TRIPLE SULFOID
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIPLE SULFOID (TRIPLE SULFOID).
Triple sulfoid (sulfadiazine, sulfamethazine, sulfamerazine) competes with para-aminobenzoic acid (PABA) to inhibit dihydropteroate synthase, blocking bacterial folate synthesis.
| Metabolism | Primarily hepatic via acetylation and glucuronidation; CYP450 involvement not significant. |
| Excretion | Renal: ~70% as unchanged drug; hepatic metabolism: ~20%; fecal: ~10% |
| Half-life | 10-12 hours in normal renal function; prolonged to 24-48 hours in severe renal impairment (CrCl <30 mL/min) |
| Protein binding | 85-90% bound to albumin |
| Volume of Distribution | 0.2-0.3 L/kg, indicating limited extravascular distribution |
| Bioavailability | Oral: 70-80% (first-pass metabolism reduces from ~100%) |
| Onset of Action | Oral: 2-4 hours; Intravenous: 15-30 minutes |
| Duration of Action | Oral: 12 hours; Intravenous: 6-8 hours |
2 tablets orally every 6 hours for 10-14 days; each tablet contains sulfadiazine 270 mg, sulfamerazine 270 mg, and sulfamethazine 270 mg.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: interval every 8-12 hours; CrCl 15-29 mL/min: interval every 12-24 hours; CrCl <15 mL/min: contraindicated. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50% or extend interval; Child-Pugh Class C: contraindicated. |
| Pediatric use | Children >2 months: 25-50 mg/kg/dose (based on total sulfonamide content) orally every 6 hours; maximum 2 g/day. |
| Geriatric use | Start at lower end of dosing range; monitor renal function and adjust per renal adjustment; avoid in severe renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRIPLE SULFOID (TRIPLE SULFOID).
| Breastfeeding | Sulfonamides are excreted into breast milk with M/P ratio approximately 0.5-1.0. Risk of kernicterus in premature infants, hyperbilirubinemia, or G6PD-deficient infants. Contraindicated in breastfeeding infants with G6PD deficiency or jaundice. Use alternatives (e.g., penicillins, cephalosporins) when possible. |
| Teratogenic Risk | Triple sulfoid (a combination of sulfonamides) poses a teratogenic risk primarily due to sulfamethoxazole. First trimester: Association with neural tube defects, cardiovascular anomalies, and cleft palate (OR 2.1-3.3). Second trimester: Risk of kernicterus if administered near delivery due to bilirubin displacement. Third trimester: Avoid after 32 weeks due to risk of neonatal hyperbilirubinemia and kernicterus. Overall, use only if benefit clearly outweighs risk. |
■ FDA Black Box Warning
WARNING: FATALITIES ASSOCIATED WITH SULFONAMIDES HAVE OCCURRED DUE TO STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA, AND OTHER BLOOD DYSCRASIAS.
| Serious Effects |
Hypersensitivity to sulfonamides; porphyria; severe hepatic or renal impairment; pregnancy at term and breastfeeding (risk of kernicterus in neonates); infants <2 months of age (except for congenital toxoplasmosis).
| Precautions | Hypersensitivity reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis; hematologic toxicity including agranulocytosis and aplastic anemia; hepatotoxicity; renal damage due to crystalluria; photosensitivity; hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency. |
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| Fetal Monitoring | Monitor complete blood count (CBC) for hemolytic anemia, leukopenia; liver function tests (LFTs); renal function (BUN, creatinine); urine analysis for crystalluria; bilirubin levels near term. Fetal ultrasound for structural anomalies if first-trimester exposure. |
| Fertility Effects | No established adverse effects on fertility in humans. Animal studies show no significant impact on reproductive performance. |