Sulfamylon

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Administration

Topical Administration

Administer topically as a cream or solution; not for injection.a b c

Apply cream only after instituting appropriate measures to control shock and pain.a b

Apply to cleansed, debrided burn wounds using a sterile, gloved hand.a b

Bathe patient daily, preferably in a whirlpool bath, to aid in debridement.a b

Dressings generally not required; if necessary, use only a thin layer.a b Some clinicians apply dressings when the eschar begins to separate (16–20 days) to expedite the separation of the eschar.a

Apply topically as a 5% reconstituted solution.c

Consult manufacturer’s information for complete directions for use.c

Reconstitute 50-g packet of sterile mafenide acetate powder with 1 L of sterile water for irrigation or 0.9% sodium chloride irrigation by adding powder to solution in suitable container and mixing until completely dissolved.c (See Storage under Stability.)

Dosage

Available as mafenide acetate; dosage expressed in terms of mafenide.a b c

Each gram of mafenide acetate cream provides the equivalent of 85 mg of mafenide.a

Pediatric Patients

Children: Apply sufficient amount to cover affected area to a thickness of 1/16th inch, once or twice daily.a b Thicker application is not recommended.a b

Burned areas should be covered with cream at all times.a b Reapply whenever necessary if cream removed from any area.a b

Continue therapy until healing is progressing well or until site is ready for grafting.a b Generally, do not discontinue mafenide topical therapy while there is the possibility of infection.a b (See Dosage Modification for Toxicity under Dosage and Administration.)

Infants and children ≥3 months to 16 years of age: Inject solution into the irrigation tubing every 4 hours or irrigate dressing with a syringe every 6–8 hours; may repeat as necessary to keep dressing wet.c

May leave wound dressings undisturbed for up to 5 days, except for irrigations.c May initiate additional soaks until engraftment is complete.c Maceration of skin may result from wet dressings applied for intervals as short as 24 hours.c Continue treatment until autograft vascularization occurs and healing is progressing, usually about 5 days.c

Adults

Apply sufficient amount to cover affected area to a thickness of 1/16th inch, once or twice daily.a b Thicker application is not recommended.a b

Burned areas should be covered with cream at all times.a b Reapply whenever necessary if cream removed from any area.a b

Continue therapy until healing is progressing well or until site is ready for grafting.a b Generally, do not discontinue mafenide topical therapy while there is the possibility of infection.a b (See Dosage Modification for Toxicity under Dosage and Administration.)

Inject solution into the irrigation tubing every 4 hours or irrigate dressing with a syringe every 6–8 hours; may repeat as necessary to keep dressing wet.c

May leave wound dressings undisturbed for up to 5 days, except for irrigations.c May initiate additional soaks until engraftment is complete.c Maceration of skin may result from wet dressings applied for intervals as short as 24 hours.c Continue treatment until autograft vascularization occurs and healing is progressing, usually about 5 days.c

Allergic manifestations: Consider mafenide discontinuance if hypersensitivity reactions occur.a b c (See Sensitivity Reactions under Cautions.)

Systemic acidosis: If systemic acidosis occurs and is difficult to control, especially in pulmonary dysfunction, discontinuing mafenide therapy for 24–48 hours may aid in restoring acid-base balance.a b c (See Systemic Acidosis under Cautions.)

During the interruption in mafenide therapy, adjust dressing changes and monitoring of site for bacterial growth accordingly.c

Prescribing Limits

Pediatric Patients

Safety and efficacy not established for use >5 days for an individual grafting procedure.c

Adults

Safety and efficacy not established for use >5 days for an individual grafting procedure.c

Special Populations

No special population dosage recommendations at this time.a b c (See Pulmonary Dysfunction and also Renal Impairment under Cautions.)

Absorption

Bioavailability

Topically applied cream and solution diffuse through devascularized areas, including burn eschar.a b c Peak concentrations in burned skin tissue occur at 2 and 4 hours, respectively.c Peak tissue concentrations are similar for cream and solution.c

Peak plasma concentrations of topical cream and its metabolite occur at 2 and 3 hours, respectively.c

Distribution

Extent

Not known whether distributed into human milk.a b c

Elimination

Metabolism

Rapidly metabolized in the liver to p-carboxybenzenesulfonamide, a weak carbonic anhydrase inhibitor.a b c

Elimination Route

Rapidly excreted in urine as metabolite.a b c

• Exact mechanism of action unknown, but appears to interfere with bacterial cellular metabolism.a

• Related chemically, but not pharmacologically, to the sulfonamides.a c

• Not antagonized by p-aminobenzoic acid (PABA), pus, serum, or tissue exudates; activity not altered by environmental acidity changes.a b c

• Bacteriostatic against many gram-negative and gram-positive organisms and several strains of anaerobes.a b c

• Active in vitro against Clostridium species, Pseudomonas aeruginosa, coagulase-positive and-negative staphylococci, and hemolytic streptococci.a b c

• Less active against Escherichia coli and Proteus species.a

• Resistance not reported.a

Mafenide acetate, USP is a synthetic antimicrobial agent designated chemically as α-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.

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 burns and in those with pulmonary or renal dysfunction. Some burn 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 pCO2, and decreased total CO2); change in arterial pO2 is variable. The etiology and significance of these findings are unknown.

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

Fungal colonization may occur concomitantly with reduction of bacterial growth in the burn wound. However, systemic fungal infection through the infected burn 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 L5178Ymouse lymphoma cells at the TK locus.

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

Pregnancy

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 burn wounds in geriatric patients.

Applies to mafenide topical: topical cream, topical powder for solution, topical powder for suspension

Along with its needed effects, mafenide topical (the active ingredient contained in Sulfamylon) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking mafenide topical:

• Itching
• skin rash or redness
• swelling of face or skin
• wheezing or troubled breathing

• Bleeding or oozing of skin
• drowsiness
• fast, deep breathing
• nausea

• Black, tarry stools
• chest pain
• chills
• cough or hoarseness
• dark urine
• dizziness
• fever
• fluid-filled skin blisters
• light-colored stools
• lower back or side pain
• numbness to feet, hands and around mouth
• painful or difficult urination
• rapid shallow breathing
• sensitivity to the sun
• shortness of breath
• skin thinness
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• swollen glands
• unusual bleeding or bruising
• unusual tiredness or weakness
• yellow eyes or skin

Some side effects of mafenide topical may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Pain or burning feeling on treated area(s)

• Blisters
• flushing
• raised red swellings on the skin, lips, tongue, or in the throat
• redness of skin
• skin rash
• softening of the skin
• swelling
• unusually warm skin

Applies to mafenide topical: compounding powder, topical cream, topical powder for reconstitution

General

In the clinical setting of severe burns, it is difficult to distinguish between an adverse reaction to this drug and burn sequelae. In a clinical study in pediatric patients with acute burns requiring autografts who received this drug 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 who received this drug was not different from that experienced with DAB dressings alone (5.7% and 1.3%, respectively).[Ref]

Local

Frequency not reported: Pain, burning sensation, rash, pruritus, excoriation, bleeding[Ref]

Dermatologic

Frequency not reported: Erythema, skin maceration, hives, blisters[Ref]

Respiratory

Frequency not reported: Tachypnea, hyperventilation, partial pressure of carbon dioxide decreased[Ref]

Metabolic

Frequency not reported: Metabolic acidosis, serum chloride increased[Ref]

Hematologic

Frequency not reported: Eosinophilia, bone marrow depression, fatal hemolytic anemia, disseminated intravascular coagulation[Ref]

Other

Frequency not reported: Face edema, swelling, porphyria[Ref]

Some side effects of Sulfamylon may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.