Abstract
Background
Fluoride varnish is widely used in dentistry as a caries preventive measure with recommendations for its use even in infants. In addition, nondental providers are also applying varnish on children’s teeth in various settings. However, there are questions from these nondental providers as to the safety of fluoride varnish.
Methods
To evaluate and describe the adverse events (AEs) related to fluoride varnish, the US Food and Drug Administration’s Manufacturer and User Facility Device Experience database was used. AEs reported for the dental product code for “varnish, cavity,” “varnish,” and “fluoride” were evaluated. The identified AEs were then reviewed and categorized using appropriate key words for the various signs and symptoms, outcomes, and treatment.
Results
Over the 10-year period, only 65 AEs were reported for fluoride varnish products. Swelling (33.8%); burning, itching, or soreness (23.1%); and rash (16.9%) were the most common signs and symptoms reported. The most common site reported was the lips (27.7%). The most common outcome was that the patient was taken to the hospital (18.5%) or emergency department (15.4%). No deaths were reported. The patients were treated primarily using diphenhydramine (Benadryl, Johnson & Johnson Consumer) (26.1%), followed by an epinephrine autoinjector (EpiPen, Mylan) and other forms of epinephrine (15.4%), and prednisolone (9.2%). In 16.9% of the cases with AEs there was a history of allergies. The rate of AEs is estimated to be between 0.099 and 0.105 per million for fluoride varnish. A concern is the likelihood of underreporting AEs in the Manufacturer and User Facility Device Experience database.
Conclusions
Given the widespread use of fluoride varnish in the United States, the number of AEs reported to the US Food and Drug Administration were few. Thus fluoride varnish can be considered a safe dental product.
Practical Implications
Provides data on the safety of fluoride varnish that can be used by the dental profession to allay concerns by nondental providers and patients on this important caries preventive measure.
Key Words
Abbreviation Key:
AE (Adverse events), FDA (US Food and Drug Administration), MAUDE (Manufacturer and User Facility Device Experience), SAE (Serious adverse event)
- Hawkins R.
- Noble J.
- Locker D.
- et al.
It is also one of the most commonly reimbursed procedures by dental insurance companies. Owing to fluoride varnish’s effectiveness, it is widely recommended for use in children,
- Marinho V.C.C.
- Worthington H.V.
- Walsh T.
- Clarkson J.E.
,
even infants.
Furthermore, because of access to dental care issues and ease of use, several nondental providers such as pediatricians, family physicians, and nurses, who are advocates for good oral health as integral to good overall health, are now also applying varnish to children’s teeth as recommended by the US Preventive Services Task Force.
Dental caries in children from birth through age 5 years: screening.
Fluoride varnish is now used in dental offices, medical offices, school-based settings, and other community settings.
,
- Mascarenhas A.K.
- Burt B.A.
,
,
,
- Milgrom P.
- Taves D.M.
- Kim A.S.
- Watson G.E.
- Horst J.A.
Nevertheless, when it comes to the specific safety of fluoride varnish, particularly for an AE after a fluoride varnish application, there is a paucity of studies or available data.
- Marinho V.C.C.
- Worthington H.V.
- Walsh T.
- Clarkson J.E.
One study of 3 clinical trials with a total sample size of 2,424 children aged 0 through 5 years reported no AEs related to fluoride varnish treatments in children, so it was unable to describe AEs related to fluoride varnish use.
- Garcia R.I.
- Gregorich S.E.
- Ramos-Gomez F.
- et al.
One reason was possibly the stricter definition used—“health events that resulted in a medically attended visit within a prescribed time frame … after the fluoride varnish application”—thus missing any events that did not result in a medical visit.
Thus the primary objective of this study is to evaluate the immediate safety of fluoride varnish and describe the AEs related to fluoride varnish using other available databases.
Methods
In the United States, the FDA is the federal agency whose mission is to protect and advance public health through making drugs, food, cosmetics, biologics, products that emit radiation, and medical devices including dental devices more effective and safer. The FDA has broad regulatory authority, which includes premarket approval and postmarket device surveillance. Postmarket surveillance is done through MAUDE, a database of medical device−associated AE reports such as deaths, serious injuries, and malfunctions submitted to the FDA by mandatory and voluntary reporters. Device manufacturers, importers, and user facilities are considered mandatory reporters, and health care professionals, patients, and consumers are considered voluntary reporters. At any given time, 10 years of data are available through MAUDE. A dental device manufacturer or importer knows that they are required to report suspected device-associated deaths, serious injuries, and malfunctions to the FDA using the medical device reports mechanism.
The MAUDE database was used and queried over a 10-year period from January 2010 through August 2020 for the dental product terms “varnish, cavity,” “varnish,” and “fluoride.” Each of these queries resulted in a dataset that was downloaded in Excel. These 3 dental product terms were used to capture a complete dataset of all available reports on fluoride varnish. The fields of interest and relevance included in the MAUDE database are date of event, event type, manufacturer, product, device problem, and event description.
Each resulting dataset was then sorted and reviewed to ensure that only reports related to the various fluoride varnish products were included. The 3 datasets were then merged and again sorted and reviewed to remove duplicate entries.
used were
- ▪
AE: “Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.”
- ▪
SAE: “ … if in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.”
Data analyses performed were descriptive analyses summarizing the signs and symptoms, affected site, outcomes, and treatment provided using percentages. For signs and symptoms, search key words were burning, itching, soreness, rash, redness, swelling, and difficulty breathing; site consisted of lips, gums, tongue, and throat; outcomes considered were emergency department visit, hospitalization, and death; and treatment, which was use of diphenhydramine (Benadryl, Johnson & Johnson Consumer), epinephrine autoinjector (EpiPen) or other forms of epinephrine, and prednisolone.
,
Annual estimates of the resident population by single year of age and sex: April 1, 2010 to July 1, 2019.
,
Children, adolescents, and adults who visited the dentist in the past year (age adjusted, percent, 2+ years).
In the first strategy, as data for the overall prevalence of fluoride varnish use in the United States were not available, the prevalence of dental visits from Healthy People 2020 was used as a proxy. In the publicly available MAUDE data, the age of the person in whom the AE occurred is redacted; thus an assumption was also made that all AEs reported were in children aged 2 through 17 years of age, as this is predominantly the age group in which fluoride varnish is applied in the United States. Furthermore, from the event description a large number seemed to be children as the narrative included terms like “parent,” “child,” “son,” and “daughter.”
In the second strategy, the 2019 prevalence of fluoride varnish use in a privately insured Midwestern US population was used. This Midwestern state is representative of the United States, and the market share of the insurance company is about 34%, similar to that nationally. Here, the assumption was made that the AEs reported in MAUDE were across the life span.
Results
Over this 10-year period of 2010 through 2019, using the search strategy, 66 cases that involved a fluoride varnish product were reported to the FDA. With 1 exception, 65 cases reported AEs, resulting in an average of 6.5 AEs per year, with a range of 1 through 10 cases reported yearly. When each of these was reviewed, 5 of the AEs (7.7%) were SAEs requiring hospitalization. In 11 of the AEs (16.9%), there was a history of allergies and 55 (84.6%) were categorized as “injury.” Most (53; 81.5%) were reported by the dental office to the manufacturer, and only 12 (18.5) were reported by the parent or patient to the manufacturer or FDA.
TableSigns, symptoms, site, outcome, and treatment for fluoride varnish adverse events.
The most common site reported for the sign and symptoms was the lips in 18 (27.7%) cases, followed by face and throat with 8 each (12.3%), and tongue in 7 cases (10.8%). After the episode or reaction, 12 (18.5%) were taken to the hospital and 10 (15.4%) went to an emergency department. Five (7.7%) were hospitalized. No deaths were reported.
Several patients were treated with medications. Benadryl was the most common, with 17 (26.1%) administered diphenhydramine, followed by EpiPen or epinephrine in 10 (15.4%) and prednisolone in 6 (9.2%).
,
Annual estimates of the resident population by single year of age and sex: April 1, 2010 to July 1, 2019.
Healthy People 2020 data for the oral health objective 7 (to increase the proportion of children, adolescents, and adults who used the oral health care system in the past year) report estimates of dental visits by children aged 2 through 17 years from 2010 through 2016.
Children, adolescents, and adults who visited the dentist in the past year (age adjusted, percent, 2+ years).
Using these estimates, it was calculated that on average 49.7% of children in this age group had a dental visit. Thus over this 10-year time period, 326,874,116 children had a dental visit. Assuming all these children would have received at least 2 fluoride varnish applications each year, which is the minimal American Academy of Pediatric Dentistry recommendation,
Periodicity of examination, preventive dental services, anticipatory guidance/counseling, and oral treatment for infants, children, and adolescents.
the AEs are estimated to be 0.099 per million fluoride varnish applications.
- Blackwell D.L.
- Villarroel M.A.
- Norris T.
that 50.2% adults with dental coverage and 100% of children were covered, there would be 1.93 billion Americans with dental coverage in the United States. Using private insurance data, of the 32% of children receiving 1 fluoride varnish application each year, 617.6 million varnish applications were applied over 10 years. With only 65 AEs over the 10-year period, the AEs are estimated to be 0.105 per million.
Discussion
Analyses of reports to the FDA using MAUDE data provide a retrospective review of reported AEs for fluoride varnish applications in the United States and show that AEs and SAEs arising from a fluoride varnish application over a 10-year period are low. Furthermore, it is reassuring that no deaths were reported and only 5 people had a serious event that needed to be hospitalized. Given the number of fluoride varnish applications performed in the United States each year, I attempted to calculate or estimate the rate of AEs using 2 scenarios and estimates. The rate of AEs is estimated to be between 0.099 per million and 0.105 per million for fluoride varnish. The close approximates of these estimates to each other provide confidence in their accuracy. Such a low rate should allay concerns of dental and nondental providers who are providing these procedures in nontraditional settings that may not have the capacity to deal with an AE.
The finding that those with a history of allergies could have an AE or reaction to fluoride varnish is interesting but should not be unexpected. This finding should be used to urge clinicians to obtain an appropriate history that includes previous allergies, document in the patient chart, and monitor patients with previous allergies after the procedure. Some of the reported allergies were to dairy, soy, seafood, nuts, pineapple, animal fur, palm oil, colophony (rosin).
Most AEs were treated with an antihistaminic such as Benadryl. The EpiPen was used in 3 reports and was available from the parent as the child had a history of allergies. Thus, it is recommended that in nontraditional settings where fluoride varnish might be applied, such as in schools and Head Start centers, to keep diphenhydramine available. In the United States, emergency kits generally have an EpiPen, but this is a more expensive alternative.
Furthermore, although device manufacturers, importers, and user facilities are required to submit adverse reports for fluoride varnish to the FDA, the adverse reports can only be submitted to the FDA if they were reported by the health professional or patient to the manufacturers or importers of the fluoride varnish products, as seen in 82% of the cases in this study. Most likely there is substantial underreporting of events. In addition, owing to the nature of the reported data, a cause-effect cannot be assumed. Furthermore, as the FDA does not verify the report and the quality and completeness of the information reported varies, conclusions should be made with care. Thus, for the AE rate estimates calculated here, caution was taken to be conservative. An article in the dental literature using MAUDE suggests that it “is an important, if imperfect, contributor to our profession’s knowledge about threats to patient safety”
- Hebballi N.B.
- Ramoni R.
- Kalenderian E.
- et al.
and encouraged the dental profession to report device-related AEs to the FDA and MAUDE. In this study, I agree and echo this sentiment. In medicine, other databases such as the FDA AE Reporting System database, the National Electronic Injury Surveillance System database, and those of large hospital systems have been used. In dentistry, similar databases are not available or are not appropriate.
- Milgrom P.
- Taves D.M.
- Kim A.S.
- Watson G.E.
- Horst J.A.
the evidence that fluoride varnish is safe is compelling.
Conclusions
Given the widespread use of fluoride varnish in the United States, the number of AEs reported to the FDA were few even after taking into consideration potential underreporting. Thus, fluoride varnish can be considered a safe dental product.
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Biography
Dr. Mascarenhas is a professor, Nova Southeastern University College of Dental Medicine and College of Osteopathic Medicine, 3200 S University Dr, Fort Lauderdale, FL 33328.
Article Info
Publication History
Published online: March 22, 2021
Publication stage
In Press Corrected Proof
Footnotes
Disclosure. The author has not reported any disclosures.
Identification
DOI: https://doi.org/10.1016/j.adaj.2021.01.013
Copyright
© 2021 Published by Elsevier Inc. on behalf of the American Dental Association.
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