Fluor-a-day

Arbor Pharmaceuticals, Inc.

FLUOR•A•DAY Sodium Fluoride and Xylitol

FULL PRESCRIBING INFORMATION: CONTENTS*

• FLUOR-A-DAY DESCRIPTION
• ACTIVE INGREDIENTS
• OTHER INGREDIENTS
• CLINICAL PHARMACOLOGY
• FLUOR-A-DAY INDICATIONS AND USAGE
• FLUOR-A-DAY CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
  • General
  • Drug Interactions
  • Carcinogenesis, Mutagenesis, Impairment of Fertility
  • Pregnancy
  • Nursing Mothers
  • Pediatric Use
  • Geriatric Use
• FLUOR-A-DAY ADVERSE REACTIONS
• OVERDOSAGE
• FLUOR-A-DAY DOSAGE AND ADMINISTRATION
• HOW SUPPLIED
  • STORAGE
• REFERENCES
• PRINCIPAL DISPLAY PANEL - 0.25 mg Bottle Label
• PRINCIPAL DISPLAY PANEL - 0.5 mg Bottle Label
• PRINCIPAL DISPLAY PANEL - 1 mg Bottle Label
• PRINCIPAL DISPLAY PANEL - 30 mL Bottle Label

FULL PRESCRIBING INFORMATION

Chewable Tablets and Oral Drops

FLUOR-A-DAY DESCRIPTION

Each Fluor-a-day^® chewable tablet is sugar free, saccharin free and erythrosine (FD&C Red Dye #3) free. Fluor-a-day^® sodium fluoride and xylitol supplement is for use as a dental caries preventative in children. Each Fluor-a-day^® 1.0 mg F (full strength) chewable tablet contains 2.2 mg sodium fluoride USP (equivalent to 1.0 mg Fluoride ion) and 236.79 mg xylitol; Each Fluor-a-day^® 0.5 mg F (half-strength) chewable tablet contains 1.1 mg sodium fluoride USP (equivalent to 0.5 mg Fluoride ion) and 236.79 mg xylitol; Each Fluor-a-day^® 0.25 mg F (quarter strength) chewable tablet contains 0.55 mg sodium fluoride (equivalent to 0.25 mg Fluoride ion) and 236.79 mg xylitol. Fluor-a-day^® Drops are flavorless, colorless, and odorless. Each ml (20 drops) contains 2.50 mg fluoride ion (F) from 5.56 mg sodium fluoride (NaF), approximately 0.125 mg F per drop.

ACTIVE INGREDIENTS

Sodium Fluoride (NaF), Xylitol

OTHER INGREDIENTS

Fluor-a-day^® Chewable Tablets also contain sorbitol, artificial raspberry flavor (contains: gum arabic, maltodextrin (corn), triacetin), raspberry permaseal, magnesium stearate kosher. Fluor-a-day^® Drops also contain methylparaben and sodium hydroxide.

CLINICAL PHARMACOLOGY

Sodium fluoride acts systemically (before tooth eruption) and topically (post-eruption) by increasing tooth resistance to acid dissolution, by promoting remineralization, and by inhibiting the cariogenic microbial process. Xylitol is a five-carbon polyol that is noncariogenic and may reduce the risk of dental caries. Xylitol is a white, odorless, sweet tasting, crystalline powder.

FLUOR-A-DAY INDICATIONS AND USAGE

For once daily systemic use as a dental caries preventive in pediatric patients. It has been established that ingestion of fluoridated drinking water (1 ppm F-) during the period of tooth development results in a significant decrease in the incidence of dental caries.1 Fluor-a-day^® Chewable Tablets and Drops were developed to provide systemic fluoride and xylitol for use as a supplement in pediatric patients from 6 months to age 16 years living in areas where the drinking water fluoride content does not exceed 0.6 ppm F-.

FLUOR-A-DAY CONTRAINDICATIONS

Do not use Fluor-a-day^® Chewable Tablets or Drops in areas where the fluoride content of the drinking water exceeds 0.6 ppm F-. Chronic renal insufficiency and failure, arthralgia, gastrointestinal ulceration and osteomalacia are contraindications to fluoride therapy. Fluor-a-day^® Tablets (any strength) and Drops are not indicated for use in adults.

WARNINGS

Prolonged daily ingestion of quantities greater than the recommended amount may result in various degrees of dental fluorosis in pediatric patients under age 6 years, especially if the water fluoridation exceeds 0.6 ppm. Read directions carefully before using. Keep out of reach of infants and children.

PRECAUTIONS

General

Please refer to the CONTRAINDICATIONS, WARNINGS and OVERDOSAGE sections for overdosage concerns. Use in pediatric patients below the age of 6 months is not recommended by current American Dental Association and American Academy of Pediatrics guidelines.

Drug Interactions

Do not eat or drink dairy products within one hour of fluoride administration. Incompatibility of fluoride with dairy foods has been reported due to formation of calcium fluoride which is poorly absorbed.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a 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 for male rats treated with 2.5 and 4.1 mg/kg of body weight. In a second study, no carcinogenesis was observed in rats, males or females, treated with fluoride up to 11.3 mg/kg of body weight. This dose is at least 400 times greater than the recommended daily dose of Fluor-a-day^® Chewable Tablets or Drops. 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 doses of fluoride (5 mg/kg of body weight) did not result in impaired fertility and reproductive capabilities. This dose is approximately 200 times greater than the recommended daily dose of Fluor-a-day^® Chewable Tablets or Drops.

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 a 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. 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 human milk and caution should be exercised when Fluor-a-day^® Chewable Tablets or Drops are administered to a nursing woman. Reduced milk production was reported in farm-raised fox when the animals were fed a diet containing a 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 5 mg/kg of body weight. This dose is at least 200 times greater than the recommended daily dose of Fluor-a-day^® Chewable Tablets or Drops. Fluor-a-day^® Chewable Tablets and Drops (any strength) are not indicated for use in adults.

Pediatric Use

The use of Fluor-a-day^® Chewable Tablets and Drops as a caries preventive in pediatric age groups 6 months to 16 years is supported by evidence from adequate and well controlled studies on fluoride supplementation from birth through adolescence.1-5

Geriatric Use

Fluor-a-day^® Chewable Tablets (any strength) or Drops are not indicated for use in geriatric patients.

FLUOR-A-DAY ADVERSE REACTIONS

Allergic rash and other idiosyncrasies have been rarely reported.

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 5 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 a few hours. If more than 5 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 a hospital facility. A treatment dose of Fluor-a-day^® Chewable Tablets contains 0.25, 0.5 or 1 mg of fluoride and each dose of Fluor-a-day^® Drops contains 0.125 mg of fluoride. The treatment of choice depends upon the age of the child and the water fluoride content. A bottle of 120 0.25 mg tablets contains 30 mg fluoride. A bottle of 120 0.5 mg tablets contains 60 mg fluoride. A bottle of 120 1 mg tablets contains 120 mg fluoride. The total amount of sodium fluoride in a bottle of 120 Fluor-a-day^® Chewable Tablets (all strengths) and Drops conforms with the recommendations of the American Dental Association for the maximum to be dispensed at one time for safety purposes.

FLUOR-A-DAY DOSAGE AND ADMINISTRATION

Dissolve in the mouth or chew before swallowing, preferably at bedtime after brushing teeth. Drops should be administered in juice or water. See schedule below to determine dosage.

Fluoride Ion Level In Drinking Water (ppm)0.1 part per million (ppm) = 1 milligram/liter (mg/L)

Age	Less than 0.3ppm	0.3-0.6 ppm	Greater than 0.6 ppm
Birth-6 months	None	None	None
6 months-3 years	0.25 mg/day2.2 mg sodium fluoride contains 1 mg fluoride ion	None	None
3-6 years	0.50 mg/day2.2 mg sodium fluoride contains 1 mg fluoride ion	0.25 mg/day	None
6-16 years	1.0 mg/day	0.50 mg/day	None

Dosing schedule approved by the American Dental Association, American Academy of Pediatrics, American Academy of Pediatric Dentistry

HOW SUPPLIED

Fluor-a-day^® 1 mg F Chewable Tablets available in bottles of 120 (NDC 24338-622-16), Raspberry flavor. Fluor-a-day^® 0.5 mg F Chewable Tablets available in bottles of 120 (NDC 24338-611-16 ), Raspberry flavor. Fluor-a-day^® 0.25 mg F Chewable Tablets available in bottles of 120 (NDC 24338-602-16), Raspberry flavor. Fluor-a-day^® 0.125 mg F Drops available in bottles of 30ML (NDC 24338-656-61).

STORAGE

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

All Fluor-a-day^® products are kosher.

REFERENCES

• Accepted Dental Therapeutics, Ed. 40, American Dental Association, Chicago, 399-402 (1984).
• J. Jakush, New Fluoride Schedule Adopted, ADA News , 12, 14 (May 16, 1994).
• Aasenden, R., and Peebles, T.C. "Effects of Fluoride Supplementation From Birth on Dental Caries and Fluorosis in Teenaged Children", Arch. Oral, Biol., 23, 111 - 115 (1974).
• Hamberg, L. "Controlled Trial of Fluoride Vitamin Drops for Prevention of Caries in Children", Lancet, 1, 441-442 (1971).
• Hennon, D.K. Stookey, G.K. and Beiswanger, B.B. "Fluoride- Vitamin Supplements: Effects on Dental Caries and Fluorosis When Used in Areas with Suboptimum Fluoride in the Water Supply", JADA, 95, 965-971 (1977)

Rx only

Manufactured in Canada

Manufactured for Arbor Pharmaceuticals Inc., Raleigh, NC 27609

REV 8/10

PRINCIPAL DISPLAY PANEL - 0.25 mg Bottle Label

NDC 24338-602-16

FLUOR•A•DAY ^®
CHEWABLE

Sodium Fluoride
USP and Xylitol
Chewable Tablets

0.25 mg F^-

Rx only

120 Tablets

arbor^™
PHARMACEUTICALS, INC.

www.arborpharma.com

PRINCIPAL DISPLAY PANEL - 0.5 mg Bottle Label

NDC 24338-611-16

FLUOR•A•DAY ^®
CHEWABLE

Sodium Fluoride
USP and Xylitol
Chewable Tablets

0.5 mg F^-

Rx only

120 Tablets

arbor^™
PHARMACEUTICALS, INC.

www.arborpharma.com

PRINCIPAL DISPLAY PANEL - 1 mg Bottle Label

NDC 24438-622-16

FLUOR•A•DAY ^®
CHEWABLE

Sodium Fluoride
USP and Xylitol
Chewable Tablets

1.0 mg F^-

Rx only

120 Tablets

arbor^™
PHARMACEUTICALS, INC.

www.arborpharma.com

PRINCIPAL DISPLAY PANEL - 30 mL Bottle Label

NDC 24338-656-16
Dental Caries Prophylaxis

FLUOR•A•DAY ^®
DROPS

Sodium Fluoride
Oral Solution
USP

arbor^™
PHARMACEUTICALS, INC.

www.arborpharma.com

30 mL

Rx only