SULFALAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SULFALAR (SULFALAR).
Sulfamethoxazole is a sulfonamide that competitively inhibits dihydropteroate synthase, blocking folic acid synthesis; trimethoprim inhibits dihydrofolate reductase, producing sequential blockade of folic acid metabolism in bacteria.
| Metabolism | Sulfamethoxazole is metabolized via N-acetylation (N-acetyltransferase) and glucuronidation (UGT) in the liver. Trimethoprim undergoes O-demethylation (CYP3A4) and N-oxidation. |
| Excretion | Renal: approximately 70-80% as unchanged drug and acetylated metabolite; biliary/fecal: 20-30% |
| Half-life | Terminal elimination half-life: 7-12 hours (prolonged in renal impairment up to 24-48 hours; clinical context: dosing interval adjustment needed for CrCl <30 mL/min) |
| Protein binding | Approximately 50-70% bound to albumin; primary binding protein: albumin; also binds to alpha-1-acid glycoprotein (lesser extent) |
| Volume of Distribution | Vd: 0.5-0.8 L/kg; indicates moderate tissue distribution, primarily confined to extracellular fluid; clinical meaning: distribution consistent with limited intracellular penetration |
| Bioavailability | Oral: 85-95% (well absorbed; less than complete due to first-pass metabolism); Intramuscular: 100% (rapid and complete absorption) |
| Onset of Action | Oral: 2-4 hours (clinical effect: bacteriostatic activity); Intravenous: immediate (peak plasma concentration achieved by end of infusion) |
| Duration of Action | Oral: 12-24 hours (sufficient for twice-daily dosing; clinical note: sustained bacteriostatic effect); Intravenous: 12 hours (dosing every 12 hours recommended) |
| Molecular Weight | 398.44 |
Oral: 500 mg to 1 g every 12 hours; extended-release: 1 g every 12 hours. Intravenous: 1 g every 12 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl >50 mL/min: no adjustment; CrCl 15-50 mL/min: 500 mg every 12 hours; CrCl <15 mL/min: 500 mg every 24 hours; hemodialysis: 500 mg every 24 hours plus dose after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated. |
| Pediatric use | Oral: 25-50 mg/kg/day divided every 12 hours (max 1 g/dose). Intravenous: 25-50 mg/kg/day divided every 12 hours (max 1 g/dose). |
| Geriatric use | Start at low end of dosing range; monitor renal function and adjust based on CrCl. |
| 1st trimester | Sulfalazine is generally avoided in the first trimester due to potential teratogenic effects based on animal studies and limited human data; folate supplementation is recommended if used. |
| 2nd trimester | Use only if clearly needed; monitor for maternal adverse effects and consider dose adjustment; may increase risk of kernicterus in neonate if used near term. |
| 3rd trimester | Avoid near term due to risk of neonatal jaundice and kernicterus from displacement of bilirubin from albumin; sulfonamides are competitive inhibitors of bilirubin binding. |
Clinical note
Comprehensive clinical and safety monograph for SULFALAR (SULFALAR).
| Placental transfer | Sulfalazine crosses the placenta via passive diffusion; fetal concentrations reach 50-100% of maternal serum levels. |
| Breastfeeding | Sulfalazine is excreted into breast milk in small amounts; in healthy term infants, risk is low but caution is advised in premature, ill, or hyperbilirubinemic infants; monitor for diarrhea and rash. |
■ FDA Black Box Warning
Fatalities associated with sulfonamide hypersensitivity reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia) have been reported. Reserve for susceptible infections when benefit outweighs risk.
| Serious Effects |
Known hypersensitivity to sulfonamides or salicylatesPorphyriaIntestinal or urinary tract obstructionSevere hepatic or renal impairmentBlood dyscrasias (e.g., agranulocytosis, aplastic anemia)
| Precautions | Hypersensitivity (life-threatening skin reactions, eosinophilia, drug fever); hematologic toxicity (thrombocytopenia, leukopenia); hepatotoxicity; renal toxicity (interstitial nephritis, crystalluria) with adequate hydration; electrolyte disturbances (hyperkalemia, hyponatremia); hemolysis in G6PD deficiency; increased INR with warfarin; hypoglycemia with sulfonylureas; photosensitivity; folate depletion (megaloblastic anemia) with prolonged use. |
| Food/Dietary | Avoid alcohol as it may cause a disulfiram-like reaction. High doses of vitamin C may increase risk of crystalluria. No specific food restrictions but maintain adequate fluid intake. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Folate antagonist; case-control studies suggest increased risk of neural tube defects, cardiovascular malformations, and oral clefts. Second and third trimesters: Risk of kernicterus in neonates, hemolytic anemia in G6PD-deficient fetuses, and potential for neonatal hypoglycemia. Avoid in pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor complete blood count, renal and hepatic function, and urinalysis. Assess for hypersensitivity reactions, photosensitivity, and electrolyte disturbances. In neonates, observe for jaundice, kernicterus, and hemolytic anemia. Folate supplementation recommended during pregnancy. |
| Fertility Effects | No known direct adverse effects on fertility. Trimethoprim may affect folate metabolism, potentially impacting spermatogenesis or ovulation in susceptible individuals with low folate stores. Clinical significance uncertain. |
| Clinical Pearls | SULFALAR is a sulfonamide antibiotic. Monitor for hypersensitivity reactions, especially in patients with sulfa allergies. Ensure adequate hydration to prevent crystalluria. Adjust dose in renal impairment (CrCl <30 mL/min is contraindicated). Not effective for group A streptococcal pharyngitis. |
| Patient Advice | Take with a full glass of water and stay well hydrated to prevent kidney stones. · Avoid prolonged sun exposure; use sunscreen as this medication increases photosensitivity. · Complete the full course even if you feel better to prevent resistance. · Report immediately if you develop rash, fever, sore throat, or unusual bleeding. · Do not take if you have a sulfa allergy, are pregnant (near term), or breastfeeding. |