Class: Local Anti-infectives, Miscellaneous
ATC Class: D06BA01
VA Class: DE500
CAS Number: 22199-08-2
Brands: Silvadene, SSD, Thermazene
Medically reviewed by Drugs.com. Last updated on Jun 1, 2018.
Uses for Silver Sulfadiazine
Prevention and Treatment of Burn Infections
Silver sulfadiazine cream is used topically as adjunct therapy to prevent and treat wound sepsis in second- and third-degree burns after resuscitative measures (e.g., control of shock and pain, correction of electrolyte imbalance) have been instituted.a b c e g h i j l
Concomitant administration of appropriate systemic anti-infective agents may be necessary if infection present or suspected.c
Although controlled, comparative studies are lacking, silver sulfadiazine and mafenide are considered by many clinicians to be among the topical anti-infective agents of choice in burn patients.c g h i j
Softening action of silver sulfadiazine cream may aid in eschar removal and preparation of wound for grafting. c
Silver Sulfadiazine Dosage and Administration
If possible, bathe patient daily to aid in debridement.c
Prevention and Treatment of Burn Infections
Apply 1% cream in a thickness of approximately 16 mm (1/16 inch) 1 or 2 times daily; cover burn area with cream at all times.a b c Reapply cream to any areas from which it has been removed by patient activity and reapply immediately following hydrotherapy.a b c
Continue applying cream as long as there is a possibility of infection unless a clinically important adverse reaction occurs.a b c Usually continue until healing is progressing well or site is ready for grafting.a b c
Cautions for Silver Sulfadiazine
Systemic Absorption and Toxicity
When applied to extensive areas of the body and/or tissue damage is present, sulfadiazine may be absorbed systemically and produce adverse reactions characteristic of the sulfonamides, including hematologic effects (e.g., agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, hemolytic anemia), dermatologic and hypersensitivity reactions (e.g., Stevens-Johnson syndrome, exfoliative dermatitis), adverse GI effects, hepatitis and hepatocellular necrosis, adverse CNS effects, and toxic nephrosis.a b c d l m Skin discoloration (including argyria) also reported with topical application of silver sulfadiazine cream.a b c
Transient leukopenia, principally manifested as decreased ANC, reported in an average of 20% of patients.a b c d e l m Maximal WBC count decrease occurs within the first 2–4 days after initiating therapy, and WBC count usually returns to normal within 2–3 days after onset of leukopenia regardless of whether silver sulfadiazine therapy is continued or discontinued.a b c d e m (See Specific Drugs under Interactions.)
Patients with G6PD Deficiency
Sensitivity Reactions and Cross-sensitivity
Possible sensitivity reactions (e.g., blood dyscrasias, skin reactions [dermatitis, rashes, facial edema, pruritus], jaundice, hepatitis).a b c e g h k If allergic reaction occurs, consider discontinuance of drug.a b c
Laboratory Testing and Propylene Glycol
Delayed Wound Healing
Not known whether topically applied silver sulfadiazine cream is distributed into milk.a b c However, because sulfonamides are distributed into milk and may cause kernicterus in premature neonates and neonates ≤2 months of age, discontinue nursing or the drug.a b c
The manufacturer states that safety and efficacy have not been established in pediatric patients;a b c however, silver sulfadiazine cream has been successfully used in some pediatric burn patients.e i
Because sulfonamide therapy has produced kernicterus in neonates, silver sulfadiazine cream is contraindicated in premature neonates or neonates ≤2 months of age.a b c (See Contraindications under Cautions.)
Common Adverse Effects
Interactions for Silver Sulfadiazine
No formal drug interaction studies to date.a b c Since systemic sulfadiazine absorption may occur following topical application, consider possible drug interactions such as those reported with systemic administration of sulfonamides and related drugs.a b c
Proteolytic enzymes, topical (e.g., collagenase, sutilains [no longer commercially available in the US])
Silver Sulfadiazine Pharmacokinetics
Silver sulfadiazine itself does not appear to be absorbed following topical administration.a b c When in contact with body tissues and fluids, silver sulfadiazine slowly reacts with sodium chloride, sulfhydryl groups, and protein, resulting in sulfadiazine release.c Sulfadiazine may then be systemically absorbed from the site of application, particularly when silver sulfadiazine is applied to extensive areas and/or to damaged tissue.a b c e l
When applied to extensive burns, serum sulfadiazine concentrations of ≤12 mg/dL reported.a b c Patients treated with 5–10 g of silver sulfadiazine daily applied as a 1% cream had blood sulfadiazine concentrations of 1–2 mg/dL.c
Actions and Spectrum
Wide spectrum of activity against most burn pathogens, including species of both gram-positive and gram-negative organisms, including most species of Klebsiella, Proteus, Pseudomonas, and Staphylococcus.a b c Also inhibits Escherichia coli, Corynebacterium diphtheriae, and species of Acinetobacter, Citrobacter, Enterobacter, Providencia, Serratia, and streptococci.a b c Also has some activity against Candida albicans, Herpesvirus hominis, and Clostridium perfringens.a b c
Resistance reported occasionally.c
Advice to Patients
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Silvadene (with methylparaben and propylene glycol)
SSD (with cetyl alcohol, methylparaben, and propylene glycol)
SSD AF (with methylparaben and propylene glycol)
Thermazene (with propylene glycol)
AHFS DI Essentials™. © Copyright 2019, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
a. Par Pharmaceutical, Inc. SSD (1% silver sulfadiazine) and SSD AF (1% silver sulfadiazine) cream prescribing information. Spring Valley, NY; 1999 May.
b. Monarch Pharmaceuticals, Inc. Silvadene cream 1% (silver sulfadiazine) prescribing information. Bristol, TN; 2003 Jul.
c. AHFS drug information 2008. McEvoy GK, ed. Silver Sulfadiazine. Bethesda, MD: American Society of Health-System Pharmacists; 2008:3570-71.
d. Choban PS, Marshall WJ. Leukopenia secondary to silver sulfadiazine: frequency, characteristics and clinical consequences. Am Surg. 1987; 53:515-7. http://www.ncbi.nlm.nih.gov/pubmed/3631764?dopt=AbstractPlus
e. Lockhart SP, Rushworth A, Azmy AAF et al. Topical silver sulphadiazine: side effects and urinary excretion. Burns. 1983; 10:9-12.
f. Liebman PR, Kennelly MM, Hirsch EF. Hypercarbia and acidosis associated with carbonic anhydrase inhibition: a hazard of topical mafenide acetate use in renal failure. Burns Incl Therm Inj. 1982; 8:95-8.
g. Castellano JJ, Shafii SM, Ko F et al. Comparative evaluation of silver-containing antimicrobial dressings and drugs. Int Wound J. 2007; 4:114-22. http://www.ncbi.nlm.nih.gov/pubmed/17651227?dopt=AbstractPlus
h. Atiyeh BS, Costagliola M, Hayek SN et al. Effect of silver on burn wound infection control and healing: review of the literature. Burns. 2007; 33:139-48. http://www.ncbi.nlm.nih.gov/pubmed/17137719?dopt=AbstractPlus
i. Palmieri TL, Greenlaugh DG. Topical treatment of pediatric patients with burns: a practical guide. Am J Clin Dermatol. 2002; 3:529-34. http://www.ncbi.nlm.nih.gov/pubmed/12358554?dopt=AbstractPlus
j. Monafo WW, West MA. Current treatment recommendations for topical burn therapy. Drugs. 1990; 40:364-73. http://www.ncbi.nlm.nih.gov/pubmed/2226220?dopt=AbstractPlus
k. McKenna SR, Latenser BA, Jones LM et al. Serious silver sulphadiazine and mafenide acetate dermatitis. Burns. 1995; 21:310-2. http://www.ncbi.nlm.nih.gov/pubmed/7662136?dopt=AbstractPlus
l. Kulick MI, Wong R, Okarma TB et al. Prospective study of side effects associated with the use of silver sulfadiazine in severely burned patients. Ann Plastic Surgery. 1985; 14:407-19.
m. Caffee HH, Bingham HG. Leukopenia and silver sulfadiazine. J Trauma. 1982; 22:586-7. http://www.ncbi.nlm.nih.gov/pubmed/7097818?dopt=AbstractPlus
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