Mafenide is a synthetic anti-infective agent that is closely related chemically, but not pharmacologically, to the sulfonamides.
Mafenide acetate cream is used as an adjunct in the treatment of second- and third-degree burns to prevent septicemia caused by susceptible organisms, especially Pseudomonas aeruginosa. Treatment with mafenide acetate cream should begin after measures to control shock and pain have been instituted. Mafenide acetate cream has been shown to markedly reduce the incidence of sepsis in patients with second- and third-degree burns resulting in a decrease in the mortality rate of patients with burns covering 60% or less of the body surface. Reduction in bacterial growth also may prevent conversion of partial thickness wounds to full thickness.
Mafenide acetate cream containing 8.5% mafenide and wet dressings of 0.5% silver nitrate appear to be of equal effectiveness for controlling burn wound sepsis; however, application of mafenide acetate cream has been reported to cause more pain than application of 0.5% silver nitrate solution.
Mafenide acetate cream is applied topically. The potency of mafenide acetate cream is expressed in terms of mafenide. Each g of mafenide acetate cream provides the equivalent of 85 mg of mafenide. Dosage and administration recommendations are the same for both adults and pediatric patients.
Mafenide acetate cream may be applied to the cleansed, debrided burned areas once or twice daily with a sterile-gloved hand. The cream should be applied to a thickness of approximately 16 mm (one-sixteenth inch); thicker application is not recommended. The burned area should be covered with cream at all times. Whenever necessary, the cream should be reapplied to any areas from which it has been removed (e.g., by patient activity). If possible, the patient should be bathed daily, preferably in a whirlpool bath, to aid in debridement. Dressings are generally not required; if they are necessary, only a thin layer of dressing should be used. Dressings have been applied by some clinicians when the eschar begins to separate (16-20 days) in order to expedite the separation of the eschar.
Therapy with mafenide acetate cream is usually continued until healing is progressing well or until the site is ready for grafting. Mafenide acetate topical therapy should generally not be withdrawn from the therapeutic regimen while there is the possibility of infection; however, if allergic manifestations occur, discontinuance of mafenide acetate should be considered. If systemic acidosis occurs and is difficult to control, especially in patients with pulmonary dysfunction, discontinuing mafenide acetate therapy for 24-48 hours while continuing fluid therapy may aid in restoring acid-base balance.
Pain or burning sensation following application of mafenide acetate cream has been the most frequently reported adverse effect. Allergic reactions, including rash, pruritus, facial edema, swelling, urticaria, blisters, erythema, and eosinophilia, have occurred 10-14 days following initiation of mafenide acetate therapy. When allergic manifestations occur, temporary discontinuance of treatment or concomitant antihistamine therapy should be considered. A single case of bone marrow depression and a single case of an acute attack of porphyria have been reported following mafenide acetate therapy. Fatal hemolytic anemia with disseminated intravascular coagulation (presumably caused by glucose-6-phosphate dehydrogenase deficiency) has also been reported.
A delay in eschar separation, excoriation of new skin, excessive body water loss, and bleeding of the skin may occur following the application of mafenide acetate cream. Accidental ingestion of mafenide acetate cream has been reported to cause diarrhea.
Systemic acidosis, manifested by tachypnea or hyperventilation, increased serum chloride concentration, and decreased arterial pCO2, may occur rarely following topical application of mafenide acetate cream. If acidosis becomes difficult to control, particularly in patients with pulmonary dysfunction, discontinuing therapy for 24-48 hours while continuing fluid therapy may aid in restoring acid-base balance. Some burn patients treated with mafenide acetate cream have reportedly developed an unexplained syndrome of marked 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 importance of these findings are not known.
Precautions and Contraindications
Mafenide acetate should be applied with caution in patients who are hypersensitive to mafenide. It is not known whether there is cross-sensitivity between mafenide acetate and the sulfonamides. The commercially available formulation of Sulfamylon® topical cream contains sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.
Mafenide acetate cream should be used with caution in burn patients with acute renal failure. In the presence of renal impairment, high blood concentrations of mafenide and its metabolite may result in substantial carbonic anhydrase inhibition; therefore, close monitoring of acid-base balance is necessary, especially in patients with extensive second-degree or partial thickness burns and in patients with pulmonary or renal dysfunction.
Superinfection with nonsusceptible organisms, both in and below burn eschar, has occurred in burn wounds treated with mafenide acetate cream. Fungal colonization in and below burn eschar may occur concomitantly with reduction of bacterial growth in the burn wound; however, fungal dissemination through the burn wound is rare.
The use of mafenide acetate cream in pediatric patients is the same as that in adults, and the usual precautions and contranindications should be observed.
Pregnancy, Fertility, and Lactation
Safe use of mafenide during pregnancy has not been established. Use of mafenide acetate cream is not recommended for treatment in women of childbearing potential unless the burned area covers more than 20% of the body surface or the therapeutic benefits to the patient justify the possible risks to the fetus.
Animal reproduction studies with mafenide acetate cream have not been performed.
It is not known whether mafenide acetate is distributed into milk. Because of the potential for serious adverse reactions to mafenide acetate in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
The exact mechanism of action of mafenide has not been determined, but the drug appears to interfere with bacterial cellular metabolism.
As a topical antibacterial agent, mafenide has a wide spectrum of activity. Limited studies indicate that the drug is bacteriostatic against many gram-negative and gram-positive organisms and several strains of anaerobes. Mafenide appears to be most active in vitro against Clostridium species, Pseudomonas aeruginosa, staphylococci coagulase positive and negative, and hemolytic streptococci.
Escherichia coli and Proteus species appear to be less sensitive to mafenide. Development of resistant organisms has not been reported. The antibacterial activity of mafenide salts is not antagonized by aminobenzoic acid ( p -aminobenzoic acid), pus, or serum.
Mafenide salts are unsuitable for systemic antibacterial therapy as they are rapidly inactivated in the blood stream. As judged by clinical antibacterial effectiveness and demonstration of mafenide acetate and its metabolite in the blood following topical application of mafenide acetate cream, it appears that mafenide acetate diffuses through burn eschar.
Following absorption, mafenide acetate is rapidly metabolized to p -carboxybenzenesulfonamide, which is a weak carbonic anhydrase inhibitor. Impairment of the renal mechanism for buffering may occur during mafenide therapy, however, resulting in increased bicarbonate and decreased ammonia excretion through the kidneys. If compensatory hyperventilation is not adequate to remove carbon dioxide, systemic acidosis results. The occurrence of acidosis may be related to the amount of drug absorbed from the application site; the amount of drug absorbed is probably proportional to the size of the burn being treated. p -Carboxybenzenesulfonamide is rapidly excreted in urine, but mafenide acetate has not been detected in urine.
Mafenide is a synthetic anti-infective agent that is closely related chemically, but not pharmacologically, to the sulfonamides. Mafenide differs structurally from the sulfonamides in that it has a methylene group between the benzene ring and the amino nitrogen of the basic sulfanilamide structure. Mafenide is commercially available as the acetate salt in a water-miscible cream formulation that also contains parabens, sodium metabisulfite, and edetate disodium as preservatives. Mafenide acetate occurs as a white, crystalline powder and is freely soluble in water. The commercially available mafenide acetate cream has a pH of 6-7 and has a slight acetic odor.
Mafenide acetate cream should be stored in tight, light-resistant containers and exposure to excessive heat (i.e., temperatures exceeding 40°C) should be avoided.
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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Cream | 8.5% (of mafenide) | Sulfamylon® | Mylan |