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Chlorhexidine Gluconate eent

Class: 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: Peridex, PerioChip, PerioGard


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: , 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: and .


Cationic bisbiguanide; a topical anti-infective agent.1 2 3 33

Uses for Chlorhexidine Gluconate

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.


Treatment of gingivitis; used between dental visits as part of a professional program.1 2

Has been used as adjunct for treatment of acute necrotizing ulcerative gingivitis.88 89


Reduction of pocket depth in the treatment of adult periodontitis; adjunct to scaling and root planing procedures.3

Prevention of Dental Caries

Prevention of dental plaque and dental caries when conventional oral hygiene measures are difficult or impossible, such as in patients with fractured jaws, periodontal surgery, or orthodontic treatments and in patients with seizure disorders, rheumatoid arthritis, mental retardation, and cerebral palsy.8 33 34 44

Mucositis and Other Oral Complications in Individuals with Altered Immunocompetence

Used to decrease incidence and severity of mucositis and other oral complications in patients with altered immunocompetence, including those undergoing bone marrow transplantation,10 11 14 20 21 radiation therapy,15 21 38 or chemotherapy.12 13 15 19 20 21 38

Has been beneficial in some individuals,10 12 13 14 15 20 21 62 but some studies have shown inconsistent results.11 19 20 21

Also has been used as adjunct to surgical debridement, plaque removal, and systemic anti-infectives in treatment of linear gingival erythema, necrotizing ulcerative gingivitis, and necrotizing ulcerative periodontitis in immunocompromised individuals, including patients with HIV infection.88 89

Oropharyngeal Decontamination in Critically Ill Patients

For oral hygiene and oropharyngeal decontamination in an attempt to decrease the incidence of nosocomial respiratory tract infections in critically ill patients, including immunocompromised patients and those undergoing mechanical ventilation or heart surgery.19 21 39 85 86

Chlorhexidine Gluconate Dosage and Administration


Administer topically as an oral solution used as a mouthwash or rinse;1 2 4 subgingivally as pellets.3

Oral, Topical Use Only

Administer the commercially available 0.12% oral solution undiluted when used as a mouthwash or rinse.1 2

Oral solution is for topical use only and should not be ingested.1 2 Solution should be expectorated after use as a mouthwash or rinse.1 2

Immediately prior to initiation of treatment, the patient should receive professional dental prophylaxis.1 2 Patients should then be reevaluated and receive a thorough dental prophylaxis throughout treatment at intervals not exceeding 6 months.1 2

Patients should brush their teeth immediately prior to use but should not rinse with water or other mouthwashes, brush their teeth, or eat immediately after using the oral solution.1 2

Subgingival Administration

Pellets are inserted into periodontal pockets by a dental health-care provider and are not meant for self-administration.3

Isolate periodontal pocket and dry surrounding area prior to insertion.3 Grasp flat end of pellet with forceps and insert (curved end first) into periodontal pocket to its maximum depth.3 Place a single pellet into each periodontal pocket that has a probing depth of ≥5 mm.3 Consult manufacturer’s information for details.1

Pellets will biodegrade within the periodontal pockets and do not need to be manually removed.3


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.


Oral, Topical Use Only

15 mL twice daily for 30 seconds (morning and evening after toothbrushing).1 2


Dosage varies depending on the size, shape, and number of periodontal pockets treated.3 One 2.5-mg pellet is inserted into each periodontal pocket that has a probing depth of ≥5 mm.3

A new pellet should be inserted every 3 months into pockets that continue to have a probing depth of ≥5 mm.3

Consider other treatment options (e.g., combination therapy, surgical intervention) if periodontal pockets with a probing depth of ≥5 mm do not respond within 9–12 months.79

Prescribing Limits



Up to 8 pellets during a single visit.3

Cautions for Chlorhexidine Gluconate


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 3



Supragingival Calculus

Possible increased supragingival calculus in patients using the oral solution; professional dental prophylaxis to remove calculus deposits recommended at intervals not exceeding 6 months.1 2

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity and generalized or localized allergic reactions reported.1 2

General Precautions

Staining of Oral Surfaces

Possible staining of teeth and other oral surfaces, such as tooth surfaces, restorations, and the dorsum of the tongue with use of topical oral solution.1 2 4 5 8 10 18

Stains usually can be removed by conventional professional prophylactic techniques, although additional time may be required to complete the prophylaxis.1 2

Taste Alteration

Alterations in taste perception1 2 4 and a burning sensation of the tongue with use of topical oral solution.4


Efficacy of topical oral solution in periodontitis has not been fully determined to date.1 2 If used as a mouthwash or rinse in patients with coexisting gingivitis and periodontitis, the presence or absence of gingival inflammation following treatment should not be used as a major indicator of underlying periodontitis.1 2

Effectiveness of pellets for subgingival administration in acutely abscessed periodontal pockets has not been established.3

Management of patients with periodontal disease should include consideration of potentially contributing medical disorders, such as cancer, diabetes, and compromised immune function.3

Dental Precautions

Avoid dental floss at the site of subgingival insertion for 10 days after placement of pellets since flossing might dislodge the pellet.3 Notify dentist if a pellet becomes dislodged.3

Some mild to moderate sensitivity is normal during the first week after placement of a subgingival pellet; however, dentist should be promptly notified if pain, swelling, or other problems occur.3

Specific Populations


Category B (oral solution)1 2 and Category C (subgingival pellets).3


Not known if chlorhexidine distributes into human milk following insertion of pellets or topical use of commercially available mouthwash.1 2 50 Caution if used in nursing women.3

Pediatric Use

Safety and efficacy of topical oral solution or subgingival pellets have not been established in children <18 years of age.1 2 3 77

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether safety and efficacy of chlorhexidine gluconate pellets (PerioChip) for the treatment of periodontitis in geriatric patients differ from safety and efficacy in younger adults.3 However, clinical experience to date has not identified differences in responses between these populations.3

Common Adverse Effects

Subgingival pellets: toothache, upper respiratory infection, headache.3 23

Topical oral solution: increase in staining of teeth, esthetic restorations, and other oral surfaces; an increase in calculus formation; and alteration of taste perception.1 2

Interactions for Chlorhexidine Gluconate

No formal drug interaction studies to date.1 2 3

Chlorhexidine Gluconate Pharmacokinetics



Systemic absorption does not appear to occur following subgingival administration of biodegradable pellets50 77 or use of topical oral solution as mouthwash or rinse.78

Following use of mouthwash or rinse, approximately 30% of the drug is retained in the oral cavity,1 2 5 8 34 bound to phosphate groups principally on coatings of mucous membrane surfaces;8 gradually released into oral fluids1 2 5 8 34 for up to 24 hours.8

Following subgingival administration of biodegradable pellet, drug is released into periodontal pocket.3 50 40% is released during first 24 hours and remainder is released in linear manner over 7–10 days.3



Peak plasma concentrations of 0.206 mcg/mL are attained 30 minutes after ingestion of a 300-mg dose; however, the drug is undetectable in plasma 12 hours after the dose.1 2 77

No detectable plasma or urine concentrations of the drug (limits of detection: 30 ng/mL) in clinical studies in adults who received pellets inserted into 4 periodontal pockets.3 50


Elimination Route

Excreted in feces via biliary elimination (90%) and urine (<1%) following ingestion of a 300-mg dose.1 2



Oral, Topical Use Only


Tight, light resistant container >0°C.1 2

Pellet, extended-release


Actions and Spectrum

  • Bacteriostatic or bactericidal in action, depending on concentration attained at site and susceptibility of organism.16 33 34

  • Cationic compound;3 5 8 adsorbed onto negatively-charged cell surfaces of susceptible organisms, with specific and strong adsorption to certain phosphate-containing compounds.8 33 34 Integrity of the cell membrane is disrupted, resulting in increased permeability.8 33 34

  • Binds to negatively charged surfaces within the oral cavity, including hydroxyapatite of tooth enamel, pellicle on tooth surface, oral mucosa, salivary glycoproteins, and bacteria and extracellular polysaccharides of bacterial origin;5 8 33 34 provides a persistent bacteriostatic effect at tooth surface.8 33 34

  • Antiplaque effects when applied topically in oral cavity involve immediate bacteriostatic or bactericidal effects on salivary bacteria and bacteria adhering to tooth surface as well as persistent antibacterial effects at tooth surface that prevent plaque from forming;34 however, antiplaque effects do not result in efficient removal of plaque that has already formed.34

  • Active against some aerobic and anaerobic gram-positive and gram-negative bacteria.8 22 33 54 55 56 57 60 Also has some activity against Chlamydia trachomatis,74 certain fungi,8 33 42 49 59 and certain viruses,33 53 but is inactive against mycobacteria.71

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.

  • Pellets are not meant for self-administration; only qualified oral health-care professionals familiar with the administration of subgingival chlorhexidine gluconate pellets should administer the drug.3

  • Importance of not using dental floss for 10 days following administration of the subgingival pellet.3

  • Notify dentist promptly if a pellet is dislodged or if pain, swelling, or other problems occur.3

  • Importance of not swallowing topical oral solution; expectorate after use of mouthwash or rinse.1 2

  • Importance of brushing teeth immediately prior to use of topical oral solution; do not rinse with water or other mouthwashes, brush teeth, or eat immediately after using oral solution.1 2

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

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

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


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


Oral (Topical Use Only)



Chlorhexidine Gluconate Oral Rinse

Actavis, Apotex, Butler, Hi-Tech, Morton Grove, Novex, Teva






Pellet, extended-release

2.5 mg


Dexcel Pharma

AHFS DI Essentials. © Copyright 2018, 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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