GYNE-SULF
Clinical safety rating: caution
Comprehensive clinical and safety monograph for GYNE-SULF (GYNE-SULF).
GYNE-SULF (sulfisoxazole) is a sulfonamide antibiotic that inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA) for the active site of dihydropteroate synthase, thereby blocking folate synthesis and bacterial growth.
| Metabolism | Primarily hepatic via acetylation and glucuronidation; minor metabolism via cytochrome P450 enzymes. |
| Excretion | Renal: 80% (unchanged). Biliary/fecal: 15% as metabolites. Metabolized by reduction and acetylation; parent and metabolites undergo glomerular filtration and active tubular secretion. |
| Half-life | Terminal elimination half-life: 10-12 hours (normal renal function). In renal impairment (CrCl <30 mL/min): up to 24-48 hours. |
| Protein binding | 20-30% bound to albumin. |
| Volume of Distribution | 0.3-0.5 L/kg. Distributes into vaginal secretions, breast milk, and cerebrospinal fluid. |
| Bioavailability | Oral: 80-90% (well absorbed). Intravaginal: 5-20% (systemic absorption, variable). |
| Onset of Action | Oral: 1-2 hours (bacteriostatic effect). Intravaginal: 3-5 days for symptom relief. |
| Duration of Action | Oral: 12 hours (bacteriostatic concentrations maintained with BID dosing). Intravaginal: course of 7-14 days required for eradication. |
| Molecular Weight | 250.3 |
Intravaginal: One full applicator (approximately 5 g of 2% cream, containing 100 mg sulfanilamide) inserted intravaginally once daily (at bedtime) for 7-10 days. Alternatively, one vaginal suppository (containing 250 mg sulfanilamide) inserted intravaginally twice daily (morning and bedtime) for 7-10 days.
| Dosage form | CREAM |
| Renal impairment | Contraindicated in patients with significant renal impairment (CrCl <30 mL/min). For CrCl 30-50 mL/min: reduce dose by 50% or use alternative therapy. Monitor renal function closely. Insufficient data for precise modifications. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For Child-Pugh class B: use with caution, monitoring liver function; consider alternative therapy. No specific dose reduction established. For Child-Pugh class A: no adjustment necessary. |
| Pediatric use | Not recommended for use in children under 12 years due to lack of safety and efficacy data. For adolescents 12 years and older: administer same as adult dose (one applicator of 2% cream per day at bedtime or one 250 mg suppository twice daily). |
| Geriatric use | Use with caution in elderly patients due to potential age-related renal impairment. Perform renal function assessment before initiating therapy; if CrCl is ≥50 mL/min, standard adult dosing may be used. Monitor for adverse effects, especially hypersensitivity reactions and local irritation. |
| 1st trimester | Generally avoided due to potential teratogenicity; use only if benefit outweighs risk. |
| 2nd trimester | Caution advised; sulfonamides may cause kernicterus in neonates if used near term. |
| 3rd trimester | Contraindicated in third trimester as sulfonamides displace bilirubin, increasing risk of kernicterus. |
Clinical note
Comprehensive clinical and safety monograph for GYNE-SULF (GYNE-SULF).
| Placental transfer | Sulfonamides readily cross the placenta; fetal serum concentrations can reach 50-90% of maternal levels. |
| Breastfeeding | Sulfonamides are excreted into breast milk; risk of kernicterus, hemolytic anemia in G6PD-deficient infants, and allergic reactions. Use only if alternative therapies are not available and infant can be monitored for adverse effects. |
■ FDA Black Box Warning
Sulfonamides have been associated with fatal hypersensitivity reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Use only for conditions for which they are indicated.
| Serious Effects |
Hypersensitivity to sulfonamides or any componentPorphyriaThird trimester of pregnancyInfants less than 2 months of age (except in congenital toxoplasmosis)Severe hepatic or renal impairment
| Precautions | Fatal hypersensitivity reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis); hematologic toxicity (agranulocytosis, aplastic anemia); hepatotoxicity; renal toxicity (crystalluria); caution in patients with impaired renal or hepatic function, glucose-6-phosphate dehydrogenase deficiency, porphyria, or thyroid dysfunction. |
| Food/Dietary | No known food interactions. Avoid alcohol as it may exacerbate vaginal irritation. |
Loading safety data…
| Lactation Rating |
| L3 - Moderately Safe (use with caution) |
| Teratogenic Risk | FDA Pregnancy Category B. First trimester: No evidence of teratogenicity in animal studies; limited human data show no increased risk of major malformations. Second and third trimesters: Avoid use due to potential for neonatal jaundice and kernicterus from bilirubin displacement by sulfonamides, especially near term. Sulfonamides cross the placenta and can cause hemolytic anemia in G6PD-deficient neonates. |
| Fetal Monitoring | Monitor complete blood count and liver function tests in mother; assess for fetal distress by nonstress test and biophysical profile in third trimester if used; ultrasound for fetal growth and amniotic fluid volume. Newborn should be monitored for jaundice, hemolysis, and kernicterus if exposed near term. |
| Fertility Effects | No known adverse effects on fertility in animal studies; effects on human fertility not reported. Sulfonamides may cause reversible spermatogenesis inhibition in high doses, but clinical significance unknown. |
| Clinical Pearls | GYNE-SULF (sulfanilamide vaginal cream) is used for bacterial vaginosis. It is a sulfonamide; caution in patients with sulfa allergy. Avoid use during pregnancy near term due to risk of kernicterus. Monitor for local irritation or overgrowth of resistant organisms. |
| Patient Advice | Use exactly as prescribed, typically twice daily for 7-10 days. · Complete full course even if symptoms improve. · Avoid sexual intercourse during treatment. · May cause local burning or irritation; report severe reactions. · Inform provider if pregnant or breastfeeding. · Discard any unused cream after treatment. |