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. |
| Molecular Weight | 250.27 Da |
| 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 | Contraindicated due to teratogenicity (neural tube defects, cardiac anomalies). Avoid use during first trimester. |
| 2nd trimester | Contraindicated due to risk of fetal harm. Alternative therapy recommended. |
| 3rd trimester | Contraindicated due to possible neonatal adverse effects including kernicterus. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for UREX (UREX).
| Placental transfer | Crosses placenta readily; achieves fetal serum concentrations 50-100% of maternal levels. Competes for bilirubin-binding sites, increasing risk of kernicterus. |
| Breastfeeding | Drug excreted into breast milk in low concentrations; however, due to potential for serious adverse reactions (e.g., kernicterus in G6PD-deficient infants, sulfonamide displacement of bilirubin), caution is advised. Use only if clearly needed and monitor infant for jaundice, rash, or diarrhea. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to sulfonamides or sulfonylureasPorphyriaSevere hepatic failureSevere renal insufficiency (CrCl <15 mL/min)Pregnancy (especially first and third trimester)Lactation (in infants <2 months old or with G6PD deficiency)Concurrent use with sulfonylureas or thiazides may increase risk of hypoglycemia or hypersensitivity
| 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). |
| Food/Dietary | Avoid large amounts of foods that alkalinize urine, such as citrus fruits (oranges, lemons), dairy products, and almonds. Cranberry juice (unless sweetened) may help acidify urine; however, avoid excessive intake that could cause gastrointestinal upset. Maintain a diet that promotes acidic urine (e.g., prunes, plums, cranberries). |
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| Lactation Rating | L3 (Moderately Safe) - limited data suggest low risk, but caution due to theoretical risks in sick or premature infants. |
| 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 | 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. |
| Clinical Pearls | UREX (methenamine hippurate) is a urinary antiseptic that requires acidic urine (pH ≤5.5) to hydrolyze to formaldehyde. Monitor urine pH with litmus paper; consider co-administering ascorbic acid to acidify urine if pH is elevated. Efficacy is limited in patients with indwelling urinary catheters or renal impairment (CrCl <10 mL/min). Not effective for upper UTI or pyelonephritis. Avoid concurrent use with sulfonamides due to risk of crystalluria. |
| Patient Advice | Take this medication with food or milk to reduce stomach upset. · Drink plenty of water (at least 8 glasses daily) unless told otherwise by your doctor. · Urinate frequently; do not hold urine for long periods. · Inform your doctor if you notice blood in urine, pain, or burning during urination. · Avoid medications that alkalinize urine (e.g., antacids, sodium bicarbonate) as they decrease drug effectiveness. · Keep all appointments to monitor urine pH and kidney function. |