ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS: The most common side effects associated withchlorhexidine gluconate oral rinses are: 1) an increase in staining of teeth and other oralsurfaces; 2) an increase in calculus formation; and 3) an alteration in taste perception; see WARNINGS and PRECAUTIONS. Oral irritation and local allergy-type symptomshave been spontaneously reported as side effects associated with use of chlorhexidinegluconate rinse. The following oral mucosal side effects were reported duringplacebo-controlled adult clinical trials: aphthous ulcer, grossly obvious gingivitis,trauma, ulceration, erythema, desquamation, coated tongue, keratinization, geographictongue, mucocele, and short frenum. Each occurred at frequency of less than 1.0%. Among post marketing reports, the most frequently reported oral mucosal symptomsassociated with chlorhexidine gluconate oral rinse are stomatitis, gingivitis, glossitis,ulcer, dry mouth, hypesthesia, glossal edema, and paresthesia.Minor irritation and superficial desquamation of the oral mucosa have been noted inpatients using chlorhexidine gluconate oral rinse. There have been cases of parotid gland swelling and inflammation of the salivary glands(sialadenitis) reported in patients using chlorhexidine gluconate oral rinse.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY: Chlorhexidine gluconate oral rinse provides antimicrobialactivity during oral rinsing. The clinical significance of chlorhexidine gluconate oral rinsesantimicrobial activities is not clear. Microbiological sampling of plaque has shown generalreduction of counts of certain assayed bacteria, both aerobic and anaerobic, ranging from54-97% through six months use. Use of chlorhexidine gluconate oral rinse in six month clinical study did not result in anysignificant changes in bacterial resistance, overgrowth of potentially opportunistic organisms orother adverse changes in the oral microbial ecosystem. Three months after chlorhexidinegluconate oral rinse use was discontinued, the number of bacteria in plaque had returned tobaseline levels and resistance of plaque bacteria to chlorhexidine gluconate was equal to that atbaseline.

DESCRIPTION SECTION.

DENTI-CAREMEDICOM DENTI-RINSE 0.12 CHLORHEXIDINE GLUCONATE ORAL RINSE MINT Item 10025-H Ingredients: 0.12 chlorhexidine gluconate in base containing water, 11.6 alcohol, glycerin, PEG-40 sorbitan diisostearate, flavor, sodium saccharin and FD and Blue No.1. Rx Only KEEP OUT OF REACH OF CHILDREN Pint (473 ml) NDC 64778-0244-1 M0701707V.2 DIRECTIONS FOR USE: Fill cap to the fill line (15 mL). Swish in mouth undiluted for 30 seconds, then spit out. Use after breakfast and before bedtime. Or, use as prescribed. NOTE: To minimize medicinal taste, do not rinse with water immediately after use. To open: Squeeze smooth areas near bottom of cap and turn.To close: Turn Cap until it locks.WHAT TO EXPECT WHEN USING CHLORHEXIDINE GLUCONATE ORAL RINSE Your dentist has prescribed chlorhexidine gluconate 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 oral rinse regularly, as directed by your dentist, in addition to daily brushing. Spit out after use; Chlorhexidine gluconate oral rinse should not be swallowed. Chlorhexidine gluconate oral rinse may cause some tooth discoloration, or increase in tartar (calculus) formation, particularly in areas where stain and tartar usually form. It is important to see your dentist for removal of any stain or tartar 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 oral rinse may cause permanent discoloration of some front-tooth fillings. To minimize discoloration, you should brush and floss daily, emphasizing areas which begin to discolor. Local hypersensitivity and sometimes generalized allergic reactions have also been reported. Chlorhexidine gluconate oral rinse should not be used by persons who have sensitivity to it or its components. Chlorhexidine gluconate oral rinse may taste bitter to some patients and can affect how foods and beverages taste. This will become less noticeable in most cases with continued use of chlorhexidine gluconate oral rinse. To avoid taste interference, rinse with chlorhexidine gluconate oral rinse after meals. Do not rinse with water or other mouthwashes immediately after rinsing with chlorhexidine gluconate oral rinse. If you have any questions or comments about chlorhexidine gluconate oral rinse, contact your dentist or pharmacist.Store at USP Controlled Room Temperature (20C 25C (68F 77F)).Manufactured for and distributed by:AMD Medicom Inc. 2555 Chemin de lAviation Pointe-Claire, Montreal, Quebec, Canada H9P 2Z2 DESCRIPTION: Chlorhexidine gluconate is an oral rinse containing 0.12% chlorhexidine gluconate (1,11-hexamethylene bis[5-(p-chlorophenyl) biguanide] di-D-gluconate) in base containing water, 11.6% alcohol, glycerin, PEG-40 sorbitan diisostearate, flavor, sodium saccharin, and FD and Blue No.1. Chlorhexidine gluconate is salt of chlorhexidine and gluconic acid.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION:. DOSAGE AND ADMINISTRATION:Chlorhexidine gluconate oral rinse therapy should be initiated directly following dental prophylaxis. Patients using chlorhexidine gluconate oral rinse should be reevaluated and given thorough prophylaxis at intervals of no longer than six months. Recommended use is twice daily rinsing for 30 seconds, morning and evening after tooth brushing. Usual dosage is 15 mL (marked in cap) of undiluted chlorhexidine gluconate oral rinse. Patients should be instructed to not rinse with water, or other mouthwashes, brush teeth, or eat immediately after using chlorhexidine gluconate oral rinse. Chlorhexidine gluconate oral rinse is not intended for ingestion and should be expectorated after rinsing.

PHARMACOKINETICS SECTION.

Pharmacokinetics: Pharmacokinetic studies with chlorhexidine gluconate oral rinse indicateapproximately 30% of the active ingredient, chlorhexidine gluconate, is retained in the oralcavity following rinsing. This retained drug is slowly released in the oral fluids. Studiesconducted on human subjects and animals demonstrate chlorhexidine gluconate is poorlyabsorbed from the gastrointestinal tract. The mean plasma level of chlorhexidine gluconatereached peak of 0.206 ug/g in humans 30 minutes after they ingested 300 mg dose of thedrug. Detectable levels of chlorhexidine gluconate were not present in the plasma of thesesubjects 12 hours after the compound was administered. Excretion of chlorhexidine gluconateoccurred primarily through the feces (~90%). Less that 1% of the chlorhexidine gluconateingested by these subjects was excreted in the urine.

PRECAUTIONS SECTION.

PRECAUTIONS: General:1. For patients having coexisting gingivitis and periodontitis, the presence of absence ofgingival inflammation following treatment with chlorhexidine gluconate oral rinseshould not be used as major indicator of underlying periodontitis.2. Chlorhexidine gluconate oral rinse can cause staining of oral surfaces, such as toothsurfaces, restorations, and the dorsum of the tongue. Not all patients will experience avisually significant increase in tooth staining. In clinical testing, 56% of chlorhexidinegluconate oral rinse users exhibited measurable increase in facial anterior stain,compared to 35% of control users after six months; 15% of chlorhexidine gluconateoral rinse users developed what was judged to be heavy stain, compared to 1% ofcontrol users after six months. Stain will be more pronounced in patients who haveheavier accumulations of unremoved plaque. Stain resulting from use of chlorhexidinegluconate oral rinse does not adversely affect health of the gingivae or other oraltissues. Stain can be removed from most tooth surfaces by conventional professionalprophylactic techniques. Additional time may be required to complete the prophylaxis.Discretion should be used when prescribing to patients with anterior facialrestorations with rough surfaces of margins. If natural stain cannot be removed fromthese surfaces by dental prophylaxis, patients should be excluded fromchlorhexidine gluconate oral rinse treatment if permanent discoloration isunacceptable. Stain in these areas may be difficult to remove by dental prophylaxisand on rare occasions may necessitate replacement of these restorations.3. Some patients may experience an alteration in taste perception while undergoingtreatment with chlorhexidine gluconate oral rinse. Rare instances of permanent tastealteration following chlorhexidine gluconate oral rinse use have been reported viapost-marketing product surveillance. Pregnancy: Teratogenic Effects Pregnancy Category B. Reproduction studies have beenperformed in rats and rabbits at chlorhexidine gluconate doses up to 300 mg/kg/day and40 mg/kg/day respectively, and have not revealed evidence of harm to fetus. However,adequate and well-controlled studies in pregnant women have not been done. Becauseanimal reproduction studies are not always predictive of human response, this drugshould be used during pregnancy only if clearly needed. Nursing Mothers: It is not known whether this drug is excreted in human milk. Becausemany drugs are excreted in human milk, caution should be exercised when chlorhexidinegluconate oral rinse is administered to nursing women. In parturition and lactation studies with rats, no evidence of impaired parturition or oftoxic effects to suckling pups was observed when chlorhexidine gluconate wasadministered to dams at doses that were over 100 times greater than that which wouldresult from persons ingesting 30 mL (2 capfuls) of chlorhexidine gluconate oral rinseper day. Pediatric Use: Clinical effectiveness and safety of chlorhexidine gluconate oral rinsehave not been established in children under age of 18. Carcinogenesis, Mutagenesis, and Impairment of Fertility: In drinking water study in rats, carcinogenic effects were not observed at doses up to38 mg/kg/day. Mutagenic effects were not observed in two mammalian in vivomutagenesis studies with chlorhexidine gluconate. The highest doses of chlorhexidineused in mouse dominant-lethal assay and hamster cytogenetics test were1000 mg/kg/day and 250 mg/kg/day, respectively. No evidence of impaired fertility wasobserved in rats at doses up to 100 mg/kg/day.