What is Hiprex (methenamine) used for?

Hiprex (Methenamine Hippurate) Use in Clinical Practice

Hiprex (methenamine hippurate) is primarily used for prophylactic or suppressive treatment of frequently recurring urinary tract infections (UTIs) when long-term therapy is considered necessary. 1

Mechanism of Action

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

• Acts as a bacteriostatic agent by releasing formaldehyde in acidic urine
• Formaldehyde is produced from the breakdown of hexamine in the urinary tract
• Unlike antibiotics, acquired bacterial resistance does not typically develop 2

Clinical Indications

Methenamine hippurate is specifically indicated for:

• Prevention of recurrent UTIs in patients with a history of frequent infections
• Alternative to prophylactic antibiotics for long-term UTI prevention
• Use after eradication of active infection with appropriate antimicrobial agents 1

Dosing and Administration

The recommended dosage is:

• 1 g twice daily for adults 2
• Should be used only after complete eradication of active infection with appropriate antibiotics 1

Efficacy Evidence

Recent high-quality evidence supports methenamine's effectiveness:

• A 2022 multicentre, pragmatic, randomized, non-inferiority trial demonstrated that methenamine hippurate is not inferior to daily low-dose antibiotics in preventing recurrent UTIs in women 3
• The ALTAR trial showed that during treatment, the incidence rate of symptomatic, antibiotic-treated UTIs decreased substantially with methenamine hippurate (1.38 episodes per person-year) compared to antibiotics (0.89 episodes per person-year) 3
• The 2024 JAMA Network Open guidelines provide a clear recommendation for methenamine hippurate use in UTI prevention 2

Advantages Over Antibiotics

Methenamine hippurate offers several benefits compared to antibiotic prophylaxis:

• Reduced development of antimicrobial resistance
• Lower risk of disrupting normal microbiome
• May give patients confidence to delay intervention for mild symptoms, reducing empiric antibiotic use 2
• The ALTAR trial showed higher proportions of antibiotic resistance in E. coli from patients on daily antibiotics (72%) compared to those on methenamine hippurate (56%) 3

Patient Selection

Methenamine is most effective in:

• Patients without urinary tract anomalies 4
• Those with intact bladder anatomy 2
• Patients without incontinence and with a fully functional bladder 2
• Individuals with recurrent UTIs defined as at least 3 episodes in 12 months or 2 episodes in 6 months 4

Limitations and Precautions

• Less effective for treating established infections; primarily for prophylaxis after achieving abacteriuria 5
• Should not be used in patients with severe renal or hepatic impairment
• Requires acidic urine to be effective (pH < 5.5)
• Not recommended for patients with urinary catheters or urinary calculi

Clinical Algorithm for Use

1. Confirm recurrent UTI diagnosis (≥3 episodes in 12 months or ≥2 in 6 months)
2. Treat any active infection with appropriate antibiotics first
3. Verify patient has normal urinary tract anatomy and function
4. Start methenamine hippurate 1 g twice daily
5. Monitor for symptom improvement and adverse effects
6. Continue treatment for at least 6-12 months based on clinical response

Common Pitfalls to Avoid

• Using methenamine as primary treatment for active UTI rather than prophylaxis
• Failing to acidify urine (methenamine requires acidic environment)
• Not completing a full course of antibiotics before starting methenamine
• Using in patients with significant urinary tract abnormalities or indwelling catheters

Methenamine hippurate represents an important non-antibiotic option for UTI prevention that can help reduce antibiotic use and resistance while maintaining effective prophylaxis against recurrent infections.