Chlorhexidine (Mucosal-Local)

VA CLASSIFICATION
Primary: OR500
Secondary: DE101

Commonly used brand name(s): Oro-Clense; Peridex; PerioGard.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antibacterial (dental)^{14}—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Gingivitis (treatment)—Chlorhexidine is indicated for use between dental visits for the treatment of gingivitis that is characterized by redness and swelling of the gingivae or gingival bleeding upon probing. ^{{01} {14} {26} {35}}

[Gingivitis, necrotizing ulcerative, acute (treatment) ]—Chlorhexidine is used along with other measures in the treatment of acute necrotizing ulcerative gingivitis (ANUG). ^{{06} {14}}

[Mouth infections (prophylaxis)] or
[Mouth infections (treatment)]—Chlorhexidine is used in the treatment of mouth infections in cancer patients who are being prepared for bone marrow transplants. Chlorhexidine is also used in the management of the oral complications that occur in leukemia patients. ^{{06} {13} {14} {17} {20} {21} {22}}
—Chlorhexidine is also used following periodontal surgery to promote healing by minimizing mouth infections and plaque that may lead to increased inflammation and infection during the healing process. ^{{14} {16} {18}}

[Stomatitis, denture (treatment)]—Chlorhexidine is used in the treatment of inflammation of the oral mucosa caused by bacterial or fungal actions associated with the wearing of dentures but should not be used when inflammation is caused by poor fit or other mechanical factors associated with dentures. ^{{04} {06} {14}}

[Stomatitis, aphthous (treatment)]—Chlorhexidine is used in the management of minor aphthous ulcers. ^{{14} {15} {16} {18}}

[Plaque, dental (prophylaxis)]—Chlorhexidine is used for reduction of dental plaque. ^{{14} {16} {18}}

—Microorganisms with high susceptibility to chlorhexidine include some staphylococci, Streptococcus mutans , Streptococcus salivarius , Candida albicans , Escherichia coli , Selenomonas , and anaerobic propionic bacteria. Streptococcus sanguis has moderate susceptibility. Microorganisms with low susceptibility to chlorhexidine include Proteus strains, Pseudomonas , Klebsiella , and gram-negative cocci resembling Veillonella . ^{{04} {06}}

—Samples of plaque taken during a 6-month period of use with chlorhexidine oral rinse showed a 54 to 97% reduction in certain aerobic and anaerobic bacteria. However, 3 months after chlorhexidine was discontinued, the number of bacteria in the plaque had returned to baseline levels. ^{{01} {04} {11} {24}}

—A 6-month clinical study did not show any significant changes in bacterial resistance, overgrowth of potentially opportunistic organisms, or other adverse changes in the oral microbial ecosystem during the use of chlorhexidine. In addition, 3 months after chlorhexidine was discontinued, the resistance of plaque bacteria to the medication was found to be the same as before therapy was initiated. ^{{01} {04} {05} {24}}


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Chlorhexidine gluconate: 897.77 ^{{08} {10}}

Mechanism of action/Effect:

Because of its positive charge, chlorhexidine gluconate is adsorbed during oral rinsing onto ^{33} the surfaces of teeth, plaque, and oral mucosa, which have a net negative charge. Subsequently, the adsorbed medication is gradually released from these sites by diffusion for up to 24 hours as the concentration of chlorhexidine gluconate in the saliva decreases. This release provides a continuing bacteriostatic ^{{04} {06}} effect.

Chlorhexidine gluconate is adsorbed onto the cell walls of microorganisms, which causes leakage of intracellular components. At low concentrations, chlorhexidine gluconate is bacteriostatic; at higher concentrations, chlorhexidine gluconate is bactericidal. ^{{04} {06}}

Absorption:

Pharmacokinetic studies indicate that approximately 30% of chlorhexidine gluconate is retained in the oral cavity following rinsing and subsequently is slowly released into the oral fluids. ^{{01} {24}}

Studies using humans and animals have shown that chlorhexidine gluconate is poorly absorbed from the gastrointestinal tract. In humans, the mean plasma level of chlorhexidine gluconate reached a peak of 0.206 mcg per gram 30 minutes following an oral dose of 300 mg. ^{{01} {04} {06} {24}}

Elimination:
    Following oral doses of 300 mg of chlorhexidine gluconate, excretion of chlorhexidine gluconate ^{{01} {33}} was primarily through the feces (approximately 90%); less than 1% of chlorhexidine gluconate ^{{01} {33}} was excreted in the urine. In addition, 12 hours after chlorhexidine gluconate was administered, it was not detectable in the plasma. ^{{01} {24}}


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to disinfectant skin cleansers containing chlorhexidine may be sensitive to chlorhexidine oral rinse also. ^{04}

Carcinogenicity

Carcinogenesis was not observed in a drinking water study in rats where the highest dose of chlorhexidine used was 38 mg per kg of body weight (mg/kg) per day. This dose is at least 500 times the amount that would be ingested from the recommended human daily dose of chlorhexidine oral rinse. ^{{01} {24}}

Mutagenicity

Mutagenicity was not observed in 2 mammalian in vivo mutagenic studies with chlorhexidine. ^{{01} {24}}

Pregnancy/Reproduction
Fertility—
Fertility studies have shown no evidence of impaired fertility in rats given chlorhexidine in doses of up to 100 mg/kg per day. This dose is approximately 100 times greater than the dose a person would receive if he/she ingested 30 mL (2 capfuls) of chlorhexidine oral rinse per day. ^{{01} {24}}

Pregnancy—
Well-controlled studies in humans have not been done.

In animal studies, no evidence of harm to the fetus was observed in rats and rabbits given doses of chlorhexidine of up to 300 mg/kg per day and up to 40 mg/kg per day, respectively. These doses are approximately 300 and 40 times, respectively, greater than the dose a person would receive if she ^{33} ingested 30 mL (2 capfuls) of chlorhexidine oral rinse per day. ^{24}

FDA Pregnancy Category B. ^{{01} {24}}

Breast-feeding

Although it is not known whether chlorhexidine is distributed into breast milk, problems in humans have not been documented. In addition, studies in rats have shown no evidence of impaired parturition and no evidence of toxic effects to suckling pups when chlorhexidine was administered to dams at doses over 100 times greater than the dose a person would receive if she ^{33} ingested 30 mL (2 capfuls) of chlorhexidine oral rinse per day. ^{{01} {24}}

Pediatrics

Appropriate studies on the relationship of age to the effects of this medicine have not been performed in the pediatric population. Safety and efficacy have not been established. ^{{01} {24}}


Geriatrics


Appropriate studies on the relationship of age to the effects of this medicine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
Anterior tooth restorations (front-tooth fillings)^{30}    (anterior tooth restorations having rough surfaces or margins may develop permanent discoloration from chlorhexidine, necessitating replacement for cosmetic reasons ^{01})


Periodontitis    (during clinical tests, an increase in supragingival calculus was noted in patients using chlorhexidine; it is not known whether use of chlorhexidine results in an increase in subgingival calculus ^{{01} {06} {24}})

    (since gingival inflammation and bleeding may occur with both periodontitis and gingivitis and chlorhexidine oral rinse may reduce these signs, the presence or absence of these signs should not be used as indicators of periodontitis after the patient has been treated with chlorhexidine ^{{01} {14}})


Sensitivity to chlorhexidine^{24}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Dental examination and prophylaxis    (tartar [calculus] deposits should be removed before therapy is initiated and during therapy at intervals of 6 months or less; the patient's condition should be reevaluated at intervals of 6 months or less, including monitoring of gingival pockets, ^{30} because of the possible masking of coexisting periodontitis by chlorhexidine ^{{01} {14} {24}})




Side/Adverse Effects

Note: Chlorhexidine causes staining of oral surfaces. Staining may be visible as early as 1 week after therapy; after 6 months of use, approximately 50% of patients may have a measurable increase in tooth stain and approximately 10% may have heavy staining. Staining is more pronounced in patients who have heavier accumulations of plaque. Tooth restorations ^{33} having rough surfaces or margins may develop permanent staining. If this occurs on anterior surfaces, it may be necessary to replace the tooth restoration ^{33} for cosmetic reasons. ^{{01} {04} {14} {16} {24}}
Some patients develop an alteration in taste perception during treatment with chlorhexidine. This effect usually becomes less noticeable with continued treatment. No cases of permanent taste alteration have been reported. ^{{01} {24}}
No serious systemic side/adverse effects associated with the use of chlorhexidine oral rinse were reported during the clinical trials. ^{{01} {04} {27} {28} {29} {33}}

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Allergic reaction^{07}{24}{26} (nasal congestion; shortness of breath or troubled breathing; skin rash, hives, or itching; swelling of face)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Change in taste^{{01}{04}{05}{06}{24}}
    
increase in tartar (calculus) on teeth^{{01}{04}{06}{24}}
    
staining of teeth, mouth, tooth restorations (fillings)^{33} , and dentures or other mouth appliances^{{01}{04}{05}{06}{24}}

Incidence less frequent or rare
    
Parotid duct obstruction^{31} or parotitis^{31} (swollen glands on side of face or neck)
    
superficial desquamative lesions^{{01}{04}{05}{06}{14}} (mouth irritation)—reported mainly in children ages 10 to 18 years;^{01}{14} the lesions are transient and may be^{16} painless^{14}
    
tongue tip irritation^{16}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Treatment of overdose
Medical attention and symptomatic treatment are recommended if signs of alcohol intoxication develop or if more than 4 ounces of chlorhexidine oral rinse is ingested by a child weighing approximately 10 kg (22 pounds) ^{33} or less. ^{{01} {14} {24} {26}}


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Chlorhexidine (Dental) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergy to chlorhexidine or to disinfectant skin cleansers containing chlorhexidine

Proper use of this medication
Using medication after brushing and flossing; rinsing toothpaste completely from mouth with water before using oral rinse; not eating or drinking for several hours after using oral rinse

Using the cap of the original container to measure the dose or acquiring another measuring device to use; asking your pharmacist for help

» Swishing medication around in mouth for 30 seconds and spitting out; using full strength; not swallowing

» Proper dosing
Missed dose: Using as soon as possible; not using if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
Not rinsing mouth with water immediately after using medication, since doing so will increase medication's bitter aftertaste and may decrease medication's effect ^{33}

Medication causes change in taste; change may last up to 4 hours after dose; change in taste should be less noticeable as medication is continued; after medication is discontinued, taste should return to normal

Staining and increase in tartar (calculus) may occur; brushing with tartar-control toothpaste and flossing teeth daily to help reduce tartar build-up; visiting dentist at least every 6 months for teeth cleaning and gum examination

» Getting emergency help at once if a child weighing 22 pounds (10 kg) or less drinks more than 4 ounces of dental rinse or if any child experiences symptoms of alcohol intoxication, such as slurred speech, sleepiness, or staggering or stumbling walk, after drinking the dental rinse


Side/adverse effects
Signs of potential side effects, especially allergic reaction


Dental Dosage Forms

Note: Bracketed uses in the Dosage Forms section refer to categories of use and/or indications that are not included in U.S. product labeling.

CHLORHEXIDINE GLUCONATE ORAL RINSE

Usual adult dose
Gingivitis
Topical, to the gingival membranes, 15 mL of a 0.12% oral rinse for 30 seconds two times a day after brushing and flossing teeth. ^{{01} {24} {26} {35}}

Note: Therapy with chlorhexidine oral rinse should start immediately following a dental prophylaxis. ^{{01} {24} {26}}


[Denture stomatitis]
Soak the dentures in chlorhexidine oral rinse 0.12% for 1 to 2 minutes two times a day. Rinsing the mouth for 30 seconds two times a day or brushing the gums or dentures two times a day with chlorhexidine oral rinse 0.12% may also be required. ^{{04} {14}}


Usual pediatric dose
Children up to 18 years of age—Safety and efficacy have not been established. ^{24}

Strength(s) usually available
U.S.—


0.12% (Rx) [Peridex^{01}{23}{26} (alcohol 11.6%)] [PerioGard^{23}{35} (alcohol 11.6%)][Generic]^{38}

Canada—


0.12% (Rx) [Oro-Clense^{36} (alcohol)] [Peridex^{37} (alcohol)]

Packaging and storage:
Store above freezing at a temperature not exceeding 25 °C (77 °F), unless otherwise specified by manufacturer. Protect from light. ^{{01} {10} {24} {26}}

Preparation of dosage form:
If the medication is not commercially available, it may be compounded as follows—3 mL chlorhexidine gluconate 20% should be added to approximately 200 mL distilled water. Separately, 5 mL essence of peppermint should be combined with 5 mL ethanol 95% and then 15 mL glycerin should be added. This mixture should be combined with the chlorhexidine and water solution and enough distilled water added to make 500 mL. ^{32}

Auxiliary labeling:
   • Do not swallow. ^{26}
   • Do not dilute. ^{26}

Note: Dispense with patient package insert. ^{{01} {02}}
Dispense in original container, which includes a measuring cap, or in an amber glass container and include a device for measuring 15 mL (1/2 fluid ounce). ^{03}

Revised: 08/14/1998

References

1. Peridex package insert (Procter & Gamble—US), Rev 8/86, Rec 1/88.
   

2. Peridex patient package insert (Procter & Gamble—US), Rec 1/88.
   

3. Peridex product label (Procter & Gamble—US), Rec 1/87.
   

4. Chlorhexidine. Biological Therapies in Dentistry 1986 Oct; 2(5).
   

5. Chlorhexidine and plaque control. Dent Manage 1986 May: 58-60.
   

6. A review of the literature on use of chlorhexidine in dentistry. J Am Dent Assoc 1986 Jun: 863-9.
   

7. Moghadam BKH, Drisko CL, Gier RE. Chlorhexidine mouthwash-induced fixed drug eruption. Oral Surg Oral Med Oral Path 1991 Apr; 71: 431-4.
   

8. Fleeger CA, editor. USAN 1993. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1992.
   

9. Open.
   

10. Reynolds JEF, editor. Martindale's The extra pharmacopeia. 28th ed. London: The Pharmaceutical Press, 1982: 554.
    

11. P&G finds rinse with chlorhexidine effective in tests. Drug Topics 1986 Jun 2: 72.
    

12. Open.
    

13. Instant Up-Date, 1987 Feb: 2.
    

14. Panel comments, 5/87.
    

15. Hunter L, Addy M. Chlorhexidine gluconate mouthwash in the management of minor aphthous ulceration. Br Dent J 1987 Feb 7; 162: 106-10.
    

16. Panel comments, 7/87.
    

17. Ferretti, Ash, Brown, et al. Chlorhexidine for prophylaxis against oral infections and associated complications in patients receiving bone marrow transplants. J Am Dent Assoc 1987 Apr; 114: 461-7.
    

18. Panel comment, 7/87.
    

19. Open.
    

20. Reviewer comment, 2/88.
    

21. Ferretti, et al. Chlorhexidine for prophylaxis against oral infections and associated complications in patients receiving bone marrow transplants. J Am Dent Assoc, 1987 Apr; 114: 461-7.
    

22. Spiers, et al. Infection prevention in patients with cancer: microbiological evaluation of portable laminar air flow isolation, topical chlorhexidine, and oral non-absorbable antibiotics. J Hyg 1980; 84: 457-65.
    

23. Reviewers' responses to Disulfiram monograph revision of 8/87 referring to interaction with chlorhexidine.
    

24. Peridex (Procter & Gamble). In: PDR Physicians' desk reference. 45th ed. 1991. Montvale, NJ: Medical Economics Data, 1991: 1742.
    

25. Open.
    

26. Peridex (Procter & Gamble). In: PDR Physicians' desk reference. 47th ed. 1993. Montvale, NJ: Medical Economics Data, 1993: 1867-8.
    

27. Okano M, et al. Anaphylactic symptoms due to chlorhexidine gluconate. Arch Dermatitis 1989 Jan; 125: 50-2.
    

28. Bergqvist-Karlsson A. Delayed and immediate-type hypersensitivity to chlorhexidine. Contact Dermatitis 1988 Feb; 18: 84-8.
    

29. Fisher AA. Contact urticaria from chlorhexidine. Cutis 1989 Jan; 43: 17-8.
    

30. Panel comment, 3/92.
    

31. Panel comment, 3/92.
    

32. Chlorhexidine mouthwash. New Drugs/Drug News 1991 Jul/Aug.
    

33. Panel comments, 11/93.
    

34. Open.
    

35. PerioGard package insert (Colgate—US), Rev 11/93, Rec 4/94.
    

36. Oro-Clense (Germiphene). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmaceutical Association; 1998. p. 1233.
    

37. Peridex (Proctor & Gamble). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmaceutical Association; 1998. p. 1298.
    

38. Chlorhexidine gluconate (Teva). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Data; 1998. p. 2923.