Mafenide acetate, USP is a synthetic antimicrobial agent designated chemically as a-amino-p- toluenesulfonamide monoacetate. It has the following structural formula:

C₇H₁₀N₂O₂S • C₂H₄O₂
M.W. 246.29

Mafenide acetate, USP is a white, crystalline powder which is freely soluble in water.

SULFAMYLON® For 5% Topical Solution is provided in packets containing 50 g of sterile mafenide acetate to be reconstituted in 1000 mL of Sterile Water for irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. After mixing, the solution contains 5% w/v of mafenide acetate. The solution is an antimicrobial preparation suitable for topical administration. The solution Is not for Injection. The reconstituted solution may be held up to 28 days after preparation if stored in unopened containers. ONCE A CONTAINER IS OPENED, ANY UNUSED PORTION SHOULD BE DISCARDED AFTER 48 HOURS. Store the reconstituted solution at 20° to 25°C (68° to 77°F). Limited storage periods at 15° to 30°C (59° to 86°F) are acceptable.

SULFAMYLON® For 5% Topical Solution is indicated for use as an adjunctive topical antimicrobial agent to control bacterial infection when used under moist dressings over meshed autografts on excised burn wounds.

SULFAMYLON® For 5% Topical Solution: Directions for Preparation of the Solution: SULFAMYLON® (mafenide acetate) For 5% Topical Solution is supplied as a sterile powder and is to be reconstituted with Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. Aseptic techniques should be observed during preparation of the solution. Pre- measured quantities of 50 g of mafenide acetate powder are provided in sterile packets. The entire quantity of SULFAMYLON® should be emptied into a suitable container which contains 1000 mL of Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP and mixed until completely dissolved. The reconstituted solution may be held up to 28 days after preparation if stored in unopened containers. ONCE A CONTAINER IS OPENED, ANY UNUSED PORTION SHOULD BE DISCARDED AFTER 48 HOURS. Store the reconstituted solution at 20° to 25°C (68° to 77°F). Limited storage periods at 15° to 30°C (59° to 86°F) are acceptable. Not for Injection - For Topical Use Only.

Directions for Use of the Solution: The grafted area should be covered with one layer of fine mesh gauze. An eight-ply bum dressing should be cut to the size of the graft and wetted with SULFAMYLON® 5% SOLUTION using an irrigation syringe and/or irrigation tubing until leaking is noticeable. If irrigation tubing is used, the tubing should be placed over the bum dressing in contact with the wound and covered with a second piece of eight-ply dressing. The irrigation dressing should be secured with a bolster dressing and wrapped as appropriate. The gauze dressing should be kept wet. In clinical studies, this has been accomplished by irrigating with a syringe or injecting the solution into the irrigation tubing every 4 hours or as necessary. If irrigation tubing is not used, the gauze dressing may be moistened every 6-8 hours or as necessary to keep wet.

Wound dressings maybe left undisturbed, except for the irrigations, for up to five days. Additional soaks may be initiated until graft take is complete. Maceration of skin may result from wet dressings applied for intervals as short as 24 hours. Treatment is usually continued until autograft vascularization occurs and healing is progressing (typically occurring in about 5 days). Safety and effectiveness have not been established for longer than 5 days for an individual grafting procedure.

If allergic manifestations occur during treatment with SULFAMYLON® 5% SOLUTION, discontinuation of treatment should be considered. If acidosis occurs and becomes difficult to control, particularly in patients with pulmonary dysfunction, discontinuing the soaks with the mafenide acetate solution for 24 to 48 hours may aid in restoring acid-base balance (see PRECAUTIONS section). Dressing changes and monitoring the site for bacterial growth during this interruption should be adjusted accordingly.

SULFAMYLON® (mafenide acetate, USP) For 5% Topical Solution is available in packets (NDC 51079-624-84) containing 50 g of sterile mafenide acetate to be prepared using 1000 mL Sterile Water for Irrigation, USP or 0.9% Sodium Chloride Irrigation, USP. (See DOSAGE AND ADMINISTRATION: SULFAMYLON® For 5% Topical Solution: Directions for Preparation of the Solution.) The packets are supplied as follows:

Carton of five 50 g packets

NDC 51079-624-85

Recommended Storage:

Packets - Store PACKETS in a dry place at room temperature 15° to 30°C (59° to 86°F).

Prepared Solution - Store SOLUTION at 20° to 25°C (68° to 77°F) with excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]

The solution may be held for up to 28 days if stored in unopened containers.

ONCE A CONTAINER IS OPENED, ANY UNUSED SOLUTION MUST BE DISCARDED WITHIN 48 HOURS.

Distributed By: UDL Laboratories, Inc. Rockford, IL 61103. REVISED APRIL 2006. FDA rev date: 12/18/2002

In the clinical setting of severe bums, it is often difficult to distinguish between an adverse reaction to mafenide acetate and bum sequelae. In a clinical study of pediatric patients with acute bums requiring autografts who received SULFAMYLON® 5% SOLUTION in addition to double antibiotic solution (DAB) wound therapy (neomycin sulfate 40 mg and polymyxin B 200,000 units/liter), the incidence of rash (4.6%) and itching (2.8%) in the group which received SULFAMYLON® 5% Solution was not different from that experienced with (DAB) dressings alone (5.7% and 1.3%, respectively).

From other clinical settings, a single case of bone marrow depression and a single case of an acute attack of porphyria have been reported following therapy with mafenide acetate. Fatal hemolytic anemia with disseminated intravascular coagulation, presumably related to a glucose-6-phosphate dehydrogenase deficiency, has been reported following therapy with mafenide acetate. The following adverse reactions have been reported with topical mafenide acetate therapy:

Dermatologlc and Allergic: Pain or burning sensation, rash and pruritus (often localized to the area covered by the wound dressing), erythema, skin maceration from prolonged wet dressings, facial edema, swelling, hives, blisters, eosinophilia.

Respiratory or Metabolic: Tachypnea, hyperventilation, decrease in pCOa, metabolic acidosis, increase in serum chloride.

No information provided.

Fatal hemolytic anemia with disseminated intravascular coagulation, presumably related to a glucose-6-phosphate dehydrogenase deficiency, has been reported following therapy with mafenide acetate.

General: Mafenide acetate and its metabolite, p-carboxybenzenesulfonamide, inhibit carbonic anhydrase, which may result in metabolic acidosis, usually compensated by hyperventilation. In the presence of impaired renal function, high blood levels of mafenide acetate and its metabolite may exaggerate the carbonic anhydrase inhibition. Therefore, close monitoring of acid-base balance is necessary, particularly in patients with extensive second-degree or partial thickness bums and in those with pulmonary or renal dysfunction. Some bum patients treated with mafenide acetate have also been reported to manifest an unexplained syndrome of masked hyperventilation with resulting respiratory alkalosis (slightly alkaline blood pH, low arterial pC02, and decreased total C02); change in arterial p02 is variable. The etiology and significance of these findings are unknown.

Mafenide acetate should be used with caution in bum patients with acute renal failure.

Fungal colonization may occur concomitantly with reduction of bacterial growth in the bum wound. However, systemic fungal infection through the infected bum wound is rare.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

No long-term animal studies have been performed to evaluate the carcinogenic potential of mafenide acetate; however, the drug did not induce mutations in L5178Y mouse lymphoma cells at the TK locus.

Animal studies have not been performed to evaluate the potential effects of mafenide acetate on fertility.

Pregnancy: Teratogenic Effects. Pregnancy Category C: A teratology study performed in rats using oral doses of up to 600 mg/kg/day revealed no evidence of harm to the fetus due to mafenide acetate. There are no adequate data regarding the potential reproductive toxicity of mafenide acetate in a non-rodent species, nor are there adequate and well-controlled studies in pregnant women. Mafenide acetate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is not known whether mafenide acetate is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from mafenide acetate, 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.

Pediatric Use: The safety and effectiveness of SULFAMYLON® For 5% Topical Solution have been established in the age groups 3 months to 16 years. Geriatric Use: No studies have been conducted to specifically examine the effects of mafenide acetate on bum wounds in geriatric patients.

Single oral doses of 2000 mg/kg of mafenide acetate as a 5% solution did not cause mortality or clinical symptoms of toxicity in rats.

SULFAMYLON® For 5% Topical Solution is contraindicated in patients who are hypersensitive to mafenide acetate. It is not known whether there is cross sensitivity to other sulfonamides.

Mechanism of Action:

The mechanism of action of mafenide is not known, but is different from that of the sulfonamides. Mafenide is not antagonized by pABA, serum, pus or tissue exudates, and there is no correlation between bacterial sensitivities to mafenide and to the sulfonamides. Its activity is not altered by changes in the acidity of the environment. The osmolality of the 5% topical solution is approximately 340 mOsm/kg.

Absorption and Metabolism: Applied topically, mafenide acetate diffuses through devascularized areas. Approximately 80% of a mafenide acetate dose is delivered to burned tissue over four hours following topical application of the 5% solution. Following application of mafenide acetate cream and solution, peak mafenide concentrations in human burned skin tissue occur at two and four hours, respectively. Peak tissue concentrations are similar following administration of the solution or cream. Once absorbed, mafenide is rapidly converted to an inactive metabolite (p-carboxybenzenesulfonamide) which is cleared through the kidneys. Clinical studies have shown that when applied topically to burns as an 11.2% mafenide acetate cream, blood levels of the parent drug peaked at 2 hours following application, ranging from 26 to 197 ug/mL for single doses of 14 to 77 g of mafenide acetate. Metabolite levels peaked at 3 hours, ranging from 10 to 340 ug/mL. Twenty-four hours after application, combined parent and metabolite blood levels had fallen to pretreatment levels.

Antimicrobial Activity: Mafenide acetate exerts broad bacteriostatic action against many gram-negative and gram-positive organisms, including Pseudomonas aeruginosa and certain strains of anaerobes.

In Vitro Cytotoxicity: Data from in vitro studies on cell culture suggests that mafenide acetate may have a deleterious effect on human keratinocytes. The clinical significance of this information is unknown.

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.

MAFENIDE ACETATE SOLUTION - TOPICAL

(MAY-feh-nide)

COMMON BRAND NAME(S): Sulfamylon

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

HOW TO USE: Follow all instructions for proper preparation and use of this drug. Consult your pharmacist.

Wash hands before and after using this medication. Use with wound dressings on the skin only. Soak the dressing completely with this medication. Keep the dressing wet by applying this medication every 6 to 8 hours or as directed by your doctor.

Length of treatment is based on your medical condition and response to treatment.

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

Tell 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 redness may occur. If any of these effects persist or worsen, tell 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: blisters, fast breathing, nausea, vomiting, diarrhea, headache, change in alertness, shaking (tremors), seizures.

Tell your doctor immediately if any of these rare but very serious side effects occur: weakness, dark urine, stomach/abdominal pain, arm/leg/back pain, fast heartbeat.

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 mafenide, tell your doctor or pharmacist if you are allergic to it; or to other sulfa drugs (e.g., sulfamethoxazole); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: lung problems (e.g., asthma), kidney disease, metabolism problems (e.g., glucose-6-phosphate dehydrogenase deficiency-G6PD), blood disorders.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Because of the possible harm to the infant, breast-feeding is not recommended while using this drug. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist 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 your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may 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 can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

This medication has been prescribed for your current condition only. Do not use it later on other wounds unless told to do so by your doctor. A different medication may be necessary in that case.

Laboratory and/or medical tests (e.g., wound cultures, acid-base balance, complete blood counts) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store unmixed packets at room temperature between 59-86 degrees F (15-30 degrees C) away from moisture. Do not store in the bathroom.

Mix the powder with the correct solution, and then close the container tightly. After mixing, if the container stays closed, you may store it for up to 28 days between 68-77 degrees F (20-25 degrees C). Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Once a container is opened for use, the solution is good for only 48 hours. Discard any unused portion. 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.