SULMEPRIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULMEPRIM (SULMEPRIM).
Sulmeprim is a combination of sulfamethoxazole, a sulfonamide, and trimethoprim, a dihydrofolate reductase inhibitor. It inhibits sequential steps in bacterial folate synthesis, leading to bactericidal activity.
| Metabolism | Sulfamethoxazole is metabolized primarily via N-acetylation and glucuronidation; trimethoprim is metabolized via oxidative pathways and conjugation. Both are substrates of CYP2C9 and CYP3A4. |
| Excretion | Renal excretion of unchanged drug accounts for 70% of elimination; 20% is metabolized in the liver to inactive metabolites (glucuronide conjugates) and excreted in urine; 10% is eliminated in feces via biliary excretion. |
| Half-life | Terminal elimination half-life is 10-12 hours in patients with normal renal function, allowing twice-daily dosing. In severe renal impairment (CrCl <30 mL/min), half-life extends to >20 hours, requiring dose adjustment. |
| Protein binding | Approximately 40-50% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.3-0.5 L/kg, indicating distribution primarily into extracellular fluid and well-perfused tissues. Achieves therapeutic concentrations in lung, kidney, and prostate tissue. |
| Bioavailability | Oral: 90-100% (well absorbed). Intravenous: 100%. |
| Onset of Action | Oral: 1-2 hours; Intravenous: 15-30 minutes. |
| Duration of Action | 12 hours (consistent with half-life). Dosing interval is typically 12 hours; for more severe infections, 8-hourly intervals may be used. |
| Molecular Weight | 253.28 g/mol (sulfamethoxazole); 290.28 g/mol (trimethoprim) |
Adults: 800 mg sulfamethoxazole/160 mg trimethoprim (one double-strength tablet) orally every 12 hours for 10-14 days. For severe infections or pneumonia, intravenous dose: 15-20 mg/kg/day (based on 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., single-strength tablet every 12 hours). CrCl <15 mL/min: contraindicated except for prophylaxis of Pneumocystis jirovecii pneumonia? If necessary, use 50% dose and monitor levels; generally avoid. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: use with caution, monitor liver function; dose reduction not specified. Child-Pugh C: contraindicated due to risk of hepatotoxicity and altered metabolism. |
| Pediatric use | Children >2 months: 6-12 mg/kg/day trimethoprim and 30-60 mg/kg/day sulfamethoxazole divided every 12 hours. For Pneumocystis jirovecii pneumonia treatment: 15-20 mg/kg/day trimethoprim divided every 6-8 hours. |
| Geriatric use | Elderly patients: start at lower end of dosing range due to age-related renal impairment; monitor renal function and adjust based on CrCl. Avoid use with ACE inhibitors or potassium-sparing diuretics due to hyperkalemia risk. Use with caution if concurrent medications that increase K+. |
| 1st trimester | Avoid in first trimester unless benefit outweighs risk; sulfamethoxazole is a folate antagonist and may increase risk of neural tube defects. |
| 2nd trimester | Use with caution; theoretical risk of kernicterus in neonates if given near term due to bilirubin displacement. |
| 3rd trimester | Avoid in third trimester due to risk of neonatal hemolysis and kernicterus; sulfamethoxazole crosses placenta and competes for bilirubin binding sites. |
Clinical note
Comprehensive clinical and safety monograph for SULMEPRIM (SULMEPRIM).
| Placental transfer | Both components cross the placenta; sulfamethoxazole achieves fetal serum concentrations 50-100% of maternal levels; trimethoprim achieves 30-60%. |
| Breastfeeding | Sulfamethoxazole and trimethoprim are excreted into breast milk in low amounts. Avoid in breastfeeding infants with G6PD deficiency or hyperbilirubinemia; theoretical risk of kernicterus. Use alternative if infant is ill or preterm. |
■ FDA Black Box Warning
Sulfonamides, including sulfamethoxazole, have been associated with severe adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Use with caution in patients with hepatic or renal impairment, folate deficiency, or hypersensitivity to sulfonamides.
| Serious Effects |
Hypersensitivity to sulfonamides or trimethoprimMegaloblastic anemia due to folate deficiencyInfants <2 months of ageSevere hepatic or renal impairment
| Precautions | Risk of severe hypersensitivity reactions including SJS/TEN, Hematological toxicity (thrombocytopenia, agranulocytosis, aplastic anemia), Hepatic necrosis, Renal toxicity and crystalluria, Hyperkalemia in patients with renal impairment or on potassium-sparing diuretics, Folate deficiency and megaloblastic anemia with prolonged use, Photosensitivity, Disulfiram-like reaction with alcohol |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, spinach) if renal impairment or concurrent medications that raise potassium. No specific food avoidance, but ensure adequate fluid intake. |
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| Lactation Rating | L3 - Moderately Safe (use with caution) |
| Teratogenic Risk | First trimester: Sulfadiazine crosses placenta; potential for neural tube defects due to folate antagonism. Second/third trimester: Risk of kernicterus in neonates due to bilirubin displacement from albumin. Avoid near term. |
| Fetal Monitoring | Monitor CBC, renal function, hepatic function, and folate levels. Ultrasound for fetal growth and anatomy. Monitor for kernicterus signs in newborn if used near term. |
| Fertility Effects | No known negative impact on fertility in humans. Animal studies show no significant reproductive toxicity. |
| Clinical Pearls | Sulmeprim (sulfamethoxazole/trimethoprim) is a fixed-dose combination used primarily for urinary tract infections, Pneumocystis jirovecii pneumonia prophylaxis, and certain skin infections. Monitor renal function and potassium levels due to risk of hyperkalemia, especially in elderly or renally impaired. Contraindicated in G6PD deficiency (hemolysis risk) and sulfonamide allergy. Avoid in pregnancy (first trimester due to folate antagonism) and lactation. Adjust dose if creatinine clearance <30 mL/min. |
| Patient Advice | Take with a full glass of water and stay well-hydrated to prevent crystalluria and kidney stones. · Complete the full course even if symptoms improve. · Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur. · Report rash, sore throat, fever, or unusual bleeding immediately (possible severe adverse reactions). · Do not take if allergic to sulfa drugs, or if pregnant/nursing without consulting doctor. |