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Silver Sulfadiazine (Monograph)

Brand names: Silvadene, SSD, Thermazene
Drug class: Local Anti-infectives, Miscellaneous
ATC class: D06BA01
VA class: DE500
CAS number: 22199-08-2

Medically reviewed by on May 22, 2023. Written by ASHP.


Sulfonamide; synthetic anti-infective agent.

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.

Control of bacterial growth may prevent conversion of deep, second-degree (partial-thickness) wounds to third-degree (full-thickness) wounds by sepsis.

Concomitant administration of appropriate systemic anti-infective agents may be necessary if infection present or suspected.

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.

Mafenide appears to penetrate burn eschar better than silver sulfadiazine and may be more effective in minimizing the growth of bacteria and early treatment of wound sepsis.

Unlike mafenide, a carbonic anhydrase inhibitor, silver sulfadiazine does not alter acid-base balance and does not have a limited duration of therapy and area of topical application.

Softening action of silver sulfadiazine cream may aid in eschar removal and preparation of wound for grafting.

Silver Sulfadiazine Dosage and Administration


  • Topically apply 1% silver sulfadiazine cream after appropriate regimens for burn care have been promptly instituted, including control of shock and pain.


Topical Administration


Apply 1% cream topically to cleansed, debrided burn wounds under sterile conditions (e.g., using a sterile-gloved hand).

Topical cream should not be applied to the eye.

If possible, bathe patient daily to aid in debridement.

Dressings usually not required but may be used.


Available as silver sulfadiazine; dosage expressed in terms of the salt.


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. Reapply cream to any areas from which it has been removed by patient activity and reapply immediately following hydrotherapy.

Continue applying cream as long as there is a possibility of infection unless a clinically important adverse reaction occurs. Usually continue until healing is progressing well or site is ready for grafting.

Special Populations

No special population dosage and administration recommendations at this time.

Cautions for Silver Sulfadiazine


  • Pregnant women approaching or at term.

  • Premature neonates or neonates ≤2 months of age.

  • Known hypersensitivity to silver sulfadiazine or any ingredient in the formulation (e.g., methylparaben).



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. Skin discoloration (including argyria) also reported with topical application of silver sulfadiazine cream.

Fungal Infections

Possible fungal proliferation in and below eschar; however, low reported incidence of fungal superinfection.


Transient leukopenia, principally manifested as decreased ANC, reported in an average of 20% of patients. 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. (See Specific Drugs under Interactions.)

Patients with G6PD Deficiency

Hemolysis may occur in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Sensitivity Reactions

Sensitivity Reactions and Cross-sensitivity

Possible sensitivity reactions (e.g., blood dyscrasias, skin reactions [dermatitis, rashes, facial edema, pruritus], jaundice, hepatitis). If allergic reaction occurs, consider discontinuance of drug.

Possible cross-sensitivity with other sulfonamides and related compounds (e.g., sulfonylureas, carbonic anhydrase inhibitors, thiazides, loop diuretics). (See Contraindications.)

General Precautions

Laboratory Testing and Propylene Glycol

In patients with extensive burns, monitor serum sulfonamide concentrations, carefully monitor renal function, and examine urine for sulfonamide crystals.

Absorption of propylene glycol (contained in silver sulfadiazine cream) may affect serum osmolality, which may affect interpretation of some laboratory test results.

Delayed Wound Healing

Possible delay in wound healing; reduced bacterial growth may result in delayed eschar separation, which in some cases may require escharotomy.

Specific Populations


Category B.

Because sulfonamides may cause kernicterus in neonates, silver sulfadiazine cream is contraindicated in pregnant women approaching or at term.


Not known whether topically applied silver sulfadiazine cream is distributed into milk. 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.

Pediatric Use

The manufacturer states that safety and efficacy have not been established in pediatric patients; however, silver sulfadiazine cream has been successfully used in some pediatric burn patients.

Because sulfonamide therapy has produced kernicterus in neonates, silver sulfadiazine cream is contraindicated in premature neonates or neonates ≤2 months of age. (See Contraindications under Cautions.)

Hepatic Impairment

Possible sulfadiazine accumulation; consider discontinuance if therapeutic benefits to the patient do not outweigh possible risks.

Renal Impairment

Possible sulfadiazine accumulation; consider discontinuance if therapeutic benefits to the patient do not outweigh possible risks. (See Laboratory Testing and Propylene Glycol under Cautions.)

Common Adverse Effects

Local effects (pain, burning, itching, rash), leukopenia.

Interactions for Silver Sulfadiazine

No formal drug interaction studies to date. 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.

Specific Drugs





Increased incidence of leukopenia when used concomitantly with topical silver sulfadiazine

Proteolytic enzymes, topical (e.g., collagenase, sutilains [no longer commercially available in the US])

Silver contained in silver sulfadiazine cream potentially may inactivate topical proteolytic enzymes used for debridement

Silver Sulfadiazine Pharmacokinetics



Silver sulfadiazine itself does not appear to be absorbed following topical administration. When in contact with body tissues and fluids, silver sulfadiazine slowly reacts with sodium chloride, sulfhydryl groups, and protein, resulting in sulfadiazine release. 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.

Plasma Concentrations

When applied to extensive burns, serum sulfadiazine concentrations of ≤12 mg/dL reported. Patients treated with 5–10 g of silver sulfadiazine daily applied as a 1% cream had blood sulfadiazine concentrations of 1–2 mg/dL.



Not known whether topically applied silver sulfadiazine cream is distributed into milk; however, sulfonamides are distributed into milk.


Elimination Route

Systemically absorbed sulfadiazine excreted in urine.






Actions and Spectrum

  • Mechanism of action of silver sulfadiazine appears to differ from sulfadiazine and silver nitrate; acts on cell membrane and cell wall to produce bactericidal effects.

  • 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. Also inhibits Escherichia coli, Corynebacterium diphtheriae, and species of Acinetobacter, Citrobacter, Enterobacter, Providencia, Serratia, and streptococci. Also has some activity against Candida albicans, Herpesvirus hominis, and Clostridium perfringens.

  • Resistance reported occasionally.

Advice to Patients

  • Importance of understanding that topical silver sulfadiazine preparations are intended for external use only.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)


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

Silver Sulfadiazine


Dosage Forms


Brand Names





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 2023, Selected Revisions June 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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