SULFATRIM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFATRIM (SULFATRIM).
Sulfatrim is a combination of sulfamethoxazole, a dihydropteroate synthase inhibitor that blocks folate synthesis, and trimethoprim, a dihydrofolate reductase inhibitor that blocks reduction of dihydrofolate to tetrahydrofolate, resulting in sequential inhibition of bacterial folate metabolism.
| Metabolism | Sulfamethoxazole is metabolized via acetylation and glucuronidation; trimethoprim is metabolized via O-demethylation and oxidation. Both are substrates of CYP450 isoenzymes (e.g., CYP2C9 for sulfamethoxazole). |
| Excretion | Renal (70-80% as unchanged sulfamethoxazole and N4-acetylated metabolite; 30-40% as unchanged trimethoprim), biliary/fecal (20-30% sulfamethoxazole; 10-20% trimethoprim) |
| Half-life | Sulfamethoxazole: 9-11 hours (prolonged in renal impairment, e.g., up to 30 hours in severe renal failure). Trimethoprim: 8-10 hours (prolonged in hepatic impairment). |
| Protein binding | Sulfamethoxazole: 65-70% bound to albumin. Trimethoprim: 42-46% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Sulfamethoxazole: 0.15-0.28 L/kg (distributes well to tissues, including CSF). Trimethoprim: 1.3-1.8 L/kg (higher Vd indicates extensive tissue penetration). |
| Bioavailability | Oral: >90% for both components. IV: 100%. |
| Onset of Action | Oral: Onset within 1-2 hours for peak serum levels; clinical effect within 24-48 hours. IV: Onset within 30-60 minutes for peak serum levels. |
| Duration of Action | Oral/IV: Duration of antibacterial effect approximately 12 hours; dosing interval typically every 12 hours. |
| Molecular Weight | Sulfamethoxazole: 253.28 Da; Trimethoprim: 290.32 Da |
| Brand Substitutes | Panam Suspension, Nolapse Suspension, Estrim Suspension, Salgatran Suspension, Hanprim Suspension, Cortina DS 800mg/160mg Tablet, Colizole DS 800mg/160mg Tablet, Tabrol DS Tablet, Trisulfose DS 800mg/160mg Tablet, Sepmax DS Tablet |
160 mg trimethoprim / 800 mg sulfamethoxazole (1 DS tablet) orally every 12 hours for 10-14 days.
| Dosage form | SUSPENSION |
| Renal impairment | CrCl >30 mL/min: no adjustment. CrCl 15-30 mL/min: reduce dose by 50% (e.g., 1 DS tablet every 24 hours). CrCl <15 mL/min: contraindicated (except for Pneumocystis jirovecii pneumonia prophylaxis where dosing is adjusted per protocol). |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: use with caution, consider monitoring liver enzymes. Child-Pugh Class C: contraindicated due to risk of hepatotoxicity and altered metabolism. |
| Pediatric use | Based on trimethoprim component: 8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole divided every 12 hours. For urinary tract infection: 6-12 mg/kg/day trimethoprim and 30-60 mg/kg/day sulfamethoxazole divided every 12 hours. Maximum daily dose: 320 mg trimethoprim/1600 mg sulfamethoxazole. |
| Geriatric use | Start at lowest effective dose (e.g., 1 SS tablet [80 mg trimethoprim/400 mg sulfamethoxazole] every 12 hours). Monitor renal function (CrCl) closely; adjust dose per renal adjustment. Increased risk of hyperkalemia (especially with NSAIDs, ACE inhibitors) and sulfonamide hypersensitivity. |
| 1st trimester | Avoid in first trimester due to risk of neural tube defects and other congenital anomalies from folate antagonism. |
| 2nd trimester | Use only if clearly indicated; increased risk of kernicterus and hemolytic anemia in neonates due to bilirubin displacement by sulfonamides. |
| 3rd trimester | Contraindicated near term (after 38 weeks) due to high risk of kernicterus in newborn. |
Clinical note
Comprehensive clinical and safety monograph for SULFATRIM (SULFATRIM).
| Placental transfer | Both components cross the placenta; trimethoprim reaches fetal concentrations ~50-100% of maternal; sulfamethoxazole reaches fetal levels ~80% of maternal; active transport of folates inhibited. |
| Breastfeeding | Sulfamethoxazole and trimethoprim are excreted into breast milk; sulfamethoxazole may cause kernicterus in jaundiced or ill infants; trimethoprim is a folate antagonist; use caution, especially in preterm or G6PD-deficient infants. |
■ FDA Black Box Warning
Fatal hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and hepatic necrosis; increased risk of kernicterus in neonates (avoid use in infants <2 months); caution in folate-deficient patients (elderly, alcoholics, anticonvulsant users).
| Serious Effects |
Hypersensitivity to sulfonamides or trimethoprimMegaloblastic anemia due to folate deficiencySevere hepatic or renal impairment (CrCl <15 mL/min)Porphyria (sulfonamides may precipitate acute attack)Infants <2 months of age (risk of kernicterus)
| Precautions | Hypersensitivity and severe skin reactions; hemolytic anemia in G6PD deficiency; hematopoietic toxicity (megaloblastic anemia); electrolyte disturbances (hyperkalemia with high doses); photosensitivity; caution in hepatic/renal impairment; pregnancy (risk of kernicterus); lactation (use with caution). |
| Food/Dietary | Avoid high-potassium foods (bananas, oranges, spinach, salt substitutes) as sulfamethoxazole may increase potassium retention. Additionally, avoid alcohol to prevent disulfiram-like reaction. Maintain adequate hydration to prevent crystalluria; avoid excessive vitamin C (ascorbic acid) as it may acidify urine and increase risk of crystalluria. |
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| Lactation Rating | L4 (Hazardous) - Avoid breastfeeding if alternative is available; monitor infant for jaundice, hemolysis, and folate deficiency. |
| Teratogenic Risk | First trimester: Avoid due to folate antagonism; risk of neural tube defects, cardiovascular malformations, and cleft lip/palate. Second/third trimester: Potential risk of kernicterus in neonates from sulfonamide displacement of bilirubin; avoid near term. |
| Fetal Monitoring | Monitor CBC, folate levels, renal and hepatic function. Fetal ultrasound for structural anomalies if used in first trimester; neonatal bilirubin monitoring if used near term. |
| Fertility Effects | No significant adverse effects on fertility reported in animal studies; human data limited. Folate antagonism may theoretically affect implantation but not clinically observed. |
| Clinical Pearls | SULFATRIM (sulfamethoxazole/trimethoprim) is a fixed-dose combination antibiotic. Key pearls: (1) Contraindicated in G6PD deficiency due to risk of hemolytic anemia. (2) Dose adjust in renal impairment (CrCl <30 mL/min avoid or reduce dose). (3) Monitor for hyperkalemia in elderly or on ACEI/ARB/NSAIDs. (4) Use with caution in folate deficiency; consider folinic acid rescue in prolonged therapy. (5) Avoid in pregnancy (third trimester) and lactation due to kernicterus risk. (6) Hypersensitivity reactions including Stevens-Johnson syndrome mandate immediate discontinuation. |
| Patient Advice | Take with a full glass of water to prevent crystalluria. · Complete the full course even if you feel better. · Avoid prolonged sun exposure; use sunscreen as photosensitivity may occur. · Report rash, fever, sore throat, or unusual bleeding immediately. · Do not take if you have a history of sulfa allergy. · Inform your doctor if you have kidney disease, G6PD deficiency, or are pregnant. |