Methenamine
Hexamethylenetetramine
Also known as: Hiprex · Hexamine hippurate · Methenamine hippurate
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Dosing by species
Dosing data for this drug is not yet available in the VetSheet formulary. Every other section below is complete. Consult the current product label before prescribing.
Overview
Methenamine (also known as hexamine) is a urinary tract antiseptic used primarily for the prophylaxis and long-term management of recurrent lower urinary tract infections.
Clinical Pearl: It is not a traditional antibiotic but acts as a prodrug. Because its efficacy relies entirely on its conversion to formaldehyde in an acidic environment, it is ineffective in alkaline urine or for systemic infections. Bacterial resistance to formaldehyde does not naturally occur, making it useful for chronic management.
Mechanism of action
Methenamine is a prodrug that is hydrolyzed in an acidic environment (urine pH < 5.5) → ammonia and formaldehyde.
Formaldehyde acts as a non-specific bactericidal agent that denatures bacterial proteins and nucleic acids. It requires sufficient time in the bladder to convert and exert its effects.
Safety & warnings
Contraindications
- Renal insufficiency (can exacerbate systemic acidosis)
- Severe hepatic disease (due to ammonia production)
- Severe dehydration
- Metabolic acidosis
- Concurrent use of sulfonamides
Adverse effects
- Gastrointestinal upset (nausea, vomiting, diarrhea)
- Dysuria or pollakiuria (due to formaldehyde irritation)
- Hematuria
- Crystalluria (at high doses)
Precautions
Urine pH must be monitored and maintained below 5.5 for the drug to be effective. Not effective for upper urinary tract infections (pyelonephritis) or systemic infections. Use with caution in patients with pre-existing gastrointestinal disease.
Drug interactions
Formaldehyde forms an insoluble precipitate with sulfonamides, increasing the risk of crystalluria and renal damage.
Raises urine pH, preventing the conversion of methenamine to its active form (formaldehyde).
May increase urine pH and promote diuresis, reducing formaldehyde concentration and contact time in the bladder.
Monitoring
- Urine pH (target < 5.5)
- Urinalysis (monitor for crystalluria or hematuria)
- Renal function
- Hepatic function (in prolonged use)
Pharmacokinetics
Half-life
Absorption
Rapidly absorbed from the gastrointestinal tract.
Distribution
Widely distributed throughout the body, but only active in the urinary tract where it concentrates and hydrolyzes.
Metabolism
Approximately 10-30% may be hydrolyzed in the acidic environment of the stomach unless administered as an enteric-coated formulation or with a salt (like hippurate) that delays gastric hydrolysis.
Elimination
Excreted almost entirely unchanged in the urine, where it subsequently hydrolyzes to formaldehyde.
Overdose
Overdosage primarily manifests as severe gastrointestinal distress (vomiting, diarrhea) and urinary tract irritation (hematuria, dysuria, crystalluria). Treatment is supportive and symptomatic. Alkalinizing the urine can halt further conversion to formaldehyde and reduce urinary irritation.
Available products
Formulations
- 150 mg methenamine + 116 mg monosodium phosphate tablet
- 1 g methenamine hippurate tablet
Human-labeled
- Hiprex 1 g tablet
Regulatory status
Human-approved formulations used off-label in veterinary medicine.
POM (Prescription Only Medicine)
POM (Prescription Only Medicine)
No regulatory data for: 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store at room temperature (15-30°C) in a tightly closed container. Protect from moisture and light.
Client information
Administer this medication with food to minimize stomach upset.
Your veterinarian may recommend a specific diet or urinary acidifier supplement; it is critical to follow these instructions, as this medication only works if the urine is acidic.
Ensure your pet has free access to fresh water. Do not give your pet any over-the-counter antacids without consulting your veterinarian.
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.