METHENAMINE HIPPURATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METHENAMINE HIPPURATE (METHENAMINE HIPPURATE).
Methenamine is hydrolyzed in acidic urine to formaldehyde, which denatures bacterial proteins and nucleic acids, exerting a bactericidal effect.
| Metabolism | Methenamine is excreted largely unchanged in urine, where it is hydrolyzed to formaldehyde and ammonia at pH <5.5. Not significantly metabolized by the liver. |
| Excretion | Primarily renal (70-90% as unchanged drug and formaldehyde). Biliary/fecal excretion is minimal (<5%). |
| Half-life | 3-6 hours for methenamine; formaldehyde half-life is negligible due to rapid metabolism. Clinical context: Requires acidic urine (pH <5.5) for optimal activity. |
| Protein binding | Minimal (<10%); primarily bound to albumin. |
| Volume of Distribution | 0.2-0.5 L/kg; distributes mainly in extracellular fluid and urine. |
| Bioavailability | Oral: ~70-80% (methenamine is well absorbed; hippuric acid component may vary). |
| Onset of Action | Oral: 1-2 hours for appearance of formaldehyde in urine; bacteriostatic effect typically within 24-48 hours. |
| Duration of Action | 12-24 hours; requires twice-daily dosing. Duration depends on urinary pH and urinary concentration of formaldehyde. |
1 gram orally twice daily (every 12 hours).
| Dosage form | TABLET |
| Renal impairment | Contraindicated in GFR <30 mL/min. For GFR 30-50 mL/min: 1 gram once daily. For GFR >50 mL/min: no adjustment needed. |
| Liver impairment | No adjustment needed for mild to moderate impairment (Child-Pugh A or B). Contraindicated in severe hepatic impairment (Child-Pugh C) due to potential for ammonia accumulation. |
| Pediatric use | Children >6 years: 0.5 gram orally twice daily. Children 6-12 years: 0.5-1 gram orally twice daily. Children <6 years: not recommended. |
| Geriatric use | Start at 0.5 gram orally twice daily; monitor renal function and adjust according to creatinine clearance. Avoid if GFR <30 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METHENAMINE HIPPURATE (METHENAMINE HIPPURATE).
| Breastfeeding | Methenamine is excreted into breast milk in low amounts (M/P ratio unknown). It is generally considered compatible with breastfeeding, but monitor infant for potential GI effects. |
| Teratogenic Risk | Methenamine hippurate is considered to have low teratogenic risk. In the first trimester, no evidence of increased malformations; second and third trimesters, continued low risk, though use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
Renal insufficiency (creatinine clearance <10 mL/min), severe hepatic disease, dehydration, concurrent therapy with sulfonamides, history of hypersensitivity to methenamine or hippurate salts.
| Precautions | Use with caution in patients with hepatic impairment, severe renal insufficiency, or gout. Monitor urine pH and maintain acidity. Avoid concurrent use with sulfonamides or alkalinizing agents. |
Loading safety data…
| Monitor for signs of maternal hypersensitivity or hepatotoxicity. In pregnancy, monitor urine culture for efficacy and renal function. |
| Fertility Effects | No known significant adverse effects on fertility in males or females. |