TRIPLE SULFA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRIPLE SULFA (TRIPLE SULFA).
Inhibits bacterial dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR), blocking folate synthesis essential for nucleic acid production.
| Metabolism | Sulfamethoxazole: primarily via N-acetylation and glucuronidation; Trimethoprim: hepatic metabolism via oxidation and conjugation (CYP450 minimal involvement). |
| Excretion | 80-90% renal (glomerular filtration and tubular secretion) as unchanged drug and acetylated metabolites; 5-10% biliary/fecal. |
| Half-life | 6-12 hours (sulfadiazine 10-13h, sulfamerazine 16-24h, sulfamethazine 7-12h); prolonged in renal impairment. |
| Protein binding | 50-70% bound to albumin (sulfadiazine ~55%, sulfamerazine ~65%, sulfamethazine ~50%). |
| Volume of Distribution | 0.5-0.8 L/kg (distributes widely including CSF, pleural, peritoneal fluids). |
| Bioavailability | Oral: 80-100% (well absorbed from GI tract); IV: 100%. |
| Onset of Action | Oral: 1-4 hours; IV: immediate (minutes). |
| Duration of Action | 12-24 hours (depends on renal function and acetylator status); maintain therapeutic levels for 7-10 days. |
| Molecular Weight | 228.25 |
1 g orally every 12 hours for 10 days (as sulfadiazine, sulfamethazine, and sulfamerazine combination).
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: 1 g every 24 hours; CrCl 10-29 mL/min: 1 g every 48 hours; CrCl <10 mL/min: Not recommended. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated. |
| Pediatric use | 2 months or older: 50-60 mg/kg/day divided every 12 hours; maximum 3 g/day. |
| Geriatric use | Use with caution, monitor renal function; reduce dose as per renal adjustment; increase fluid intake to prevent crystalluria. |
| 1st trimester | Avoid; associated with congenital malformations (neural tube defects, cardiovascular) due to folate antagonism. |
| 2nd trimester | Use only if clearly needed; risk of kernicterus and hemolytic anemia in fetus. |
| 3rd trimester | Contraindicated; risk of kernicterus, hemolytic anemia, and methemoglobinemia in neonate. |
Clinical note
Comprehensive clinical and safety monograph for TRIPLE SULFA (TRIPLE SULFA).
| Placental transfer | Crosses placenta readily; achieves fetal serum concentrations 50-80% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low amounts; risk of kernicterus in premature or hyperbilirubinemic infants. Consider alternatives. |
| Lactation Rating |
■ FDA Black Box Warning
Fatalities associated with sulfonamide hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Contraindicated in patients with a history of sulfonamide hypersensitivity.
| Serious Effects |
Hypersensitivity to sulfonamidesPorphyriaInfants <2 months (except in congenital toxoplasmosis)Pregnancy (3rd trimester)Breastfeeding of premature or jaundiced infants
| Precautions | Severe hypersensitivity reactions (SJS/TEN), hematologic toxicity (monitor CBC), hepatotoxicity, renal impairment (adjust dose), hypoglycemia in elderly/non-insulin-dependent diabetes, kernicterus in neonates, caution with G6PD deficiency (hemolysis), advanced age, concomitant warfarin/phenytoin. |
| Food/Dietary | Avoid foods high in vitamin K (e.g., leafy greens) if also on warfarin; no specific dietary restrictions for this drug alone. Maintain high fluid intake (2-3 L/day) to prevent crystalluria. |
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| L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: sulfonamides are associated with a small increased risk of neural tube defects, cardiovascular malformations, and oral clefts based on some studies; however, the absolute risk is low. Second and third trimesters: risk of kernicterus in the newborn due to displacement of bilirubin from albumin, especially near term. Avoid use in third trimester. |
| Fetal Monitoring | Monitor maternal CBC, renal function, hepatic function, and urinalysis. In the neonate, monitor for signs of hemolytic anemia, jaundice, and kernicterus. Ultrasound for fetal anatomy if used in first trimester. |
| Fertility Effects | No well-documented effects on fertility. Sulfonamides may transiently reduce sperm count in males in animal studies, but clinical significance is unknown. |
| Clinical Pearls | Monitor renal function and urine output due to risk of crystalluria; ensure adequate hydration. Caution in G6PD deficiency as hemolysis may occur. Triple sulfa (sulfadiazine, sulfamerazine, sulfamethazine) is rarely used due to resistance; confirm susceptibility. Avoid in infants <2 months due to bilirubin displacement risk. |
| Patient Advice | Take with a full glass of water and drink extra fluids throughout the day to prevent kidney problems. · Complete the full course even if you feel better; do not skip doses. · Avoid prolonged sun exposure; use sunscreen as this drug may increase sun sensitivity. · Report immediately if you experience rash, fever, sore throat, unusual bleeding, or dark urine. · Inform your doctor if you have glucose-6-phosphate dehydrogenase deficiency or are pregnant/nursing. |