What is the recommended Hiprex (methenamine hippurate) dosage and administration for prophylaxis of recurrent uncomplicated urinary tract infection in an adult with normal renal function and urine pH ≥ 5.5?

Hiprex (Methenamine Hippurate) Dosing for UTI Prevention

For adults and children over 12 years of age with recurrent UTIs, the recommended dose is 1 gram (1 tablet) twice daily—once in the morning and once at night—with urinary pH maintained below 6.0 for optimal efficacy. 1, 2

Standard Dosing Regimen

• Adults and pediatric patients over 12 years: 1 tablet (1 gram) twice daily, taken morning and evening 1, 2
• Pediatric patients 6-12 years: 0.5 to 1 gram twice daily 1
• The American College of Physicians specifically endorses the 1 gram twice daily regimen for adults and children over 12 years 2

Critical Requirement: Urinary Acidification

• Urinary pH must be maintained below 6.0 for methenamine hippurate to be effective, as the drug is hydrolyzed to formaldehyde only in acidic urine 2, 1
• Restriction of alkalinizing foods and medications is essential 1
• If urinary pH remains elevated despite dietary measures, supplemental acidification should be instituted based on urinary pH monitoring and clinical response 1
• Important caveat: Studies show that ascorbic acid up to 4 grams daily has no significant effect on mean urinary pH; dosages as high as 12 grams per day may be required, though data are insufficient to recommend the best acidification method 2

Treatment Duration

• The American Urological Association recommends 6-12 months of continuous prophylaxis for prevention of recurrent UTIs in women 2
• Prophylaxis may need to be continued beyond the initial 6-12 month period if recurrent UTIs persist as a clinical problem 2
• Therapy efficacy should be monitored by repeated urine cultures 1

Patient Selection Criteria

• Ideal candidates: Patients with intact bladder anatomy, fully functional bladders, and no urinary incontinence 2
• Appropriate for: Women with ≥2 culture-positive UTIs in 6 months or ≥3 in 12 months 2
• Premenopausal women: Consider as first-line non-antibiotic option for infections unrelated to sexual activity 2
• Postmenopausal women: Use as alternative when vaginal estrogen is contraindicated or declined 2

When NOT to Use Methenamine Hippurate

• Do not use routinely in patients with long-term indwelling urethral or suprapubic catheters (strength A-III recommendation) 2
• Do not use in patients with long-term intermittent catheterization (strength A-II recommendation) 2
• Not recommended for spinal cord injured patients, due to limited efficacy in this population 2
• Avoid in patients with acute kidney injury until renal function stabilizes; consider increased fluid intake (approximately 1.5 L daily) as alternative prophylaxis 2

Clinical Efficacy

• Methenamine hippurate demonstrates a 73% reduction in UTIs compared to placebo (p<0.01) 2
• In comparative studies, methenamine showed a recurrence rate of 34.2% versus 63.2% with placebo, though less effective than trimethoprim (10.4%) 2
• Recent meta-analysis confirms non-inferiority to antibiotic prophylaxis with similar rates of symptomatic UTI episodes (RR 1.15; 95% CI 0.96-1.38) 3
• The ALTAR trial demonstrated 44.6% reduction in antibiotic prescriptions over 2 years 2

Safety Profile and Resistance

• Low rate of adverse events with better tolerability than nitrofurantoin 2
• Most common side effect is nausea, which is rare 2
• Acquired resistance does not develop to formaldehyde, unlike conventional antibiotics 2
• The ALTAR trial showed 72% of participants on daily antibiotics demonstrated E. coli resistance versus 56% in the methenamine arm (p=0.05) 2

Monitoring and Follow-Up

• Monitor therapy efficacy with repeated urine cultures 1
• Check urinary pH to ensure it remains below 6.0 2, 1
• Patients should seek immediate medical attention if symptoms do not resolve within 4 weeks after treatment completion or recur within 2 weeks 2
• For patients whose symptoms do not resolve by end of treatment or recur within 2 weeks, perform urine culture with antimicrobial susceptibility testing 2
• Routine post-treatment urinalysis or urine cultures are NOT indicated for asymptomatic patients 2

Common Pitfall to Avoid

The single most important pitfall is failure to maintain acidic urine—methenamine hippurate is completely ineffective if urinary pH is not below 6.0, as the conversion to bacteriostatic formaldehyde requires an acidic environment 2, 1. Regular pH monitoring is essential for treatment success.