MICROSUL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MICROSUL (MICROSUL).
MICROSUL inhibits bacterial dihydropteroate synthase, preventing folate synthesis, and also acts as a competitive antagonist of para-aminobenzoic acid (PABA).
| Metabolism | MICROSUL is primarily metabolized in the liver via N-acetylation and glucuronidation; 70-90% of drug is excreted renally as metabolites and unchanged drug. |
| Excretion | Renal: 70% unchanged; biliary/fecal: 30% as metabolites |
| Half-life | Terminal elimination half-life: 24-36 hours; prolonged in renal impairment |
| Protein binding | 95-98% bound to albumin |
| Volume of Distribution | 0.8-1.2 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 80-90% |
| Onset of Action | Oral: 1-2 hours; Intravenous: 15-30 minutes |
| Duration of Action | 12-24 hours; dose-dependent, extended in renal dysfunction |
Adult: 160 mg/800 mg (trimethoprim/sulfamethoxazole) orally every 12 hours for 14 days; intravenous dosing: 8-10 mg/kg/day (as trimethoprim) divided every 6, 8, or 12 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl >30 mL/min: standard dose; CrCl 15-30 mL/min: 50% of usual dose every 12 hours; CrCl <15 mL/min: contraindicated for urinary tract infections; use with caution and monitor for toxicity. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: use with caution, monitor liver function; Child-Pugh Class C: avoid use due to risk of hepatotoxicity. |
| Pediatric use | 8-12 mg/kg/day (as trimethoprim) divided every 12 hours orally or intravenously; for Pneumocystis jirovecii pneumonia: 15-20 mg/kg/day (as trimethoprim) divided every 6 hours. |
| Geriatric use | Start at lower end of dosing range due to age-related renal impairment; monitor renal function and electrolytes; avoid in severe hepatic impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MICROSUL (MICROSUL).
| Breastfeeding | Sulfamethoxazole (component of MICROSUL) is excreted into breast milk. M/P ratio approximately 0.5-1.0. Caution in breastfeeding infants with G6PD deficiency, hyperbilirubinemia, or prematurity. American Academy of Pediatrics considers compatible with breastfeeding if infant is healthy, but alternative agents preferred. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: sulfonamides may increase risk of neural tube defects, cardiovascular malformations; data limited. Second and third trimesters: risk of kernicterus in neonates if administered near term due to bilirubin displacement; avoid use after 32 weeks gestation. |
■ FDA Black Box Warning
Sulfonamides have been associated with fatal reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. MICROSUL should be discontinued at the first appearance of skin rash or any sign of adverse reaction.
| Serious Effects |
Hypersensitivity to sulfonamides or any component; marked hepatic damage; severe renal insufficiency; porphyria; concurrent use with methenamine; pregnancy at term and during lactation; infants <2 months of age (except for treatment of congenital toxoplasmosis).
| Precautions | Caution in patients with severe allergy or bronchial asthma; may cause hemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficiency; caution in impaired hepatic or renal function; maintain adequate fluid intake to prevent crystalluria; avoid in porphyria. |
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| Fetal Monitoring | Monitor maternal for hypersensitivity reactions (Stevens-Johnson syndrome), hepatotoxicity, nephrotoxicity, and hematologic toxicity (agranulocytosis, aplastic anemia). Fetal monitoring includes ultrasound for structural anomalies if exposed in first trimester, and assessment for neonatal jaundice and kernicterus if exposed near term. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment of fertility at therapeutic doses. However, sulfonamides may affect spermatogenesis in some animal species at high doses; clinical relevance unknown. |