TRYSUL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRYSUL (TRYSUL).
Trypanocidal agent; forms a complex with DNA and inhibits nucleic acid synthesis.
| Metabolism | Hepatic; undergoes N-demethylation and hydroxylation via cytochrome P450 enzymes (CYP3A4). |
| Excretion | Renal: approximately 70-80% as unchanged drug via glomerular filtration and tubular secretion; biliary/fecal: 15-20% as metabolites; small amount in feces. |
| Half-life | Terminal elimination half-life: 8-10 hours in adults with normal renal function; prolonged to 20-30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 95-98% bound primarily to albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.15-0.3 L/kg, indicating distribution primarily in extracellular fluid and plasma. |
| Bioavailability | Oral: 80-95% (first-pass metabolism negligible). |
| Onset of Action | Oral: 30-60 minutes; intravenous: immediate (within minutes). |
| Duration of Action | 6-12 hours for oral, 4-8 hours for intravenous; dosing interval adjusted based on renal function. |
2 tablets (each containing sulfamethoxazole 400 mg and trimethoprim 80 mg) orally every 12 hours for 10-14 days.
| Dosage form | CREAM |
| Renal impairment | CrCl >30 mL/min: no adjustment; CrCl 15-30 mL/min: 50% of usual dose every 12 hours; CrCl <15 mL/min: not recommended. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C); use with caution in moderate impairment (Child-Pugh class B) with monitoring; no dosage adjustment in mild impairment (Child-Pugh class A). |
| Pediatric use | 8-12 mg/kg/day of trimethoprim component divided every 12 hours; for severe infections, up to 20 mg/kg/day of trimethoprim component divided every 6-8 hours. Maximum: 320 mg/day of trimethoprim component. |
| Geriatric use | Initiate at lower end of dosing range due to age-related renal function decline; monitor renal function and adjust dose accordingly; consider folate supplementation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TRYSUL (TRYSUL).
| Breastfeeding | TRMS enters breast milk (M/P ratio ~0.25 for trimethoprim, 0.2-0.5 for sulfamethoxazole). Use caution in breastfeeding, especially for infants with G6PD deficiency or hyperbilirubinemia. Consider alternatives due to risk of kernicterus and hemolysis. |
| Teratogenic Risk | TRYSUL (trimethoprim/sulfamethoxazole) is contraindicated in pregnancy due to teratogenic risks. First trimester: Sulfonamides are associated with neural tube defects, cardiovascular anomalies, and oral clefts (folate antagonist). Second and third trimesters: Risk of kernicterus in neonates; trimethoprim may cause folic acid deficiency and neural tube defects. Category D. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to trivalent arsenicals; severe hepatic or renal impairment; concurrent use of drugs prolonging QT interval.
| Precautions | Cardiotoxicity (QT prolongation, arrhythmias); encephalopathy; hypersensitivity reactions; monitor ECG, hepatic function, and electrolytes. |
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| Fetal Monitoring | Monitor CBC, renal function, and folate levels during pregnancy. Assess fetal neural tube development via ultrasound in first trimester. In third trimester, monitor for neonatal jaundice, kernicterus. Advise folate supplementation. |
| Fertility Effects | TRMS may impair folate metabolism, potentially affecting ovulation and spermatogenesis. Folate supplementation recommended for both sexes attempting conception. No conclusive evidence of permanent fertility impairment. |