Silver diammine fluoride


Silver diammine fluoride, also known as Silver diamine fluoride in most of the dental literature, is a topical medication used to treat and prevent dental caries and relieve dentinal hypersensitivity. It is a colorless or blue-tinted, odourless liquid composed of silver, ammonium and fluoride ions at a pH of 10.4 or 13. Ammonia compounds reduce the oxidative potential of SDF, increase its stability and helps to maintain a constant concentration over a period of time, rendering it safe for use in the mouth. Silver and Fluoride ions possess antimicrobial properties and are used in the remineralization of enamel and dentin on teeth for preventing and arresting dental caries.
SDF is also known as diammine silver fluoride, silver fluoride, and silver ammonium fluoride. It is frequently spelled "silver diamine fluoride" ; however, this is a misnomer, as SDF contains two ammine groups, not amine groups.
Based on the current, best available evidence, SDF can be used by licensed dental professionals. In the UK, this is classified as 'off-label' use of a topical medicament for arresting caries as it is licensed for treatment of dentine hypersensitivity. It is supported by a robust, extensive evidence base with regard to its efficacy and can be used as long as the following criteria are realised: there is a body of evidence supporting its efficacy; and there is no alternative, licensed medicine.
The product was cleared for sale by the U.S. Food and Drug Administration as a Class II medical device for the treatment of dentinal hypersensitivity, and has been classified as an ‘effective, efficient, equitable and safe caries-preventative agent’ by the Institute of Medicine and the Millennium Goals of the World Health Organization in 2009.

Brand names

Indications

SDF use is indicated in the clinical scenarios listed below.

Patients

The use of SDF is contraindicated in the following scenarios:

Patients

SDF's mode of action is well documented, but remains contested. Rosenblatt et al. summarized how the constituents in SDF each have a role in the arrest of microbial species that cause dental caries. The higher the concentration of fluoride in a compound, the more effective its mechanisms in inhibiting bacterial biofilm formation. Fluorides can bind to bacterial cell walls, inhibiting enzymatic processes associated with sugar uptake and metabolism of carbohydrate, therefore producing a surface more resistant to acid dissolution.
Similarly, the silver in SDF kills cariogenic bacteria by interacting with DNA and cellular proteins. This leads to cessation of cellular metabolism preventing bacterial cell wall synthesis and DNA synthesis, and mitochondrial failure. These actions destroy plaque biofilms, and subsequently arrest dental caries.
SDF hardens carious dentin, such that it is twice as hard as healthy dentin

Effect on cariogenic bacteria

counts and studies of multispecies carious biofilms were carried aiming to examine the action of SDF on cariogenic bacteria. CFU counts on Streptococci mutans, Actinomyces naeslundii, Lactobacillus acidophilus, Streptococcus sobrinus, Lactobacillus rhamnosus were significant lower in both dentin surfaces and demineralized dentin treated with SDF when compared to water application. SDF also inhibits the adherence of S.mutans to tooth surfaces.
Targino et al reported that minimum bacterial concentration and minimum inhibitory concentration of SDF for S.mutans were 50.0 ug/ml and 33.3 ug/ml respectively. This shows that SDF as a compound has better bactericidal effects than silver ammonium nitrate and sodium fluoride.

Effect on organic content on dentin

The affected layer of carious dentin in teeth can be identified by the presence of intact collagen fibres. Studies have revealed that a larger amount of intact collagen fibres remain on dentine surfaces when treated with SDF as compared to water.
SDF inhibits proteolytic activities such as enzymatic degradation of collagen fibres by matrix metalloproteinases MMP-2, 8 and 9. Furthermore, SDF stops the degradation of cysteine cathepsins, which are also responsible for dentine collagen degradation.

Recommended concentration

A systematic review conducted by Contreras et al. in 2017 concluded that 30% and 38% concentrations of SDF were most effective for caries arrest. One of the clinical trials in this systematic review found 38% SDF to be significantly more effective for the prevention of caries in primary teeth, with 80% fewer new lesions in primary teeth, and 65% fewer new lesions in first permanent molars. Yee et al compared the effectiveness of 38% against 12% SDF, with or without using a reducing agent for the caries arrest. Over a 24 month period, it was concluded that there was a higher rate of lesion arrest in teeth treated with 38% SDF as compared to 12% SDF.

Frequency of application

A randomised clinical trial conducted by Zhi et al. found that increasing the frequency of SDF application from once to twice per year increased the rate of caries arrest. The American Academy of Paediatric Dentistry recommends a 2-4 week follow-up to assess the arrest of carious lesions treated with SDF. If the lesions do not appear to have arrested, it is suggested by them to reapply. Subsequent restoration of the carious lesion may be indicated following the application of SDF to restore aesthetics. If these lesions are not restored following SDF application, the AAPD recommends application biannually, as this has shown an increased caries lesion arrest rate as compared to annual application.

Maximum dose

Average LD50 in mice and rats by oral administration was 520 mg/kg, and by subcutaneous administration was 380 mg/kg. The subcutaneous route is taken here as a worst-case scenario. One drop is ample material to treat 5 teeth, and contains 12.35 mg silver diamine fluoride. Assuming the smallest child with caries would be in the range of 10 kg, the dose would be 1.235 mg / kg child. Based on this, UCSF recommended 1 drop per 10 kg of body weight per visit.
The US FDA reviewed the dose limit based on all evidence for the US multi-centered clinical trial sponsored by the NIH and FDA run by UM, NYU, and UIowa, and set a dose limit of 260 µL for any patient 12 - 59 months old at the start of the study. ClinicalTrials.gov Identifier: NCT03649659.

Precautions and adverse effects

The main side effect of SDF is non-medical and is the prominent black staining of carious tooth tissue where the solution is applied.
SDF will stain most things it touches, including skin, mucous membranes, clothing and work surfaces. Chu et.al reported on the first modern clinical trial of SDF that the stain was generally acceptable and "the presence of darkened teeth was mentioned by around 7% of the parents."
Another side effect is an intensely bitter metallic flavor, which subsides in minutes.
No serious adverse reactions have been reported in the scientific literature. Two safety studies have been done in children.
Pharmacokinetic studies in adults found no adverse effects and demonstrated a lack of any increase of Fluoride in the blood. Increases in serum Silver were observed.
Systematic reviews reported adverse reactions following SDF use. These reactions manifested as small, white lesions of the oral mucosa that healed over the course of 48 hours. Furthermore, an umbrella review by Seifo et al. did not report any serious adverse reactions.

Arresting caries progression