Silver Sulfadiazine

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) , 25 g (NDC 61570-131-25), 50 g (NDC 61570-131-55) and 85 g (NDC 61570-131-85).

Store at Controlled Room Temperature 20° to 25°C (68° to 77°F).

Distributed by: Pfizer Inc, New York, NY 10017. Revised: Jan 2016

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

Apply the missed dose as soon as you remember. Your burn wounds should be kept covered with silver sulfadiazine cream at all times.

Take silver sulfadiazine exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Silver Sulfadiazine dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Silver Sulfadiazine is available in the following doses:

• Silver Sulfadiazine Topical 1% Topical Cream
• Silver Sulfadiazine Topical Compounding Powder

Contraindications

• Pregnant women approaching or at term.a b c

• Premature neonates or neonates ≤2 months of age.a b c

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

Warnings/Precautions

Warnings

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

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

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

Sensitivity Reactions

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

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

General Precautions

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

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

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

Specific Populations

Category B.a b

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

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.)

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

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

Common Adverse Effects

Local effects (pain, burning, itching, rash),a b c e k leukopenia.a b c d e m

Absorption

Bioavailability

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

Plasma Concentrations

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

Distribution

Extent

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

Elimination

Elimination Route

Systemically absorbed sulfadiazine excreted in urine.a b c e

Storage

Topical

15–30°C.a c

For all patients taking silver sulfadiazine:

• If you have an allergy to silver sulfadiazine or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you are pregnant and near term.
• If you are breast-feeding or plan to breast-feed.

Children:

• If your child is a premature baby or is a newborn. Do not give silver sulfadiazine to a premature baby or a newborn.
• If your child is younger than 2 months of age. Do not give this medicine to an infant younger than 2 months of age.

This medicine may interact with other drugs or health problems.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take silver sulfadiazine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

(SIL ver sul fa DYE a zeen)

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Cream, External:

Silvadene: 1% (20 g, 25 g, 50 g, 85 g, 400 g, 1000 g) [contains methylparaben, propylene glycol]

SSD: 1% (25 g, 50 g, 85 g, 400 g) [contains cetyl alcohol, methylparaben, propylene glycol]

Thermazene: 1% (20 g [DSC], 50 g [DSC], 85 g [DSC], 400 g [DSC], 1000 g [DSC]) [contains methylparaben, propylene glycol]

Generic: 1% (20 g, 25 g, 50 g, 85 g, 400 g)

Hypersensitivity to silver sulfadiazine or any component of the formulation; pregnant women approaching or at term; premature infants or neonates ≤2 months of age.

Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Concerns related to adverse effects:

• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Fungal proliferation may rarely occur in and below the eschar.

• Systemic effects: Systemic absorption may be significant and adverse reactions may occur.

Disease-related concerns:

• G6PD deficiency: Use with caution in patients with G6PD deficiency; hemolysis may occur.

• Hepatic impairment: Use with caution in patients with hepatic impairment; sulfadiazine may accumulate.

• Renal impairment: Use with caution in patients with renal impairment; sulfadiazine may accumulate.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007).

Other warnings/precautions:

• Appropriate use: For topical use only. Avoid contact with eyes.