Hiprex is a drug made from methenamine hippurate (formerly hexamine hippurate). This compound is broken down (hydrolysed) into formaldehyde in urine, and exerts an antimicrobial effect on both bacteria and fungi in the bladder and urinary tract. This is a very useful adjunct to other urinary tract infection treatments and can work on its own.
Methenamine is used to suppress or eliminate bacteria in the urine (bacteriuria), particularly associated with pyelonephritis, cystitis, and chronic urinary tract infections. It is also used to help keep UTIs to a minimum in those with neurological diseases (see the neurogenic bladder).
Methenamine treats uncomplicated urinary tract infections and suppresses these infections in those who use catheters intermittently.
What bacteria and fungi are killed?
Almost all, and the microbes don’t become resistant to this treatment either, unlike antibiotics.
Don’t use methenamine when:
If urine is not acidic, the treatment does not work – a pH of 5.5 or above is required, so urinary alkalisers are out of the question. If this is impossible to achieve, treatment with methenamine is not advised and will not work. If a person has a permanent (indwelling) urinary catheter, methenamine is also ineffective. Caution in those who are dehydrated, or have impaired kidneys or liver.
How to take methenamine
Follow the directions on the jar, which will be tailored to the type of methenamine you are taking.
A full course of therapy is advised. If you miss a dose, don’t double up the next dose, but take it as soon as possible or skip a dose if it is near to the next dose. If symptoms do not improve over the course of a couple of days, see a doctor, as you may have something else problematic occurring that needs a different treatment.
How to keep urine acidic during treatment
This is essential for treatment to work, but it’s easy to do. Eat plenty of protein, cranberries, vitamin C (ascorbic acid), plums or prunes. If you want to check your urinary pH (which you should because it’s fun), find a local pharmacy that sells pH tester paper – they are inexpensive and come in packs. Your pH must remain at 5.5 or lower (with low numbers meaning high acidity).
You can also take vitamin C (ascorbic acid – but avoid anything with ascorbate sodium, as it is alkalising), up to 4 grams per day. Watch out for diarrhoea, since vitamin C draws water to the bowel. Maintain fluid levels.
Some bacteria (urea-splitting organisms like Proteus mirabilis and some strains of Pseudomonas and Enterobacter) can actually increase urinary pH, and can problematically interfere with methenamine action. This is why it’s important to measure urine pH while taking methenamine.
If urinary tract infections are successfully prevented by using 4 grams of methenamine mandelate daily, this dose can be reduced to a maintenance level of 1 gram of mandelate twice daily – check efficacy.
What is methenamine?
Methenamine is what’s known as a weak base. After ingestion, and once in the bladder, methenamine breaks down (hydrolyses) into ammonia and formaldehyde, a known nonspecific antibacterial agent.
How does it work?
It is thought that formaldehyde works by damaging (denaturing) proteins of microbes, killing them. The pH (acidity) controls the amount of formaldehyde released, so the more acidic the urine, the more formaldehyde released, and the more powerful the antimicrobial effect. The flow rate and volume of urine also makes a difference.
Methenamine is freely distributed in body tissues and fluids, but this is apparently not clinically significant, since methenamine does not break down at pH over 6.8 – human body tissue has a pH of 7.2. Saliva and urine have a pH of between 6.6 and 6.8.
Digestion and the different forms of methenamine
The tablets may be enteric coated (methenamine mandelate), which prevents the tablet dissolving in your acidic stomach, but instead makes it as far as possible down the intestine and into the body tissues. But, the tablets may not be – methenamine alone will be rapidly absorbed, but 30-60 per cent will be hydrolysed by stomach acid. Methenamine hippurate is rapidly absorbed via the gastrointestinal tract.
Some formaldehyde is bound to some substances in urine and surrounding tissues. It has a half-life of 4.3 hours, and is excreted via the kidneys almost completely (90 per cent) within 24 hours. Around 20 per cent of this is formaldehyde.
The peak of the urinary formaldehyde concentration (with a pH of 5.6) is as follows:
- Methenamine – 0.5-1.5 hours
- Methenamine hippurate – 2 hours
- Methenamine mandelate (enteric-coated tablets) 3-8 hours.
People with impaired kidney function
Methenamine can accumulate in the body when the kidneys are not functioning properly, but it does not hydrolyse in blood (which has a pH of 7.4), and is not considered toxic, but hippuric acid and mandelic acid can accumulate in those with severely impaired kidney function, and could be toxic. In people with impaired kidney function, formaldehyde concentrations may not be sufficient to work as expected.
Care should be taken in those with kidney impairment, with crystalluria (crystals in the urine) a risk with low urinary output.
Precautions when using methenamine
Pregnancy and fertility considerations
Methenamine crosses the placenta, but study is insufficient at this time in animals and humans. There has been no demonstrated risk of foetal abnormalities during pregnancy when using methenamine. It is considered an FDA Pregnancy Category C, which means, “Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.”
Methenamine is found in breast milk, but no problems have been recorded so far.
No problems have been yet identified regarding methenamine and children, but it is recommended for use in children 12 years and above.
There is no information available regarding the use of methenamine in old people.
Those with severe liver impairment should seek medical guidance when using this drug.
Use with other drugs or supplements (drug interactions)
- Urinary alkalisers – don’t use (methenamine needs acidity to work)
- Antacids (methenamine needs acidity to work)
- Carbonic anhydrase inhibitors
- Sodium bicarbonate, or
- Diuretics, thiazide
- Sulfamethizole (may increase the risk of crystalluria)
- Don’t use with Azulfidine, Bactrim, Septra, SMZ-TMP, Sulfazine, and others
Side-effects of methenamine
Note: large, ongoing doses of methenamine (8 grams per day for 3-4 weeks) have caused bladder irritation, painful and frequent urination, and blood in the urine.
Infrequent side-effects include skin rashes, and rarely, methenamine can cause crystalluria or hematuria – those are characterised by blood in the urine, lower back pain, and pain or burning on urination. Methenamine can sometimes cause nausea and vomiting. Sometimes methenamine can cause painful urination – adjust dose accordingly.
If side-effects occur, take after meals or at bedtime.