Off-label use of fluoride varnish as a caries prevention agent adds another valuable tool to the topical fluoride armamentarium.
By Rama Oskouian, DMD; Peter K. Domoto, DDS, MPH; and Joel H. Berg, DDS, MS
IN THE UNITED STATES over the past half century, the incidence of dental caries has dramatically decreased. While the causes of this decrease are varied, enormous benefits in caries reduction must be attributed to both systemic and topical mechanisms of fluoride ion. The efficacy of topical fluoride—in both home and professional applications—is well established.1 In recent years, as caries rates have decreased, a rise of mild to moderate dental fluorosis in permanent teeth has occurred.1,2 Thus, there are concerns regarding excessive ingestion of fluoride, especially in children under the age of 3 years.3-7
At the same time, both national data and small area data indicate that some 20% of the population experiences 80% of dental caries.8,9 Clearly, the benefits of fluoride are essential in the group at high risk for caries. The challenge for further reduction in caries lies in decreasing the rates in the high risk groups.
Teeth can be remineralized with a variety of topical fluoride products including dentifrice, foams, gels, rinses, and varnishes. See Table for a list of manufacturers that provide fluoride products. However, fluoride varnishes are an underused option in the United States. Fluoride varnishes have been shown to be effective as a caries preventive agent over the past three decades.10-16 They appear to be comparable in efficacy to traditional fluoride gels currently used in dental practice.
The FDA and Federal Law
The Food and Drug Administration (FDA) administers the Federal Food, Drug and Cosmetic Act that requires manufacturers to demonstrate safety and effectiveness of all new drugs for their indications, ie, “(the new drug) will have the effect it purports or is represented to have under the conditions or use prescribed, recommended, or suggested in the proposed labeling.”17 The FDA requires substantial evidence from adequate and well-controlled investigations in order to approve a new drug for marketing.17,18
Fluoride varnishes became available in the United States in 1991. Other varnishes have FDA approval as root desensitizers or cavity varnishes, but not as a therapeutic topical fluoride. Varnishes are considered by the FDA to fall into a category of drugs and devices that “present minimal risk and is (are) subject to the lowest level of regulation.”19 The FDA will not accept the extensive findings from European investigations as adequate evidence for approval for labeling as a caries preventive agent, primarily because European research compares the active drug to no treatment and not to a placebo.
Off-label Use of Approved Drugs
Use of approved fluoride varnishes for caries prevention therefore is an unapproved use or more commonly “off-label” use of an approved drug. Such use is not considered unlawful; indeed, the use of drugs off-label is common practice in medicine. Three fourths of the prescription drugs currently marketed in the US lack full pediatric approval.17 Recommendations of the Committee on Drugs of the American Academy of Pediatrics state: “Unapproved use does not imply an illegal use. The word unapproved is used merely to indicate lack of approval, not to imply disapproval or contraindication based on positive evidence of a lack of safety or efficacy.”17
The labeling of many drugs contain pediatric disclaimers and are being used extensively off-label. Albuterol (Ventolin) is an example of a commonly used off-label drug for children with pediatric disclaimers.18 In addition, some drugs are used off-label when their use is not covered by the drug’s labeling.
Both medical and dental professionals assume the responsibility for justifying off-label use of approved drugs. If the application of topical fluoride for patients who are at risk for caries is the standard of dental practice for their community then it seems the selection of an approved fluoride varnish is a reasonable choice.
Justification for Off-label Use of Fluoride Varnish
Fluoride varnish is safe. A typical varnish is 0.9% fluor silane, which yields a fluoride concentration approximately one half of conventional acidulated phosphate fluoride (APF). For applications in the primary dentition, 0.1 ml to 0.3 ml are used (2.3 mg to 6.8 mg of fluoride ion).20 The toxic dose of fluoride varnish is reached with 10 times the normal dose. The toxic dose of APF gel is reached with about double the normal dose. In essence, there are no alternatives for use of a topical fluoride on very young children. Fluoride varnishes offer the safest topical fluoride available for the young (under age 3), at-risk child. An additional advantage of fluoride varnish is its slow release over time.
Professionally applied topical fluorides actually present little risk for fluorosis. Burt found that dietary supplements, inadvertent swallowing of fluoride toothpaste, and increased fluoride in food and beverages are the most likely sources of increased fluoride ingestion.21 In addition, Burt states that “...there is no evidence that swallowing of fluoride gels has been a factor in the increase in fluorosis among North American children.” Since the amount of fluoride that is applied in the application of fluoride varnish is small and the varnish sticks to the tooth surface, the risk for fluorosis is almost negligible.22
Caries reductions with fluoride varnishes have been shown to be in the range of 40%, which is comparable to APF.10-16 The principle of the varnish delivery system is based on contact of topical fluoride with the teeth over a sustained period of time. By the mid ’70s, the benefits of fluoride varnishes were accepted by the European dental community and were being used extensively.
By the early 1990s, almost 93% of all professionally applied topical fluorides in Scandinavia were varnishes.23 In addition to the well-accepted benefits for smooth surface caries prevention, there is some evidence that varnishes are more effective than other topical fluorides in reducing caries on fissured surfaces.24
Fluoride varnishes offer several advantages over traditional topical fluoride, such as speed, ease of application, and a greater range of applications. Varnish can be safely and effectively applied to infants and toddlers, developmentally disabled patients, and patients with active gag reflexes. An effective application is quick and easy. In addition, patients at high risk for caries, including adults with root caries and/or xerostomia, can benefit greatly from regular application of fluoride varnish.
Fluoride varnish provides a useful and effective means of delivering topical fluoride to the teeth of patients. As with any topical fluoride, those at risk for caries will benefit the most from periodic applications of this material. The fact that fluoride varnish as a caries preventive measure currently must be used off-label should not be a barrier to its use in clinical practice. If a patient requires a professionally applied topical fluoride and is too young, too uncooperative, or too medically compromised for a 4 minute (or even 1 minute) APF treatment, fluoride varnish offers an efficacious and safe alternative.
Fluoride supplementation is not a substitute for topical fluorides in the child less than 3 years of age. Supplementation is prescribed for the infant and toddler in the form of drops or other liquid medium. There is no evidence that the child at high risk for caries would receive any meaningful topical effect from this systemic method of fluoride supplementation. Since the caries preventive effect of a chewable supplement is primarily posteruptive it is reasonable to encourage a chewable tablet as soon as possible in order to exploit these topical benefits.25
The literature is clear that a major benefit of fluoride varnishes is their caries preventive properties.10-16,24 The FDA requirements for substantial evidence from well-controlled investigations should be met as soon as possible. An approved status from the FDA for one or more fluoride varnish products will greatly facilitate the use of effective caries preventive measures in both public and private programs.
Varnish is currently classified as a “device” but the FDA has ruled that it is a drug if used for caries prevention. There are, unfortunately, significant cost barriers for companies to support the investigations for full approval as a therapeutic agent. The reality is that dentistry may have to choose to use fluoride varnishes off-label for an extended time.
The key to an effective primary prevention program with infants and toddlers is to deliver topical fluoride early and often to children at risk (see Table 1). At risk children include those with existing caries (including white spot lesions), family histories of moderate to severe dental caries, and congenital enamel defects. Other risk factors include high-risk pregnancy or complicated delivery.
Dental care providers and policy makers are encouraged to review the existing data and practices carefully involving the use of fluoride varnishes. A thorough assessment of the caries status of all patients and the potential risks and benefits of fluoride varnish application should result in the adoption of varnishes as a valid means of delivering fluoride. Fluoride varnishes are safe, effective, and can readily be incorporated into both public and private programs of caries prevention.
Rama Oskouian, DMD, is a fellow, Peter K. Domoto, DDS, MPH, is professor emeritus and former chair, and Joel H. Berg, DDS, MS, is professor and chair all in the Department of Pediatric Dentistry at the University of Washington in Seattle.
From Dimensions of Dental Hygiene. June 2004;2(6):18, 20, 22, 24.
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