Hiprex - Drug Monograph

Introduction

Hiprex (methenamine hippurate) is an antibacterial agent specifically indicated for the suppression or elimination of bacteriuria associated with recurrent urinary tract infections (UTIs). Unlike conventional antibiotics, Hiprex functions as a urinary antiseptic through a unique pH-dependent mechanism. It is particularly valuable for long-term prophylaxis in patients with recurrent UTIs and is often used when conventional antibiotic therapy is not desirable.

Mechanism of Action

Hiprex exerts its antibacterial effects through a chemical process rather than direct antimicrobial activity. After oral administration, methenamine is hydrolyzed to formaldehyde in acidic urine (pH < 6.0). Formaldehyde is a non-specific bactericidal agent that denatures proteins and nucleic acids, effectively eliminating susceptible microorganisms throughout the urinary tract. The hippurate component helps acidify urine, creating optimal conditions for formaldehyde release. This mechanism provides broad-spectrum activity against common uropathogens including Escherichia coli, Enterobacter species, Klebsiella species, and Enterococcus species.

Indications

• Suppression or elimination of bacteriuria in patients with recurrent urinary tract infections
• Long-term prophylaxis of recurrent UTIs
• Particularly useful in patients with neurogenic bladder, spinal cord injuries, or other conditions predisposing to recurrent UTIs

Dosage and Administration

• Should be administered after meals to minimize gastric upset
• Tablets should be swallowed whole with a full glass of water
• Consistent fluid intake is recommended to maintain adequate urine output

• Renal Impairment: Contraindicated in patients with severe renal impairment (CrCl < 10 mL/min) or significant hepatic impairment
• Hepatic Impairment: Use with caution; monitor for potential accumulation
• Geriatric: No dosage adjustment typically required unless renal function is impaired
• Pediatric: Safety and effectiveness in children under 12 years have not been established

Pharmacokinetics

Contraindications

• Hypersensitivity to methenamine or any component of the formulation
• Severe renal impairment (creatinine clearance < 10 mL/min)
• Severe hepatic impairment
• Metabolic acidosis
• Concomitant use of sulfonamides (due to crystallization risk)

Warnings and Precautions

• Renal Function: Requires adequate renal function for proper excretion and effectiveness
• Urine pH Monitoring: Effectiveness depends on acidic urine (pH < 6.0); may require periodic urine pH testing
• Crystalluria: May cause crystalluria; ensure adequate hydration
• Superinfection: As with all antibacterial agents, may result in superinfection
• Pregnancy: Category C - Use only if potential benefit justifies potential risk to fetus
• Lactation: Caution advised; unknown if excreted in human milk

Drug Interactions

• Urine Alkalinizers: Drugs that alkalinize urine (acetazolamide, sodium bicarbonate, thiazides) may reduce effectiveness
• Sulfonamides: Increased risk of crystalluria when used concomitantly
• Carbonic Anhydrase Inhibitors: May reduce efficacy by increasing urine pH
• Anticholinergics: May decrease urinary excretion of formaldehyde

Adverse Effects

• Gastrointestinal disturbances (nausea, vomiting, abdominal pain)
• Dysuria
• Rash
• Pruritus

• Hepatotoxicity
• Urinary tract irritation
• Hematuria
• Allergic reactions including Stevens-Johnson syndrome (rare)
• Metabolic acidosis (with high doses or renal impairment)

Monitoring Parameters

• Regular assessment of UTI symptoms and bacteriuria
• Urine pH (target < 6.0 for optimal efficacy)
• Renal function (serum creatinine, BUN)
• Liver function tests (periodically)
• Complete blood count (with long-term use)
• Signs of superinfection or crystalluria

Patient Education

• Take medication exactly as prescribed, typically twice daily after meals
• Maintain adequate fluid intake (6-8 glasses of water daily)
• Report any signs of worsening UTI symptoms (fever, chills, flank pain)
• Notify healthcare provider if gastrointestinal symptoms persist
• Understand that urine may have a medicinal odor
• Regular follow-up appointments are essential for monitoring effectiveness
• Do not take antacids or other urine-alkalinizing agents without consulting healthcare provider
• Report any skin rashes or unusual side effects immediately

References

1. Pharmaceutical manufacturer prescribing information 2. Hooton TM. Uncomplicated urinary tract infection. N Engl J Med. 2012;366(11):1028-1037. 3. Nicolle LE. Urinary tract infections in the older adult. Clin Geriatr Med. 2016;32(3):523-538. 4. American Geriatrics Society. Guidelines for improving the care of older adults with diabetes mellitus. J Am Geriatr Soc. 2013;61(11):2020-2026. 5. Micromedex Solutions. Methenamine hippurate monograph. Truven Health Analytics. 6. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2023. 7. FDA-approved product labeling for Hiprex (methenamine hippurate)