From the Guidelines
Methenamine can cause several side effects, including stomach upset, nausea, vomiting, diarrhea, and abdominal cramps, as well as less common effects like headaches, dizziness, or a burning sensation during urination, and it is essential to use it cautiously, especially in patients with certain medical conditions, as recommended by recent guidelines 1. When considering the use of methenamine, it is crucial to weigh the potential benefits against the possible side effects. The medication works by releasing formaldehyde in acidic urine, which can help prevent urinary tract infections (UTIs) but may also irritate the bladder lining. Some key points to consider when using methenamine include:
- Taking the medication with food and drinking plenty of water to minimize side effects
- Maintaining acidic urine, especially when taking the hippurate form, by avoiding excessive alkaline foods and beverages
- Using methenamine cautiously in patients with liver or kidney disease, gout, or dehydration
- Monitoring for signs of allergic reaction, such as rash, itching, or hives, and seeking immediate medical attention if they occur
- Being aware of the potential for less common side effects, such as headaches or dizziness, and reporting them to a healthcare provider if they persist or worsen. According to a recent study published in JAMA Network Open, methenamine hippurate was found to be noninferior to daily low-dose antibiotics in preventing recurrent UTIs in women aged 18 years and older, with similar adverse effects 1. However, another study published in Clinical Infectious Diseases in 2010 noted that methenamine salts should not be used routinely to reduce catheter-associated bacteriuria or UTI in patients with long-term intermittent or indwelling urethral or suprapubic catheterization 2. It is essential to follow the recommended guidelines and consult with a healthcare provider to determine the best course of treatment and minimize potential side effects. The most recent and highest-quality study recommends using methenamine as an alternative to prophylactic antibiotics in patients with intact bladder anatomy, while emphasizing the importance of maintaining acidic urine and monitoring for side effects 1.
From the FDA Drug Label
ADVERSE REACTIONS Adverse effects of Methenamine Hippurate Tablets have been reported in fewer than 3.5% of patients treated. These reactions have included the following, in decreasing order of frequency: nausea, vomiting and rarely pruritus, rash, dysuria. Large doses of methenamine (8 g daily for 3 to 4 weeks) have caused bladder irritation, painful and frequent micturition, albuminuria and gross hematuria. In a few instances in one study, the serum transaminase levels showed a mild elevation during treatment which returned to normal while the patients were still receiving Methenamine Hippurate Tablets.
The side effects of Methenamine (Hexamine) include:
- Gastrointestinal symptoms: nausea, vomiting
- Dermatological symptoms: pruritus, rash
- Urinary symptoms: dysuria, bladder irritation, painful and frequent micturition, albuminuria, gross hematuria
- Hepatic symptoms: mild elevation of serum transaminase levels 3, 4
From the Research
Side Effects of Methenamine (Hexamine)
- The side effects of methenamine are reported to be few, with one patient experiencing nausea and another being intolerant in a study published in 2019 5.
- A 1975 study found no deterioration of renal function or haematological change, and no patient developed urinary calculus during treatment with methenamine hippurate 6.
- A 2012 review of 13 studies found that the rate of adverse events was low, but poorly described 7.
- A 2024 systematic review found that adverse effects reported with methenamine were similar to comparators and included nausea, abdominal pain, and headache 8.
- A 2014 review discussed the adverse reactions and safety of methenamine, but did not provide specific details on the frequency or severity of side effects 9.
Common Side Effects
Rare Side Effects
- No rare side effects were reported in the studies reviewed. However, it is essential to note that the rate of adverse events was low, but poorly described in some studies 7.