Silver sulfadiazine

Silver sulfadiazine is a sulfonamide and has broad antimicrobial activity against both Gram-positive and Gram-negative organisms.

Silver sulfadiazine acts on the cell membrane and cell wall. Unlike sulfadiazine or other sulfonamides, the antibacterial action of the silver salt of sulfadiazine does not appear to depend on inhibition of folic acid synthesis. Its action is not antagonised by p-aminobenzoic acid.

Silver sulfadiazine has broad antimicrobial activity against both Gram-positive and Gram-negative organisms including Pseudomonas aeruginosa, some yeasts and fungi. It has also been reported to be active in vitro against herpes virus and Treponema pallidum. Sulfonamides act by interfering with the synthesis of nucleic acids in sensitive micro-organisms by blocking the conversion of paminobenzoic acid to the co-enzyme dihydrofolic acid. Silver sulfadiazine has a bactericidal action; in contrast to sulfadiazine, the silver salt acts primarily on the cell membrane and cell wall and its action is not antagonised by p-aminobenzoic acid. Resistance to silver sulfadiazine has been reported and may develop during therapy.

Absorption

There is evidence that in large area wounds and/or after prolonged application, systemic absorption of silver can occur causing clinical argyria. The sulfadiazine readily diffuses across wounds and enters the general circulation. The degree of uptake will significantly depend upon the nature of the wound and the dosing regime.

Elimination

Sulfadiazine is excreted in the urine.

Gentoxicity

Silver sulfadiazine was not genotoxic in an in vitro bacterial mutation assay or an in vivo mouse micronucleus test (PO administration), although the doses administered were considered low.

Carcinogenicity

Long-term carcinogenicity studies of silver sulfadiazine have not been conducted. Silver sulfadiazine is well established in clinical practice in several countries over a number of decades without any grounds for suspicion of carcinogenic potential in humans.

Reproductive toxicology

No data were available from studies in animals following topical administration of silver sulfadiazine.

No treatment-related effects on male or female fertility were documented following subcutaneous administration of silver sulfadiazine to rats at doses up to 500mg/kg/day for two (females) or ten (males) weeks prior to mating.

Fetal findings (abdominal hernia and laevorotation of the heart) occurred in low incidence in rats at subcutaneous doses of ≥250mg/kg/day during early embryonic development and organogenesis. The significance of these findings for clinical topical administration is unknown.