PRODUCT MONOGRAPH

CHLORHEXIDINE GLUCONATE 0.12% ORAL RINSE, USP

Chlorhexidine Gluconate 0.12% Oral Rinse

Liquid, 0.12% Chlorhexidine Gluconate

Antigingivital Oral Rinse

Sage Product LLC Date of Preparation:

3909 Three Oaks Road February 17, 2015
Cary, IL 60013
USA

Submission Control No: 180308

Page 1 of 19
 Table of Contents

PART I: HEALTH PROFESSIONAL INFORMATION .........................................................3

SUMMARY PRODUCT INFORMATION ........................................................................3
INDICATIONS AND CLINICAL USE ..............................................................................3
CONTRAINDICATIONS ...................................................................................................3
WARNINGS AND PRECAUTIONS ..................................................................................4
ADVERSE REACTIONS....................................................................................................6
DOSAGE AND ADMINISTRATION ................................................................................6
OVERDOSAGE ..................................................................................................................7
ACTION AND CLINICAL PHARMACOLOGY ..............................................................8
STORAGE AND STABILITY ............................................................................................9
SPECIAL HANDLING INSTRUCTIONS .........................................................................9
DOSAGE FORMS, COMPOSITION AND PACKAGING .............................................10

PART II: SCIENTIFIC INFORMATION ...............................................................................11

PHARMACEUTICAL INFORMATION..........................................................................11
CLINICAL TRIALS ..........................................................................................................12
DETAILED PHARMACOLOGY .....................................................................................13
MICROBIOLOGY ............................................................................................................13
TOXICOLOGY .................................................................................................................14
REFERENCES ..................................................................................................................15

PART III: PATIENT MEDICATION INFORMATION ........................................................16

Page 2 of 19
 CHLORHEXIDINE GLUCONATE 0.12% ORAL RINSE, USP

chlorhexidine gluconate 0.12% oral rinse

PART I: HEALTH PROFESSIONAL INFORMATION

SUMMARY PRODUCT INFORMATION

Route of Dosage Form / All Nonmedicinal Ingredients

Administration Strength
Oral Liquid/0.12% w/w Alcohol, FD&C Blue # 1, flavour, glycerine,
PEG 40-sorbitan diisostearate, saccharin
sodium and USP Purified water.

INDICATIONS AND CLINICAL USE

Chlorhexidine gluconate 0.12% oral rinse is indicated for use as part of a professional program
for the treatment of moderate to severe gingivitis, and for the management of associated gingival
bleeding and inflammation between dental visits. For patients having coexisting gingivitis and
periodontitis, see PRECAUTIONS

Geriatrics (> 65 years of age):

No data is available

Pediatrics (< 18 years of age):

Since the safety and efficacy of chlorhexidine gluconate oral rinse has not yet been fully
established, the benefits of its use should be weighed against the possible risks.

CONTRAINDICATIONS

Chlorhexidine gluconate 0.12 % oral rinse should not be used by persons who are known to be
hypersensitive to chlorhexidine gluconate or other formula ingredients.

Page 3 of 19
WARNINGS AND PRECAUTIONS

General

1. For patients having coexisting gingivitis and periodontitis, the absence of gingival
inflammation following treatment with chlorhexidine gluconate oral rinse may not be
indicative of the absence of underlying periodontitis. Appropriate treatment of
periodontitis is therefore indicated.

2. Chlorhexidine gluconate oral rinse may cause staining of oral surfaces such as the film on
tooth surfaces, restorations, and the dorsum of the tongue. Stain will be more pronounced
in patients who have heavier accumulations of un-removed plaque. Stain resulting from
use of chlorhexidine gluconate oral rinse does not adversely affect the health of gingivae
or other oral tissue. Stain can be removed from most tooth surfaces by conventional
professional prophylactic techniques. Additional time may be required to complete the
prophylaxis. Discretion should be used when treating patients with exposed root surfaces
or anterior facial restorations with rough surfaces or margins. If natural stains cannot be
removed from these surfaces by a dental prophylaxis, patients should be excluded from
chlorhexidine gluconate oral rinse treatment if the risk of permanent discolouration is
unacceptable. Stains in these areas may be difficult to remove by dental prophylaxis and
on rare occasions may necessitate replacement of these restorations.

3. A few patients may experience an alteration in taste perception while undergoing

treatment with chlorhexidine gluconate oral rinse. Most of these patients accommodate to
this effect with continued use of chlorhexidine gluconate oral rinse. Rare instances of
permanent taste alteration following chlorhexidine gluconate oral rinse use have been
reported via post-marketing product surveillance.

4. For maximum effectiveness the patient should avoid rinsing their mouth (with water or
other mouthwashes), brushing their teeth, eating or drinking for about 30 minutes after
using chlorhexidine gluconate oral rinse.

Carcinogenesis and Mutagenesis

No evidence of carcinogenicity was reported in two rat studies in which chlorhexidine was
administered in their drinking water. The studies were two years in duration and delivered
chlorhexidine at dose levels of up to 200 mg/kg/day.

No evidence of mutagenicity was observed when chlorhexidine gluconate was evaluated by the
dominant lethal assay in mice and micronucleus assay in hamsters. Mutagenicity studies, using
bacterial cell system, with or without metabolic activation, produced contradictory results, which
are unexpected with drugs having antibacterial activity. While Suessmuth et al. (1979) and
Ackerman-Schmidt et al. (1982) obtained positive results, Evans et al. (1978) and Sakagami et

Page 4 of 19
al. (1988) found no evidence of genotoxicity for chlorhexidine. The clinical significance of these
results is unclear

Special Populations

Pregnant Women:

Reproduction and fertility studies with chlorhexidine gluconate have been conducted. No
evidence of impaired fertility was observed in male and female rats at doses up to 100
mg/kg/day, and no evidence of harm to the fetus was observed in rats and rabbits at doses up to
300 mg/kg/day and 40 mg/kg/day, respectively. These doses are approximately 100, 300, and 40
times that which would result from a person ingesting 30 mL (2 capfuls) of chlorhexidine
gluconate 0.12% oral rinse per day. Since controlled studies in pregnant women have not been
conducted, the benefits of use of the drug in pregnant women should be weighed against possible
risk to the fetus.

Nursing Women:

It is unknown whether this drug is excreted in human milk. In parturition and lactation studies
with rats, no evidence of impaired parturition or of toxic effects to suckling pups was observed
when chlorhexidine gluconate was administered to dams at doses that were over 100 times
greater than the dose which would result if a person ingested the entire recommended dose of
chlorhexidine gluconate 0.12% oral rinse on a daily basis.

Pediatrics (< 18 years of age):

Since the safety and efficacy of chlorhexidine gluconate oral rinse has not yet been fully
established, the benefits of its use should be weighed against the possible risks.

Geriatrics (> 65 years of age):

No data is available

Page 5 of 19
ADVERSE REACTIONS

Adverse Drug Reaction Overview

No serious systemic reactions associated with use of chlorhexidine Gluconate 0.12% oral rinse
were observed in clinical testing. However, some adverse reactions have been reported in studies
with chlorhexidine gluconate 0.12% oral rinse or other chlorhexidine containing mouth rinses.
The most common side effects associated with chlorhexidine gluconate oral rinse are (1) an
increase in staining of oral surfaces, (2) an increase in supragingival tartar (3) an alteration in
taste perception to which most patients accommodate (see PRECAUTIONS).

Epithelial irritation and superficial desquamation of the oral mucosa have been noted in studies
of children using 0.12% chlorhexidine gluconate which were reversible upon discontinuation.

There have been rare cases of parotid gland swelling and inflammation of the salivary glands, in
patients using chlorhexidine gluconate oral rinse.

Oral irritation and local allergy-type symptoms have been spontaneously reported as side effects
associated with use of chlorhexidine gluconate rinse.

The following oral mucosal side effects were reported during placebo-controlled adult clinical
trials: apthous ulcer, grossly obvious gingivitis, trauma, ulcerations, erythma, desquamation,
coated tongue, keratinization, geographic tongue, mucocele, and short frenum. Each occurred at
a frequency of less than 1.0%.

Among postmarketing reports, the most frequently reported oral mucosal symptoms associated
with chlorhexidine gluconate oral rinse are stomatitis, gingivitis, glossitis, ulcer, dry mouth,
hypesthesia, glossal edema, and parestesia.

DOSAGE AND ADMINISTRATION

Dosing Considerations

Chlorhexidine gluconate 0.12% oral rinse therapy should be initiated directly following a
dental prophylaxis. Patients using chlorhexidine gluconate oral rinse should be reevaluated
and given a thorough prophylaxis at intervals no longer than six months; they should be
referred for periodontal consultation as necessary.

The suggested initial course of therapy is 3 months, at which time patients should be
recalled for evaluation. At the time of the recall visit, the dental professional should:

- Evaluate progress, remove any stain, and reinforce proper home care techniques.

Page 6 of 19
- If gingival inflammation and bleeding is controlled, discontinue chlorhexidine gluconate
oral rinse therapy and recall the patient in 3 months to assess gingival health.
- If gingival inflammation and bleeding persist, continue chlorhexidine gluconate oral rinse
therapy for an additional 3 months and schedule a three-month recall for evaluation.
- Evaluate for evidence of epithelial irritation, desquamation and parotitis.

The following generally accepted grading scheme may be of use in evaluating the severity
of gingivitis.

Loe and Silness Gingival Index (GI)

Grade Description
1 Normal gingival, no inflammation, no discolouration, no bleeding
2 Mild inflammation, slight colour change, mild alteration of gingival surface.
No
bleeding.
3 Moderate inflammation, erythema, swelling, bleeding on probing or when
pressure applied.
4 Severe inflammation, severe erythema and swelling, tendency toward
spontaneous haemorrhage, some ulceration.

Recommended Dose and Dosage Adjustment

Recommended use is twice daily oral rinsing for 30 seconds, morning and evening after
tooth brushing. Usual dosage is 15 mL (3 tsp) of undiluted chlorhexidine gluconate oral
rinse. Chlorhexidine gluconate oral rinse is not intended for ingestion and should be
expectorated after rinsing. Rinsing the mouth (with water or other mouthwashes),
brushing teeth, or eating or drinking should be avoided for about 30 minutes after using
chlorhexidine gluconate oral rinse.

Missed Dose

An occasional missed dose can be ignored if the patient is generally compliant with the
prescribed regimen.

OVERDOSAGE

Ingestion of 30 or 60 mL of chlorhexidine gluconate 0.12% oral rinse by a small child (10

kg or less in body weight) might result in gastric distress, including nausea, or signs of
alcohol intoxication. Medical attention should be sought if more than 120 mL of
chlorhexidine gluconate 0.12% oral rinse is ingested by a small child or if signs of alcohol
intoxication develop.

For management of a suspected drug overdose, contact your regional Poison Control Centre
immediately.

Page 7 of 19
ACTION AND CLINICAL PHARMACOLOGY

Mechanism of Action

Chlorhexidine gluconate 0.12% oral rinse provides antimicrobial activity during oral
rinsing which is maintained between rinsings. Microbiologic sampling of plaque has shown
a general reduction of both aerobic and anaerobic bacterial counts ranging from 54-97%
through six months’ clinical use. Rinsing with chlorhexidine gluconate oral rinse inhibits
the buildup and maturation of plaque by reducing certain microbes regarded as gingival
pathogens, thereby reducing gingivitis1,4,5.

Chlorhexidine gluconate oral rinse provided antimicrobial activity during rinsing and for
several hours thereafter.

No significant changes in bacterial sensitivity, overgrowth of potentially opportunistic

organisms or other adverse changes in the oral microbial flora were observed following the
use of chlorhexidine gluconate oral rinse for six months. Three months after chlorhexidine
gluconate oral rinse use was discontinued, the number of bacteria in plaque had returned
to pre-treatment levels and sensitivity of plaque bacteria to chlorhexidine gluconate
remained unchanged.

Studies conducted with human subjects and animals demonstrate that any ingested
chlorhexidine gluconate is poorly absorbed from the gastrointestinal tract. Excretion of
chlorhexidine gluconate occurred primarily through the feces (approximately 90%). Less
than 1% of the chlorhexidine gluconate ingested by these subjects was excreted in the
urine.

Pharmacodynamics

Two clinical studies examined dose-response relationships and confirmed earlier animal studies.
One short term study demonstrated equal efficacy, as measured by plaque reduction, for 0.10%
and 0.20% chlorhexidine gluconate solutions while a 0.05% chlorhexidine gluconate solution
was less effective. In a three month study, anti-gingivitis efficacy was equal for 0.12% and
0.20% chlorhexidine gluconate mouth rinses. However, tooth and tongue discolouration
increases with chlorhexidine concentration in both studies. Therefore, the chlorhexidine
gluconate concentration for chlorhexidine gluconate oral rinse was set at 0.12% to optimize
efficacy while minimizing side effects.

The effect of duration and frequency of rinsing on plaque formation and tooth and tongue
discolouration was examined in another 88 day study. The data demonstrated that shorted,
more frequent rinsing (i.e. 2 x 30 sec.) provided optimal efficacy as compared to longer, less
frequent rinsing (i.e. 1 x 60 sec.).

Page 8 of 19
Pharmacokinetics

Approximately 30% of the chlorhexidine present in the mouth rinse is retained in the oral cavity
after rinsing. The amount retained was directly related to drug concentration, with an average of
6.3 and 2.7 mg (mean) of chlorhexidine being retained orally after a single use of a mouth rinse
containing 0.12% and 0.06% chlorhexidine gluconate, respectively. The release rate of
chlorhexidine from oral surfaces was similar for both treatments. Based on morning/evening
rinses, previous exposure to a chlorhexidine-containing mouth rinse was observed to have little
effect on subsequent retention of chlorhexidine.

Absorption:

Chlorhexidine gluconate 0.12% oral rinse is to be used topically as an oral rinse, not to be
ingested. Studies were conducted to study its metabolic pathway in the event of oral ingestion.

Human studies using radiological markers indicated that chlorhexidine gluconate is poorly
absorbed from the gastrointestinal tract. This is in agreement with the findings from animal
studies. Among five normal male volunteers, GI transit time was 31 to 53 hours as indicated by
radio-opaque markers.

Excretion:

The primary route for the excretion of chlorhexidine was through the feces (approximately 90%).
The mean peak plasma level of chlorhexidine was 0.206 μg/g, reached 30 minutes after ingestion
of a 300 mg dose of the drug. Chlorhexidine was not detectable in plasma 12 hours after
ingestion. Urine samples contained 0.5 to 1% of the 14C-chlorhexidine gluconate administered to
the study subjects.

STORAGE AND STABILITY

Temperature/Light:

Preserve in tight containers, protected from light, at controlled room temperature (15°C to 30°C).

Incompatibilities:

Chlorhexidine gluconate 0.12% oral rinse is not to be mixed/diluted with any other product.

SPECIAL HANDLING INSTRUCTIONS

None

Page 9 of 19
DOSAGE FORMS, COMPOSITION AND PACKAGING

Chlorhexidine gluconate oral rinse contains 0.12% of the medicinal ingredient, chlorhexidine
gluconate and the following non-medicinal ingredients: alcohol, FD&C Blue # 1, flavour,
glycerin, PEG 40-sorbitan diisostearate, saccharin sodium and USP Purified water.

Chlorhexidine gluconate 0.12% oral rinse is supplied as a blue liquid in 1-oz (15 mL) and 16-oz
(473 mL) amber plastic bottles with child-resistant dispensing closures.

Page 10 of 19
 PART II: SCIENTIFIC INFORMATION

PHARMACEUTICAL INFORMATION

Drug Substance

Proper name: Chlorhexidine gluconate (U.S.A.N.)

Chemical name: 1,1’-hexamethylene bis [5- (p-chlorophenyl) biguanide] di-D-gluconate

Molecular formula and molecular mass: C22H30Cl2N10•2C6H12O7

Structural formula:

Molecular Weight: 897.8

Physicochemical properties:

Chlorhexidine has basic character and exists in the di-cationic form at physiological pH.
The two protonic positive charges become somewhat localized on the bi-guanide portion
of the molecule. Both pKa’s are reported6 as 10.78 + 0.06. The gluconate salt is soluble
in excess of 70% (w/v) in water at 20°C.

At 19-21% w/v chlorhexidine gluconate solution is colourless to pale straw-coloured and

Is odourless to almost odourless (British Pharmacopeia).

Page 11 of 19
CLINICAL TRIALS

Efficacy and Safety Studies

The efficacy of 0.12% chlorhexidine gluconate oral rinse in the treatment and prevention of
gingivitis has been supported in three pivotal clinical trials and in several supporting studies.
The pivotal clinical studies are summarized in the following chart:

Reduction in*
Gingival
Study Study No. Usage Plaque Bleeding
Age Sex Inflammation
Location Duration Patients Regimen Index Scores Sites
Scores
San
Antonio, 3 Mon. 597 18-60 36.1% 27.8-45.8% 48.4%
TX According to
pkg.
Northfield, M&F
6 Mon. 430 18-60 instructions 60.9% 33.5-45.4% 41.6-52.2%
NJ
15 mL bid
London,
2 Yr. 456 18-72 34.6-56.4% 39.6% 50.3%
ON

1-
Results shown are those obtained for the final examination at completion of test product use. The data
are expressed as covariance adjusted % reduction vs. placebo; a range is reported when there were
duplicate examiners. All reductions were significantly different from placebo (p<0.05; nonparametric
Wilcoxon pair test)

Page 12 of 19
DETAILED PHARMACOLOGY

MICROBIOLOGY

In Vitro
Because of its nonspecific mechanism of action, chlorhexidine has a wide range of anti-
microbial activity against both Gram-positive and Gram-negative bacteria. An in-vitro study of
the microbicidal effect of 0.12% chlorhexidine gluconate oral rinse following a 30 second
exposure resulted in greater than a 99.9% reduction in the following micro-organisms:
Actinomyces viscosus, Candida albicans, Staphylococcus aureaus, Streptococcus mutans,
Streptococcus sanguis, Fusobacterium nucleatum, Neisseria sicca, Pseudomonas aeruginosa,
Veillonella parvula.

In Vivo
To determine the efficacy of chlorhexidine gluconate oral rinse in vivo, various bacteria in the
microbial flora of plaque were assayed in subjects who had used either chlorhexidine gluconate
oral rinse or a placebo.

During six months’ chlorhexidine gluconate oral rinse use, 2,3 subjects showed reductions in
total load/tooth, streptococci and actinomyces ranging from 54% to 97%. Neisseria and
fusobacteria were not detected in over half of the subjects assayed. No changes in numbers of
yeast-like organisms and Gram-negative enterics were observed. There were no adverse changes
in the oral microbial flora. Three months following cessation of treatment, the reductions
observed during mouth rinsing were no longer evident, indicating no “carryover” effect. The
results were interpreted as indicating that the use of chlorhexidine gluconate oral rinse was
associated only with a decrease in the number of microbes in plaque and no change in bacterial
sensitivity.

Another study was conducted to investigate whether changes occurred in resistance to

chlorhexidine which might limit efficacy of the mouth rinse, and if such changes occurred,
whether they dissipated or disappeared after cessation of use of the mouth rinse. Minimum
Inhibitory Concentrations (MIC’s) for chlorhexidine were determined on isolates of streptococci
and actinomyces obtained from patients during six months’ use of the mouth rinse and three
months after cessation of use of the mouth rinse5. Changes in bacterial sensitivity due to
exposure to chlorhexidine were slight, sporadic and had returned to pre-treatment values three
months after product usage was discontinued.

These results support that chlorhexidine gluconate oral rinse usage does not result in significant
changes in plaque bacterial resistance and does not cause significant changes in the plaque flora.

Page 13 of 19
TOXICOLOGY

Acute Toxicity Studies

The oral LD50 of chlorhexidine gluconate was estimated as 1.476 g/kg in rats and 0.1122 g/kg in
rabbits. The oral LD50 of the mouth rinse formulation was estimated at > 20 g/kg in rats.

• Chronic and Subchronic Toxicity Studies

The only consistently observed finding in eight subchronic and chronic toxicity studies was the
accumulation of foamy macrophages in the mesenteric lymph nodes of rats. Representative
samples of these lesions were evaluated by two independent pathologists. They concluded that
the lesions did not represent a significant toxic effect. This conclusion is supported by the
following facts: 1) The macrophages do not contain bacteria, indicating that a significant change
in the intestinal flora has not occurred. 2) The reaction is not associated with increased morbidity
or mortality. 3) The reaction does not become progressively more severe with continued
exposure to chlorhexidine. 4) The reaction is reversible after administration of chlorhexidine is
discontinued.

Reproduction and Teratology

No adverse reproductive or teratologic effects on rats or rabbits were observed in studies with the
mouth rinse formulation.
The effect of chlorhexidine gluconate on various aspects of reproductive processes has been
evaluated using both the rat and rabbit as a model. An apparent embryotoxic effect was observed
in rabbits that received a daily 40 mg/kg dose of chlorhexidine by gavage and in rats that
ingested a 300 mg/kg dose of chlorhexidine from their diet each day. These doses are about 140
and 1040 times, respectively, the estimated daily ingestion from chlorhexidine gluconate oral
rinse with the recommended dose.

Carcinogenicity
No evidence of carcinogenicity was reported in two rat studies in which chlorhexidine was
administered in their drinking water. The studies were two years in duration and delivered
chlorhexidine at dose levels of up to 200 mg/kg/day.

Mutagenicity
No evidence of mutagenicity was observed when chlorhexidine gluconate was evaluated by the
dominant lethal assay in mice and micronucleus assay in hamsters. Mutagenicity studies, using
bacterial cell system, with or without metabolic activation, produced contradictory results,
which are unexpected with drugs having antibacterial activity. While Suessmuth et al. (1979) and
Ackerman-Schmidt et al. (1982) obtained positive results, Evans et al. (1978) and Sakagami et
al. (1988) found no evidence of genotoxicity for chlorhexidine. The clinical significance of these
results is unclear.

Immediate Hypersensitivity
A variety of regimens were used in an attempt to induce and elicit immediate hypersensitivity to
chlorhexidine gluconate in guinea pigs, rabbits, rats and man. No evidence of immediate
hypersensitivity was observed in any of the tests.

Page 14 of 19
Other Studies
The emetic dose, irritation potential, and sensitization potential have also been determined for
0.12% chlorhexidine gluconate oral rinse. chlorhexidine gluconate oral rinse has an emetic ED50
of approximately 13.4 mL/kg (tested in dogs using the oral route of administration), is only
slightly irritating to the eye (tested in rabbits), and was not irritating to the oral mucosa (tested in
dogs). In addition, the mouth rinse does not induce delayed contact sensitization.

REFERENCES

1. Grossman, E.; Reiter, G.; Sturzenberger, O.P.; De la Rosa, M.; Dickinson, T.D.; Ferretti, G.A.;
Ludlam, G.E.; Meckel, A.H.: “Six-month study of the effects of a chlorhexidine mouth rinse on gingivitis
in adults.” J. Periodont. Res. 1986; 21 (Suppl. 16): 33-43.

2. Briner, W.W.; Grossman, E.; Buckner, R.Y.; Rebitski, G.F.; Sox, T.E.; Setser, R.E.; Ebert, M.L.:
“Effect of Chlorhexidine gluconate mouthrinse on plaque bacteria.” J. Periodont. Res. 1986; 21 (Suppl.
16): 44-52.

3. Briner, W.W.; Grossman, E.; Buckner, R.Y.; Rebitski, G.F.; Sox, T.E.; Setser, R.E.; Ebert, M.L.:
“Assessment of susceptibility of plaque bacteria to chlorhexidine after six months’ oral use.” J. Periodont.
Res. 1986; 21 (Suppl. 16): 53-59.

4. Loe, H.; Rindom-Schiott, C.; Glavind, L.; Karring, T.: “Two years’ oral use of chlorhexidine in man: I.
General design and clinical effects.” J. Periodont. Res. 1976: 11: 135-144.

5. Rindom Schiott, C.; Briner, W.W.; Loe, H.: “Two Years Oral Use of Chlorhexidine In Man. II. The
effect on the Salivary Bacterial Flora.” J. Periodont. Res. 1976: 11: 145- 152.

6. Warner, V.D.; Lunch, D.M.; Kim, K.H.; Grunewald, G.L.: “Quantitative Structure – Activity
Relationships for Biguanides, Carbamimidates and Bisbiguanides as Inhibitors of Streptococcus Mutans.”
J. Med. Chem.. 22: Issue 4, 1978, 359-66

7. Suessmuth, R.; Lingens, F.; Ackermann, B.: “Mutagenic effect of 1,1’-Hexamethylene-Bis ((5-p-
Chlorophenyl)-Biguanide).” Chem-Biol. Interact.: 28 (2-3) 1979, 249-258

8. Achermann-Schmidt, B.; Suessmuth, R; Lingens F.: “Effects of 1,1’-Hexamethylene-Bis ((5-p-

Chlorophenyl)-Biguanide) on the genome and on the synthesis of nucleic
acid and proteins in the bacterial cells.” Chem-Biol. Interact.; Vol. 40, Iss. 1, 1982. 85-96.

9. Evans, R.T.; Baker, P.J.; Coburn, R.A.; Genco, R.J.; Paigen, B.J.:” Evaluation of chlorhexidine,
Tribromsalan and a limited series of alkyl bis biguanides in an in-vitro
mutagenicity assay.” J. Dent. Res.; 1978, 57:290

10. Product Monograph: Peridex® Oral Rinse, Preparation Date December 12, 2007, 3M Canada
Company Dental Products

Page 15 of 19
 READ THIS FOR SAFE AND EFFECTIVE USE OF YOUR MEDICINE
PATIENT MEDICATION INFORMATION

CHLORHEXIDINE GLUCONATE 0.12% ORAL RINSE

Chlorhexidine Gluconate 0.12% Oral Rinse, USP

Read this carefully before you start taking chlorhexidine gluconate 0.12% oral rinse and each
time you get a refill. This leaflet is a summary and will not tell you everything about this drug.
Talk to your healthcare professional about your medical condition and treatment and ask if there
is any new information about chlorhexidine gluconate 0.12% oral rinse.

“WHAT TO EXPECT WHEN USING CHLORHEXIDINE GLUCONATE 0.12% ORAL

RINSE”

Your dentist has prescribed Chlorhexidine Gluconate 0.12% Oral Rinse to treat your gingivitis –
to help reduce the redness and swelling of your gums, and also to help you control any gum
bleeding. Use Chlorhexidine Gluconate 0.12% Oral Rinse regularly, as directed by your dentist,
in addition to daily brushing and flossing. Do not swallow Chlorhexidine Gluconate 0.12% Oral
Rinse.

Chlorhexidine Gluconate 0.12% Oral Rinse may cause some tooth discolouration or increases in
tartar (calculus) formation, particularly in areas where plaque is more difficult to remove with
normal brushing alone. It is important to do a thorough job of cleaning your teeth and to see your
dentist at least every six months, or more frequently if your dentist advises.

- Both stain and tartar can be removed by your dentist or hygienist. Chlorhexidine Gluconate
0.12% Oral Rinse may cause permanent discolouration of some front-tooth fillings. To minimize
discolouration, you should brush and floss daily, emphasizing areas which begin to discolour. In
some cases discolouration may be permanent.

- Chlorhexidine Gluconate 0.12% Oral Rinse should not be used by persons who have a
sensitivity to chlorhexidine gluconate.

- Chlorhexidine Gluconate 0.12% Oral Rinse may taste bitter to some patients and may affect the
taste of foods and beverages. This will become less noticeable in most cases with continued use
of Chlorhexidine Gluconate 0.12% Oral Rinse. To avoid taste interference, rinse with
Chlorhexidine Gluconate 0.12% Oral Rinse after meals. Do not rinse with water or other mouth
rinses immediately after rinsing with Chlorhexidine Gluconate 0.12% Oral Rinse.

- For maximum effectiveness avoid rinsing your mouth, brushing your teeth, eating or drinking
for about 30 minutes after using Chlorhexidine Gluconate 0.12% Oral Rinse.

Page 16 of 19
If you have any questions or comments about Chlorhexidine Gluconate 0.12% Oral Rinse,
contact your dentist or pharmacist.

What is chlorhexidine gluconate 0.12% oral rinse used for?

• Treatment of moderate to severe gingivitis and management of associated gingival
bleeding and inflammation between dental visits.

How does chlorhexidine gluconate 0.12% oral rinse work?

Chlorhexidine gluconate 0.12% oral rinse provides antimicrobial activity during oral
rinsing which is maintained between rinsings. Microbiologic sampling of plaque has shown
a general reduction of both aerobic and anaerobic bacterial counts ranging from 54-97%
through six months’ clinical use. Rinsing with chlorhexidine gluconate 0.12% oral rinse
inhibits the buildup and maturation of plaque by reducing certain microbes regarded as
gingival pathogens, thereby reducing gingivitis.

What are the ingredients in chlorhexidine gluconate 0.12% oral rinse?

Medicinal ingredients: Chlorhexidine gluconate
Non-medicinal ingredients: Alcohol, FD&C Blue # 1, flavour, glycerine, PEG-40 sorbitan
diisostearate, saccharin sodium, USP purified water.

Chlorhexidine gluconate 0.12% oral rinse comes in the following dosage forms:
Chlorhexidine gluconate 0.12% oral rinse is supplied as a blue liquid in 1-oz (15-mL) and 16-
ounce (473-mL) amber bottles.

Do not use chlorhexidine gluconate 0.12% oral rinse if:

• You have any allergies to this drug or its ingredients or components of the container
(Contraindications).

To help avoid side effects and ensure proper use, talk to your healthcare professional
before you take chlorhexidine gluconate 0.12% oral rinse. Talk about any health conditions
or problems you may have, including if you:

• Have allergies to this drug or its ingredients or components of the container

Tell your healthcare professional about all the medicines you take, including any drugs,
vitamins, minerals, natural supplements or alternative medicines.

Usual dose:
Usual dose is 15-mL of undiluted chlorhexidine gluconate 0.12% oral rinse used twice daily for
oral rinsing for 30 seconds. Chlorhexidine gluconate 0.12% oral rinse is not intended for
ingestion and should be expectorated after rinsing.

Overdose:
Ingestion of 30 or 60 mL of chlorhexidine gluconate 0.12% oral rinse by a small child (10
kg or less in body weight) might result in gastric distress, including nausea, or signs of

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alcohol intoxication. Medical attention should be sought if more than 120 mL of
chlorhexidine gluconate 0.12% oral rinse is ingested by a small child or if signs of alcohol
intoxication develop.

If you think you have taken too much chlorhexidine gluconate oral rinse, contact your
healthcare professional, hospital emergency department or regional Poison Control Centre
immediately, even if there are no symptoms.

Missed Dose:
An occasional missed dose can be ignored if the patient is generally compliant with the
prescribed regimen.

What are possible side effects from using chlorhexidine gluconate 0.12% oral rinse?

The most common side effects associated with chlorhexidine gluconate 0.12% oral rinse are (1)
an increase in staining of oral surfaces, (2) an increase in supragingival tartar (3) an alteration in
taste perception to which most patients accommodate.

These are not all the possible side effects you may feel when taking chlorhexidine gluconate
0.12% oral rinse. If you experience any side effects not listed here, contact your healthcare
professional. Please also see Warnings and Precautions.

If you have a troublesome symptom or side effect that is not listed here or becomes bad enough
to interfere with your daily activities, talk to your healthcare professional.
Reporting Side Effects
You can help improve the safe use of health products for Canadians by reporting serious and
unexpected side effects to Health Canada. Your report may help to identify new side effects
and change the product safety information.
3 ways to report:
• Online at MedEffect;
• By calling 1-866-234-2345 (toll-free);
• By completing a Consumer Side Effect Reporting Form and sending it by:
- Fax to 1-866-678-6789 (toll-free), or
- Mail to: Canada Vigilance Program
Health Canada, Postal Locator 0701E
Ottawa, ON
K1A 0K9
Postage paid labels and the Consumer Side Effect Reporting Form are available
at MedEffect.

NOTE: Contact your health professional if you need information about how to manage your
side effects. The Canada Vigilance Program does not provide medical advice.

Storage:
Preserve in tight containers, protected from light, at controlled room temperature (15°C to 30°C).

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Keep out of reach and sight of children.

If you want more information about chlorhexidine gluconate 0.12% oral rinse:

• Talk to your healthcare professional

• Find the full product monograph that is prepared for healthcare professionals and
includes this Patient Medication Information by visiting the Health Canada website; the
manufacturer’s website; www.sageproducts.com, or by calling 1-800-587-3721.

This leaflet was prepared by:

Sage Products LLC.

3909 Three Oaks Road
Cary, IL 60013
USA

Last Revised: February 17, 2015

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