Vademecum

SULFACETAMIDA

Description: Sulfacetamide is a synthetic sulfonamide antibiotic for ophthalmic or topical administration. Sulfacetamide, because it is water soluble and because a 30% solution has a pH of 7.4, is an ideal sulfonamide for ophthalmic administration. Despite the favorable pharmaceutical properties, use of sulfonamides in general has declined due to development of resistance. Sulfacetamide 10% lotion is used topically for the treatment of scaling dermatoses such as seborrheic dermatitis and seborrheic sicca, and also for topical bacterial skin infection caused by susceptible organisms. Sulfacetamide was approved by the FDA in 1946 for the treatment of conjunctivitis, corneal ulcers and other superficial eye infections caused by susceptible organisms. Mechanism of Action: Sulfacetamide inhibits bacterial dihydrofolate synthetase. This action interferes with the conversion of p-aminobenzoic acid (PABA) into folic acid, an essential component of bacterial development. Folic acid is a coenzyme responsible for the transport of one-carbon fragments from one molecule to another and is crucial during the synthesis of thymidine, purines, and certain amino acids. Sulfonamides do not affect bacterial cells that use preformed (dietary) folic acid or mammalian cells. Organisms that show susceptibility to sulfacetamide sodium are: streptococci, staphylococci, E. coli, Klebsiella pneumoniae, Pseudomonas pyocyanea, Salmonella species, Proteus vulgaris, Nocardia, and Actinomyces. Pharmacokinetics: Sulfacetamide is administered topically and ophthalmically. Ophthalmic sulfacetamide sodium penetrates ocular fluid and tissues. Systemic absorption produces concentrations that are inadequate for therapy but may be sufficient for sensitization to occur upon readministration. No pharmacokinetic data are available regarding systemic absorption following topical application to the head and scalp, but significant absorption has been reported. Sulfonamides are metabolized in the liver by N[4] -acetylation and the metabolites have no antibacterial activity. Excretion of parent drug and metabolites is via the kidneys through glomerular filtration.

Indications...Dosage The following organisms are generally considered susceptible to sulfacetamide in vitro: Actinomyces sp.; Chlamydia trachomatis; Enterobacter sp.; Escherichia coli; Haemophilus aegyptius; Klebsiella pneumoniae; Klebsiella sp.; Neisseria gonorrhoeae; Nocardia sp.; Proteus vulgaris; Salmonella sp.; Staphylococcus aureus (MSSA); Streptococcus pneumoniae; Streptococcus pyogenes (group A beta-hemolytic streptococci); Streptococcus sp.; Viridans streptococci. For the treatment of conjunctivitis, corneal ulcer and other superficial ophthalmic infections caused by susceptible organisms, and as adjunctive treatment in systemic sulfonamide therapy of chlamydial conjunctivitis including trachoma and inclusion conjunctivitis: Ophthalmic dosage (10% ophthalmic solution): Adults and children > 2 months: Instill 1ï¿½2 drops to the affected eye(s) every 1ï¿½3 hours during the day, less frequently at night. Dosage frequency depends on the severity of the infection. Ophthalmic dosage (30% ophthalmic solution): Adults and children > 2 months: Instill 1 drop to the affected eye(s) every 2 hours for conjunctivitis or corneal ulcers. For trachoma, instill 2 drops every 2 hours in conjunction with systemic sulfonamide therapy. Ophthalmic dosage (10% ophthalmic ointment): Adults and children > 2 months: Apply a small amount to the affected eye(s) 4 times per day and at bedtime. The ointment may be used adjunctively with sulfacetamide solutions. For the topical treatment of scaling dermatoses, such as seborrheic dermatitis, and seborrheic sicca: Topical application (10% lotion): Adults: Apply at bedtime to affected area, leave on overnight. For severe cases where there is crusting, heavy scaling and/or inflammation, apply twice per day. Repeat regimen until the eruption subsides, then apply once or twice per week or every other week to help prevent recurrence. Children: Safe use has not been established. For the treatment of secondary bacterial skin and skin structure infections due to organisms susceptible to sulfonamides: Topical application (10% lotion): Adults: Apply to the affected area 2ï¿½4 times daily until the infection has cleared. Children: Safe use has not been established. For the treatment of acne vulgaris: Topical application (10% lotion): Adults: Apply a thin film to the affected area twice per day. Patients with renal impairment: Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Administration Ophthalmic Administration ï¿½Apply topically to the eye taking care to avoid contamination. For ophthalmic use only. ï¿½Instruct patient on proper instillation of eye ointment or solution into the lower conjunctival sac (see Patient Information). ï¿½Do not to touch the tip of the dropper or tube to the eye, fingertips, or other surface. ï¿½The ointment may be applied at night in combination with daytime use of the solution or before application of an eye patch. Topical Administration ï¿½If the hair and scalp are oily or greasy, or if there is considerable debris, the application should be preceded by use of a non-irritating shampoo. Cleansing of the skin should be as frequent as necessary to insure intimate contact with the medication. ï¿½Rub lotion gently into cleansed affected area.

Contraindications The vehicles used in ophthalmic ointments have been implicated in retarding corneal wound healing, which may be sustained as a result of ocular trauma or ocular surgery. Improvements in ophthalmic ointment vehicles have largely addressed this situation, however manufacturers still warn that sulfacetamide sodium ophthalmic ointment may retard corneal wound healing. Sulfacetamide sodium ophthalmic ointment is not effective against fungal infection, viral infection, or against all types of bacterial infection. Continued use may result in overgrowth of non-susceptible organisms. Purulent exudate which contains para-aminobenzoic acid can inactivate sulfacetamide antibacterial activity. Because of structural similarity, sulfonamides should be used cautiously in patients with known allergic reactions to oral sulfonylureas, thiazide diuretics, or carbonic anhydrase inhibitors. Despite the chemical similarities between furosemide and sulfonamides and the logical conclusion that cross-sensitivity would occur, a thorough review of the published literature and direct communication with the manufacturer revealed no data supporting the conclusion that patients with sensitivity to sulfonamides also develop sensitivity to furosemide.[178] Less is known regarding the cross-sensitivity between sulfonamides and the other agents, although some clinicians doubt that significant risk exists.[53] Nevertheless, sulfacetamide should be used cautiously in patients with furosemide hypersensitivity, thiazide diuretic hypersensitivity, sulfonylurea hypersensitivity, or carbonic anhydrase inhibitor hypersensitivity. Although there is little systemic absorption from topical use of sulfonamides, the possibility of a hypersensitivity reaction exists. Patients known to have sulfonamide hypersensitivity should not be treated with sulfacetamide ophthalmic or topical preparations. Excretion of sulfacetamide sodium into breast milk has not been ascertained. The drug should be used with caution in breast-feeding women. Sulfonamides are classified as pregnancy category B, except for near-term pregnancy where they are classified as category D. In general, sulfonamides should be avoided in near-term pregnancy. Sulfonamides can displace bilirubin from protein binding sites and theoretically precipitate kernicterus in neonates. While this adverse reaction has occured when a sulfonamide was administered directly to the neonate, it has not been demonstrated in a newborn when exposed to the drug in utero. Since sulfacetamide is administered ophthalmically or topically, it seems even less likely than systemically administered sulfonamides to invoke this adverse reaction. Nevertheless, sulfonamides should be used with caution during near term pregnancy because of the potential risk of causing kernicterus in neonates. Do not use for premature or newborn infants up to the age of one month. Safe and effective use of sulfonamides in children has not been established.

Interactions Based on the possibility of in vitro antagonism, some drug compendia warn against using sulfacetamide sodium concomitantly with gentamicin sulfate. It is unclear if this interaction is clinically significant, or if this warning should be extended to other ophthalmically administered aminoglycosides such as tobramycin. Ester-type local anesthetics are metabolized to para-aminobenzoic acid, PABA. This compound, in turn, can antagonize the therapeutic actions of sulfonamides. Although this interaction may be more theoretical than real, whenever possible, ester-type local anesthetics should be avoided in patients receiving sulfonamides. Ester-type local anesthetics include: benzocaine, chloroprocaine, cocaine, procaine, propoxycaine, and tetracaine. Similarly, topical preparations containing para-aminobenzoic acid, PABA should not be used concomitantly with topical sulfonamides. Patients treated with prilocaine who are receiving sulfonamides concurrently are at greater risk for developing methemoglobinemia. Topical sulfonamides are incompatible with preparations containing silver. Sulfacetamide sodium should not be used with products containing silver salts, including ophthalmic preparations such as silver nitrate or mild silver protein. The addition of zinc sulfate solution to sulfacetamide solution will form a precipitate at certain concentrations of both drugs. Concomitant use of sulfacetamide sodium and ophthalmic preparations containing zinc salts is not recommended. Sulfonamides may cause photosensitization and may increase the photosensitizing effects of griseofulvin, phenothiazines, retinoids, sulfonylureas, tetracyclines, thiazide diuretics, and photosensitizing agents used during photodynamic therapy.

Adverse Reactions Ocular irritation, accompanied by stinging and burning may occur, especially with the 30% sulfacetamide sodium solution. Irritation to the skin after topical administration is uncommon. If irritation does occur, it is generally transient, but if persistent the medication should be discontinued. The use of topical sulfacetamide sodium may precipitate a hypersensitivity reaction in patients who have previously demonstrated sulfonamide hypersensitivity. There has been one case of Stevens-Johnson syndrome following sulfacetamide sodium ophthalmic ointment administration in a patient who had a history of bullous lesions following systemic sulfonamide therapy. Local hypersensitivity has also progressed to a lupus syndrome displaying lupus-like symptoms, in one case with a fatal outcome.

178. Schneiweiss F. Cross-sensitivity between sulfonamides and furosemide. Clin Pharm 1983;2:510.

53. Sullivan TJ. Cross-reactions among furosemide, hydrochlorothiazide, and sulfonamides. JAMA 1991;265:120ï¿½1.