BACTRIM PEDIATRIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BACTRIM PEDIATRIC (BACTRIM PEDIATRIC).
Bactrim (sulfamethoxazole/trimethoprim) is a combination of two antifolate agents. Sulfamethoxazole inhibits dihydropteroate synthase, blocking the conversion of PABA to dihydrofolic acid. Trimethoprim inhibits dihydrofolate reductase, preventing the reduction of dihydrofolic acid to tetrahydrofolic acid. Sequential blockade of folate synthesis leads to bacteriostasis.
| Metabolism | Sulfamethoxazole is metabolized via acetylation and glucuronidation; trimethoprim is metabolized via oxidation (demethylation) and conjugation. CYP450 enzymes have minor involvement. |
| Excretion | Renal: sulfamethoxazole 85% (30% unchanged, rest as acetylated and glucuronide conjugates), trimethoprim 60-80% (10-30% unchanged). Fecal/biliary: <4%. |
| Half-life | Sulfamethoxazole: 9-12 hours (prolonged in renal impairment; up to 30 hours with CrCl <30 mL/min). Trimethoprim: 8-10 hours (prolonged to 20-30 hours in severe renal impairment). |
| Protein binding | Sulfamethoxazole: 70% bound to albumin. Trimethoprim: 42-46% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Sulfamethoxazole: 0.15-0.3 L/kg. Trimethoprim: 1.3-2.0 L/kg indicating extensive tissue distribution. |
| Bioavailability | Oral: sulfamethoxazole 100%; trimethoprim 100% (both well absorbed). |
| Onset of Action | Oral: clinical effect within 2-3 days for urinary tract infections; antibiotic concentrations in urine reach therapeutic levels within 2 hours. |
| Duration of Action | Therapeutic effect persists for the dosing interval (every 12 hours); bacteriostatic action continues until drug levels fall below MIC. |
| Molecular Weight | Sulfamethoxazole: 253.28 Da; Trimethoprim: 290.32 Da; Combination: Weighted average varies per ratio (typical 5:1 ratio gives average ~261 Da). |
Oral: 160 mg trimethoprim / 800 mg sulfamethoxazole (one DS tablet) every 12 hours for 14 days. For Pneumocystis jirovecii pneumonia: 15-20 mg/kg/day of trimethoprim component divided every 6-8 hours.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl >30 mL/min: No adjustment. CrCl 15-30 mL/min: Reduce dose by 50% (e.g., one DS tablet every 24 hours). CrCl <15 mL/min: Contraindicated (unless with hemodialysis). For PJP: CrCl 15-29 mL/min: 15-20 mg/kg/day (trimethoprim) divided every 8 hours; CrCl <15 mL/min: Not recommended. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Caution; consider reducing dose or monitoring liver function. Child-Pugh Class C: Avoid use due to potential hepatotoxicity and altered metabolism. |
| Pediatric use | Trimethoprim component dosing: 8 mg/kg/day divided every 12 hours for urinary tract infection or otitis media. For Pneumocystis jirovecii pneumonia (PJP) prophylaxis: 150 mg/m2/day of trimethoprim divided every 12 hours, given 3 times per week. For PJP treatment: 15-20 mg/kg/day of trimethoprim divided every 6-8 hours. Maximum daily dose: 960 mg trimethoprim. |
| Geriatric use | Monitor renal function and adjust dose based on CrCl. Increased risk of hyperkalemia, hematologic toxicity, and adverse reactions. Consider starting at lower end of dosing range. Avoid in patients with CrCl <15 mL/min. |
| 1st trimester | Avoid during first trimester due to potential teratogenic effects (folate antagonist). Use only if benefit outweighs risk. |
| 2nd trimester | Use with caution; risk of hyperbilirubinemia and kernicterus in neonates if given near term. Avoid if possible. |
| 3rd trimester | Contraindicated near term due to risk of kernicterus from sulfonamide displacement of bilirubin. Avoid during pregnancy unless essential for serious infection. |
Clinical note
Comprehensive clinical and safety monograph for BACTRIM PEDIATRIC (BACTRIM PEDIATRIC).
| Placental transfer | Both sulfamethoxazole and trimethoprim cross the placenta. Sulfamethoxazole reaches fetal plasma levels approximately 70-100% of maternal levels; trimethoprim approximately 50-60%. Degree of transfer is sufficient to achieve therapeutic concentrations in fetal tissues. |
| Breastfeeding | Sulfamethoxazole and trimethoprim are excreted into breast milk in low concentrations. Potential risk of kernicterus in jaundiced or G6PD-deficient infants. Avoid in nursing mothers of premature or ill infants. Use only if clearly needed. |
■ 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 have been reported. Use in pregnant women at term and in nursing mothers may cause kernicterus.
| Serious Effects |
Hypersensitivity to sulfonamides, trimethoprim, or any componentMegaloblastic anemia due to folate deficiencySevere hepatic or renal impairment (CrCl <15 mL/min) if not for PCP treatmentPregnancy near term (risk of kernicterus)Breastfeeding in infants with hyperbilirubinemia or G6PD deficiencyConcurrent use with dofetilide (risk of QT prolongation and torsades de pointes)
| Precautions | Monitor for hypersensitivity reactions, blood dyscrasias, and hepatic injury. Caution in elderly, folate deficiency, impaired renal/hepatic function, G6PD deficiency, and severe allergies or bronchial asthma. Avoid in infants <2 months of age. Use with caution in patients with porphyria or thyroid dysfunction. |
| Food/Dietary | Avoid high-potassium foods if at risk for hyperkalemia (e.g., bananas, oranges, salt substitutes). May reduce folic acid levels; encourage folate-rich foods (leafy greens, legumes). Take with food if GI upset occurs. Avoid alcohol due to disulfiram-like reaction. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: associated with increased risk of neural tube defects, cardiovascular malformations, and urinary tract anomalies due to folate antagonism (trimethoprim). Second and third trimesters: risk of kernicterus in the newborn due to sulfamethoxazole displacing bilirubin from albumin. Avoid during pregnancy, especially in the first and third trimesters. |
| Fetal Monitoring | Monitor maternal CBC, renal function, and liver function. Fetal ultrasound for anomalies if exposed in first trimester. Neonatal monitoring for jaundice, kernicterus, and hemolytic anemia after delivery. |
| Fertility Effects | No clinically significant effects on fertility reported in humans. In animal studies, high doses of trimethoprim have been associated with impaired fertility due to folate metabolism disruption, but relevance to humans is minimal at therapeutic doses. |
| Clinical Pearls | Bactrim Pediatric (sulfamethoxazole/trimethoprim) is contraindicated in infants <2 months due to risk of kernicterus. Monitor for hyperkalemia, especially in elderly or renal impairment. Use with caution in folate deficiency; supplement folinic acid if prolonged therapy. Avoid in G6PD deficiency due to hemolytic anemia risk. |
| Patient Advice | Take with a full glass of water to prevent crystalluria. · Complete full course even if symptoms improve. · Avoid prolonged sun exposure; use sunscreen. · Report rash, fever, sore throat, or bruising immediately. · Do not use if allergic to sulfa drugs or thiazide diuretics. |