Methenamine Hippurate
Hexamethylenetetramine hippurate
Also known as: Hiprex · Urex · Hexamine amygdalate · Hexamine mandelate · Mandelato de metenamina · Aci-steril · Reflux · Urocedulamin
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Urinary tract infection prophylaxis | 10 mg/kg | PO | q6h | — | 🌎 NA |
| Urinary tract infection prophylaxis | 10 mg/kg | PO | q6h | — | 🌎 NA |
| Urinary tract infection prophylaxis | 10-20 mg/kg | PO | q8-12h | — | 🌎 NA |
- Urinary tract infection prophylaxis: Methenamine mandelate; use with ammonium chloride to acidify urine and increase effectiveness
- Urinary tract infection prophylaxis: Methenamine mandelate
- Urinary tract infection prophylaxis: Methenamine mandelate; urine pH may need to be lowered by use of an acidifying diet and/or urinary acidifiers
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Urinary tract infection prophylaxis | 250 mg | PO | q12h | — | 🌎 NA |
- Urinary tract infection prophylaxis: Methenamine hippurate
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Methenamine hippurate is a urinary tract antiseptic primarily utilized for the prophylaxis of recurrent urinary tract infections (UTIs).
- Clinical Utility: It is not commonly used as a first-line agent in veterinary medicine, and robust evidence confirming its efficacy in dogs and cats is limited. It is generally reserved for highly resistant, recurrent lower UTIs where conventional antibiotic therapy has failed or is contraindicated.
- Mechanism Dependency: Its efficacy is strictly dependent on an acidic urinary environment (pH < 6.5, ideally < 5.5). In alkaline urine, the drug remains inactive.
- Spectrum: When activated, it provides broad-spectrum, non-specific bactericidal activity against both gram-positive (Staphylococcus, Enterococcus) and gram-negative (E. coli, Pseudomonas, Proteus) organisms, and reportedly some fungal pathogens.
- Clinical Pearl: Because it converts to formaldehyde, bacteria do not develop plasmid-mediated or chromosomal resistance to it, making it uniquely valuable for chronic prophylaxis.
Mechanism of action
Methenamine is a prodrug that requires an acidic environment for activation.
- Hydrolysis Pathway: In an acidic urinary environment (pH < 6.5) → methenamine is hydrolyzed → formaldehyde + ammonia.
- Bactericidal Action: Formaldehyde acts as a non-specific bactericidal agent by denaturing bacterial proteins and nucleic acids.
- Role of Hippurate: The hippuric acid salt component serves a dual purpose: it acts as a weak acid to help lower the urinary pH (facilitating the conversion to formaldehyde) and possesses mild, non-specific antibacterial activity of its own.
- Systemic Inactivity: At physiological blood pH (7.4), methenamine remains stable and inactive, ensuring that formaldehyde is only generated locally within the urinary bladder.
Safety & warnings
Contraindications
- Hypersensitivity to methenamine or its salts
- Renal insufficiency
- Metabolic acidosis
- Severe hepatic impairment (due to ammonia production during hydrolysis)
- Severe dehydration
Adverse effects
- Gastrointestinal irritation (nausea, vomiting, anorexia)
- Dysuria (secondary to formaldehyde irritation with long-term use)
- Systemic acidosis (potential)
- Lipoid pneumonitis (reported in humans using oral suspension)
Precautions
Crucial Efficacy Requirement: Urine pH MUST be kept below 6.5 (ideally ≤ 5.5) for the drug to be effective.
- Urea-Splitting Bacteria: Infections with urea-splitting organisms (e.g., Proteus, some Staphylococcus, Pseudomonas) naturally alkalinize the urine, potentially rendering methenamine ineffective.
- Acidification Therapy: Concurrent use of urinary acidifiers (e.g., methionine, ammonium chloride, ascorbic acid) or prescription acidifying diets is often required.
- Species Sensitivity: Cats reportedly do not tolerate methenamine as well as dogs.
- Pregnancy: FDA Category C. Crosses the placenta; use with caution during pregnancy. Enters milk, but no adverse effects reported in nursing offspring.
Drug interactions
Not recommended; an insoluble precipitate may form in the urine.
May reduce the efficacy of methenamine by preventing its conversion to formaldehyde in the urine.
Monitoring
- Urine pH (must remain < 6.5)
- Clinical efficacy (resolution or prevention of UTI symptoms)
- Urinalysis and urine cultures
Pharmacokinetics
Absorption
Well absorbed from the GI tract. Up to 30% of a dose may be hydrolyzed by gastric acid to ammonia and formaldehyde (reduced with enteric-coated tablets).
Distribution
Crosses the placenta and is distributed into milk. Plasma concentrations of formaldehyde and methenamine are very low and have negligible systemic antibacterial activity.
Metabolism
Hydrolyzed in acidic urine (pH < 6.5, maximal at ≤ 5.5) to ammonia and formaldehyde.
Elimination
70-90% of a dose is excreted unchanged into the urine within 24 hours. Peak formaldehyde concentrations occur in the urine at about 2 hours post-dose (3-8 hours with enteric-coated tablets).
Overdose
Dogs have tolerated single IV dosages of up to 600 mg/kg of methenamine hippurate without overt toxic effects.
Management of Large Oral Overdoses:
- Implement established gut emptying protocols (emesis/gastric lavage) if ingestion is recent.
- Maintain hydration status with intravenous fluids.
- Provide symptomatic and supportive care as required, monitoring for systemic acidosis and gastrointestinal distress.
Available products
Formulations
- Oral tablets
Human-labeled
- Methenamine Hippurate Oral Tablets: 1 gram (Hiprex, Urex)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store commercially available methenamine products at room temperature. Because acids hydrolyze methenamine to formaldehyde and ammonia, do not mix with acidic vehicles before administering. Physically incompatible when mixed with most alkaloids and metallic salts.
Client information
- Administration: Give this medication exactly as prescribed. If your pet experiences stomach upset (vomiting or loss of appetite), try giving the medication after meals.
- Dietary Importance: This drug only works if your pet's urine is acidic. It is critical to strictly feed any special prescription diets or administer urinary acidifiers exactly as directed by your veterinarian.
- Compliance: Do not skip doses. Consistent administration is required to prevent recurrent infections.
- Monitoring: Your veterinarian will likely need to check your pet's urine pH regularly to ensure the medication is working properly.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.