Side Effects of Methenamine
Methenamine is generally well-tolerated with adverse effects occurring in fewer than 3.5% of patients, primarily consisting of mild gastrointestinal symptoms that rarely require discontinuation. 1
Common Side Effects (in decreasing order of frequency)
- Nausea is the most frequently reported adverse effect 1
- Vomiting occurs less commonly than nausea 1
- Pruritus (itching) is rarely reported 1
- Rash occurs rarely 1
- Dysuria (painful urination) is an uncommon side effect 1
Pediatric Safety Profile
- In children receiving methenamine hippurate as prophylactic therapy after treatment of acute pyuria, side effects were encountered in only 1.1% of patients 1
- This demonstrates excellent tolerability in the pediatric population 1
Dose-Related Adverse Effects
Large doses (8 grams daily for 3-4 weeks) can cause more serious urinary tract symptoms, though these are not seen with standard dosing: 1
- Bladder irritation 1
- Painful and frequent urination 1
- Albuminuria (protein in urine) 1
- Gross hematuria (visible blood in urine) 1
Hepatic Considerations
- Mild elevation in serum transaminase levels has been reported in a few instances during treatment, which returned to normal while patients continued receiving the medication 1
- Periodic liver function studies are recommended, especially in patients with pre-existing liver dysfunction 1
Clinical Trial Safety Data
Recent systematic reviews and clinical trials consistently demonstrate low rates of adverse events: 2, 3
- A Cochrane review of 13 studies (2,032 participants) found that the rate of adverse events was low, though poorly described in many studies 2
- A 2024 systematic review of seven recent studies confirmed that adverse effects with methenamine were similar to comparators and included nausea, abdominal pain, and headache 3
- In renal transplant recipients, methenamine was well-tolerated with only one patient experiencing nausea and one patient being intolerant 4
Long-Term Safety
- A study of 24 patients treated for an average of 16 months showed no development of urinary calculi during treatment 5
- No deterioration of renal function or hematological changes were observed with long-term use 5
- No emergence of bacteria with extensive resistance patterns occurred 5
Drug Interactions and Laboratory Interference
- Concomitant administration with sulfamethizole or sulfathiazole may result in precipitate formation in urine 1
- Methenamine causes spuriously elevated urinary 17-hydroxycorticosteroid and catecholamine levels on laboratory testing 1
Contraindications and Special Populations
- Pregnancy Category C: Should only be used if potential benefit justifies potential risk to the fetus 1
- Nursing mothers: Methenamine is excreted in human milk; decision should be made whether to discontinue nursing or the drug 1
- Renal impairment: Care should be taken to maintain acid urine pH, especially when treating infections with urea-splitting organisms 1
Comparative Safety Profile
Methenamine offers a favorable safety profile compared to long-term antibiotic prophylaxis, with similar or lower rates of adverse effects and no contribution to antibiotic resistance. 6, 3