SULMEPRIM PEDIATRIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULMEPRIM PEDIATRIC (SULMEPRIM PEDIATRIC).
Sulfamethoxazole inhibits bacterial dihydropteroate synthase, blocking folate synthesis; trimethoprim inhibits bacterial dihydrofolate reductase, blocking folate reduction; sequential blockade leads to bactericidal effect.
| Metabolism | Sulfamethoxazole undergoes acetylation and glucuronidation; trimethoprim undergoes oxidation (CYP3A4) and glucuronidation. Both are primarily renally excreted. |
| Excretion | Renal excretion accounts for approximately 70% (as unchanged sulfamethoxazole and trimethoprim) and 20% as metabolites; biliary/fecal elimination is minor at <10%. |
| Half-life | Terminal elimination half-life: Sulfamethoxazole 9–12 hours, Trimethoprim 8–11 hours; prolonged in renal impairment (creatinine clearance <15 mL/min) requiring dose adjustment. |
| Protein binding | Sulfamethoxazole: ~70% bound primarily to albumin; Trimethoprim: ~44% bound to albumin. |
| Volume of Distribution | Sulfamethoxazole: 0.21–0.36 L/kg; Trimethoprim: 1.3–1.8 L/kg. Indicates extensive tissue distribution for trimethoprim, including CSF, lungs, and kidneys. |
| Bioavailability | Oral: ≥90% for both components; well absorbed from gastrointestinal tract. |
| Onset of Action | Oral: Therapeutic effect typically within 24–48 hours; intravenous: within 6–12 hours for systemic infections. |
| Duration of Action | Duration 12 hours; dosing interval commonly every 12 hours. Clinical effect persists as long as drug levels exceed MIC; typically 2–3 days after last dose for susceptible organisms. |
For Pneumocystis jirovecii pneumonia (PCP): 15-20 mg/kg/day (based on trimethoprim component) intravenously divided every 6-8 hours for 14-21 days. For other infections: 8-10 mg/kg/day (trimethoprim) orally or intravenously divided every 12 hours.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl 15-30 mL/min: reduce dose by 50% and increase interval to every 12 hours. CrCl <15 mL/min: use only with therapeutic drug monitoring and extended intervals (e.g., every 24-48 hours); consider alternative. Hemodialysis: administer after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% and monitor. Child-Pugh C: avoid use due to risk of hepatotoxicity and accumulation. |
| Pediatric use | For PCP: 15-20 mg/kg/day (trimethoprim) intravenously divided every 6 hours for 21 days. For UTI: 6-12 mg/kg/day (trimethoprim) orally divided every 12 hours for 10 days. Maximum daily dose (trimethoprim): 20 mg/kg/day. |
| Geriatric use | Monitor renal function closely; adjust dose based on CrCl (see renal adjustment). Avoid use if sulfonamide allergy. Increased risk of hyperkalemia with high doses; monitor serum potassium. Use with caution in patients with folate deficiency. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SULMEPRIM PEDIATRIC (SULMEPRIM PEDIATRIC).
| Breastfeeding | Small amounts excreted in breast milk; M/P ratio 0.3 (sulfamethoxazole). Considered compatible with breastfeeding if infant healthy; monitor for jaundice or rash. |
| Teratogenic Risk | First trimester: Folate antagonist effect increases risk of neural tube defects; contraindicated unless benefit outweighs risk. Second/third trimesters: Risk of kernicterus in neonates due to bilirubin displacement from albumin; avoid near term. |
| Fetal Monitoring |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hepatic necrosis have been reported. Co-administration with leucovorin in Pneumocystis jirovecii pneumonia may increase mortality.
| Serious Effects |
["Hypersensitivity to sulfonamides, trimethoprim, or any component","History of drug-induced immune thrombocytopenia with sulfonamides or trimethoprim","Megaloblastic anemia due to folate deficiency","Severe renal impairment (CrCl <15 mL/min) unless dialysis is available","Infants <2 months of age (except for treatment of congenital toxoplasmosis)","Pregnancy at term or nursing mothers (risk of kernicterus in neonates)","Concomitant use with dofetilide (increased risk of ventricular arrhythmias)"]
| Precautions | ["Monitor for hypersensitivity reactions (rash, fever, arthralgia) and discontinue immediately","Risk of hemolytic anemia in G6PD-deficient patients","Risk of kernicterus in neonates with hyperbilirubinemia; avoid in infants <2 months","Risk of hyperkalemia due to trimethoprim's potassium-sparing diuretic effect","Risk of hypoglycemia, especially in renal impairment or with concurrent sulfonylureas","Adequate fluid intake to prevent crystalluria and stone formation","Hematologic monitoring (CBC) for megaloblastic anemia, granulocytopenia, or thrombocytopenia","Use cautiously in elderly patients, those with folate deficiency, or renal/hepatic impairment"] |
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| Monitor for hemolysis in G6PD-deficient patients; complete blood counts, renal function; fetal ultrasound for neural tube defects if exposure in first trimester. |
| Fertility Effects | No established effects on fertility in humans. May reduce folate levels, potentially impacting oocyte quality; folate supplementation recommended. |