Hiprex, a urinary antiseptic, is used by specialists to treat chronic UTI.
Hiprex is an older medication, prescribed and used in the treatment of lower urinary tract infections for nearly 100 years.
Methenamine Hippurate or Hiprex acts as an antibacterial agent against a wide range of bacteria, covering both gram-positive and gram-negative organisms.
- Hiprex is often prescribed alongside antibiotics or on its own.
- If an infection has significantly improved and antibiotics are no longer required on a daily basis, Hiprex is often prescribed as an ongoing treatment to prevent infections reoccurring.
- Hiprex can be taken during pregnancy under clinician management.
What is in Hiprex?
Urinary antiseptic not an antibiotic
Because Hiprex is not an antibiotic but a urinary antiseptic, it can be available for purchase over the counter in some countries without a prescription. This means there is little risk of pathogenic bacteria developing resistance.
The active ingredient is methenamine hippurate with each tablet containing 1 gram. It has antibacterial activity because the methenamine component is broken down to formaldehyde and ammonia in acid urine. By converting to bactericidal formaldehyde it prevents bacterial growth by destroying the proteins and replication abilities within a bacterium
Hippuric acid, the other component, has some antibacterial activity and also acts to keep the urine acidic.
The key to the effectiveness of Hiprex is maintaining concentrated, acid urine so that the main ingredients are activated. If the urine is too dilute and alkaline with a urinary PH of over 6.0, Hiprex will be ineffective.
Some people find that taking Hiprex with vitamin C can help to maintain an acid urine balance but this is by personal choice and is not essential to the activation of Hiprex.
So what is the evidence for Hiprex?
A Cochrane review of Hiprex and it’s effectiveness for those with recurrent UTI was carried out in 2012. It included thirteen studies incorporating 2032 participants.
Overall, the quality amongst the studies was mixed but analysis suggested that Hiprex:
- May have some benefit in patients without renal tract abnormalities but not in patients with known renal tract abnormalities.
- For short‐term treatment (one week or less) there was a significant reduction in symptomatic UTI in those without renal tract abnormalities.
- Had low side effects.
But the authors concluded that more extensive randomised control trials were needed to clarify its long term usage and effectiveness of Hiprex.
More recent data has come from a ten year patient study by the Lower Urinary Tract Symptoms Clinic at the Whittington Hospital, London, published in the International Urogynecology Journal in 2018.
The study reviewed 624 women between 2004 and 2014 where Hiprex was prescribed alongside high dose, long-term antibiotics. 64 percent of the women said that their symptoms were very much better, with another 20 percent reporting that they were much better. The mean treatment time was just over one year.
In 2019 a trial of 86 adult patients was undertaken at Chicago’s NorthShore University Health System in the US comparing low dose prophylaxis Trimethoprim against Hiprex for recurrent UTI within a 12 month period. Results of the study showed that there was no difference between groups with regard to recurrent urinary tract infections, with 65% recurrence in the trimethoprim group versus 65% recurrence in the methenamine hippurate group. The authors concluded that methenamine hippurate may be an alternative for the prevention of recurrent urinary tract infections, with similar rates of recurrence and adverse effects to trimethoprim.
In December 2021 a published patient trial study at Newcastle University Hospitals in the UK recruited women from eight secondary care urology and urogynaecology centres in the UK from June 2016 and incorporated a 12 month treatment period followed by a six month follow-up period. Participants were adult women aged 18 years and over with recurrent UTI who had decided, in conjunction with their responsible clinician, that prophylaxis was appropriate, were eligible for inclusion. The study noted that recurrent UTI was defined as at least three episodes of symptomatic UTI in the previous 12 months or at least two episodes in the past six months.
Between 23 June 2016 and 20 June 2018, 240 participants were recruited and randomly assigned to antibiotic prophylaxis or methenamine hippurate. For those allocated to antibiotic prophylaxis, 66 (55%) received nitrofurantoin, 30 (25%) trimethoprim, 24 (20%) cefalexin. A total of 22 (18%) participants allocated to methenamine hippurate switched to receive antibiotic prophylaxis and seven (6%) vice versa. Patient follow-up was completed in January 2020.
The results of this trial noted that “incidence of antibiotic treated urinary tract infections during the 12 month treatment period was 0.9 episodes per person year in the antibiotics group and 1.4 in the methenamine hippurate group confirming non-inferiority”.
The authors concluded “In the ALTAR trial, we have demonstrated high levels of efficacy from methenamine hippurate in terms of UTI prevention, and have shown that this efficacy is comparable to the current guideline recommended prophylaxis (that is, around six month, low dose antibiotic treatment)”.
Swabs were taken during the trial to check for antibiotic-resistant bacteria. During the treatment period, more women in the antibiotic group tested positive for bacteria that were resistant to one or more antibiotics. But in the 6 months after treatment had finished, more women in the methenamine group tested positive for resistant bacteria. This unexpected (secondary) finding could be because women on methenamine received more short-course antibiotics after the study finished. More research is needed to determine whether methenamine reduces antibiotic resistance.
In 2023 the UK National Institute for Health and Care Research concluded in a published paper discussing the ALTAR trial that the results have led to an ongoing review by the National Institute for Health and Care Excellence (NICE) in the UK on whether methenamine can be offered to women with recurrent urinary tract infections. The researchers say that guidelines, such as European Association of Urology Urological Infections Guidelines, could be updated to include methenamine as an option for preventing recurrent infections. This study, along with the NICE review, will allow clinicians and patients to make shared decisions and consider using methenamine rather than antibiotics.
How is Hiprex taken?
Available in tablet form the recommended dose for adults is one tablet twice a day. For children aged 6 – 12 years the recommended dose is half a tablet (500mg) twice a day. It should not be given to children under the age of six.
Some patients report gastric issues with its use. Taking Hiprex with food or placing the tablet in a size 000 gelatin capsule may help with the digestion of Hiprex.
Do not take Hiprex at the same time as urinary alkalisers such bicarbonate of soda or cystitis sachets sold in supermarkets or pharmacies. These make the urine alkaline but prevent Hiprex from working properly. Acidic urine is a key agent to activating the medication’s ingredients.
D Mannose, which is often used to treat e-coli infections can be used whilst taking Hiprex but be aware that the mannose will be less effective because it works best in more alkaline urine.
Start with a small dose and work up slowly to the full prescribed dose to test tolerance.
Are there any issues with Hiprex?
Before starting Hiprex, you should always discuss its usage with a physician as there are drug interactions. We list below medical conditions that may prevent its usage.
Hiprex is best described as a marmite drug. From some it is well-tolerated and patients experience good results. For others it causes problems with burning causing bladder pain (due to the need to acidify the urine) and increased frequency. Some find that even after using it for several weeks, these side effects have not declined.
If you are using Hiprex and experience significant side effects, you should always contact your specialist or GP for advice on its continuation.
Studies have suggested that in patients with indwelling catheters, adequate urine concentration doesn’t develop and thus the conversion to formaldehyde is not achieved making methenamine ineffective. (i)
Do not use Hiprex if:
- You are allergic to methenamine hippurate or any of the other ingredients of this medicine
- You are taking antibiotic medicines called sulphonamides. These can damage your kidneys when taken at the same time as Hiprex
- You are severely dehydrated (this can be issue in the older generation)
- You have serious problems with your kidneys (renal impairment)
- You have problems with your liver
- You have gout
- You have a condition called metabolic acidosis (a chemical imbalance in the blood).
Find out about other treatments for chronic UTI.
References:
(i) Lo TS, Hammer KDP, Zegarra M, Cho WCS. Methenamine: a forgotten drug for preventing recurrent urinary tract infection in a multidrug resistance era. Expert Review of Anti-Infective Therapy. 2015; 12(5):549-554.