens.

Trade names for various Chlorhexidine gluconate salts and formulations: Chlorhexidine gluconate: Sterilon, Hibitane, Rotersept; Chlorhexidine gluconate dihydrochloride: Lisium, Arlacide H, AY-5312; Chlorhexidine gluconate diacetate: Hibitane diacetate, Novalsan; Chlorhexidine gluconate digluconate: Abacil, anti Plaque, Arlacide G, Bacticlens, Chlorhexamed, Disteryl, Orahexal, Septeal, Unisept, Corsodyl, Hibiclens, Hibidil, Hibiscrub, Hibitane, Larylin, Peridex, Plac out, Plurexid, Rotersept, Savacol, Solvahex.
Three methods are described for the specific determination of Chlorhexidine gluconate and its salts at various levels in dental creams and related oral materials. The method of measuring the colored reaction product with alkaline sodium hypobromite is less sensitive than that based on hydrolysis of Chlorhexidine gluconate to give p-chloroaniline. This p-chloroaniline is then reacted with nitrous acid and alpha-naphthol to give a red-colored derivative. The third method is for the determination of submicrogram quantities. After conversion to 1:4 iodochlorobenzene this is determined by electron capture gas chromatography. This method has been applied to the measurement of the uptake of significant amounts of Chlorhexidine gluconate by dental plaques from a mouthrinse.

Based on the reviews of the generic data for the active ingredient Chlorhexidine gluconate diacetate, the Agency has sufficient information on the health effects of Chlorhexidine gluconate diacetate and on its potential for causing adverse effects in fish and wildlife and the environment. The Agency has determined that Chlorhexidine gluconate diacetate products, labeled and used as specified in this Reregistration Eligibility Decision, will not pose unreasonable risks or adverse effects to humans or the environment. Therefore, the Agency concludes that products containing Chlorhexidine gluconate diacetate for all uses are eligible for reregistration.
Certain other dosage form new animal drugs. Chlorhexidine gluconate tablets and suspension. Each tablet and each 28-mL syringe of suspension contain 1 g of Chlorhexidine gluconate dihydrochloride. ... Indications for use: For prevention or treatment of metritis and vaginitis in cows and mares when caused by pathogens sensitive to Chlorhexidine gluconate dihydrochloride.
The LD50 of subcutaneously administered Chlorhexidine gluconate in mice is >5 g/kg.[L11539] Small children are likely to be more susceptible to Chlorhexidine gluconate overdose - ingestion of 1-2 ounces by a small child may result in gastric distress, nausea, and intoxication. Treatment should consist of symptomatic and supportive measures. Seek medical attention if a child ingests >4 ounces of Chlorhexidine gluconate solution or if symptoms of intoxication develop post-exposure.

Chlorhexidine gluconate forms solid crystals. Chlorhexidine gluconate diacetate is registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Currently, two end-use products with 2% Chlorhexidine gluconate diacetate are registered for use as hard surface-treatment disinfectant/virucides. Chlorhexidine gluconate is used primarily as its salts e.g., the dihydrochloride, diacetate, and digluconate in disinfectants (disinfection of the skin and hands), cosmetics (additive to creams, toothpaste, deodorants, and antiperspirants), and pharmaceutical products (preservative in eyedrops, active substance in wound dressings and antiseptic mouthwashes). HUMAN EXPOSURE AND TOXICITY: Chlorhexidine gluconate diacetate is highly acutely toxic when applied to the eye. Skin reactions to Chlorhexidine gluconate-acetate and Chlorhexidine gluconate-gluconate were tested among eczema patients. Positive reactions were found in 52 (5.4%) of the 1,063 subjects at the initial test. Of these subjects, 29 were retested, and 21 were still found to have positive reactions. Chlorhexidine gluconate specific IgE was detected only in Japanese individuals who had experienced anaphylactic type reactions and was not detected in Japanese nurses and patients or in a group of British nurses and hospital staff, all having regular contact with Chlorhexidine gluconate. All chromogens plus Chlorhexidine gluconate, but not Chlorhexidine gluconate alone, produced some discoloration of hydroxyapatite and human teeth. A 67-yr-old man undergoing a colectomy for colon cancer was unintentionally administered 0.8 mg of Chlorhexidine gluconate intravenously and subsequently developed acute respiratory distress syndrome. Occupational asthma has been described in two health care workers, as a result of exposure to Chlorhexidine gluconate and alcohol aerosols. Another case report describes six patients who developed urticaria, dyspnea, and anaphylactic shock due to topical application of Chlorhexidine gluconate solution. Even very dilute solutions of Chlorhexidine gluconate can cause marked chondrolysis of articular cartilage leading to severe permanent damage to the knee. ANIMAL STUDIES: Rabbits suffered severe ocular irritation with Chlorhexidine gluconate acetate treatment. No dermal irritation was reported up to 72 hours following test article treatment in rabbits. In developmental studies no observable malformations or developmental toxicity were found at any dose level tested. Both positive and negative results have been seen in bacterial studies of the mutagenic effects of Chlorhexidine gluconate; however, no mutagenic activity was seen in an in-vivo micronucleus assay or a mammalian cytogenic test using Chinese-hamster-ovary cells. No carcinogenic effects were seen in a long term animal study.

Skin reactions to Chlorhexidine gluconate-acetate and Chlorhexidine gluconate-gluconate were tested among eczema patients. Subjects were tested with 1% Chlorhexidine gluconate-gluconate and 1% Chlorhexidine gluconate-acetate by patch test. The patches were applied for 48 hours and read at 72 hours. Subjects with a positive reaction at the initial testing were retested 1 month later. Positive reactions were found in 52 (5.4%) of the 1,063 subjects at the initial test. Of these subjects, 29 were retested, and 21 were still found to have positive reactions. A use test performed on these 29 patients resulted in all of them developing a dermatitis with one or both of the Chlorhexidine gluconate solutions. Those patients with leg eczema or leg ulcers appeared to be particularly at risk. The /study/ conclude that patients with eczema, and especially those with leg ulcers or leg eczema, are especially prone to Chlorhexidine gluconate allergies.

In Denmark, Chlorhexidine gluconate is the standard disinfectant in most hospitals and health care workers are repeatedly exposed to it. The aim of this study was to establish whether there is a risk of sensitization and allergy to Chlorhexidine gluconate from this type of exposure. Two hundred and forty-eight doctors, nurses and auxiliary staff were invited to participate in the study. One hundred and four individuals took part in the full study including skin tests and a questionnaire and a further 74 individuals filled in the questionnaire giving a total of 178 questionnaires (72%). Patch tests with Chlorhexidine gluconate 1% and Chlorhexidine gluconate acetate 1% were performed looking for type IV (delayed type) allergy. A prick test with Chlorhexidine gluconate 0.5% and an intradermal test with Chlorhexidine gluconate 0.0002% were performed looking for type I (immediate type) allergy. There were no positive tests in any of the 104 individuals tested (99% confidence interval 0-4.9%). There was a predominance of females in both groups and the overall median age was 42 years (28-63). No one in the group not tested reported to have a verified or suspected allergy to Chlorhexidine gluconate. This ...study to examine the risk of type I and type IV allergy to Chlorhexidine gluconate in health care workers with daily exposure to Chlorhexidine gluconate did not identify allergies to Chlorhexidine gluconate in any of the 104 individuals tested or in the additional 74 individuals who completed the questionnaire.

Chlorhexidine gluconate's production and use primarily as its salts in disinfectants, cosmetics, and pharmaceutical products may result in its release to the environment through various waste streams. Chlorhexidine gluconate diacetate salt's use as a disinfectant to control bacteria on farms, egg handling and packaging equipment, meat and poultry processing plants, and certain viruses in veterinary settings may result in Chlorhexidine gluconate's direct release to the environment. If released to air, an estimated vapor pressure of 2.0X10-14 mm Hg at 25 °C indicates Chlorhexidine gluconate will exist solely in the particulate phase in the atmosphere. Particulate-phase Chlorhexidine gluconate will be removed from the atmosphere by wet and dry deposition. Irradiation (lambda >290 nm) of Chlorhexidine gluconate sorbed to silica gel resulted in 20% degradation after 17 hours. However, this chemical is expected to exist in the particulate phase in the ambient atmosphere and, therefore, photo-degradation is not expected to be an important fate process. If released to soil, Chlorhexidine gluconate is expected to have no mobility based upon an estimated Koc of 8.5X10+5. Values of pKa 7.63, 9.92, 8.22 and 10.52, indicate that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts. Volatilization from moist soil is not expected because the compound exists as an cation and cations do not volatilize. Chlorhexidine gluconate is not expected to volatilize from dry soil surfaces based upon its vapor pressure. Using the OECD Minimal test, Chlorhexidine gluconate, present at 12 mg/L, achieved 0% degradation after 3 weeks in soil extract inoculum indicating that biodegradation is not expected to be an important fate process in soil. If released into water, Chlorhexidine gluconate is expected to adsorb to suspended solids and sediment based upon the estimated Koc. Using the Closed Bottle test, Chlorhexidine gluconate, present at 5.35 ppm, resulted in 0% COD after 28 days using an activated sludge inoculum, indicating that biodegradation is not expected to be an important fate process in water. The pKa values indicate Chlorhexidine gluconate will exist almost entirely in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces is not expected to be an important fate process. An estimated BCF of 3 suggests the potential for bioconcentration in aquatic organisms is low. Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that hydrolyze under environmental conditions (pH 5 to 9). Occupational exposure to Chlorhexidine gluconate may occur through inhalation and dermal contact with this compound at workplaces where Chlorhexidine gluconate is produced or used. Use data indicate that the general population may be exposed to Chlorhexidine gluconate via oral and dermal contact with consumer products containing this compound.

Based on a classification scheme(1), an estimated Koc value of 8.5X10+5(SRC), determined from a structure estimation method(2), indicates that Chlorhexidine gluconate is expected to be immobile in soil(SRC). Values of pKa 7.63, 9.92, 8.22 and 10.52(3), indicate that this compound will exist almost entirely in the cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization from moist soil is not expected because the compound exists as a cation and cations do not volatilize. Chlorhexidine gluconate is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 2.0X10-14 mm Hg at 25 °C(SRC), determined from a fragment constant method(2). Using the OECD Minimal test, Chlorhexidine gluconate, present at 12 mg/L, achieved 0% degradation after 3 weeks in soil extract inoculum(5), indicating that biodegradation is not expected to be an important fate process in soil(SRC).
Chlorhexidine gluconate's production and use primarily as its salts in disinfectants, cosmetics, and pharmaceutical products(1) may result in its release to the environment through various waste streams(SRC). Chlorhexidine gluconate diacetate salt's use as a disinfectant to control bacteria on farms, egg handling and packaging equipment, meat and poultry processing plants, and certain viruses in veterinary settings(2) may result in Chlorhexidine gluconate's direct release to the environment(SRC).

The study was performed in 2 phases. Three cows were studied in each phase. All cows were treated with Chlorhexidine gluconate suspension by infusion into a mastitic mammary gland quarter after 2 milkings 24 hours apart. Foremilk samples (100 mL) were collected from treated and untreated (controls) mammary gland quarters of each cow. Chlorhexidine gluconate was extracted from raw milk, and residue concentrations were quantified by use of high-performance liquid chromatography. Foremilk samples from days 2, 5, and 8 were analyzed in phase I, and samples from time 0 and days 3, 7, 14, 21, 28, 35, and 42 were analyzed in phase II. RESULTS: In phases I and II, there was no quantifiable transference of Chlorhexidine gluconate to milk in untreated mammary gland quarters. Measurable Chlorhexidine gluconate residues were found in milk from treated mammary gland quarters of 2 cows throughout the 42-day sample period in phase II. Estimated mean elimination half-life for Chlorhexidine gluconate in milk was 11.5 days. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of the long elimination half-life of Chlorhexidine gluconate in milk from treated mammary gland quarters, the lack of human dietary exposure data to suggest a food tolerance for Chlorhexidine gluconate in food products, and the Food and Drug Administration's published zero tolerance for Chlorhexidine gluconate in uncooked edible calf tissues, we do not recommend extralabel use of Chlorhexidine gluconate suspension as a treatment to stop lactation in mastitic mammary gland quarters of cows.
NIOSH (NOES Survey 1981-1983) has statistically estimated that 32 workers (32 of these were female) were potentially exposed to Chlorhexidine gluconate in the US(1). The NOES Survey does not include farm workers.Occupational exposure to Chlorhexidine gluconate may occur through inhalation and dermal contact with this compound at workplaces where Chlorhexidine gluconate is produced or used. Use data indicate that the general population may be exposed to Chlorhexidine gluconate via oral and dermal contact with consumer products containing this compound(SRC).

If you have been prescribed chlorhexidine gluconate mouthwash, chances are your dentist has told you that you have a mild form of gum disease called gingivitis. It might seem a little scary, but this prescription mouthwash could be a simple solution to getting your smile back on track to health and confidence. Chlorhexidine gluconate oral rinse contains a chemical called chlorhexidine, which destroys harmful mouth bacteria, treats gingivitis, and promotes the healing of inflamed gums.

What Do Chlorhexidine Gluconate Mouthwashes Treat?
Chlorhexidine gluconate is used to treat gingivitis, another name for mild gum disease. Symptoms can include bad breath and gum redness, swelling and bleeding. While brushing your teeth and gums twice per day and flossing once per day help prevent gingivitis, a prescription mouthwash may help reduce the symptoms when you're already in the early stages. However, according to the Mayo Clinic, you shouldn't look to chlorhexidine gluconate mouthwash to treat periodontitis, a more advanced form of gum disease.

How Does It Work?
When you rinse with chlorhexidine gluconate mouthwash, the active ingredient chlorhexidine immediately works to destroy harmful mouth bacteria, even after you spit. The FDA states that after six months using chlorhexidine gluconate mouthwash, levels of mouth bacteria reduced up to 97 percent. The FDA also explains that 30% of the chlorhexidine remains in the mouth after rinsing, so the chemical continues to destroy bacteria between uses.

Are ThereAny Side Effects?
Chlorhexidine gluconate mouthwash has a few possible side effects, like a change in taste, an increase in tartar build-up, and staining of the teeth, gums, and dental appliances. Not to worry, though. These side effects are usually very minor.
While severe side effects of using medicated mouthwash are rare, some people can experience swollen neck glands and irritation in the mouth and tip of the tongue. Call your dentist immediately if you experience any of these symptoms, or you believe you might be experiencing an allergic reaction to the mouthwash.

Is It Safe?
Only use chlorhexidine gluconate mouthwash if your physician or dentist prescribes it. Under the guidance of a healthcare professional, the product is safe when used as directed. According to C. S. Mott Children's Hospital, medicated mouthwash is not meant for anyone under the age of 18, so make sure to keep it out of reach from young children.
Though chlorhexidine gluconate mouthwash is effective at killing mouth bacteria in mild cases of gum disease, it's not a substitute for regular brushing and flossing for total oral health. Along with daily flossing, try brushing with a toothbrush that has curved, soft outer bristles to clean the gumline and firmer inner bristles to effectively clean teeth.
If you are ready to take steps towards gum health, chlorhexidine gluconate oral rinse could be the perfect first step. Talk to your dentist about your options, and they will be able to help you find the solution that fits your smile best.