Silver diammine fluoride

Silver diammine fluoride (also spelled "diamine" 38% w/v Ag(NH3)2F, 30% w/w;) is also known as diammine silver fluoride, silver fluoride, and silver ammonium fluoride.[2]

Silver diammine fluoride
Clinical data
Trade namesFAgamin, Topamine, Saforide, Advantage Arrest, Cariesop, Bioride, FluoroplatV, Riva Star, e-SDF
Other namesDiammine Silver Fluoride, Diamine silver fluoride (chemically erroneous)
Legal status
Legal status
  • US: ℞-only and 510(k) cleared class II medical device
Identifiers
CAS Number
ChemSpider
UNII
Chemical and physical data
FormulaAgF(NH3)2
Molar mass160.927643 g/mol[1]

SDF is a topical medicament (drug) used to treat and prevent dental caries (cavities) and relieve dentinal hypersensitivity.[3] It is a colorless topical agent composed of 24.4-28.8% (w/v) silver and 5.0-5.9% fluoride at a pH of 10.4. [2]

Silver diammine fluoride has been available in many countries including China, Japan, Germany, Nepal, Brazil, Argentina, New Zealand, Australia and others for many decades. The product was cleared for sale by the U.S. FDA as a class II medical device for the treatment of dentinal hypersensitivity.[4]

SDF is in the market and in use for more than 50 years as a caries-arresting drug in Japan and other countries such as Brazil and Argentina. It is marketed as Advantage Arrest™ by Elevate Oral Care, LLC (West Palm Beach, FL). Other companies may market silver diamine fluoride in the future depending on the FDA clearance.

How to apply SDF

Professional application of SDF is considered safe. No serious adverse effects are reported from clinical trials of SDF. Application of SDF is a noninvasive and painless procedure which shown to be effective in carries arrest. Silver diamine fluoride can be applied simply with cotton isolation.[6] Excavation of caries is not required prior to application. Teeth are air‐dried, and SDF is applied to the carious lesions using a microbrush for 1 minute and rinsed.

Effectiveness in Children

The use of SDF is more effective in controlling/arresting dents caries than active treatment (ART) tested. Results shows the use of SDF is more effective in controlling/arresting dental caries than placebo or no treatment.[7]

Overall analysis shows that the use of SDF is up to 89% (ranges from 49-138%) more effective controlling/arresting caries than other treatments or no treatments.[7]

Effectiveness in Adult/Elderly
  • When silver diamine fluoride was applied only to carious lesions, impressive prevention was seen for other tooth surfaces. SDF has been used in adults to prevent and arrest caries on exposed root surfaces
  • A systematic review examining effectiveness in prevention and arrest of caries in elderly adults included three studies. One of the study(three year study) calculated SDF root caries prevention factor (PF) as 71% compared to 57% for chlorhexidine and 64% for sodium fluoride varnish (P<0.001)[8]
  • PF was defined as reduction of incidence of caries surface or reduction of carious surface progression. Furthermore, the number of patients needed to be treated in order to prevent one lesion from occurring or prevented from progressing was 2.5 for SDF compared to 3.2 for chlorhexidine and 3.1 for sodium fluoride.


Chemistry/nomenclature and Mechanism of action

Silver diammine fluoride is an ammine (ammonia) complex of silver fluoride. The ammonia ligands are thus "ammine", but the term "amine" is sometimes used incorrectly for this chemical.[9] In addition to that spelling difference, it is sometimes also called "ammoniacal silver fluoride", which is also sometimes improperly spelled as "ammonical silver fluoride".

Effect on Enamel[2] Effect on Dentin[2] Antimicrobial action[2]
Increase micro-hardness

Increase calcium

Decrease mineral loss

 Decrease lesion depth

Forms precipitate

increase micro-hardness

less mineral loss

forms highly re-mineralized surfaces

Less degradation of collagen (MMP-2, MMP-8, MMP-9, and Cysteine cathespin

 Less growth of S. mutant and lactobacillus in biofilms

Minimum bactericidal concentration for S, mutan

33.3ug/mL-50.0ug/mL (more effective than silver ammonium nitrate and sodium flourdie

No effect on bonding in non-carious dentin using self-etch or full-etch system has been reported. [10]

Maximum Dose

Average LD50 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 (25 μL) is ample material to treat 5 teeth, and contains 9.5 mg silver diamine fluoride. Assuming the smallest child with caries would be in the range of 10 kg, the dose would be 0.95 mg / kg child.[10]

Precautions/adverse effects

Silver diammine fluoride (SDF) is a clear liquid that will stain most oxidizable surfaces black upon exposure to light due to the formation of a silver oxide layer. Skin and soft tissue will discolor within minutes to hours after contact and fade away (via surface shedding) within a few days. SDF should not be placed in patients who are allergic to silver or patients suffering from ulcerative gingivitis or stomatitis.[10]

Silver diamine fluoride darkens carious lesions. At least for children, many parents have seen the color changes as a positive indication that the treatment was effective and it was reported to be acceptable by parents and young children, possibly because primary teeth exfoliate.

For adults acceptability may also vary depending on patient expectations. Application of a saturated solution of potassium iodide (SSKI) immediately following silver diamine fluoride treatment is thought to decrease staining (patent US6461161).

Patients note a transient metallic or bitter taste Even a small amount of silver diamine fluoride can cause a “temporary tattoo” to skin (on the patient or provider), like a silver nitrate stain or henna tattoo, and does no harm. Stain on the skin resolves with the natural exfoliation of skin, in 2-14 days.

The main adverse events associated with SDF applications are pulpal irritation, dental staining, and oral soft tissue irritation or a minor oral mucosa irritation

History of SDF
  • Dental use of silver nitrate can be traced back to Japan around 1000 AD, where it was used for cosmetic purposes of blackening of teeth. Silver nitrate followed by application of fluoride varnish was the only non-invasive option available for caries treatment before the advent for silver diamine fluoride (SDF). Cases of carious lesions treated and arrested by the application of silver nitrate date to 19th century. Medical research study that dates back to 19th century showed 87 of 142 treated carious lesions were arrested.  [6]
  • SDF was formed when ammonia was added to silver nitrate to make it stable and effective as an antibacterial for application to caries lesions and infected root canals. SDF has been widely used in Australia and Brazil since 1980 with in vivo studies done in the respective countries[6]
  • Silver diamine fluoride (SDF) derives from the conjunction of silver nitrate and fluoride. It reduces the growth of cariogenic bacteria, hampers degradation of collagen in dentin, inhibits demineralization and promotes remineralization of both enamel and dentin [2]
  • SDF has been used for decades in Japan [Nishino et al., 1969], China [Lo et al., 2001], Brazil [Bijella et al., 1991], and Argentina [Mauro et al., 2004] at concentrations varying from 10 to 38% [Mei et al., 2016] in order to promote dental caries arrest. In 2014, after being approved by the Food and Drug Administration (FDA) for tooth desensitization, it began to be used off-label for caries control in the USA [Horst et al., 2016].[11]
  • In January 2016 in the US, a new Code on Dental Procedures and Nomenclature (CDT) D1354 allowed billing claims for off‐label use of SDF as an interim caries arresting medicament


See also

References
  1. "SILVERDIAMINEFLUORIDE (CAS No. 34445-07-3) Suppliers @ ChemicalRegister.com". chemicalregister.com. Retrieved 14 July 2016.
  2. Zhao IS, Gao SS, Hiraishi N, Burrow MF, Duangthip D, Mei ML, Lo EC, Chu CH (April 2018). "Mechanisms of silver diamine fluoride on arresting caries: a literature review". International Dental Journal. 68 (2): 67–76. doi:10.1111/idj.12320. hdl:10722/242975. PMID 28542863.
  3. Rosenblatt A, Stamford TC, Niederman R (February 2009). "Silver diamine fluoride: a caries "silver-fluoride bullet"". Journal of Dental Research. 88 (2): 116–25. doi:10.1177/0022034508329406. PMID 19278981.
  4. "510(k) Premarket Notification".
  5. Slayton RL, Urquhart O, Araujo MW, Fontana M, Guzmán-Armstrong S, Nascimento MM, Nový BB, Tinanoff N, Weyant RJ, Wolff MS, Young DA, Zero DT, Tampi MP, Pilcher L, Banfield L, Carrasco-Labra A (October 2018). "Evidence-based clinical practice guideline on nonrestorative treatments for carious lesions: A report from the American Dental Association". Journal of the American Dental Association. 149 (10): 837–849.e19. doi:10.1016/j.adaj.2018.07.002. PMID 30261951.
  6. Subbiah GK, Gopinathan NM (2018). "Is Silver Diamine Fluoride Effective in Preventing and Arresting Caries in Elderly Adults? A Systematic Review". Journal of International Society of Preventive & Community Dentistry. 8 (3): 191–199. doi:10.4103/jispcd.JISPCD_99_18. PMC 5985673. PMID 29911054.
  7. Chibinski AC, Wambier LM, Feltrin J, Loguercio AD, Wambier DS, Reis A (2017). "Silver Diamine Fluoride Has Efficacy in Controlling Caries Progression in Primary Teeth: A Systematic Review and Meta-Analysis". Caries Research. 51 (5): 527–541. doi:10.1159/000478668. PMID 28972954.
  8. Subbiah GK, Gopinathan NM (2018). "Is Silver Diamine Fluoride Effective in Preventing and Arresting Caries in Elderly Adults? A Systematic Review". Journal of International Society of Preventive & Community Dentistry. 8 (3): 191–199. doi:10.4103/jispcd.JISPCD_99_18. PMC 5985673. PMID 29911054.
  9. Lou YL, Botelho MG, Darvell BW (September 2011). "Reaction of silver diamine [corrected] fluoride with hydroxyapatite and protein". Journal of Dentistry. 39 (9): 612–8. doi:10.1016/j.jdent.2011.10.009. PMID 21745530.
  10. Horst JA, Ellenikiotis H, Milgrom PL (January 2016). "UCSF Protocol for Caries Arrest Using Silver Diamine Fluoride: Rationale, Indications and Consent". Journal of the California Dental Association. 44 (1): 16–28. PMC 4778976. PMID 26897901.
  11. Oliveira BH, Rajendra A, Veitz-Keenan A, Niederman R (2019). "The Effect of Silver Diamine Fluoride in Preventing Caries in the Primary Dentition: A Systematic Review and Meta-Analysis". Caries Research. 53 (1): 24–32. doi:10.1159/000488686. PMC 6292783. PMID 29874642.
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