Mafenide (Topical) (Monograph)

Brand name: Sulfamylon
Drug class: Antibacterials

Introduction

Synthetic anti-infective agent.

Uses for Mafenide (Topical)

Treatment and Prevention of Burn Infections

Mafenide acetate cream is used topically as adjunctive therapy in second- and third-degree burns to prevent septicemia caused by susceptible organisms, especially Pseudomonas aeruginosa.

Control of bacterial growth may prevent conversion of second-degree (partial-thickness) wounds to third-degree (full-thickness) wounds; however, delayed eschar separation reported.

Although controlled, comparative studies are lacking, mafenide and silver sulfadiazine are considered by many clinicians to be among the topical anti-infective agents of choice in burn patients.

Mafenide appears to penetrate burn eschar better than silver sulfadiazine and may be more effective in minimizing the growth of bacteria and early treatment of wound sepsis. Unlike mafenide, silver sulfadiazine does not alter acid-base balance and does not have a limited duration of therapy and area of topical application; softening action of silver sulfadiazine cream may aid in eschar removal and preparation of wound for grafting.

Alternative therapies include wet dressings of 0.5% silver nitrate; appears to be of equal efficacy as mafenide cream; mafenide cream may cause more pain on application.

Mafenide acetate solution is used topically as adjunctive therapy to control bacterial infections under moist dressings over meshed autografts on excised burn wounds.

Mafenide (Topical) Dosage and Administration

Administration

Topical Administration

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

Cream

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

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

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

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

Solution

Apply topically as a 5% reconstituted solution.

Consult manufacturer’s information for complete directions for use.

Reconstitution

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. (See Storage under Stability.)

Dosage

Available as mafenide acetate; dosage expressed in terms of mafenide.

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

Pediatric Patients

Treatment and Prevention of Burn Infections

Topical (Cream)

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

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

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

Topical (Solution)

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.

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

Adults

Treatment and Prevention of Burn Infections

Topical (Cream)

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

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

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

Topical (Solution)

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.

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

Dosage Modification for Toxicity

Topical (Cream, Solution

Allergic manifestations: Consider mafenide discontinuance if hypersensitivity reactions occur. (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. (See Systemic Acidosis under Cautions.)

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

Prescribing Limits

Pediatric Patients

Topical (Solution)

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

Adults

Topical (Solution)

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

Special Populations

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

Cautions for Mafenide (Topical)

Contraindications

• Known hypersensitivity to mafenide or any ingredient in the formulation. Unknown if cross-sensitivity to other sulfonamides occurs. (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Warnings

Hemolytic Anemia

Fatal hemolytic anemia with disseminated intravascular coagulation reported, presumably related to glucose-6-phosphate dehydrogenase deficiency.

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions (e.g., rash, pruritus, facial edema, swelling, urticaria, blisters, erythema, eosinophilia) reported 10–14 days after initiation of therapy.

If hypersensitivity reaction occurs, consider discontinuing mafenide therapy temporarily or initiating concomitant antihistamine therapy.

Potential for cross-sensitivity with other sulfonamides is unknown.

Sulfite Sensitivity

Cream contains a sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

Major Toxicities

Systemic Acidosis

May cause systemic acidosis (tachypnea or hyperventilation, increased serum chloride concentration, and decreased arterial pCO₂). Closely monitor acid-base balance in patients with extensive second-degree (partial-thickness) burns, pulmonary dysfunction, or renal impairment. (See Dosage Modification for Toxicity under Dosage and Administration and see Pulmonary Dysfunction and also Renal Impairment under Cautions.)

Syndrome of marked hyperventilation with resulting respiratory alkalosis (slightly alkaline blood pH, low arterial pCO₂, decreased total CO₂) has been reported; change in arterial pO₂ is variable. Etiology and significance unknown.

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi, both in and below burn eschar.

Fungal colonization in wound and in and below burn eschar may occur concomitantly with reduction of bacterial growth; however, systemic fungal infection via dissemination through the burn wound is rare.

Pulmonary Dysfunction

Closely monitor acid-base balance in pulmonary dysfunction. (See Systemic Acidosis under Cautions.)

Specific Populations

Pregnancy

Category C.

Not recommended for women of childbearing potential unless the burned area covers >20% of total body surface area or the therapeutic benefits justify the possible risks to the fetus.

Lactation

Not known whether mafenide is distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Safety and efficacy of topical solution not established in infants <3 months of age.

Renal Impairment

Increased risk for metabolic acidosis in renal impairment due to substantial carbonic anhydrase inhibition. Closely monitor acid-base balance. (See Systemic Acidosis under Cautions.)

Use with caution in acute renal failure.

Common Adverse Effects

Pain on application, burning sensation.

Mafenide (Topical) Pharmacokinetics

Absorption

Bioavailability

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

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

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

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

Elimination Route

Rapidly excreted in urine as metabolite.

Stability

Storage

Topical

Cream

Avoid exposure to excessive heat (>40°C).

Solution

Packets: 15–30°C in a dry place.

Reconstituted solution: 20–25°C (may be exposed to 15–30°C); up to 28 days in unopened containers. Once opened, discard within 48 hours.

Actions and Spectrum

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

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

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

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

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

• Less active against Escherichia coli and Proteus species.

• Resistance not reported.

Advice to Patients

• Importance of understanding that mafenide preparations are for external topical use only.

• Importance of informing clinician if any signs or symptoms of an allergic reaction occur (e.g., rash, itching, facial or other swelling, blisters, redness).

• Importance of informing clinicians of existing concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., kidney or lung disease).

• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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