What is methenamine?

Methenamine: A Urinary Tract Antiseptic

Methenamine is a urinary tract antiseptic that works by releasing formaldehyde in acidic urine, providing broad-spectrum antimicrobial activity without promoting bacterial resistance. 1, 2

Mechanism of Action

• Methenamine salts (hippurate and mandelate) are hydrolyzed to ammonia and formaldehyde in the urinary tract
• Formaldehyde acts as a denaturant of proteins and nucleic acids, providing the antibacterial activity
• Antimicrobial activity depends on:
  • Concentration of methenamine in urine
  • Urine pH (optimal pH below 6.0)
  • Time the drug remains in the bladder 1

Available Formulations

• Methenamine hippurate: 1 gram tablets
• Methenamine mandelate: 1 gram tablets 2, 3

Dosing Recommendations

• Methenamine hippurate: 1 gram twice daily for adults and children over 12 years
• Methenamine mandelate: 1 gram every 6 hours for adults 2, 3

Clinical Indications

Methenamine is FDA-approved for:

• Prophylactic or suppressive treatment of frequently recurring urinary tract infections when long-term therapy is necessary
• Should only be used after eradication of active infection by appropriate antimicrobial agents 3

Appropriate Patient Selection

Methenamine is most effective in:

• Patients with normal urinary tract anatomy and function
• Patients with intact bladder function
• Patients with recurrent UTIs (≥3 episodes in 12 months or ≥2 episodes in 6 months) 2

Limitations and Contraindications

Methenamine is less effective or not recommended for:

• Patients with long-term intermittent catheterization
• Patients with long-term indwelling urethral or suprapubic catheterization
• Patients with neuropathic bladder or renal tract abnormalities 1, 2

Advantages Over Antibiotics

• Does not select for resistant organisms
• Minimal risk of developing bacterial resistance
• Lower risk of disrupting normal microbiome
• Effective alternative when antibiotics fail to suppress recurrent UTIs 1, 2, 4

Monitoring and Optimization

• Maintain urinary pH below 6.0 for optimal effectiveness
• Treatment duration typically 6-12 months based on clinical response
• Consider treatment failure if symptoms persist beyond 7 days or recur within 6-8 weeks despite consistent use 2

Common Adverse Effects

• Generally well-tolerated
• May cause nausea, abdominal pain, and headache 5

Important Clinical Considerations

• Effectiveness depends on maintaining acidic urine (pH <6.0)
• Inadequate acidification significantly reduces effectiveness
• Should be used only after treating any active infection with appropriate antibiotics first 2

Methenamine represents an important non-antibiotic option for UTI prevention in the era of increasing antimicrobial resistance, particularly for patients with recurrent UTIs who have normal urinary tract anatomy and function.