Sulfonamides (Vaginal)
1) Sulfanilamide
2) Triple Sulfa
VA CLASSIFICATION
Primary: GU301
Commonly used brand name(s): AVC1; Sultrin2; Trysul2.
Another commonly used name for triple sulfa is
sulfathiazole, sulfacetamide, and sulfabenzamide .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Anti-infective (vaginal)—
Indications
Unaccepted
The U.S. Food and Drug Administration (FDA) announced on May 31, 1979, that its Anti-infective and Topical Drugs Advisory Committee and Fertility and Maternal Health Advisory Committee, as well as other studies, had concluded there was no adequate evidence that the then-available vaginal sulfonamides formulations were effective either for the treatment of vulvovaginitis caused by Candida albicans , Trichomonas vaginalis , or Gardnerella vaginalis (Haemophilus vaginalis) or for relief of the symptoms of these conditions.
In addition, in the opinion of USP medical experts, triple sulfa vaginal preparations are not effective for any indication, including vulvovaginitis caused by Gardnerella vaginalis and use as a deodorant in saprophytic infections following radiation therapy. Also, USP medical experts do not recommend the use of vaginal sulfonamides, including the reformulated single-entity preparations, for the treatment of fungal infections of the vagina. {07}
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
Sulfabenzamide: 276.32 {02}
Sulfacetamide: 214.25 {02}
Sulfanilamide: 172.21 {02}
Sulfathiazole: 255.32 {02}
Sulfisoxazole: 267.31 {02}
Mechanism of action/Effect:
Sulfonamides—See Sulfonamides (Systemic) .
Absorption:
Sulfonamides are absorbed through the vaginal mucosa.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to one sulfonamide may be sensitive to other sulfonamides also.
Patients sensitive to furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors may be sensitive to sulfonamides also.
Use of topical sulfonamides may lead to sensitization, resulting in hypersensitivity reactions with subsequent topical or systemic use of the medication.
Carcinogenicity/Tumorigenicity
Studies in rats have shown that long-term administration of sulfonamides may cause thyroid malignancy. However, rats appear to be especially susceptible to the goitrogenic effects of sulfonamides. {11}
Pregnancy/Reproduction
Pregnancy—
Safe use of vaginal sulfonamides during pregnancy has not been established {06}. Sulfonamides are absorbed from the vaginal mucosa, readily cross the placenta, and appear in the fetal circulation. Fetal serum concentrations are approximately 50 to 90% of maternal serum concentrations. Adequate and well-controlled studies of most sulfonamides have not been done in either animals or humans. However, studies in rats and mice given high oral doses (7 to 25 times the human therapeutic dose) have shown that certain short-, intermediate-, and long-acting sulfonamides cause a significant increase in the incidence of cleft palate and other bony abnormalities in the fetus. {04} {09}
FDA Pregnancy Category C {04} {09}.
Breast-feeding
Sulfonamides are absorbed from the vaginal mucosa and are distributed into breast milk {04}. Use is not recommended in nursing mothers since sulfonamides may cause hyperbilirubinemia {07} in the infant. {09} In addition, sulfonamides may cause hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD)–deficient neonates. {07}
Pediatrics
No information is available on the relationship of age to the effects of sulfonamides in pediatric patients.
Geriatrics
No information is available on the relationship of age to the effects of sulfonamides in geriatric patients.
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
Glucose-6-phosphate dehydrogenase (G6PD) deficiency (hemolytic anemia may occur in G6PD-deficient patients)
Hepatic function impairment (sulfonamides are metabolized in the liver; may cause hyperbilirubinemia in nursing infants)
Porphyria (sulfonamides may precipitate an acute attack of porphyria)
Renal function impairment{06}{07}
Sensitivity to sulfonamides, furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors or, depending on product, to peanut oil, lanolin, or parabens{06}
Side/Adverse Effects
Note: Treatment should be discontinued if local or systemic toxicity or hypersensitivity occurs. {09} One case of agranulocytosis has occurred on use of vaginal triple sulfa cream, and Stevens-Johnson syndrome has occurred rarely and can be fatal {06}.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence less frequent
Hypersensitivity (itching, burning, skin rash, redness, swelling, or other sign of irritation not present before therapy){09}
Incidence rare
Skin reaction, local (burning at site of application){09}{12}
Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
Rash or irritation of penis of sexual partner{07}
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Sulfonamides (Vaginal) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to sulfonamides, furosemide, thiazide diuretics, sulfonylureas, or carbonic anhydrase inhibitors, or, depending on product, to peanut oil, lanolin, or parabens
Pregnancy—Sulfonamides are absorbed from vaginal mucosa and appear in fetal circulation
Breast-feeding—Distributed into breast milk; not recommended for use in nursing mothers
Proper use of this medication
Reading patient instructions before using
Proper administration technique; checking with physician before using applicator if pregnant
» Compliance with full course of therapy, even if menstruation begins
» Proper dosing
Missed dose: Inserting as soon as possible; not inserting if almost time for next dose
» Proper storage
Precautions while using this medication
Checking with physician if no improvement within a few days
Protecting clothing because of possible soiling with vaginal sulfonamides; avoiding the use of tampons
»
Using hygienic measures to cure infection and prevent reinfection
Wearing cotton panties instead of synthetic underclothes
Wearing only freshly washed underclothes
» Use of condom by partner to prevent reinfection; possible need for concurrent treatment of male partner; continuing medication if intercourse occurs during treatment
» Use of douche for hygienic purposes, if advised by doctor, prior to next dose; not overfilling vagina with douche solution; avoiding use of a douche during pregnancy
Side/adverse effects
Sulfonamides may cause thyroid malignancy with long-term administration in rats; however, rats may be more susceptible to goitrogenic effects of sulfonamides
Signs of potential side effects, especially hypersensitivity or local skin reaction
General Dosing Information
Treatment should be continued for 30 days or through one complete menstrual cycle, unless otherwise directed by physician. {09}
SULFANILAMIDE
Vaginal Dosage Forms
SULFANILAMIDE VAGINAL CREAM
Usual adult and adolescent dose
Intravaginal, 1 applicatorful (approximately 6 grams) one or two times a day for thirty days. {09}
Usual pediatric dose
Use and dose have not been established {04} {09}.
Strength(s) usually available
U.S.—
15% (Rx) [AVC (methylparaben) (propylene glycol) (propylparaben){09}][Generic]{04}
Canada—
15% (Rx) [AVC (methylparaben) (propylene glycol) (propylparaben){11}]
Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer. Protect from freezing. {01}
Stability:
Sulfanilamide vaginal cream darkens with age. However, this does not affect potency. {09}
Auxiliary labeling:
• For the vagina.
• Continue medicine for full time of treatment.
Note: When dispensing, include patient instructions and brochure.
SULFANILAMIDE VAGINAL SUPPOSITORIES
Usual adult and adolescent dose
Intravaginal, 1 suppository one or two times a day for thirty days {09}.
Usual pediatric dose
Use and dose have not been established.
Strength(s) usually available
U.S.—
1.05 grams (Rx) [AVC (methylparaben) (propylparaben){09}]
Canada—
Not commercially available.
Packaging and storage:
Store below 30 °C (86 °F), in a well-closed container, unless otherwise specified by manufacturer {09}. Protect from freezing and moisture {01}.
Auxiliary labeling:
• For the vagina.
• Continue medicine for full time of treatment.
Note: When dispensing, include patient instructions and brochure.
TRIPLE SULFA
Vaginal Dosage Forms
TRIPLE SULFA VAGINAL CREAM USP
Usual adult and adolescent dose
Intravaginal, 1 applicatorful (approximately 4 to 5 grams) {07} two times a day for four to six days. The dose may then be reduced to one-half or one-fourth applicatorful two times a day. {06}
Usual pediatric dose
Use and dose have not been established {06}.
Strength(s) usually available
U.S.—
3.42% of sulfathiazole, 2.86% of sulfacetamide, and 3.7% of sulfabenzamide (Rx) [Sultrin (methylparaben) (peanut oil) (propylparaben) (propylene glycol){05}] [Trysul (methylparaben) (peanut oil) (propylparaben){05}][Generic]
Canada—
3.42% of sulfathiazole, 2.86% of sulfacetamide, and 3.7% of sulfabenzamide (Rx) [Sultrin (lanolin) (methylparaben) (peanut oil) (propylparaben) (propylene glycol){12}]
Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F) {06}, unless otherwise specified by manufacturer. Store in a well-closed, light-resistant container or in a collapsible tube. Protect from freezing. {01}
Auxiliary labeling:
• For the vagina.
• Continue medicine for full time of treatment.
Note: When dispensing, include patient instructions and brochure.
TRIPLE SULFA VAGINAL TABLETS USP
Usual adult and adolescent dose
Intravaginal, 1 tablet two times a day for ten days. May be repeated if necessary. {05}
Usual pediatric dose
Use and dose have not been established.
Strength(s) usually available
U.S.—
172.5 mg of sulfathiazole, 143.75 mg of sulfacetamide, and 184 mg of sulfabenzamide (Rx) [Sultrin{05}][Generic]{08}
Canada—
Not commercially available.
Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. {05} Store in a well-closed, light-resistant container. {01}
Auxiliary labeling:
• For the vagina.
• Continue medicine for full time of treatment.
Note: When dispensing, include patient instructions and brochure.
Revised: 08/13/1998
References
- United States pharmacopeia. The national formulary. USP 23rd revision (January 1, 1995). NF 18th ed. (January 1, 1995). Rockville, MD: The United States Pharmacopeial Convention Inc, 1995. p. 1448-9.
- Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention Inc; 1997. p. 691, 694, 695.
- FDA Consumer. 1984 Feb: 32-4.
- Sulfanilamide package insert (Teva—US), Rev 12/96, Rec 02/13/98.
- Sultrin (Ortho-McNeil). In: PDR Physicians' desk reference. 52nd ed. 1998. Montvale, NJ: Medical Economics Company Inc; 1998. p. 2054.
- Triple sulfa package insert (Trysul, Savage—US), Rev 7/94, Rec 7/17/98.
- Reviewers' responses to monograph revision of 8/1/86.
- Triple sulfa (generic). In: Red book 1998. Montvale, NJ: Medical Economics Data, 1997. p. 577-8.
- Sulfanilamide cream/suppositories package insert (AVC, Merrell Dow—US), Rev 3/96, Rec 1/25/98.
- Reviewers' responses to monograph revision of 3/28/87.
- Sulfanilamide vaginal cream (AVC, Hoechst Marion Roussel). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 160.
- Triple Sulfa vaginal cream (Sultrin, Janssen-Ortho). In: Gillis MC, editor. CPS Compendium of pharmaceuticals and specialties. 33rd ed. Ottawa: Canadian Pharmacists Association; 1998. p. 1593.
