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Chlorhexidine (Topical)

Class: Local Anti-infectives, Miscellaneous
Chemical Name: N,N′′-Bis(4-chlorophenyl)-3,12-diimino- 2,4,11,13-tetraazatetradecanediimidamide di-d-gluconate
Molecular Formula: C22H30Cl2N10•2C6H12O7
CAS Number: 18472-51-0
Brands: Avagard, Betasept, Biopatch, Chlorostat, Hibiclens, Hibistat

Medically reviewed by Last updated on Jan 23, 2020.


Special Alerts:

[Posted 02/02/2017]

AUDIENCE: Nursing, Surgery, Dentistry, Patient

ISSUE: FDA is warning that rare but serious allergic reactions have been reported with the widely used skin antiseptic products containing chlorhexidine gluconate. Although rare, the number of reports of serious allergic reactions to these products has increased over the last several years. See the FDA Drug Safety Communication, available at: [Web], for a data summary.

As a result, FDA is requesting the manufacturers of over-the-counter (OTC) antiseptic products containing chlorhexidine gluconate to add a warning about this risk to the Drug Facts labels.

BACKGROUND: Chlorhexidine gluconate is mainly available in OTC products to clean and prepare the skin before surgery and before injections in order to help reduce bacteria that potentially can cause skin infections. These products are available as solutions, washes, sponges, and swabs and under many different brand names and as generics. Chlorhexidine gluconate is also available as a prescription mouthwash to treat gingivitis and as a prescription oral chip to treat periodontal disease.

Prescription chlorhexidine gluconate mouthwashes and oral chips used for gum disease already contain a warning about the possibility of serious allergic reactions in their labels.

In 1998, FDA issued a Public Health Notice to warn health care professionals about the risk of serious allergic reactions with medical devices such as dressings and intravenous lines that contain chlorhexidine gluconate.

RECOMMENDATION: Health care professionals should always ask patients if they have ever had an allergic reaction to any antiseptic before recommending or prescribing a chlorhexidine gluconate product. Advise patients to seek immediate medical attention if they experience any symptoms of an allergic reaction when using the products. Consider using alternative antiseptics such as povidone-iodine, alcohols, benzalkonium chloride, benzethonium chloride, or parachlorometaxylenol (PCMX) when any previous allergy to chlorhexidine gluconate is documented or suspected.

Patients and consumers should stop using the product that contains chlorhexidine gluconate and seek medical attention immediately or call 911 if they experience symptoms of a serious allergic reaction. These reactions can occur within minutes of exposure. Symptoms include wheezing or difficulty breathing; swelling of the face; hives that can quickly progress to more serious symptoms; severe rash; or shock, which is a life-threatening condition that occurs when the body is not getting enough blood flow.

For more information visit the FDA website at: [Web] and [Web].


Cationic bisbiguanide; a topical anti-infective agent.1 4 5

Uses for Chlorhexidine (Topical)

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Surgical Hand Antisepsis

Preoperative hand antisepsis in health-care personnel1 18 105 107 108 to inactivate microorganisms (normal and transient flora) present on the hands and forearms.5 18 104

Chlorhexidine gluconate 2 or 4% skin cleanser solutions have more persistent anti-infective activity compared with other available anti-infective cleansers.105

Surgical Site Preparation

Anti-infective skin cleanser for preoperative skin preparation at the surgical site.1 15 18 107

Preoperative Whole-body Disinfection

Anti-infective skin cleanser for patient preoperative showering and bathing5 18 35 36 37 39 44 to decrease bacterial flora on the skin.18

Hand Hygiene in Health-care Personnel

Routine hand hygiene in health-care personnel1 2 18 105 107 to prevent transmission of nosocomial infection.5 17 25 83 105

Considered an alternative for decontaminating hands; alcohol-based preparations are recommended instead for decontaminating hands (if they are not visibly soiled) since alcohol-based preparations are most effective for standard hand antisepsis by health-care personnel.105

Superficial Skin Wound and General Skin Cleansing

Used as a cleanser of superficial skin wounds and for general cleansing of skin.1 53 54 78

Should not be used routinely in wounds that involve more than the superficial layers of the skin.1 78

Advantage over alcohol because of a duration of action of 5–6 hours and retention of the drug’s activity in the presence of blood and organic material.1 5 54

Catheter Site Preparation and Catheter Site Care

Skin disinfection prior to insertion of intravascular, central venous, or arterial catheters and for postinsertion site care to prevent catheter-related infections in patients with vascular and nonvascular percutaneous devices.47 51 55 100 11

Chlorhexidine gluconate 2% solution is the preferred agent for such antisepsis.106


Management of burns to clean the affected area and prevent wound infection.4 5 56

Blood Collection Site Preparation

Skin disinfection prior to collection of venous blood cultures7 or blood donations.116

Genitourinary Uses

Periurethral cleansing prior to urinary catheterization.103

Topical lubricant on urinary catheters.3 5

Bladder irrigation5 57 104 in an attempt to decrease the incidence of bacteriuria and bacteremia associated with the use of indwelling catheters.3 5 103 (See Hypersensitivity Reactions under Cautions.)

Prevent maternal-fetal transmission of vaginal bacteria, including Streptococcus agalactiae (group B streptococci), to reduce maternal and neonatal infections.95 96 97 98 115

Chlorhexidine (Topical) Dosage and Administration


Topical Administration

Preparations are for external use only; avoid contact with the eyes, ears, or mouth.1 2 78 107 108

Apply solutions in a sudsing base (skin cleanser) and solutions in an alcohol base with emollients (hand rub) topically to the skin and hands.1 2 78 107 108

Do not use solutions in sudsing base on the face or head for preoperative skin preparation.1 78 107

Apply chlorhexidine containing dressings at the site of vascular and nonvascular percutaneous devices.111


Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.


Surgical Hand Antisepsis
Chlorhexidine Gluconate Solution 2 or 4% (Skin Cleanser)

Wet hands and forearms with water.1 78 107 Apply approximately 5 mL of the skin cleanser onto the hands and rub into a copious lather by adding small amounts of water.1 78 107

Spread suds over the hands and forearms and scrub well with a wet brush for the time interval recommended by the manufacturer (e.g., 3 minutes).1 78 107

Pay particular attention to the nails, cuticles, and interdigital spaces; a separate nail cleaner may be used.1 78 107

After scrubbing, rinse the hands and forearms thoroughly under running water.1 78 107

Apply a second application (5 mL) and scrub the hands and forearms for an additional 3 minutes.1 78 107 Then rinse thoroughly with running water and dry with a sterile towel.1 18 78 107

Prolonged scrub times (e.g., 10 minutes) not necessary and may increase incidence of skin damage.105

Sponge/brush containing 4% skin cleanser: open package and remove nail cleaner.1 Wet hands with water and use nail cleaner under fingernails and to clean cuticles.1 Wet hands and forearms to elbows with warm water (avoid use of very cold or very warm water).1 Wet sponge side of sponge/brush; squeeze and pump immediately to work up adequate lather.1 Apply lather to hands and forearms using only sponge side of product; then start 3-minute scrub using brush side of product to scrub only nails, cuticles, and interdigital areas.1 Rinse hands and forearms thoroughly with warm water, then scrub for an additional 3 minutes using sponge side only.1 Rinse hands and forearms thoroughly with running water and dry with sterile towel.1

Chlorhexidine Gluconate 1% Solution in Alcohol Base (Hand Rub)

Wash hands, forearms, and nails with an unmedicated soap (without an anti-infective) and dry completely.105 108 Apply 2 mL of solution onto palm of one hand; dip fingertips of other hand into solution and massage under nails.108

Spread remaining solution over hand and forearms, up to just above the elbow, making certain to cover all surfaces.108

Repeat procedure using another 2 mL of solution using opposite hand.108

Finally, apply additional 2 mL of solution onto palm of either hand and reapply to both hands, up to wrists.108

Rub hands together briskly until all solution is rubbed into hands and forearms and dries completely; do not use towels to dry since this decreases solution efficacy.108

Hands and forearms should be completely dry prior to donning surgical gloves.105 108

Never use water in conjunction with the alcohol-based solution.108

Surgical Site Preparation
Chlorhexidine Gluconate 2 or 4% Solution (Skin Cleanser)

Apply liberally to the incision site and swab for at least 2 minutes; dry with a sterile towel.1 78 107

Repeat procedure for an additional 2 minutes and dry area again with a sterile towel.1 78 107

Hand Hygiene in Health-care Personnel
Chlorhexidine Gluconate 2 or 4% Solution (Skin Cleanser)

Wet hands with warm water (avoid use of very cold or very hot water); dispense approximately 5 mL of the skin cleanser into cupped hands.1 78 107 Work up a lather (do not use excessive pressure to produce additional lather) and wash hands for 15 seconds.1 78 Rinse hands thoroughly with warm water, then dry.1 78 107

Chlorhexidine Gluconate 0.5 or 1% in Alcohol Base (Hand Rub)

Hands must first be physically clean and dry before application of solution.2 108 Dispense approximately 5 mL of the 0.5% solution or 2 mL of 1% solution into cupped hands and rub vigorously until dry (about 15 seconds); pay particular attention to nails and interdigital spaces.2 108 Solution dries rapidly while hands are rubbed; do not use water or other toweling.2 108

Pledgets: vigorously rub hands with a hand wipe for approximately 15 seconds, paying particular attention to nails and interdigital spaces.2 Solution dries rapidly while hands are rubbed; do not use water or other toweling.2

Superficial Skin Wound and General Skin Cleansing
Chlorhexidine Gluconate 2 or 4% Solution (Skin Cleanser)

Rinse the area thoroughly with water before application of the solution.1 78 107 Apply the minimum amount of skin cleanser to cover the skin or wound area.1 78 107 Wash the area gently with the skin cleanser, then thoroughly rinse again.1 78 107

Catheter Site Preparation and Catheter Site Care

Apply solution and air dry before catheter insertion.106

Dressing: Apply to the site using aseptic technique.111 Dressing may be left in place for up to 7 days.111 Consult manufacturer’s information for details.111

Cautions for Chlorhexidine (Topical)


Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.1 2 78 107 108



Topical Use

Skin cleanser and alcohol-based solutions are for external use only; do not use in eyes, ears, or mouth.1 2 78 107 108 Skin cleanser should not be used for preoperative skin preparation of the face or head.1

Skin cleanser and alcohol-based chlorhexidine solutions should not be used routinely on individuals who have wounds involving more than the superficial layers of the skin.1 78 107 108

Use with caution on mucous membranes and apply on wound surfaces at the lowest bactericidal concentration (0.05%) (not commercially available in the US) to decrease the risk of anaphylactic reactions.63

Avoid direct contact of the drug with brain tissue or meninges.1 105 107

Ocular and Otic Effects

Possible irreversible corneal damage after accidental ocular exposure.60

Do not touch eyes with hands that have been treated with chlorhexidine.108 If ocular contact occurs, rinse eye promptly and thoroughly with water.1 2 78 107 108

Possible sensorineural deafness after direct application for perioperative disinfection of the ear prior to vascular myringoplasty.1 5


Alcohol-based preparations (Hibistat, Avagard) should not be exposed to excessive heat (i.e., temperatures exceeding 40°C); keep away from flames or devices that may generate an electric spark.2 108 These preparations dry rapidly as the hands are rubbed together2 108 and are no longer flammable after drying.108

Sensitivity Reactions

Hypersensitivity Reactions

Serious, systemic hypersensitivity reactions, including hypotension, tachycardia, shortness of breath, skin erythema, and anaphylaxis, have been reported with preparations applied topically to the skin3 4 63 64 66 or given intraurethrally,3 4 64 65 intranasally,67 or on central venous catheter (CVCs) impregnated with the drug.3 4 68 69


Local contact dermatitis reported when chlorhexidine-impregnated dressings were used to cover CVC insertion site in neonates.3 62 100 May be severe, may require discontinuance of the chlorhexidine dressing, and have occurred most frequently in low birthweight neonates.62 100

General Precautions

Fabric Stains

Binds to many fabrics, particularly cotton, and may not be removed by washing.79 Permanent brown stain may occur if sufficient chlorine is present during washing.79 Consult manufacturer’s recommendations for laundering advice.79

Specific Populations


Category B.b


Unlikely to be distributed into human milk following topical or intravaginal application.71

Multiple episodes of bradycardia and cyanosis reported in a neonate when chlorhexidine was applied to the nursing mother’s breasts for prevention of mastitis.74 Wash nipples thoroughly with water prior to nursing if used for skin cleansing.71

Pediatric Use

Keep preparations out of the reach of children.1 2 107 108

Common Adverse Effects

Irritation, sensitization, generalized allergic reactions,1 2 4 5 100 107 108 118 especially when used in the genital area.1 2 78 107 108

Interactions for Chlorhexidine (Topical)

No formal drug interaction studies to date.1 2 3

Chlorhexidine (Topical) Pharmacokinetics



Poorly absorbed from GI tract4 or percutaneously following topical application to skin.1 4 5

Low concentrations appear to be absorbed systemically following intravaginal administration.71

Adsorbed onto outer layers of skin following topical application to intact skin, resulting in a persistent (residual) antimicrobial effect.1 5 6 14

In pregnant women who received a 2% solution intravaginally as a vaginal wash during labor, concentrations ranging from 0.01–0.083 mcg/mL were detected in the blood (limits of detection 0.01 mcg/mL) of approximately 33% of these women.71

Serum concentrations of 11 ng/mL reported in a neonate after oral exposure when chlorhexidine gluconate was used on the nursing mother’s nipples to prevent mastitis.74

Special Populations

Possible systemic absorption when topical preparations used as skin cleansers in neonates or infants.4 5 12 13



Not known whether chlorhexidine crosses the placenta or is distributed into milk.a


Elimination Route

If absorbed percutaneously following topical application to the skin, appears to be mainly excreted unchanged in feces.5




Dressing, Pledgets, Solution

Tight, light resistant containers; protect from excessive heat (i.e., >40°C).1 2 11

Keep alcohol-based preparations (Hibistat and Avagard) away from flames or devices that may generate an electric spark.2 108

Actions and Spectrum

  • Bacteriostatic or bactericidal in action, depending on concentration attained at site and susceptibility of organism.5 15

  • Cationic compound;5 6 adsorbed onto negatively charged cell surfaces of susceptible organisms, with specific and strong adsorption to certain phosphate-containing compounds.5 6 Integrity of the cell membrane is disrupted, resulting in increased permeability.5 6

  • Active against some aerobic and anaerobic gram-positive and gram-negative bacteria.1 2 4 5 6 102 Also has some activity against Chlamydia trachomatis,77 certain fungi,4 5 6 and certain viruses,4 5 52 but inactive against mycobacteria48 and generally inactive against bacterial spores.15

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • Importance of avoiding contact with eyes, ears, and mouth.1 2 78 107 108 If ocular contact occurs, rinse eye promptly and thoroughly with water to prevent irreversible injury.1 2 60 78 107 108

  • Avoid exposure to excessive heat (i.e., >40°C) with alcohol-based preparations (Hibistat, Avagard); keep away from flames or devices that may generate an electric spark.2 108

  • Importance of discontinuing drug and informing clinician if an allergic or hypersensitivity reaction occurs.1 2 108

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.71 93

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.1 2 108

  • Importance of informing patients of other important precautionary information. (See Cautions.)1 2 108


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Chlorhexidine Gluconate


Dosage Forms


Brand Names




20% w/w


J & J

Pledgets (saturated with solution)

0.5% w/w with isopropyl alcohol 70%

Hibistat Hand Wipe

Regent Medical


0.5% w/w with isopropyl alcohol 70%

Hibistat Hand Rinse

Regent Medical

1% w/w with alcohol 61%

Avagard Hand Antiseptic


2% w/w

Chlorostat Skin Cleaner and Surgical Scrub


4% w/v

Betasept Surgical Scrub

Purdue Frederick

Hibiclens Skin Cleanser

Regent Medical


4% w/v

Hibiclens Skin Cleanser

Regent Medical

AHFS DI Essentials™. © Copyright 2021, Selected Revisions February 2, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


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