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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: Paroex, Peridex, PerioChip, PerioGard

Medically reviewed on April 16, 2018

Introduction

Topical anti-infective; cationic bisbiguanide.1 2 3 33 90 91

Uses for Chlorhexidine Gluconate

Gingivitis

Used as a mouthwash or oral rinse (topical oral solution) for treatment of gingivitis; used between dental visits as part of a professional program.1 2 90 91

Periodontitis

Used subgingivally (extended-release insert) for treatment of adult periodontitis as an adjunct to scaling and root planing to reduce periodontal pocket depth;3 used as part of a periodontal maintenance program that includes good oral hygiene.3

Prevention of Dental Caries

Has been used as a topical oral solution for 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

Has been used as a topical oral solution 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 used as a topical oral solution 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

Such use has been beneficial for prevention or treatment of oral complications in some immunocompromised individuals,10 12 13 14 15 20 21 62 but inconsistent results reported in some studies.11 19 20 21

Oropharyngeal Decontamination in Critically Ill Patients

Has been used as a topical oral solution 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

Administration

Oral, Topical Use Only

Topical oral solution (0.12%): Administer topically as mouthwash or oral rinse.1 2 90 91

Oral solution is for topical use only and should not be ingested.1 2 90 91

Consider that some commercially available topical oral solutions of the drug contain 11.6% alcohol1 2 and some are alcohol free.90 91

Administer undiluted.1 2 90 91

Immediately prior to initiation of treatment, provide professional dental prophylaxis.1 2 90 91 Reevaluate patient with thorough dental prophylaxis throughout treatment at intervals not exceeding 6 months.1 2 90 91

Instruct patients to brush their teeth immediately prior to each use of the topical oral solution.1 2 90 91 Then, place appropriate volume of the oral solution into the mouth, swish for 30 seconds, and expectorate the solution.1 2 90 91

Instruct patients to not rinse with water or other mouthwashes and to not brush their teeth or eat immediately after using the topical oral solution.1 2 90 91

Subgingival Administration

Administered subgingivally as extended-release inserts into periodontal pockets by a dental health-care provider.3

Place a single insert containing 2.5 mg of chlorhexidine gluconate into each periodontal pocket that has a probing depth ≥5 mm.3

Isolate periodontal pocket and dry surrounding area prior to insertion.3 Grasp flat end of insert with forceps and place (curved end first) into periodontal pocket to its maximum depth.3 If necessary, further maneuver insert into position using tips of forceps or a flat instrument.3

Advise patients to avoid dental floss at insertion sites for 10 days after placement.3

If insert dislodges ≤48 hours after placement, place a new insert.3 If insert dislodges >48 hours but <7 days after placement, do not replace insert; reevaluate at 3 months and place new insert if pocket depth has not been reduced to <5 mm.3 If insert dislodges ≥7 days after placement, no action required since this is considered a full course of treatment.3

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

Consult manufacturer’s literature for additional information on subgingival administration of chlorhexidine inserts.3

Dosage

Available as chlorhexidine gluconate; dosage expressed in terms of the salt.1 2 3 90 91

Adults

Gingivitis
Oral, Topical Use Only

0.12% topical oral solution: 15 mL as a mouthwash or oral rinse twice daily for 30 seconds (morning and evening after toothbrushing).1 2 90 91

Periodontitis
Subgingival

Dosage varies depending on size, shape, and number of periodontal pockets treated.3

2.5-mg insert: Place one insert into each periodontal pocket that has a probing depth ≥5 mm.3 Manufacturer states up to 8 inserts may be placed during a single visit.3

Place new insert 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

Adults

Periodontitis
Subgingival

Maximum of 8 inserts during a single visit.3

Cautions for Chlorhexidine Gluconate

Contraindications

  • Hypersensitivity to the drug or any ingredient in the formulation.1 2 3 90 91 (See Hypersensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylaxis and other serious allergic reactions reported in patients receiving dental preparations containing chlorhexidine.1 2 3 90 91

Serious allergic reactions, including fatal anaphylaxis, reported rarely with topical chlorhexidine preparations used on the skin (e.g., solutions, washes, sponges, swabs), including OTC topical preparations.4 45 48 63 64 66 92

Hypersensitivity reactions can occur within minutes following topical exposure.92 Symptoms may include wheezing or difficulty breathing, facial swelling, urticaria that can quickly progress to more serious symptoms, severe rash, or life-threatening shock.92

Prior to prescribing or recommending any preparation that contains chlorhexidine, ask patients whether they have ever had an allergic reaction to antiseptics or any preparation containing chlorhexidine.92

If allergic reaction occurs or is suspected, discontinue the drug and carefully monitor the reaction and provide immediate respiratory and/or cardiovascular support as needed.92

Precautions Related to Topical Oral Solution

Possible staining of teeth and other oral surfaces, such as tooth surfaces, restorations, and dorsum of the tongue.1 2 4 5 8 10 18 90 91 Stains usually can be removed by conventional professional prophylactic techniques, although additional time may be required to complete the prophylaxis.1 2 90 91

Possible increased supragingival calculus; professional dental prophylaxis to remove calculus deposits recommended at intervals not exceeding 6 months.1 2 90 91

Alterations in taste perception reported.1 2 4 90 91 May be avoided if used after meals.2 90 91

Effect on periodontitis not determined.1 2 90 91 If used as a mouthwash or oral rinse in patients with coexisting gingivitis and periodontitis, presence or absence of gingival inflammation following treatment should not be used as a major indicator of underlying periodontitis.1 2 90 91

Precautions Related to Subgingival Inserts

Use in acutely abscessed periodontal pockets not studied and not recommended.3 Management of periodontal disease should include consideration of potentially contributing medical disorders, such as cancer, diabetes, and compromised immune function.3

Avoid dental floss at insertion site for 10 days after placement; flossing might dislodge insert.3

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

Specific Populations

Pregnancy

Topical oral solution: No adequate and controlled studies to date in pregnant women;1 2 90 91 use during pregnancy only when clearly needed.1 2 90 91

Subgingival insert: No adequate and controlled studies to date in pregnant women;3 use during pregnancy only when clearly needed.3

Lactation

Topical oral solution: Not known if chlorhexidine distributes into human milk following use as a mouthwash or oral rinse.1 2 90 91 Use with caution in nursing women.1 2 90 91

Pediatric Use

Topical oral solution: Safety and efficacy not established in pediatric patients <18 years of age.1 2 90 91

Subgingival insert: Safety and efficacy not established in pediatric patients <18 years of age.3 77

Geriatric Use

Subgingival insert: Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.3 No overall differences in safety or efficacy between geriatric and younger adults.3

Common Adverse Effects

Topical oral solution: Increased staining of teeth, esthetic restorations, and other oral surfaces; increased calculus formation; alteration of taste perception.1 2 90 91

Subgingival inserts: Toothache, upper respiratory infection, headache.3 23

Chlorhexidine Gluconate Pharmacokinetics

Absorption

Bioavailability

Topical oral solution: Systemic absorption does not appear to occur following use as a mouthwash or oral rinse.78

Subgingival insert: Systemic absorption does not appear to occur.50 77

Following use of a 0.12% topical oral solution of chlorhexidine gluconate as a mouthwash or oral rinse, approximately 30% of drug is retained in oral cavity.1 2 5 8 34 90 91 The drug is bound to phosphate groups principally on coatings of mucous membrane surfaces8 and gradually released into oral fluids1 2 5 8 34 90 91 for up to 24 hours.8

Following subgingival administration of biodegradable extended-release insert containing 2.5 mg of chlorhexidine gluconate, the drug is slowly released into periodontal pocket.3 50 In vitro study indicates approximately 40% of the drug is released during first 24 hours and remainder is released in almost linear manner over 7–10 days.3

Distribution

Extent

Following oral administration of a 300-mg dose of chlorhexidine gluconate, peak plasma concentrations of 0.206 mcg/mL were attained 30 minutes after the dose; however, the drug was undetectable in plasma 12 hours after the dose.1 2 77 90

Following subgingival administration of biodegradable chlorhexidine inserts into 4 periodontal pockets in adults, the drug was not detectable in plasma or urine (limits of detection: 30 ng/mL).3 50

Elimination

Elimination Route

Following oral administration of a single 300-mg dose, the drug is excreted in feces via biliary elimination (90%) and urine (<1%).1 2 90 91

Stability

Storage

Oral, Topical Use Only

Solution

20–25° C (may be exposed to 15–30°).1 2 90 91

Subgingival

Insert, extended-release

20–25° C (may be exposed to 15–30°).3

Actions and Spectrum

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

  • Cationic compound; antibacterial activity results from attraction between positively charged chlorhexidine and negatively charged bacterial cell surfaces.3 5 8 Becomes adsorbed onto cell surfaces of susceptible organisms and disrupts cell membrane integrity resulting in increased permeability.8 33 34

  • Topical oral solution: When used as a mouthwash or oral rinse, chlorhexidine 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 Can provide a persistent bacteriostatic effect at tooth surface.8 33 34 May provide antiplaque effects because of bacteriostatic or bactericidal effects on salivary bacteria and bacteria adhering to tooth surfaces.34

  • Subgingival insert: After placement into periodontal pockets, numbers of some organisms associated with periodontal disease, including Porphyromonas gingivalis, Prevotella intermedia, Bacteroides forsythus, and Campylobacter rectus, were reduced.3 Clinical importance unknown.3

  • 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

  • Topical oral solution: Advise patients to use the solution on a regular basis as directed by their dental health-care provider and to brush their teeth immediately prior to each use.1 2 90 91 Importance of expectorating the solution after 30 seconds and importance of not rinsing with water or other mouthwashes and not brushing their teeth or eating immediately after using the solution.1 2 90 91

  • Topical oral solution: Advise patients that the solution may cause some tooth discoloration or increase in tartar (calculus) formation.1 2 90 91 Importance of contacting dental health-care provider for removal of any stain or tartar at least every 6 months or more frequently if needed.1 2 90 91

  • Topical oral solution: Advise patients that the solution may taste bitter and can affect how foods and beverages taste; this usually becomes less noticeable with continued use.2 90 91 Using the solution after meals may avoid taste interference.2 90 91

  • Subgingival insert: Advise patients to avoid dental floss at the insertion site for 10 days following insert placement.3 Importance of notifying dental health-care professional if an insert is dislodged or if pain, swelling, or other problems occur.3

  • Subgingival insert: Advise patients that some mild to moderate sensitivity is normal during first week after insert placement; importance of promptly notifying dental health-care provider if pain, swelling, or other problems occur.3

  • Advise patients receiving topical oral solution or subgingival insert to immediately contact a clinician and stop using the product if they experience any symptoms of an allergic reaction (e.g., rash, itching, hives, generalized or facial swelling, wheezing or breathing difficulties, lightheadedness, rapid heart rate, shock, upset stomach or diarrhea).2 3 90 91 92

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.1 2 3 90 91

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 3 90 91

  • Importance of informing patients of other important precautionary information.1 2 3 90 91 (See Cautions.)

Preparations

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.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chlorhexidine Gluconate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral (Topical Use Only)

Solution

0.12%*

Chlorhexidine Gluconate Oral Rinse

Paroex

Sunstar

Peridex

3M ESPE

PerioGard

Colgate

PerioGard Alcohol Free

Colgate

Subgingival

Insert, extended-release

2.5 mg

PerioChip

Dexcel Pharma

AHFS DI Essentials. © Copyright 2018, Selected Revisions April 16, 2018. 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.

References

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2. 3M ESPE Dental Products. Peridex (chlorhexidine gluconate) 0.12% oral rinse prescribing information. St. Paul, MN; 2017 Oct.

3. Dexcel Pharma Technologies. PerioChip (chlorhexidine gluconate) 2.5 mg extended-release insert prescribing information. Yokneam, Israel; 2012 Nov.

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