CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGY. Frequent topical applications to the teeth with preparations having relatively high fluoride content increase tooth resistance to acid dissolution and enhance penetration of the fluoride ion into tooth enamel.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. Do not use in pediatric patients under age years unless recommended by dentist or physician.

ADVERSE REACTIONS SECTION.

ADVERSE REACTIONS. Allergic reactions and other idiosyncrasies have been rarely reported.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

Carcinogenesis, Mutagenesis, Impairment of Fertility. In study conducted in rodents, no carcinogenesis was found in male and female mice and female rats treated with fluoride at dose levels ranging from 4.1 to 9.1 mg/kg of body weight. Equivocal evidence of carcinogenesis was reported in male rats treated with 2.5 and 4.1 mg/kg of body weight. In second study, no carcinogenesis was observed in rats, males or females, treated with fluoride up to 11.3 mg/kg of body weight. Epidemiological data provide no credible evidence for an association between fluoride, either naturally occurring or added to drinking water, and risk of human cancer. Fluoride ion is not mutagenic in standard bacterial systems. It has been shown that fluoride ion has potential to induce chromosome aberrations in cultured human and rodent cells at doses much higher than those to which humans are exposed. In vivo data are conflicting. Some studies report chromosome damage in rodents, while other studies using similar protocols report negative results.Potential adverse reproductive effects of fluoride exposure in humans have not been adequately evaluated. Adverse effects on reproduction were reported for rats, mice, fox, and cattle exposed to 100 ppm or greater concentrations of fluoride in their diet or drinking water. Other studies conducted in rats demonstrated that lower concentrations of fluoride (5 mg/kg of body weight) did not result in impaired fertility and reproductive capabilities.

DESCRIPTION SECTION.

DESCRIPTION. Self-topical neutral fluoride dentifrice containing 1.1% (w/w) sodium fluoride for use as dental caries preventive in adults and pediatric patients.. Active Ingredient. Sodium fluoride 1.1% (w/w). Inactive Ingredients. blue 1, cellulose gum, flavor, fumaric acid, hydrated silica, mica, poloxamer 338, PEG-12, sodium benzoate, sodium lauryl sulfate, sodium saccharin, sorbitol, titanium dioxide, tricalcium phosphate, water, xanthan gum.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATION. Follow these instructions unless otherwise instructed by your dental professional:1. Adults and pediatric patients years of age or older, apply thin ribbon of PreviDent(R) 5000 Ortho Defense(TM) to toothbrush. Brush teeth thoroughly twice daily for two minutes in place of your regular toothpaste.2. After use, adults expectorate. For best results, do not eat, drink, or rinse for 30 minutes. Pediatric patients, age 6-16, expectorate after use and rinse mouth thoroughly.

GENERAL PRECAUTIONS SECTION.

General. Not for systemic treatment. DO NOT SWALLOW.

GERIATRIC USE SECTION.

Geriatric Use. Of the total number of subjects in clinical studies of 1.1 (w/v) sodium fluoride, 15 percent were 65 and over, while percent were 75 and over.No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.5.

HOW SUPPLIED SECTION.

HOW SUPPLIED. 3.4 FL OZ (100mL) in plastic bottles. Mild Mint: NDC 0126-0289-92. STORAGE. Store at Controlled Room Temperature, 68-77F (20-25C).

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. dental caries preventive; for twice daily self-applied topical use. PreviDent(R) 5000 Ortho Defense(TM) 1.1% sodium fluoride toothpaste in squeeze bottle is easily applied onto toothbrush. This prescription toothpaste should be used twice daily in place of your regular toothpaste unless otherwise instructed by your dental professional. May be used in areas where drinking water is fluoridated since topical fluoride cannot produce fluorosis. (See WARNINGS for exception.).

NURSING MOTHERS SECTION.

Nursing Mothers. It is not known if fluoride is excreted in human milk. However, many drugs are excreted in milk, and caution should be exercised when products containing fluoride are administered to nursing woman. Reduced milk production was reported in farm-raised fox when the animals were fed diet containing high concentration of fluoride (98-137 mg/kg of body weight). No adverse effects on parturition, lactation, or offspring were seen in rats administered fluoride up to mg/kg of body weight.

OVERDOSAGE SECTION.

OVERDOSAGE. Accidental ingestion of large amounts of fluoride may result in acute burning in the mouth and sore tongue. Nausea, vomiting, and diarrhea may occur soon after ingestion (within 30 minutes) and are accompanied by salivation, hematemesis, and epigastric cramping abdominal pain. These symptoms may persist for 24 hours. If less than mg fluoride/kg body weight (i.e., less than 2.3 mg fluoride/lb body weight) has been ingested, give calcium (e.g., milk) orally to relieve gastrointestinal symptoms and observe for few hours. If more than mg fluoride/kg body weight (i.e., more than 2.3 mg fluoride/lb body weight) has been ingested, induce vomiting, give orally soluble calcium (e.g., milk, 5% calcium gluconate or calcium lactate solution) and immediately seek medical assistance. For accidental ingestion of more than 15 mg fluoride/kg of body weight (i.e., more than 6.9 mg fluoride/lb body weight), induce vomiting and admit immediately to hospital facility.A treatment dose (a thin ribbon) of PreviDent(R) 5000 Ortho Defense(TM) contains approximately 2.5 mg fluoride. 3.4 FL OZ (100 mL) bottle contains approximately 605 mg fluoride.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 100 mL Bottle Label. NDC 0126-0289-92Colgate(R)PreviDent(R)5000 ppmORTHODEFENSE(TM)1.1% Sodium FluoridePRESCRIPTION STRENGTHTOOTHPASTE FOR ORTHODONTIC PATIENTSCONTAINS TRI-CALCIUM PHOSPHATEMILD MINT3.4 FL OZ (100 mL)Rx ONLYP9931266. PRINCIPAL DISPLAY PANEL 100 mL Bottle Label.

PEDIATRIC USE SECTION.

Pediatric Use. The use of PreviDent(R) 5000 Ortho Defense(TM) in pediatric age groups to 16 years as caries preventive is supported by pioneering clinical studies with 1.1% sodium fluoride gels in mouth trays in students age 11 to 14 years conducted by Englander et al.2-4 Safety and effectiveness in pediatric patients below the age of years have not been established. Please refer to the CONTRAINDICATIONS and WARNINGS sections.

PRECAUTIONS SECTION.

PRECAUTIONS. General. Not for systemic treatment. DO NOT SWALLOW. Carcinogenesis, Mutagenesis, Impairment of Fertility. In study conducted in rodents, no carcinogenesis was found in male and female mice and female rats treated with fluoride at dose levels ranging from 4.1 to 9.1 mg/kg of body weight. Equivocal evidence of carcinogenesis was reported in male rats treated with 2.5 and 4.1 mg/kg of body weight. In second study, no carcinogenesis was observed in rats, males or females, treated with fluoride up to 11.3 mg/kg of body weight. Epidemiological data provide no credible evidence for an association between fluoride, either naturally occurring or added to drinking water, and risk of human cancer. Fluoride ion is not mutagenic in standard bacterial systems. It has been shown that fluoride ion has potential to induce chromosome aberrations in cultured human and rodent cells at doses much higher than those to which humans are exposed. In vivo data are conflicting. Some studies report chromosome damage in rodents, while other studies using similar protocols report negative results.Potential adverse reproductive effects of fluoride exposure in humans have not been adequately evaluated. Adverse effects on reproduction were reported for rats, mice, fox, and cattle exposed to 100 ppm or greater concentrations of fluoride in their diet or drinking water. Other studies conducted in rats demonstrated that lower concentrations of fluoride (5 mg/kg of body weight) did not result in impaired fertility and reproductive capabilities.. Pregnancy. Teratogenic Effects. Pregnancy Category B. It has been shown that fluoride crosses the placenta of rats, but only 0.01% of the amount administered is incorporated in fetal tissue. Animal studies (rats, mice, rabbits) have shown that fluoride is not teratogen. Maternal exposure to 12.2 mg fluoride/kg of body weight (rats) or 13.1 mg/kg of body weight (rabbits) did not affect the litter size or fetal weight and did not increase the frequency of skeletal or visceral malformations. There are no adequate and well-controlled studies in pregnant women. However, epidemiological studies conducted in areas with high levels of naturally fluoridated water showed no increase in birth defects. Heavy exposure to fluoride during in utero development may result in skeletal fluorosis which becomes evident in childhood.. Nursing Mothers. It is not known if fluoride is excreted in human milk. However, many drugs are excreted in milk, and caution should be exercised when products containing fluoride are administered to nursing woman. Reduced milk production was reported in farm-raised fox when the animals were fed diet containing high concentration of fluoride (98-137 mg/kg of body weight). No adverse effects on parturition, lactation, or offspring were seen in rats administered fluoride up to mg/kg of body weight.. Pediatric Use. The use of PreviDent(R) 5000 Ortho Defense(TM) in pediatric age groups to 16 years as caries preventive is supported by pioneering clinical studies with 1.1% sodium fluoride gels in mouth trays in students age 11 to 14 years conducted by Englander et al.2-4 Safety and effectiveness in pediatric patients below the age of years have not been established. Please refer to the CONTRAINDICATIONS and WARNINGS sections.. Geriatric Use. Of the total number of subjects in clinical studies of 1.1 (w/v) sodium fluoride, 15 percent were 65 and over, while percent were 75 and over.No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.5.

PREGNANCY SECTION.

Pregnancy. Teratogenic Effects. Pregnancy Category B. It has been shown that fluoride crosses the placenta of rats, but only 0.01% of the amount administered is incorporated in fetal tissue. Animal studies (rats, mice, rabbits) have shown that fluoride is not teratogen. Maternal exposure to 12.2 mg fluoride/kg of body weight (rats) or 13.1 mg/kg of body weight (rabbits) did not affect the litter size or fetal weight and did not increase the frequency of skeletal or visceral malformations. There are no adequate and well-controlled studies in pregnant women. However, epidemiological studies conducted in areas with high levels of naturally fluoridated water showed no increase in birth defects. Heavy exposure to fluoride during in utero development may result in skeletal fluorosis which becomes evident in childhood.

REFERENCES SECTION.

REFERENCES. 1. American Dental Association, Accepted Dental Therapeutics Ed. 40 (Chicago, 1984): 405-407. 2. H.R. Englander et al., JADA 75 (1967): 638-644. 3. H.R. Englander et al., JADA 78 (1969): 783-787. 4. H.R. Englander et al., JADA 83 (1971): 354-358. 5. Data on file. Colgate Oral Pharmaceuticals.

SPL UNCLASSIFIED SECTION.

Rx ONLY1.1% Sodium uoridePrescription Strength Toothpaste.

STORAGE AND HANDLING SECTION.

STORAGE. Store at Controlled Room Temperature, 68-77F (20-25C).

TERATOGENIC EFFECTS SECTION.

Teratogenic Effects. Pregnancy Category B. It has been shown that fluoride crosses the placenta of rats, but only 0.01% of the amount administered is incorporated in fetal tissue. Animal studies (rats, mice, rabbits) have shown that fluoride is not teratogen. Maternal exposure to 12.2 mg fluoride/kg of body weight (rats) or 13.1 mg/kg of body weight (rabbits) did not affect the litter size or fetal weight and did not increase the frequency of skeletal or visceral malformations. There are no adequate and well-controlled studies in pregnant women. However, epidemiological studies conducted in areas with high levels of naturally fluoridated water showed no increase in birth defects. Heavy exposure to fluoride during in utero development may result in skeletal fluorosis which becomes evident in childhood.

WARNINGS SECTION.

WARNINGS. Prolonged daily ingestion may result in various degrees of dental fluorosis in pediatric patients under age years, especially if the water fluoridation exceeds 0.6 ppm, since younger pediatric patients frequently cannot perform the brushing process without significant swallowing. Use in pediatric patients under age years requires special supervision to prevent repeated swallowing of toothpaste which could cause dental fluorosis. Pediatric patients under age 12 should be supervised in the use of this product. Read directions carefully before using. Keep out of reach of infants and children.