UROPLUS DS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UROPLUS DS (UROPLUS DS).
UROPLUS DS is a combination of sulfamethoxazole, a sulfonamide, and trimethoprim, a dihydrofolate reductase inhibitor. Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid (PABA). Trimethoprim inhibits dihydrofolate reductase, blocking the reduction of dihydrofolic acid to tetrahydrofolic acid. This sequential blockade disrupts folic acid synthesis, leading to bacterial growth inhibition.
| Metabolism | Sulfamethoxazole is metabolized primarily by N-acetylation and glucuronidation; its major metabolite is N-acetyl-sulfamethoxazole. Trimethoprim undergoes O-demethylation and N-oxidation. Both are substrates of hepatic enzymes including CYP2C9 for sulfamethoxazole and CYP3A4 for trimethoprim. |
| Excretion | Renal excretion of unchanged drug accounts for approximately 40-50% of elimination; hepatic metabolism (primarily via CYP3A4) and subsequent biliary/fecal excretion constitute the remainder with about 20-30% recovered in feces as metabolites. |
| Half-life | Terminal elimination half-life is 11-13 hours in adults with normal renal function; prolonged to 16-20 hours in moderate renal impairment (CrCl 30-50 mL/min) and up to 25 hours in severe impairment (CrCl <30 mL/min). |
| Protein binding | Approximately 60-70% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd is 1.6-2.4 L/kg (extensive extravascular distribution, consistent with high tissue binding). |
| Bioavailability | Oral bioavailability is 70-80% (extensive but variable first-pass metabolism). |
| Onset of Action | Oral: 30-60 minutes to detectable plasma concentrations; clinical effect (anticholinergic) noted within 1-2 hours. |
| Duration of Action | Anticholinergic effects (reduced bladder contractions) persist for 6-8 hours after single dose; clinical benefit in overactive bladder sustained with twice-daily dosing. |
UROPLUS DS (methenamine mandelate 1 g + sodium acid phosphate 500 mg) oral: 1 tablet twice daily.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in renal insufficiency (CrCl < 50 mL/min). Not recommended for use in patients with GFR < 50 mL/min. |
| Liver impairment | No specific adjustment recommended; use with caution in severe hepatic impairment (Child-Pugh class C). |
| Pediatric use | Not recommended for children under 12 years. For children 12 years and older: same as adult dose. |
| Geriatric use | Use with caution; monitor renal function and avoid in CrCl < 50 mL/min. Lower doses may be considered in elderly due to age-related renal decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UROPLUS DS (UROPLUS DS).
| Breastfeeding | Sulfamethoxazole and trimethoprim are excreted into human milk. The M/P ratio for trimethoprim is approximately 1.25. Although concentrations are low, there is a risk of kernicterus in jaundiced or G6PD-deficient infants. Use while breastfeeding is generally avoided, especially during the first month of life or in ill/premature infants. |
| Teratogenic Risk | UROPLUS DS (sulfamethoxazole/trimethoprim) is contraindicated in pregnancy, especially in the first trimester and near term. First trimester exposure is associated with an increased risk of neural tube defects and cardiovascular malformations due to folate antagonism. In the second and third trimesters, use increases risk of jaundice and kernicterus in the newborn. Trimethoprim crosses the placenta; sulfonamides may cause hemolytic anemia in neonates with G6PD deficiency. |
■ FDA Black Box Warning
Fatal hypersensitivity reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and fulminant hepatic necrosis, have occurred. Sulfonamides should be discontinued at the first sign of skin rash or any sign of adverse reaction.
| Serious Effects |
Hypersensitivity to sulfonamides, trimethoprim, or any component; megaloblastic anemia due to folate deficiency; infants <2 months of age; pregnancy (especially at term) and breastfeeding; severe hepatic or renal impairment (CrCl <15 mL/min); concomitant use with dofetilide.
| Precautions | Hypersensitivity reactions, including severe skin reactions (SJS, TEN), hepatotoxicity, blood dyscrasias, renal toxicity, crystalluria, hyperkalemia, hypoglycemia, photosensitivity, and increased risk of kernicterus in neonates. Avoid use in patients with folate deficiency, G6PD deficiency, or porphyria. Monitor renal function, CBC, and electrolytes. |
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| Fetal Monitoring | Monitor complete blood count, renal function, and folate levels in pregnant women. Fetal ultrasound for neural tube defects after first-trimester exposure. Monitor newborn for jaundice, kernicterus, hemolytic anemia, and G6PD deficiency status. In pregnancy, weekly serum folate may be considered. |
| Fertility Effects | Sulfamethoxazole/trimethoprim may impair fertility in both sexes. In males, it has been associated with reduced sperm count and motility, possibly reversible. In females, folate antagonism may interfere with ovulation and early embryonic development. |