SILVADENE 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 SILVADENE 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. SILVADENE Cream 1% (silver sulfadiazine) spreads easily and can be washed off readily with water.

SILVADENE Cream 1% (silver sulfadiazine) 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.

Prompt institution of appropriate regimens for care of the burned patient is of prime importance and includes the control of shock and pain. The burn wounds are then cleansed and debrided, and SILVADENE Cream 1% (silver sulfadiazine) is applied under sterile conditions. The burn areas should be covered with SILVADENE Cream 1% at all times. The cream should be applied once to twice daily to a thickness of approximately 1/16 inch. Whenever necessary, the cream should be reapplied to any areas from which it has been removed by patient activity. Administration may be accomplished in minimal time because dressings are not required. However, if individual patient requirements make dressings necessary, they may be used.

Reapply immediately after hydrotherapy.

Treatment with SILVADENE Cream 1% should be continued until satisfactory healing has occurred, or until the burn site is ready for grafting. The drug should not be withdrawn from the therapeutic regimen while there remains the possibility of infection except if a significant adverse reaction occurs.

SILVADENE Cream 1% (silver sulfadiazine) is available in jars containing 50 g (NDC 61570-131-50), 400 g (NDC 61570-131-40), and 1000 g (NDC 61570-131-98) and tubes containing 20 g (NDC 61570-131-20) and 85 g (NDC 61570-131-85).

REFERENCES

1. Caffee F, Bingham H. Leukopenia and silver sulfadiazine. J Trauma. 1982;22: 586-587.

2. Jarret F, Ellerbe S, Demling R. Acute leukopenia during topical burn therapy with silver sulfadiazine. Amer J Surg. 1978;135:818-819.

3. Kiker RG, Carvajal HF, Micak RP, Larson DL. A controlled study of the effects of silver sulfadiazine on white blood cell counts in burned children. J Trauma. 1977; 17:835-836.

Prescribing Information as of July 2003. Distributed by: Monarch Pharmaceuticals, Inc., Bristol, TN 37620. (A wholly owned subsidiary of King Pharmaceuticals, Inc.) Manufactured by: King Pharmaceuticals, Inc., Bristol, TN 37620. FDA Rev date: 1/29/2004

Several cases of transient leukopenia have been reported in patients receiving silver sulfadiazine therapy.1,2,3 Leukopenia associated with silver sulfadiazine administration is primarily characterized by decreased neutrophil count. Maximal white blood cell depression occurs within 2 to 4 days of initiation of therapy. Rebound to normal leukocyte levels follows onset within 2 to 3 days. Recovery is not influenced by continuation of silver sulfadiazine therapy. An increased incidence of leukopenia has been reported in patients treated concurrently with cimetidine.

Other infrequently occurring events include skin necrosis, erythema multiforme, skin discoloration, burning sensation, rashes, and interstitial nephritis.

Reduction in bacterial growth after application of topical antibacterial agents has been reported to permit spontaneous healing of deep partialthickness burns by preventing conversion of the partial thickness to full thickness by sepsis. However, reduction in bacterial colonization has caused delayed separation, in some cases necessitating escharotomy in order to prevent contracture.

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 Stevens-Johnson syndrome and exfoliative dermatitis; gastrointestinal reactions; hepatitis and hepatocellular necrosis; CNS reactions; and toxic nephrosis.

No information provided.

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 SILVADENE Cream 1% (silver sulfadiazine) in some cases of glucose-6-phosphate dehydrogenase-deficient individuals may be hazardous, as hemolysis may occur.

General

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

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

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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term dermal toxicity studies of 24 months' duration in rats and 18 months' in mice with concentrations of silver sulfadiazine three to ten times the concentration in SILVADENE Cream 1% revealed no evidence of carcinogenicity.

Pregnancy

Teratogenic Effects.

Pregnancy Category B. A reproductive study has been performed in rabbits at doses up to three to ten times the concentration of silver sulfadiazine in SILVADENE Cream 1% and has revealed no evidence of harm to the fetus due to silver sulfadiazine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly justified, especially in pregnant women approaching or at term. (See CONTRAINDICATIONS.)

Nursing Mothers

It is not known whether silver sulfadiazine is excreted in human milk. However, sulfonamides are known to be excreted in human milk, and all sulfonamide derivatives are known to increase the possibility of kernicterus. Because of the possibility for serious adverse reactions in nursing infants from sulfonamides, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Geriatric Use

Of the total number of subjects in clinical studies of Silvadene Cream 1%, seven percent were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. (See CONTRAINDICATIONS.)

No information provided.

SILVADENE Cream 1% (silver sulfadiazine) 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, SILVADENE 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.

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 SILVADENE® Cream 1% (silver sulfadiazine) Concentration of Silver Sulfadiazine Number of Sensitive Strains/Total Number of Strains Tested

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

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

SILVER SULFADIAZINE - TOPICAL

(SILL-ver sull-fuh-DYE-uh-zeen)

COMMON BRAND NAME(S): Silvadene

USES: This medication is used alone or with other medications to help prevent and treat wound infections in patients with severe burns. Silver sulfadiazine belongs to a class of drugs known as topical antibiotics. It works by killing bacteria that may infect an open wound. This helps to decrease the risk of the bacteria spreading to surrounding skin or to the blood, causing a serious blood infection (sepsis).

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to help prevent and treat wound infections in patients with skin ulcers from constant pressure (bedsores).

HOW TO USE: Apply this medication to a wound using sterile techniques (e.g., using sterile rubber gloves and sterile application swab or tongue depressor), usually 1-2 times daily or as directed by your doctor. The layer of cream should be about one-sixteenth of an inch (1-2 millimeters) thick. The wound should be covered with the cream at all times. Bandages may be applied over the cream, but this is not necessary. If some of the cream rubs off the wound, reapply it immediately. The cream should also be reapplied immediately after hydrotherapy.

Treatment usually continues until the wound is completely healed.

Dosage is based on your medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day.

Inform your doctor if your condition persists or worsens or if you notice increasing redness/tenderness of the skin around the wound.

SIDE EFFECTS: Pain, burning, or itching may occur at the site of application. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: change in skin color.

Tell your doctor immediately if any of these rare but very serious side effects occur: fever, chills, cough, breathing problems, new diarrhea, sore throat, decrease in the amount of urine, blackening of skin, new/severe tiredness, weakness, bluish fingernails/lips, pale skin, fast heartbeat, persistent nausea, stomach/abdominal pain, dark urine, yellowing eyes/skin, easy bruising/bleeding.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using silver sulfadiazine, tell your doctor or pharmacist if you are allergic to it; or to other sulfa antibiotics; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a certain blood enzyme deficiency (G-6-PD, glucose-6-phosphate dehydrogenase).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, liver problems, low white blood cells.

Silver sulfadiazine should not be used to treat premature babies or newborns during the first 2 months of life.

Tell your doctor if you are pregnant before using this medication. This medication is not recommended for use during the last month of pregnancy because of possible harm to the unborn baby. Consult your doctor for more details.

Based on information for similar drugs, this medication may pass into breast milk. Therefore, breast-feeding while using this medication is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: skin products that contain sodium sulfacetamide, topical proteolytic enzymes for removing non-living tissue/fluids from wounds.

If you are currently using any of these medications listed above, tell your doctor or pharmacist before starting silver sulfadiazine.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: This medication may be harmful if swallowed. If swallowing or overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., white blood cell count, liver function tests) should be performed periodically to check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. This medicine should be on the wounds at all times as directed by your doctor.

STORAGE: Store the US product at room temperature at 68 degrees F (20 degrees C) away from light and moisture. Do not store in the bathroom.

Store the Canadian product at 46-77 degrees F (8-25 degrees C) away from light and moisture. The Canadian 250- and 500-gram jars should be discarded 24 hours after opening. The Canadian tubes should be discarded 7 days after opening. Do not store in the bathroom.

Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.