Methenamine Hippurate for Preventing Recurrent Urinary Tract Infections

Table of Contents

1. What Methenamine Hippurate Is
2. How It Works in Acidic Urine
3. Why It Is Called an Antiseptic, Not an Antibiotic
4. From a Forgotten Drug to Renewed Interest
5. The ALTAR Trial
6. What the Cochrane Review Found
7. Later Trials and Meta-Analyses
8. Where It Worked Less Well
9. What Guideline Panels State
10. What the Label States
11. What Is Not Known
12. Key Research Papers
13. Connections
14. Featured Videos

What Methenamine Hippurate Is

Methenamine hippurate is a salt made of two parts. The first part, methenamine (also called hexamethylenetetramine or hexamine), is the part that turns into formaldehyde. The second part, hippuric acid, is a mild acid. The current United States label describes each tablet as containing 1 gram of methenamine hippurate, “the hippuric acid salt of methenamine (hexamethylene tetramine).” A related form, methenamine mandelate, pairs methenamine with a different acid; a 2014 review describes both forms as approved by the U.S. Food and Drug Administration (FDA).

The medicine is approved for one use. The label states that it is indicated “for prophylactic or suppressive treatment of frequently recurring urinary tract infections when long-term therapy is considered necessary,” and that it is used only after an existing infection has been cleared by another antimicrobial medicine. In other words, it is a background medicine taken between infections, not a treatment for the burning, urgency and pain of an infection that has already started.

On dosing, the label states 1 tablet (1 gram) twice a day, morning and night, for adults and for children over 12 years old, and half to one tablet twice a day for children aged 6 to 12. The ALTAR trial and the later ImpresU trial in older women both gave 1 gram twice a day.

A urinary tract infection (UTI) is most often a bladder infection (cystitis) caused by bacteria from the gut, above all Escherichia coli (E. coli). Recurrent urinary tract infection is usually defined as two or more infections in six months or three or more in twelve months, the definition used in a 2026 overview of prevention studies. For many years the usual way to prevent repeat infections was a small daily dose of an antibiotic taken for months, which is the comparison at the centre of the ALTAR trial below.

How It Works in Acidic Urine

The label explains the action in one sentence: the tablets have antibacterial activity “because the methenamine component is hydrolyzed to formaldehyde in acid urine.” Hydrolysis here means that methenamine slowly breaks apart when it meets water and acid. Formaldehyde is a small chemical that a 2026 study of the medicine describes as “highly toxic” to bacteria and cells alike. The label adds that hippuric acid “has some antibacterial activity and also acts to keep the urine acid.”

The key word is acid. The label states that over 90% of the methenamine part of a single 1-gram dose leaves the body in the urine within 24 hours, with antibacterial activity measurable in the urine within half an hour of a dose. How much formaldehyde is actually released there depends on how acidic the urine is.

How much the acidity matters was measured in a 1993 laboratory study of pooled human urine kept at body temperature. The researchers found that the half-life of methenamine conversion, the time for half of it to change into formaldehyde, rose about 20-fold, from 20 hours at pH 5.0 to about 400 hours at pH 6.5. (pH is the scale of acidity; lower numbers are more acidic, and 7 is neutral.) In urine at pH 6.0, formaldehyde levels known to kill bacteria (more than 28 micrograms per millilitre) were reached in 3 hours. The authors concluded that unless urine stays below pH 6, only a small fraction of the methenamine is converted each day. In the same study, urine collected from people taking ascorbic acid (vitamin C) converted methenamine at the same rate as normal urine.

The label states that the medicine is generally active against E. coli, enterococci and staphylococci, and that Enterobacter aerogenes is generally resistant. It also states that urine has to be kept acidic enough for “urea-splitting organisms such as Proteus and Pseudomonas” to be held back. These bacteria break down urea, a waste product in urine, into ammonia, which makes urine more alkaline and so works against the formaldehyde mechanism. For the same reason the label describes restricting alkalinising foods and medicines as “desirable” during treatment.

A 2026 analysis of urine from the ALTAR trial confirmed the mechanism in real patients: formaldehyde was detected in 85% of the urine samples from participants taking methenamine hippurate, and urine from these participants contained higher levels of formate, the substance bacteria make when they break formaldehyde down.

Why It Is Called an Antiseptic, Not an Antibiotic

Most antibiotics act on a specific target inside bacteria, and bacteria that change or protect that target become resistant. Methenamine works through a chemical that is toxic in general rather than through one target, and reviews and trial reports describe it as a urinary antiseptic rather than an antibiotic. The 2025 ImpresU trial authors describe its “low potential for selection for antimicrobial resistance.”

The ALTAR trial measured resistance directly. During treatment, antibiotic-resistant E. coli grown from skin swabs near the urethra was found in 72% of the women taking daily antibiotics (46 of 64) and in 56% of the women taking methenamine hippurate (39 of 70), a difference at the edge of statistical significance (p = 0.05). Urine cultures during treatment showed more E. coli resistant to trimethoprim, co-trimoxazole and cephalosporins in the antibiotic group. After treatment stopped, however, the pattern reversed for one measure: multidrug-resistant E. coli was found on swabs from 20% of the methenamine group (9 of 45) and 5% of the antibiotic group (2 of 39), a difference that could be chance (p = 0.06).

“No resistance in the usual sense” does not mean bacteria have no defence at all. Bacteria carry their own systems for clearing formaldehyde, because small amounts are made during normal metabolism. The 2026 study of ALTAR samples tested E. coli taken from trial participants and found that 5.8% could grow in more than 1 millimolar formaldehyde. Gene analysis found four altered versions of a gene called frmR, which normally holds back the bacterium’s formaldehyde-clearing enzymes, and two copies of a formaldehyde-clearing gene carried on plasmids, small rings of DNA that can pass between bacteria. In artificial urine, strains with the altered frmR genes grew in the presence of more than 1 milligram per millilitre of methenamine at pH 5.6. The authors wrote that “MH, like antibiotics, has its own associated risks, including bacterial resistance.” This was a laboratory study of bacterial isolates, and it did not measure whether these strains caused more infections in the women who carried them.

The United States label carries the standard paragraph printed on antibacterial medicines about using them only for proven or strongly suspected bacterial infections, to reduce the development of drug-resistant bacteria.

From a Forgotten Drug to Renewed Interest

A 2024 systematic review describes methenamine as “an antiseptic agent initially available in 1967” that “has re-emerged as a potential option for UTI prophylaxis.” A 2014 review titled it “a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era.” Those authors argued that it was worth considering when more commonly used antibiotics fail to suppress recurrent infections.

Trials of the hippurate form go back decades. In a 1983 trial, 64 women with a history of recurrent infections were randomly given one of three year-long prevention regimens: 100 milligrams of trimethoprim at night (20 women), 1,000 milligrams of methenamine hippurate every 12 hours (25 women), or twice-daily washing of the skin around the urethra with povidone-iodine (19 women). All three reduced symptomatic attacks compared with the year before, with little difference between them, although trimethoprim was tolerated better. In the trimethoprim group, 71.4% of the breakthrough infections were caused by trimethoprim-resistant bacteria, compared with 2.7% in the other two groups.

The Cochrane review of methenamine hippurate was first published in 2002, updated in 2007 and updated again in 2012. The renewed attention since 2018 has come mainly from concern over antibiotic resistance: the ALTAR investigators wrote that emerging resistance is “a global health concern, prompting research interest in non-antibiotic agents such as methenamine hippurate.”

The ALTAR Trial

ALTAR (ALternatives To prophylactic Antibiotics for the treatment of Recurrent urinary tract infection in women) was run at eight National Health Service hospitals in the United Kingdom, recruiting from June 2016 to June 2018. It enrolled 240 adult women with recurrent urinary tract infections who needed preventive treatment. Half were randomly assigned to methenamine hippurate 1 gram twice a day and half to a once-daily low-dose antibiotic (50 or 100 milligrams of nitrofurantoin, 100 milligrams of trimethoprim or 250 milligrams of cefalexin), each for 12 months, followed by 6 months of observation off treatment. Both the women and their doctors knew which treatment they were on, and switching between groups was allowed.

What non-inferiority means

ALTAR was a non-inferiority trial. It did not ask whether methenamine hippurate was better than antibiotics; it asked whether it was not worse by more than an agreed amount. A patient and public involvement group set that amount in advance at one urinary tract infection per person per year. If the extra infections in the methenamine group stayed below that line, methenamine hippurate would count as non-inferior.

The main result

The main analysis included 205 women (85%) with at least six months of data. During the 12 months of treatment, symptomatic infections treated with antibiotics fell substantially in both groups, to 1.38 episodes per person-year with methenamine hippurate (95% confidence interval 1.05 to 1.72) and 0.89 episodes per person-year with antibiotics (95% confidence interval 0.65 to 1.12). The absolute difference was 0.49 episodes per person-year (90% confidence interval 0.15 to 0.84). Because the upper end of that range stayed below one infection per person-year, the investigators concluded that methenamine hippurate was not inferior to daily antibiotics.

Put plainly, women on methenamine hippurate had about half an infection more per year on average than women on antibiotics, and that gap was within the limit the trial set as acceptable. A 2026 laboratory paper by researchers including the ALTAR lead investigator described this as “an elevated incidence risk with respect to breakthrough UTI.”

Other findings

• After stopping. In the six months after treatment ended, the infection rate was 1.72 episodes per year in the methenamine group and 1.19 in the antibiotic group.
• Laboratory confirmation. Only 52% of urine samples taken during symptomatic infections during treatment were confirmed as infections by laboratory culture.
• Side effects. Adverse reactions were reported by 35 of 127 women (28%) taking methenamine hippurate and 34 of 142 (24%) taking antibiotics, and most were mild. All other secondary outcomes and adverse events were similar in both groups.
• Resistance. As described above, resistant E. coli on skin swabs was more common in the antibiotic group during treatment (72% versus 56%).
• Cost. A 2024 economic analysis of 205 participants found that, on average, methenamine hippurate cost £40 less per person and gave a small gain of 0.014 quality-adjusted life years, with wide uncertainty in both figures. The probability of it being judged cost-effective ranged from 51% to 67% depending on the value placed on a year of good health.

The trial report notes its own limits: it could not show whether one particular antibiotic did better than the others, and loss of data over time weakened the economic analysis.

What the Cochrane Review Found

The 2012 Cochrane review, written before ALTAR, pooled 13 randomised or quasi-randomised studies with 2,032 participants that compared methenamine hippurate with a placebo or no treatment. Six studies (654 patients) reported symptomatic infections and eight (796 patients) reported bacteriuria, meaning bacteria found in the urine with or without symptoms. The reviewers rated study quality as mixed, and the results varied so much between studies that the overall pooled figures could not be interpreted.

Splitting the studies by the type of patient gave a clearer picture:

• People without abnormalities of the urinary tract: symptomatic infections were lower with methenamine hippurate (risk ratio 0.24, 95% confidence interval 0.07 to 0.89), and so was bacteriuria (risk ratio 0.56, 0.37 to 0.83).
• Short-term use of one week or less in people without abnormalities: symptomatic infections were markedly lower (risk ratio 0.14, 0.05 to 0.38).
• People with known abnormalities of the urinary tract: no benefit was found for symptomatic infections (risk ratio 1.54, 0.38 to 6.20) or bacteriuria (risk ratio 1.29, 0.54 to 3.07).

A risk ratio below 1 means fewer infections in the methenamine group; a confidence interval that crosses 1 means the result could be chance. The reviewers concluded that methenamine hippurate “may be effective for preventing UTI in patients without renal tract abnormalities, particularly when used for short-term prophylaxis,” that it “does not appear to work in patients with neuropathic bladder or in patients who have renal tract abnormalities,” and that the rate of side effects was low but poorly described. They called for larger, well-run trials, particularly of longer-term use.

Later Trials and Meta-Analyses

A 2021 review that found the evidence uncertain

A 2021 systematic review in the British Journal of General Practice, completed before the main ALTAR results were included, looked at six studies with 557 women living in the community (447 analysed). Compared with antibiotics over 12 months, methenamine hippurate showed a trend toward more women staying free of symptoms (risk ratio 0.65, 95% confidence interval 0.40 to 1.07), but the trend was not statistically significant. Comparisons with placebo or no treatment were also not statistically significant and varied greatly between studies. The authors concluded that there was “insufficient evidence to be certain of the benefits of methenamine hippurate to prevent UTI,” and noted that antibiotic use and resistance were not consistently reported.

A 2025 meta-analysis that included ALTAR

A 2025 meta-analysis in BMC Urology pooled five randomised trials of adult women with confirmed recurrent infections that compared methenamine hippurate with antibiotics, covering 216 women on methenamine and 205 on antibiotics. The rate of symptomatic infections did not differ significantly between the two (risk ratio 1.15, 95% confidence interval 0.96 to 1.38), which the authors read as non-inferiority. Positive urine cultures (risk ratio 1.20, 0.91 to 1.57) and side effects (risk ratio 0.98, 0.86 to 1.12) also did not differ. Bacteria in the urine without symptoms (asymptomatic bacteriuria) were less frequent in the antibiotic group (risk ratio 1.91, 1.29 to 2.81). A further test of whether enough evidence had been gathered, called trial sequential analysis, found that the existing studies had not yet reached the point where more trials would be unnecessary, and the authors called for more trials. The studies did not report side effects related to antibiotic resistance. A correction to the paper was published in 2026.

A placebo-controlled trial in women aged 70 and over

The ImpresU trial, published in 2025, was triple-blind, meaning the treatment was hidden from patients, doctors and those analysing the results. It recruited 289 women aged 70 or older with recurrent infections from general practices in Norway, Sweden, Poland and the Netherlands, and gave them methenamine hippurate 1 gram twice a day or a dummy tablet for 6 months, followed by 6 months off treatment. Among the 281 women analysed:

• During treatment, the methenamine group needed fewer antibiotic courses for urinary infections than the placebo group, an incidence rate ratio of 0.75 (95% confidence interval 0.57 to 1.0, p = 0.049), which the authors summarised as a 25% reduction.
• In the six months after treatment stopped, the result reversed: the methenamine group needed more antibiotic courses than the placebo group, an incidence rate ratio of 1.7 (1.3 to 2.3, p < 0.001).
• There were no important differences in symptom severity, episode length or complications.

The authors wrote that stopping after six months “seems to increase the risk of UTI relapses.”

Reviews of the wider evidence

A 2024 systematic review in Pharmacotherapy identified 11 studies and concluded that methenamine “generally appears to be an effective and well-tolerated antibiotic-sparing option,” noting use in older adults and kidney transplant recipients, while stating that further studies are needed. A 2026 overview of 27 systematic reviews of non-antibiotic prevention in women found that methenamine hippurate (three reviews) and cranberry are supported by systematic reviews, as is vaginal oestrogen in women after menopause, while reviews of probiotics, D-mannose, herbal medicine, acupuncture and vaccines concluded that stronger evidence is needed. For methenamine, the overview named treatment duration as the main open question.

Where It Worked Less Well

Spinal cord injury and the neurogenic bladder

People with spinal cord injury often have a neurogenic (neuropathic) bladder, one that does not empty normally because its nerve supply is damaged; many use catheters. The Spinal-Injured Neuropathic Bladder Antisepsis (SINBA) trial, published in 2007, randomly assigned 305 community-dwelling people with spinal cord injury and neurogenic bladder to methenamine hippurate 1 gram twice a day, cranberry tablets 800 milligrams twice a day, both, or matching placebos, with all tablets looking and tasting the same. Methenamine hippurate did not lengthen the time free of symptomatic infection compared with placebo (hazard ratio 0.96, 95% confidence interval 0.68 to 1.35), and neither did cranberry (hazard ratio 0.93, 0.67 to 1.31). The investigators concluded there was no benefit from adding either to the usual care of these patients. This matches the Cochrane finding that methenamine hippurate did not appear to work in neuropathic bladder or other abnormal urinary tracts.

Short-term catheters after surgery

A different result came from a 2022 double-blind trial of women sent home with a short-term bladder catheter after pelvic reconstructive surgery, a group with very high infection rates. All 182 women analysed took cranberry capsules; 93 also took methenamine hippurate and 89 took a placebo. Treated infections within one week were less common with methenamine (66.7% versus 79.8%; odds ratio 1.97, 95% confidence interval 1.01 to 3.87), and the gap grew by six weeks (72.0% versus 89.9%; odds ratio 3.45, 1.51 to 7.87). There were fewer infections caused by Pseudomonas in the methenamine group. Urine pH did not differ between the groups. This was a short, single-setting study of one surgical group, and the infection rates in both arms remained high.

After the medicine is stopped

Two trials found that the protection did not last once treatment ended. In ALTAR, infections in the six months after treatment were 1.72 per year in the methenamine group and 1.19 in the antibiotic group. In ImpresU, the methenamine group needed 1.7 times as many antibiotic courses as the placebo group in the six months after stopping.

When urine is not acidic

Because the formaldehyde mechanism depends on acidity, the label states that urine must be kept sufficiently acidic when infections involve urea-splitting bacteria such as Proteus and Pseudomonas, which push urine toward alkaline. The laboratory evidence that conversion slows about 20-fold between pH 5.0 and pH 6.5 is the reason this matters.

What Guideline Panels State

The National Institute for Health and Care Excellence (NICE) in England updated its guideline on antimicrobial prescribing for recurrent urinary tract infection (NG112) in 2024. Its recommendation 1.2.8 states: “Consider methenamine hippurate as an alternative to daily antibiotic prophylaxis for recurrent UTI” in women, and in trans men and non-binary people with a female urinary system, if they are not pregnant, any current infection has been adequately treated, and recurrent infection has not adequately improved with behavioural and personal hygiene measures, vaginal oestrogen or single-dose antibiotic prophylaxis where those were appropriate. The guideline further states:

• Specialist advice is sought before using it during pregnancy, for recurrent upper urinary tract infection (kidney infection) or complicated lower infection, in men and people with a male genitourinary system, and in children and young people. NICE notes that in December 2024 these uses, and use in children under 6, were off label.
• People taking it are told that over-the-counter sachets that make urine more alkaline, such as potassium citrate or sodium citrate sachets sold to ease urinary symptoms, can make methenamine hippurate less effective and are not used alongside it, and that medical help is sought for symptoms of an acute infection.
• Treatment is reviewed within 6 months and then every 12 months.

A 2022 comparison of nine national and international guidelines, including those of the European Association of Urology, NICE and the combined American Urological Association, Canadian Urological Association and Society of Urodynamics, Female Pelvic Medicine and Urogenital Reconstruction, found that the guidelines agreed on antibiotic prevention but varied in their positions on antibiotic-sparing options such as cranberry, vaginal oestrogen and others. The authors noted that “recent randomised evidence supports the use of methenamine hippurate,” that some conflicts between guidelines reflect when each was written, and that none of the guidelines was tailored to recurrent complicated infections.

What the Label States

The following points come from a current generic United States label on DailyMed (revised May 2025).

Contraindications

• Kidney failure (the label’s term is renal insufficiency).
• Severe liver failure (severe hepatic insufficiency).
• Severe dehydration.
• Taking sulfonamide medicines (sulfa drugs). The label gives the reason that “some sulfonamides may form an insoluble precipitate with formaldehyde in the urine,” meaning a solid deposit that does not dissolve.

Warnings and precautions

• High doses. The label states that large doses of methenamine, 8 grams a day for 3 to 4 weeks, have caused bladder irritation, painful and frequent urination, protein in the urine and visible blood in the urine. This is four times the standard daily amount of 2 grams.
• Liver tests. In a few instances in one study, liver enzyme levels (serum transaminases) rose slightly during treatment and returned to normal while patients were still taking the medicine. Because of this report, the label recommends periodic liver function tests, especially in people with liver problems.
• Urine acidity. The label states that the antibacterial activity is greater in acidic urine, describes restricting alkalinising foods and medicines as desirable, and states that extra acidification of the urine is added if urine pH and the clinical response indicate it. The label also states that the effect of treatment is monitored with repeated urine cultures.
• Pregnancy. The label states that safe use in early pregnancy is not established, and that in the last trimester safety is “suggested, but not definitely proved.” No harm to the fetus was seen in studies in pregnant rats and rabbits. The medicine can interfere with one laboratory method of measuring urine estriol, a pregnancy hormone, producing falsely very low results.
• Tartrazine. The tablet described contains the yellow colouring tartrazine (FD&C Yellow No. 5), which the label states may cause allergic-type reactions, including asthma, in susceptible people, most often in people who also react to aspirin.
• Older adults. The label states that clinical studies did not include enough people aged 65 and over to tell whether they respond differently.

Side effects

The label states that minor adverse reactions have been reported in less than 3.5% of treated patients, including nausea, upset stomach, painful urination (dysuria) and rash. In ALTAR, where side effects were actively collected over a year, 28% of the methenamine group reported an adverse reaction, most of them mild, a rate similar to the antibiotic group.

Interactions

The two interactions the label and NICE describe both follow from the mechanism: sulfonamides, because of the precipitate with formaldehyde, and anything that makes urine alkaline, including alkalinising foods, alkalinising medicines and the citrate sachets named by NICE, because alkaline urine slows the release of formaldehyde.

What Is Not Known

• How long to take it. ALTAR ran for 12 months and ImpresU for 6, and both found more infections after stopping. The 2026 overview of reviews named duration as the main unanswered question for methenamine hippurate.
• Whether making urine more acidic helps. The label describes acidification when urine pH and response indicate it, and vitamin C is often discussed for this purpose. The one laboratory study read for this page found that urine from people taking vitamin C converted methenamine at the same rate as normal urine. No trial on this page tested whether adding vitamin C changes infection rates.
• Formaldehyde-tolerant bacteria. The 2026 laboratory study found E. coli from trial participants that tolerated formaldehyde, but it is not known how common such strains become with long-term use or whether they lead to more breakthrough infections.
• Men, children, pregnancy and complicated infection. The large trials enrolled women only. NICE lists use in men, children, pregnancy and complicated or upper urinary tract infection as situations for specialist advice, and the 2022 comparison of guidelines found none tailored to recurrent complicated infection.
• Long-term catheters. The trial of short-term catheters after surgery found fewer infections, while the SINBA trial in people with neurogenic bladder found no benefit. Evidence for people living with long-term catheters remains limited.
• Whether enough trials exist. The 2025 meta-analysis found that the pooled trials had not yet reached the boundary at which further trials would be unnecessary.

Decisions about preventive medicines for urinary tract infections belong with a clinician who knows the person’s history, kidney and liver function and other medicines.

Key Research Papers

1. Harding C, Chadwick T, Homer T, Lecouturier J, Mossop H, Carnell S, et al. Methenamine hippurate compared with antibiotic prophylaxis to prevent recurrent urinary tract infections in women: the ALTAR non-inferiority RCT. Health Technol Assess. 2022;26(23):1-172. PubMed PMID: 35535708
2. Harding C, Mossop H, Homer T, Chadwick T, King W, Carnell S, et al. Alternative to prophylactic antibiotics for the treatment of recurrent urinary tract infections in women: multicentre, open label, randomised, non-inferiority trial. BMJ. 2022;376:e068229. PubMed PMID: 35264408
3. King W, Homer T, Harding C, Mossop H, Chadwick T, Abouhajar A, et al. Cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis for the management of recurrent urinary tract infections in secondary care: a multicentre, open-label, randomised, non-inferiority trial. BMJ Open. 2024;14(4):e074445. PubMed PMID: 38684270
4. Lee BS, Bhuta T, Simpson JM, Craig JC. Methenamine hippurate for preventing urinary tract infections. Cochrane Database Syst Rev. 2012;10(10):CD003265. PubMed PMID: 23076896
5. Hobaica NC, De Oliveira GC, Porto BC, Passerotti CC, Da Silva Sardenberg RA, Otoch JP, et al. Effectiveness of methenamine hippurate in preventing urinary tract infections: an updated systematic review, meta-analysis and trial sequential analysis of randomized controlled trials. BMC Urol. 2025;25(1):30. PubMed PMID: 39955521 (correction published 2026, PubMed PMID: 41664093)
6. Bakhit M, Krzyzaniak N, Hilder J, Clark J, Scott AM, Mar CD. Use of methenamine hippurate to prevent urinary tract infections in community adult women: a systematic review and meta-analysis. Br J Gen Pract. 2021;71(708):e528-e537. PubMed PMID: 34001538
7. Heltveit-Olsen SR, Arnljots ES, Sundvall PD, Gunnarsson R, Kowalczyk A, Godycki-Cwirko M, et al. Methenamine hippurate as prophylaxis for recurrent urinary tract infections in older women-a triple-blind, randomised, placebo-controlled, phase IV trial (ImpresU). Clin Microbiol Infect. 2025;31(11):1873-1879. PubMed PMID: 40669691
8. Lee BB, Haran MJ, Hunt LM, Simpson JM, Marial O, Rutkowski SB, et al. Spinal-injured neuropathic bladder antisepsis (SINBA) trial. Spinal Cord. 2007;45(8):542-50. PubMed PMID: 17043681
9. Tam TY, Aldrich ER, Crisp CC, Yook E, Yeung J, Pauls RN. Methenamine Hippurate With Cranberry Capsules Versus Cranberry Alone for Urinary Tract Infection Prevention in a Short-Term Indwelling Foley Catheter Population After Urogynecologic Surgery: A Double-Blinded Randomized Controlled Trial. Female Pelvic Med Reconstr Surg. 2022;28(3):e55-e61. PubMed PMID: 35272334
10. Strom JG Jr, Jun HW. Effect of urine pH and ascorbic acid on the rate of conversion of methenamine to formaldehyde. Biopharm Drug Dispos. 1993;14(1):61-9. PubMed PMID: 8427945
11. Hodgkinson NC, Al-Rubaye T, Reed TCP, Mowbray C, Sarkissian D, Cowley L, et al. Implications for methenamine hippurate use in recurrent urinary tract infection management: Formaldehyde resistance and altered urinary composition. PLoS Pathog. 2026;22(3):e1014081. PubMed PMID: 41875198
12. Brumfitt W, Hamilton-Miller JM, Gargan RA, Cooper J, Smith GW. Long-term prophylaxis of urinary infections in women: comparative trial of trimethoprim, methenamine hippurate and topical povidone-iodine. J Urol. 1983;130(6):1110-4. PubMed PMID: 6227756
13. Lo TS, Hammer KD, Zegarra M, Cho WC. Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era. Expert Rev Anti Infect Ther. 2014;12(5):549-54. PubMed PMID: 24689705
14. Li JM, Cosler LE, Harausz EP, Myers CE, Kufel WD. Methenamine for urinary tract infection prophylaxis: A systematic review. Pharmacotherapy. 2024;44(2):197-206. PubMed PMID: 37986168
15. Kwok M, McGeorge S, Mayer-Coverdale J, Graves B, Paterson DL, Harris PNA, et al. Guideline of guidelines: management of recurrent urinary tract infections in women. BJU Int. 2022;130 Suppl 3:11-22. PubMed PMID: 35579121
16. Santer M, Miller S, Fraser S, Francis N, Lown M, Becque T, et al. Non-antibiotic interventions to prevent recurrent urinary tract infections in women: overview of systematic reviews of randomised controlled trials. Br J Gen Pract. 2026 (online ahead of print). PubMed PMID: 42225392

Other Sources

1. DailyMed, National Library of Medicine. Methenamine hippurate tablets USP: prescribing information, including the indication, contraindications, warnings, precautions, adverse reactions and dosage (generic tablet label, revised May 2025). DailyMed label
2. National Institute for Health and Care Excellence. Urinary tract infection (recurrent): antimicrobial prescribing. NICE guideline NG112, recommendations 1.2.8 to 1.2.11 on methenamine hippurate (2024 update). NICE NG112 recommendations

PubMed Topic Searches

1. methenamine hippurate recurrent urinary tract infection
2. methenamine hippurate randomized
3. methenamine formaldehyde urine pH
4. methenamine spinal cord injury
5. non-antibiotic prophylaxis recurrent urinary tract infection

Connections

• Drugs — every drug page on the site
• Urinary Tract Infections — the infections, their symptoms and treatment
• Uva Ursi and Urinary Tract Infection Evidence — the herbal trials, with D-mannose, cranberry and water intake compared
• E. coli Urinary Tract Infections — the bacterium behind most bladder infections
• Antibiotics for E. coli Infections — the antibiotics and the resistance problem
• Pyelonephritis (Kidney Infection) — the upper urinary tract infection guidelines treat separately
• Cranberries — the fruit, also tested in the SINBA and catheter trials

Featured Videos