UCSF Protocol for Caries Arrest Using Silver Diamine Fluoride : Rationale , Indications and Consent
Longer studies are needed to determine whether caries arrest and prevention can be maintained with decreased application after two to three years , and whether more frequent use would enhance efficacy . Traditional or nontraditional restorative approaches such as the atraumatic restorative technique ( ART ) 44 and Hall crowns 45 should be performed as dictated by the response of the patient , disease progression and the nature of individual lesions .
SAFETY
Maximum Dose and Safety Margin The margin of safety for dosing is of paramount concern . In gaining clearance from the FDA , female and male rat and mouse studies were conducted to determine the lethal dose ( LD50 ) of silver diamine fluoride by oral and subcutaneous administration . 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 five 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 . Thus , the relative safety margin of using an entire drop on a 10 kg child is 380 mg / kg LD50 / 0.95 mg / kg dose = four-hundredfold safety margin . The actual dose is likely to be much smaller , for example 2.37 mg total for three teeth was the largest dose measured in six patients . 46 The most frequent application monitored in a clinical trial was weekly for three weeks , annually . 43 Thus we set our recommended limit as one drop ( 25 μL ) per 10 kg per treatment visit , with weekly intervals at most . This dose is commensurate with the Environmental Protection Agency ’ s ( EPA ) allowable short-term exposure of 1.142 mg silver per liter of drinking water for one to 10 days ( Agency for Toxic Substances and Disease Registry , ATSDR , 1990 ).
Cumulative exposure from lower-level acute or chronic silver intake has no real physiologic disease importance , but the bluing of skin in argyria should obviously be avoided . The EPA set the lifetime exposure conservatively at 1 gm to safely avoid argyria . The highest applied dose for three teeth measured in the pharmacokinetic study , 2.37 mg , would enable > 400 applications . 46 Silver nitrate ( typically a 25 % solution ) has been used for more than 100 years in the U . S . without incident , including acceptance by the ADA , and in other countries for arresting dental caries . 3
ADVERSE EFFECTS Not a single adverse event has been reported to the Japanese authorities since they approved silver diamine fluoride ( Saforide , Toyo Seiyaku Kasei Co . Ltd ., Osaka , Japan ) more than 80 years ago . 47 The manufacturer estimates that more than 2 million multi-use containers have been sold , including > 41,000 units in each of the last three reporting years .
In the nine randomized clinical trials in which silver diamine fluoride was applied to multiple teeth to arrest or prevent dental caries , the only side effect noted was for three of 1,493 children or elderly patients monitored for one to three years who experienced “ a small , mildly painful white lesion in the mucosa , which disappeared at 48 [ hours ] without treatment .” 29 , 31-33 , 35 , 38 , 40 , 41 , 48 The occurrence of reversible localized changes to the oral mucosa was predicted in the first reports of longitudinal studies . 49 No adverse pulpal response was observed .
Gingival responses have been minimal . In a pharmacokinetic study of silver diamine fluoride application to three teeth in each of six 48 to 82 year olds , no erythema , bleeding , white changes , ulceration or pigmentation was found after 24 hours . Serum fluoride hardly went up from baseline , while serum silver increased about tenfold and stayed high past the four hours of measurement . 46 In a two-site hypersensitivity trial of 126 patients in Peru , at baseline 9 percent of patients presented redness scores of 2 ( 1 being normal , 2 being mild to moderate redness and 3 being severe ); and after one day 13 percent in silver diamine fluoride treated patients versus 4 percent in controls . All redness was gone at seven days . Meanwhile , gingival index improved slightly in silver diamine fluoride treated patients . 7 Nonetheless , gingival contact should be minimized . In our experience , it has been adequate to coat the nearby gingiva with petroleum jelly , use the smallest available microsponge and dab the side of the dappen dish to remove excess liquid before application .
Concerns for fluoride safety are most relevant to chronic exposure , 50 whereas this is an acute exposure . Chronically high systemic fluoride results in dental fluorosis . The ubiquitous use of fluoride-based gas in general anesthetics has shown that the first acute response is transient renal holding , and is rare . 51 Concerns have been raised about poorly controlled silver diamine fluoride concentrations 52 and fluorosis appearing in treated rats . 53 However , silver and fluoride levels are closely monitored for the U . S . product , and the Health Department of Western Australia conducted a study that found no evidence of fluorosis resulting from long-term proper use of silver diamine fluoride . 54 Therefore , we have concluded that the development of fluorosis after application of the U . S . -approved product is not a clinically significant risk .
Silver allergy is a contraindication . Relative contraindications include any significant desquamative gingivitis or mucositis that disrupts the protective barrier formed by stratified squamous epithelium . Increased absorption and pain would be expected with contact . Heightened caution and use of a protective gingival coating may suffice .
JANUARY / FEBRUARY 2017 | PENNSYLVANIA DENTAL JOURNAL 21