Perry Medical Fluorabon Chewable Tablets (quarter strength) by Kirkman Laboratories

EFFECTIVE

• Dental caries. Fluoride can reduce dental caries in primary and secondary teeth when used appropriately in toothpastes providing at least 1000 ppm fluoride, when used in other dental products, or when added to drinking water. It is unclear if oral fluoride supplements are beneficial for caries prevention. Details: Fluoride added to drinking water and fluoride in toothpastes, mouthwashes, gels, and other dental products can reduce dental caries in secondary, or permanent, teeth (7555,8950,9128,94406,94407,101102,101105,107647). A meta-analysis of 8 clinical trials including adults and children aged 6 years and older shows that high fluoride toothpastes, providing at least 2500 ppm fluoride, reduce the odds of dental caries by an additional 47% when compared with standard toothpastes providing up to 1500 ppm fluoride (7555,8950,9128,94402,94406,94407,101102,101105). Also, the application of fluoride gel, most commonly 12,300 ppm fluoride, at least once per year for up to 4 years reduces the rate of dental caries by 28% on average in children aged 2-15 years (94406). Population research has found that intake of fluoride from food and beverages is greater in adolescents with no lesions when compared with those with at least one lesion of any severity (107649). The regular use of fluoride mouthwash for 1-2 minutes per 5-10 mL application reduces the rate of dental caries by 27% on average. These mouthwashes usually contains fluoride 230 ppm when used weekly or 900 ppm when used daily (94407). Fluoride supplements might also be beneficial for prevention of caries in permanent teeth, although the available clinical research is of moderate quality. A meta-analysis of clinical research in children 6 years of age and older shows that the use of fluoride supplements, such as drops, tablets, and lozenges, usually providing 0.1 mg daily, is associated with a 24% reduction in decayed, missing, or filled surfaces when compared with no fluoride supplementation. It is unclear if fluoride supplementation would provide additional benefit in children already using fluoride toothpaste on a regular basis (94410). Fluoride in toothpastes, varnishes, gels, and other dental products can also reduce dental caries in primary, or deciduous, teeth (94402,94406,101105,107639,107647,107648). Meta-analyses of the available clinical research in mainly preschool-aged children shows that using standard fluoride toothpastes containing 1000-1500 ppm fluoride reduces the risk of dental caries in primary teeth (94402,101105). In one analysis, the reduction was 31% when compared with no intervention. The effect of toothpastes containing lower quantities of fluoride could not be evaluated from the existing literature (94402). A small number of studies have shown that the use of fluoride gels at least once per year reduces the risk of dental caries in primary teeth by 20% (94406). Another study shows that using sodium fluoride in a varnish in combination with a silver nitrate solution every 6 months reduces dental caries in young children (107639). It is unclear whether professionally applied varnishes have beneficial effects on caries in young children when used alongside regular fluoride toothpastes. One meta-analysis in children using regular fluoride toothpastes daily shows that use of a professionally applied fluoride varnish every 6 months does not have additive effects on caries reduction (107647). However, a more recent clinical trial shows that the use of either an ammonium fluoride or sodium fluoride varnish every 3 months reduces dental caries in young children brushing their teeth with fluoride toothpaste twice daily (107648). The children in these studies had supervised daily brushing, which might not reflect daily life. The effect of fluoride supplements on primary teeth is unclear; the existing clinical research is limited and conflicting, possibly due to the different populations studied (94410).

POSSIBLY EFFECTIVE

• Dental plaque. Topical fluoride seems to reduce dental plaque when used appropriately in toothpastes. Details: A meta-analysis of the available clinical research shows that manual brushing with toothpaste containing stannous fluoride is as effective as toothpaste containing triclosan for reducing the amount of plaque (94409). Furthermore, clinical research shows that amine fluoride/stannous chloride-containing toothpaste, stannous fluoride 0.454% toothpaste, zinc/arginine sodium fluoride toothpaste, and monofluorophosphate toothpaste twice daily for 12 or 24 weeks all reduce dental plaque when compared with baseline in individuals with gingivitis. However, the amine fluoride/stannous chloride- and stannous fluoride-containing toothpastes were more effective than monofluorophosphate or zinc/arginine sodium fluoride toothpastes (101103,101106,107646). Manual toothbrushing, usually 1-2 minutes twice per day, with a toothpaste containing stannous fluoride 0.454%, sodium monofluorophosphate, or amine fluoride/stannous chloride has been used (94409,101103).
• Gingivitis. Topical fluoride seems to reduce gingivitis when used appropriately in toothpastes. Details: A meta-analysis of the available clinical research shows that manual brushing with toothpaste containing stannous fluoride is as effective as toothpaste containing triclosan for improving symptoms of gingivitis, including gingival bleeding (94409). Furthermore, clinical research shows that amine fluoride/stannous chloride-containing toothpaste, stannous fluoride 0.454% toothpaste, zinc/arginine sodium fluoride toothpaste, and monofluorophosphate toothpaste twice daily for 12 or 24 weeks all reduce gingivitis and gingival bleeding when compared with baseline in individuals with gingivitis (101103,101106,107646). However, the amine fluoride/stannous chloride- and stannous fluoride-containing toothpastes seem to be slightly more effective than monofluorophosphate or zinc/arginine sodium fluoride toothpastes (101103,101106).
• Osteoporosis. Oral fluoride seems to be beneficial for improving bone density in patients with osteoporosis. However, it is unclear if oral fluoride prevents fractures. Details: Elemental fluoride taken daily, continuously, or cyclically, might increase bone mineral density. Monofluorophosphate containing 20 mg elemental fluoride taken daily on a continuous basis for 96 weeks by postmenopausal adults with osteopenia appears to increase spinal bone mineral density (BMD) by 2.4%. In combination with hormone replacement therapy, monofluorophosphate may increase spinal BMD by 11.8% (9125). However, lower doses do not seem to be effective. Doses of fluoride 2.5-10 mg daily for 12 months did not improve BMD in the lumbar spine, hip, or forearm of these patients (94405). In postmenopausal adults with osteoporosis, taking monofluorophosphate containing 20 mg elemental fluoride daily for 4 years seems to increase spinal BMD by 10% (9124). In males with osteoporosis, taking monofluorophosphate containing 15 mg elemental fluoride daily on a cyclical basis (three months on, one month off) for 3 years seems to increase spinal BMD by 3% per year (8948). The effect of fluoride on fractures is less clear. Sustained-release sodium fluoride 25 mg daily (equivalent to 11.3 mg elemental fluoride) given cyclically for 12 months on, followed by 2 months off, for 42 months seems to reduce the risk for vertebral fracture by 32% in postmenopausal adults with osteoporosis (9103). Monofluorophosphate appears to reduce the risk of vertebral fracture from 10% in individuals taking only calcium to 2.4% in those taking fluoride plus calcium (9124). In males with osteoporosis, fluoride treatment seems to reduce the risk of vertebral fracture by 30% and also to reduce back pain (8948). However, other studies have found no effect on fractures (9132,9133). Studies have generally been small and have used various fluoride preparations including sodium fluoride, enteric-coated sodium fluoride, sustained-release sodium fluoride, and sodium monofluorophosphate (8948,8949,9103,9124,9125,9129,9132,9133). Some researchers suggest that starting fluoride early in the course of osteoporosis and treating with 20 mg daily along with calcium 800-1000 mg daily for at least 3 years is necessary for efficacy (9162). However, due to the narrow therapeutic index for fluoride dosing to avoid decreased bone mineralization, other experts do not consider fluoride to be a viable treatment option (94405). There have been concerns that exposure to fluoridated water might increase the risk of hip fracture in some populations. Overall, the evidence from population research does not support an increased risk (94411). In fact, some studies suggest that long-term exposure of 20 years or more to fluoridated water is associated with a reduced risk of hip fracture. In older females, the reduction in risk of hip fracture and vertebral fracture was 31% and 27%, respectively (9102).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Crohn disease. It is unclear if oral fluoride is beneficial for improving bone density in patients with Crohn disease. Details: Preliminary clinical research shows that fluoride might increase vertebral bone mass in patients with Crohn disease who have low bone mass. Slow-release sodium fluoride 25 mg three times daily for one year, in conjunction with calcium 500 mg twice daily and vitamin D 1,000 IU daily, has been used (9134).
• Rheumatoid arthritis (RA). It is unclear if oral fluoride is beneficial for improving bone density in patients with RA. Details: Preliminary clinical research shows that taking sodium fluoride 40 mg daily for 18 months might increase vertebral bone mass in patients with RA who have low bone mass (9130). More evidence is needed to rate fluoride for these uses.

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LIKELY SAFE ...when used orally and appropriately. Fluoride is safe when used in doses below the tolerable upper intake level (UL) of 10 mg daily of elemental fluoride (7555). ...when used topically and appropriately. Fluoride is safe when used in quantities typically found in toothpastes, mouth rinses, and professionally applied fluoride dental treatments (8950,101102,101105).

CHILDREN: LIKELY SAFE
when used orally and appropriately. Elemental fluoride is safe when used in doses below the daily tolerable upper intake level (UL) of 0.7 mg for 0-6 months of age, 0.9 mg for 7-12 months of age, 1.3 mg for 1-3 years of age, 2.2 mg for 4-8 years of age, and 10 mg for children 8 years and older (7555). Although infants and children have consumed fluoridated water with apparent safety for many years, some population research suggests that more information is needed to determine a safe level of fluoride exposure in infants and children living in regions with fluoridated water. Population research has found an association between urinary fluoride levels and diagnosis of ADHD with higher inattention scores at age 14 years, but not at age 9 years (103551). Also, there is some concern that reconstitution of infant formula with fluoridated water might result in fluoride intakes above the UL in infants under 6 months of age, which may be linked to negative cognitive effects (103529). The Canadian Dental Association recommends that when infant formulas are used as the main source of nutrition, drinking water that contains natural fluoride above recommended levels should not be used to reconstitute the formula (103545). More research is needed to determine whether these effects are due to fluoride or to confounding factors such as socioeconomic status, use of formula instead of breast-feeding, parental intelligence, choice of IQ tests used in studies, and other factors (103542,103544). ...when used topically and appropriately. Fluoride is safe in quantities typically found in toothpastes, mouth rinses, and professionally applied fluoride dental treatments (8950,9100,94406,107648).

CHILDREN: POSSIBLY UNSAFE
when used orally in high doses, long-term. Exposure to high doses above the UL for greater than 10 years can cause skeletal fluorosis (7555). To reduce fluoride intake, toothpaste and fluoride rinses should not be routinely swallowed. Recommend limiting the use of toothpaste to a pea-sized amount for children 6 years and younger in case of accidental swallowing (9100). When infant formulas are used as the main source of nutrition, drinking water that contains natural fluoride above recommended levels should not be used to reconstitute the formula (103545).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately. Elemental fluoride is safe when used in doses below the tolerable upper intake level (UL) of 10 mg daily (7555). Although fluoridated water has been consumed during pregnancy with apparent safety for many years, some population research suggests that more information is needed to determine a safe level of fluoride exposure for those living in regions with fluoridated water. Some emerging population research suggests that increased fluoride intake during pregnancy, from appropriately fluoridated water or fluoridated salt, might be associated with negative cognitive effects in the infant (103543,103547). However, more information is needed to determine if these results are clinically significant at the population level, as well as whether these effects are due to fluoride or to confounding factors such as socioeconomic status, use of formula instead of breast-feeding, parental intelligence, choice of IQ tests used in studies, and other factors (103542,103544,103546,103547,103548,103549,103550). ...when used topically and appropriately. Fluoride is safe in quantities typically found in toothpastes, mouth rinses, and professionally applied fluoride dental treatments (8950).

PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally at doses above the tolerable upper intake level (UL) of 10 mg daily of elemental fluoride for prolonged periods. Long-term exposure to high doses can cause skeletal fluorosis, but pregnancy or lactation doesn't seem to affect susceptibility to skeletal fluorosis (7555).

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General ...Orally, fluoride seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal symptoms.
Topically: Stained teeth.
Serious Adverse Effects (Rare):
Orally: Allergic reactions, including atopic dermatitis, exfoliative dermatitis, gastrointestinal allergic reactions, inflamed lips, respiratory allergic reactions, stomatitis, and urticaria.

Cardiovascular ...A meta-analysis shows that exposure to drinking water high in fluoride is associated with increases in both systolic and diastolic blood pressure, and possibly an increased risk of developing hypertension, when compared with exposure to drinking water with low to normal levels. High levels of fluoride were defined as 1.02-4.06 mg/L and low to normal levels were defined as 0.18-0.84 mg/L (107650).

Gastrointestinal ...Orally, fluoride can cause gastrointestinal symptoms (94405). Enteric-coated and sustained-release dosage forms of sodium phosphate and sodium monofluorophosphate may cause fewer adverse effects than plain sodium fluoride (9127,9129). Adverse effects appear to be dose related. Sodium fluoride at high daily doses of 40-65 mg can cause nausea, vomiting, and GI bleeding (15,9127).
Fluoride can cause enamel fluorosis, a condition in which the ingestion of excessive amounts of fluoride during the development of permanent teeth may cause discoloration and pitting. This is a cosmetic effect only; tooth enamel may be stronger and more resistant to caries with enamel fluorosis (7555). Topically, use of stannous fluoride in toothpaste has caused staining of the teeth (94409).

Immunologic ...Exposure to fluoride can cause allergic reactions including urticaria, exfoliative dermatitis, atopic dermatitis, stomatitis, and gastrointestinal allergic reactions. Respiratory allergic reactions occur rarely (15,94408). A case of dermatitis around the mouth was thought to be related to the high fluoride levels in a specific toothpaste (NeutraFluor 5000 Plus) (94408). In another case report, lip inflammation occurred in reaction to the amine fluoride in a toothpaste product (94404). Lip inflammation and urticaria were also reported in reaction to a specific brand of toothpaste (Crest Pro-Health). However, it is not clear if this reaction occurred in response to the fluoride or tin component of stannous fluoride (94403).

Musculoskeletal ...Orally, sodium fluoride 40-65 mg daily can cause lower extremity pain and stress fractures (15,9127,94405). Fluoride at high doses for prolonged periods, over 10 mg daily for 10 or more years, can cause skeletal fluorosis. Skeletal fluorosis initially presents as joint stiffness and pain, followed by crippling, osteosclerosis, muscle wasting, and neurological defects due to hyper calcification of the vertebra. Crippling skeletal fluorosis is extremely rare in the US (7555).

Neurologic/CNS ...Exposure to high levels of natural fluoride during neurodevelopment in childhood is associated with a decreased IQ score. This relationship has been shown in numerous population studies comparing areas with water containing high levels of natural fluoride (e.g. up to 11.5 mg/L) with the standard concentrations (0.7-1.2 mg/L) normally found in fluoridated water (94401,103544). The Canadian Dental Association recommends that when infant formulas are used as the main source of nutrition, drinking water that contains natural fluoride above recommended levels should not be used to reconstitute the formula (103545).
There is some concern that levels of fluoride found in optimally fluoridated water sources might also impact neurodevelopment during infancy or childhood. For example, population research in Canada has found a relationship between urinary fluoride levels and diagnosis of ADHD with higher inattention scores at age 14 years, but not at age 9 years. At 14 years, the predicted odds of an ADHD diagnosis was 2.8 times greater than the odds for youth in non-fluoridated regions (103551). In addition, in infants under 6 months of age using formula as the main source of energy, there is some concern that reconstitution of formula with fluoridated water might result in fluoride intakes above the tolerable upper intake level (UL). One observational study in Canada found that for each 0.5-gram increase in fluoride from reconstituted formula, there is an 8.8-point decrement in performance IQ, which measures non-verbal reasoning and visual-motor coordination, at 3-4 years of age. However, there was no association with global intellectual functioning or verbal reasoning (103529).
There is also some concern that levels of fluoride found in optimally fluoridated water sources might impact fetal neurodevelopment. Emerging population research found that increased fluoride intake during pregnancy, from appropriately fluoridated water or fluoridated salt, might be associated with negative cognitive effects. One observational study in Canada found that for each 1 mg/L increase in maternal urinary fluoride, there is a 3.7-point decrement in IQ in children aged 3-4 years, with a greater reduction in non-verbal abilities than verbal abilities. A sub-analysis revealed a decrement of 4.5 points in males, with no decrement in females (103543,103547). Another study found that increased exposure to fluoride during pregnancy is associated with symptoms of inattention in the offspring at age 6-12 years (103550).
The findings of these studies are interesting and support further research. More information is needed to know if these results are clinically significant at the population level (103548,103549,103550). In addition, although effort was made to take confounding factors into consideration, more information is needed to determine whether these neurological effects are related to fluoride exposure during pregnancy or to other factors such as socioeconomic status, use of formula instead of breast-feeding, parental intelligence, choice of IQ tests used in studies, and others. Also, the actual intake of fluoride was not known in most cases (94401,103542,103544,103546,103547,103548,103549,103550).

Other ...Population research in adolescents has found that having plasma fluoride levels of at least 0. 32 micromol/L or consuming water with fluoride levels of at least 0.73 mg/L increases the odds of hyperuricemia by approximately 1.8-fold when compared with the lowest quartiles. In addition, serum uric acid levels are increased by 0.212 mg/dL for each icromole/L increase in plasma fluoride levels (107645).

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