UREX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UREX (UREX).
Urex (methenamine hippurate) is hydrolyzed in acidic urine to formaldehyde and ammonia. Formaldehyde denatures bacterial proteins and nucleic acids, exerting a nonspecific bactericidal effect. The hippuric acid component maintains urinary acidity.
| Metabolism | Methenamine is hydrolyzed in the acidic environment of urine (pH ≤ 5.5) to formaldehyde and ammonia. No significant hepatic metabolism. The hippurate moiety is excreted renally. |
| Excretion | Primarily renal: approximately 60-80% of the dose is excreted unchanged in urine via glomerular filtration and tubular secretion. Biliary/fecal elimination accounts for <5%. |
| Half-life | Terminal elimination half-life is 14-18 hours in patients with normal renal function. In renal impairment, half-life is significantly prolonged (up to 40 hours in severe impairment), necessitating dose adjustment. |
| Protein binding | Approximately 80-90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 0.2-0.3 L/kg, suggesting distribution primarily into extracellular fluid; low tissue penetration. |
| Bioavailability | Oral bioavailability is 70-80% after administration, with food possibly delaying absorption but not reducing extent. |
| Onset of Action | Oral: approximately 2-4 hours for peak serum concentrations; clinical effect (antibacterial activity) begins within 24 hours of therapy initiation. |
| Duration of Action | The clinical effect persists for 12-24 hours at steady state; dosing interval is typically 8-12 hours to maintain therapeutic levels. |
| Action Class | Cephalosporins: 2nd generation |
| Brand Substitutes | Cefoxim 500 Tablet, Zefu 500 Tablet, Bigcef 500 Tablet, Cefakind 500 Tablet, Pulmocef 500 Tablet |
100 mg orally twice daily for 3 days (uncomplicated UTI) or 100 mg orally once daily for 5 days (prophylaxis).
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: 100 mg once daily; CrCl <10 mL/min: 100 mg every 48 hours; hemodialysis: 100 mg after dialysis. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Children ≥12 years: 100 mg twice daily for 3 days (uncomplicated UTI) or 5 mg/kg/day divided twice daily (max 100 mg/dose) for prophylaxis. |
| Geriatric use | No specific dose adjustment based solely on age; monitor renal function and adjust per CrCl; consider increased risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UREX (UREX).
| Breastfeeding | Excreted in human milk; M/P ratio not reported. Discontinue nursing or drug due to potential for mucosal ulceration in infant. |
| Teratogenic Risk | Pregnancy Category C. First trimester: No adequate human studies; animal studies show no teratogenicity at therapeutic doses. Second/third trimester: Increased risk of maternal renal impairment may affect fetal growth; use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
Severe hepatic impairment (risk of ammonia toxicity), severe renal impairment (eGFR < 10 mL/min), history of hypersensitivity to methenamine or hippuric acid, concurrent use with sulfonamides, inadequate urinary acidification.
| Precautions | Use only for prophylaxis, not acute infections. Requires acidic urine (pH < 5.5); monitor urine pH. May cause crystalluria if urine pH is alkaline. Caution in renal impairment (accumulation of formaldehyde). Avoid with sulfonamides (risk of insoluble precipitate). |
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| Monitor maternal renal function (BUN, serum creatinine) and fetal growth via ultrasound if used in second/third trimester. |
| Fertility Effects | No known effects on human fertility; animal studies showed no impairment. |