Can you take methenamine and Bactrim (trimethoprim/sulfamethoxazole)?

From the Guidelines

It is not recommended to take methenamine and Bactrim (trimethoprim/sulfamethoxazole) together without consulting a healthcare provider first, as this combination may increase the risk of adverse effects such as crystalluria and kidney problems, as well as potentially reduce the effectiveness of one or both medications. According to a recent study published in JAMA Network Open in 2024 1, methenamine hippurate is recommended as an antimicrobial-sparing intervention to reduce UTIs in patients without incontinence and a fully functional bladder, at a dose of 1 g twice daily. However, the study does not provide guidance on the concomitant use of methenamine with other antibiotics like Bactrim. Key considerations when taking these medications together include:

• The potential for increased risk of crystalluria and kidney problems
• The effect of Bactrim on urine pH, which may make it more alkaline and reduce the effectiveness of methenamine
• The need for careful monitoring and potential adjustment of the treatment plan by a healthcare provider. Given the potential risks and interactions, it is essential to consult a healthcare provider before taking methenamine and Bactrim together, as they may need to adjust the treatment plan or find alternative options 1.

From the Research

Interaction between Methenamine and Bactrim (Trimethoprim/Sulfamethoxazole)

• The study 2 found that methenamine hippurate (MH) and trimethoprim (TMP) have a synergistic interaction in vitro against 11/11 bacteria in urine, suggesting that the combination of TMP and MH may be more efficient than TMP alone in the treatment of urinary tract infections.
• The same study 2 also found that low concentrations of MH had an additive or synergistic effect with TMP against 14/14 bacteria in brain-heart broth and 20/26 bacteria in Mueller-Hinton broth.
• Preliminary pharmacokinetic studies with TMP and MH showed no marked interaction between the drugs 2.
• Another study 3 compared methenamine hippurate with trimethoprim for the prevention of recurrent urinary tract infections and found no difference between groups in recurrent UTI, suggesting that methenamine hippurate may be an alternative for the prevention of recurrent UTI, with similar rates of recurrence and adverse effects to trimethoprim.

Safety and Efficacy of Methenamine and Bactrim (Trimethoprim/Sulfamethoxazole)

• A study 4 found that methenamine hippurate was effective in reducing the number of reinfections in patients with recurrent urinary tract infection, but it was only of limited value for treatment of established infection.
• The study 5 found that methenamine hippurate had fewer side effects than nitrofurantoin and was preferred for prophylaxis in patients with an indwelling catheter.
• The study 6 found that methenamine hippurate was not inferior to daily low-dose antibiotics in preventing recurrent urinary tract infections in women, and that antimicrobial resistance was proportionally higher in women taking prophylactic antibiotics.

Combination Therapy

• The study 2 suggests that the combination of trimethoprim and methenamine hippurate may be more efficient than trimethoprim alone in the treatment of urinary tract infections.
• However, the study 3 found that methenamine hippurate may be an alternative for the prevention of recurrent UTI, with similar rates of recurrence and adverse effects to trimethoprim, suggesting that combination therapy may not be necessary in all cases.