SILVER SULFADIAZINE

SILVER SULFADIAZINE- silver sulfadiazine cream
Greenstone LLC

DESCRIPTION

Silver Sulfadiazine Cream 1% is a soft, white, water-miscible cream containing the antimicrobial agent silver sulfadiazine in micronized form, which has the following structural formula:

Each gram of silver sulfadiazine cream 1% contains 10 mg of micronized silver sulfadiazine. The cream vehicle consists of white petrolatum, stearyl alcohol, isopropyl myristate, sorbitan monooleate, polyoxyl 40 stearate, propylene glycol, and water, with methylparaben 0.3% as a preservative. Silver Sulfadiazine Cream 1% spreads easily and can be washed off readily with water.

CLINICAL PHARMACOLOGY

Silver sulfadiazine has broad antimicrobial activity. It is bactericidal for many gram-negative and gram-positive bacteria as well as being effective against yeast. Results from in vitro testing are listed below.

Sufficient data have been obtained to demonstrate that silver sulfadiazine will inhibit bacteria that are resistant to other antimicrobial agents and that the compound is superior to sulfadiazine.

Studies utilizing radioactive micronized silver sulfadiazine, electron microscopy, and biochemical techniques have revealed that the mechanism of action of silver sulfadiazine on bacteria differs from silver nitrate and sodium sulfadiazine. Silver sulfadiazine acts only on the cell membrane and cell wall to produce its bactericidal effect.

Results of In Vitro Testing with Silver Sulfadiazine Cream 1% Concentration of Silver Sulfadiazine Number of Sensitive Strains/Total Number of Strains Tested

Genus & Species	50 μg/mL	100 μg/mL
Pseudomonas aeruginosa	130/130	130/130
Xanthomonas (Pseudomonas) maltophilia	7/7	7/7
Enterobacter species	48/50	50/50
Enterobacter cloacae	24/24	24/24
Klebsiella species	53/54	54/54
Escherichia coli	63/63	63/63
Serratia species	27/28	28/28
Proteus mirabilis	53/53	53/53
Morganella morganii	10/10	10/10
Providencia rettgeri	2/2	2/2
Providencia species	1/1	1/1
Proteus vulgaris	2/2	2/2
Citrobacter species	10/10	10/10
Acinetobacter calcoaceticus	10/11	11/11
Staphylococcus aureus	100/101	100/101
Staphylococcus epidermidis	51/51	51/51
β-Hemolytic Streptococcus	4/4	4/4
Enterococcus species	52/53	53/53
Corynebacterium- diphtheriae	2/2	2/2
Clostridium perfringens	0/2	2/2
Candida albicans	43/50	50/50

Silver sulfadiazine is not a carbonic anhydrase inhibitor and may be useful in situations where such agents are contraindicated.

SILVER SULFADIAZINE Indications and Usage

Silver Sulfadiazine Cream 1% is a topical antimicrobial drug indicated as an adjunct for the prevention and treatment of wound sepsis in patients with second- and third-degree burns.

CONTRAINDICATIONS

Silver Sulfadiazine Cream 1% is contraindicated in patients who are hypersensitive to silver sulfadiazine or any of the other ingredients in the preparation.

Because sulfonamide therapy is known to increase the possibility of kernicterus, silver sulfadiazine cream 1% should not be used on pregnant women approaching or at term, on premature infants, or on newborn infants during the first 2 months of life.

WARNINGS

Absorption of silver sulfadiazine varies depending upon the percent of body surface area and the extent of the tissue damage. Although few have been reported, it is possible that any adverse reaction associated with sulfonamides may occur. Some of the reactions, which have been associated with sulfonamides, are as follows: blood dyscrasias including agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, and hemolytic anemia; dermatologic and allergic reactions, including life-threatening cutaneous reactions [Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and exfoliative dermatitis]; gastrointestinal reactions; hepatitis and hepatocellular necrosis; CNS reactions; and toxic nephrosis.

There is potential cross-sensitivity between silver sulfadiazine and other sulfonamides. If allergic reactions attributable to treatment with silver sulfadiazine occur, continuation of therapy must be weighed against the potential hazards of the particular allergic reaction.

Fungal proliferation in and below the eschar may occur. However, the incidence of clinically reported fungal superinfection is low.

The use of silver sulfadiazine cream 1% in some cases of glucose-6-phosphate dehydrogenase-deficient individuals may be hazardous, as hemolysis may occur.

PRECAUTIONS

General

If hepatic and renal functions become impaired and elimination of drug decreases, accumulation may occur, and discontinuation of silver sulfadiazine cream 1% should be weighed against the therapeutic benefit being achieved.

In considering the use of topical proteolytic enzymes in conjunction with silver sulfadiazine cream 1%, the possibility should be noted that silver may inactivate such enzymes.

Silver Sulfadiazine Cream 1% is for topical use only. Avoid contact of silver sulfadiazine cream 1% with the eye.

Laboratory Tests

In the treatment of burn wounds involving extensive areas of the body, the serum sulfa concentrations may approach adult therapeutic levels (8 mg% to 12 mg%). Therefore, in these patients it would be advisable to monitor serum sulfa concentrations. Renal function should be carefully monitored and the urine should be checked for sulfa crystals. Absorption of the propylene glycol vehicle has been reported to affect serum osmolality, which may affect the interpretation of laboratory tests.