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 |
| Molecular Weight | 250.3 Da |
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 | Contraindicated due to risk of congenital malformations, particularly neural tube defects, based on animal studies and limited human data. |
| 2nd trimester | Contraindicated; may cause fetal harm including nephrotoxicity and oligohydramnios. |
| 3rd trimester | Contraindicated; risk of neonatal hemorrhage and maternal/fetal bleeding due to interference with vitamin K metabolism. |
Clinical note
Comprehensive clinical and safety monograph for MICROSUL (MICROSUL).
| Placental transfer | Crosses placenta readily; fetal levels can reach 50-80% of maternal serum concentrations. |
| Breastfeeding | Excreted into breast milk in small amounts; potential for kernicterus in neonates due to displacement of bilirubin from albumin binding sites. Avoid breastfeeding if possible. |
■ 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 |
PregnancyBreastfeedingSevere hepatic impairmentKnown hypersensitivity to sulfonamidesInfants less than 2 months of age (except for 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. |
| Food/Dietary | Avoid alcohol during therapy and for 3 days after stopping due to disulfiram-like reaction. High potassium foods (bananas, oranges, potatoes) should be limited, especially in elderly or those on ACE inhibitors, due to risk of hyperkalemia. Maintain adequate fluid intake. |
Loading safety data…
| Lactation Rating |
| L5 |
| 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. |
| 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. |
| Clinical Pearls | Microsul (sulfamethoxazole/trimethoprim) is a folate synthesis inhibitor. Use with caution in sulfonamide allergy, G6PD deficiency, and renal impairment. Monitor for hypersensitivity reactions and hyperkalemia, especially in elderly on ACE inhibitors. Adjust dose if CrCl <30 mL/min. Avoid in pregnancy near term due to kernicterus risk. |
| Patient Advice | Take with a full glass of water to prevent crystalluria. · Complete the full course even if symptoms improve. · Avoid prolonged sun exposure; use sunscreen. · Report any rash, fever, or sore throat immediately. · May cause photosensitivity, diarrhea, or metallic taste. |