What is Hiprex (methenamine hippurate) used for and how does it work?

Hiprex (Methenamine Hippurate): Uses and Mechanism of Action

Hiprex (methenamine hippurate) is used for prophylactic or suppressive treatment of frequently recurring urinary tract infections (UTIs) when long-term therapy is considered necessary, serving as an antimicrobial-sparing alternative to antibiotics in patients with intact bladder function. 1

Mechanism of Action

Methenamine hippurate works through a unique mechanism that differs from conventional antibiotics:

1. Formaldehyde Production: When methenamine reaches the bladder, it hydrolyzes in acidic urine to release formaldehyde and ammonia 2

2. Bacteriostatic Effect: The released formaldehyde acts as a denaturant of bacterial proteins and nucleic acids, creating a broad-spectrum bacteriostatic effect against urinary pathogens 2

3. pH Dependency: The antimicrobial activity is dependent on:

   • Acidic urinary pH (ideally below 6.0)
   • Concentration of methenamine in urine
   • Time the drug remains in the bladder 2

Clinical Applications

Methenamine hippurate is particularly useful in:

• Prevention of recurrent UTIs in patients aged 12 years and older 1
• Alternative to prophylactic antibiotics in patients with intact bladder anatomy 2
• Patients without incontinence and with fully functional bladders 2

Dosing

• Standard dosage: 1 g twice daily 2
• Alternative formulation (methenamine mandelate): 1 g every 6 hours 2

Advantages Over Antibiotics

• No development of bacterial resistance: Unlike conventional antibiotics, acquired resistance to methenamine hippurate does not appear to develop 2
• Non-inferiority to antibiotics: Recent evidence shows methenamine hippurate is non-inferior to daily low-dose antibiotics for preventing recurrent UTIs 2
• Similar adverse effects profile to antibiotics used for UTI prophylaxis 2

Important Considerations

1. Urinary pH: Maintaining urinary pH below 6.0 is necessary for optimal efficacy 2

   • Methods to acidify urine may include:
   • Ascorbic acid (vitamin C), though doses up to 4g/day may have limited effect
   • Ammonium chloride may be more effective but is less commonly used 2

2. Patient Selection: Most effective in:

   • Patients with intact bladder anatomy
   • Those without long-term catheterization 2

3. Not for Active Infection: Methenamine hippurate is primarily for prevention rather than treatment of established UTIs 1

Limitations

• Not recommended for patients with long-term indwelling urethral or suprapubic catheterization 2
• Limited efficacy in treating established UTI infections 3
• Requires acidic urine to be effective, which may be difficult to maintain consistently 2

Methenamine hippurate represents an important antimicrobial-sparing option for UTI prevention, particularly valuable in the context of increasing antibiotic resistance concerns.