How Does Methenamine (Hiprex) Prevent a UTI?

If you have recurrent urinary tract infections (UTIs), your healthcare provider may recommend taking a urinary antiseptic called methenamine hippurate (brand name Hiprex) for prophylactic treatment for UTI. Unlike UTI treatments for an active infection, prophylaxis is used for the prevention of recurrent UTI. Please continue reading to find out how methenamine works to prevent urinary tract infections.

What is methenamine hippurate?

Methenamine hippurate is an antibiotic that kills certain bacteria that cause urinary tract infections. It is used for antibiotic prophylaxis (preventive treatment) in people with recurrent urinary tract infections. Recurrent UTI (chronic UTI) is defined as at least two UTI episodes in the past 6 months or at least three UTI episodes in the past year. Methenamine (Hiprex) is only used for preventing urinary tract infections (recurrent UTIs). It is not used to treat an active urinary tract infection (symptomatic UTI). It is important to know that other antibiotics have to be used to treat the infection before methenamine can be used.

Is methenamine hippurate the same as methenamine mandelate?

Yes, methenamine hippurate and methenamine mandelate are used for UTI prophylaxis. They contain the same active ingredient, with different salt forms in the formulation. The most significant difference between the two formulas is their dosing regimen. Methenamine hippurate has a twice-daily dosing, while methenamine mandelate is dosed four times daily.

How does Hiprex prevent UTI?

The antibacterial activity of methenamine hippurate is due to the fact that the methenamine component, when coming in contact with the acidic environment of the urine, is broken down to formaldehyde, a chemical that can damage the bacterial protein. Over 90% of methenamine is excreted into the urine within 24 hours of taking a dose. The other component, hippuric acid, further helps the antibacterial activity of methenamine by keeping the urine acidic. That’s how methenamine provides continuous antibacterial activity when taken at the recommended dose, thus helping to prevent recurrent urinary tract infections.

Is methenamine always successful at UTI prophylaxis?

Available since 1967, the FDA approved methenamine hippurate for the prevention of UTI for adults and children as young as 12 years old. As mentioned, methenamine hippurate’s bactericidal activity is based on it being broken down to formaldehyde in the acidic environment of the urine. A review of previously published data on clinical trials identified some notable shortcomings. For example, those trials were not blinded, randomized clinical trials. In addition, these clinical trials did not have well-defined endpoints. While there are treatment failures, the good news is that pooled analyses still suggest a treatment benefit of using methenamine hippurate for UTI prevention.

What do you need to watch out for success with methenamine hippurate?

Keep in mind methenamine hippurate’s mechanism of action. There are specific factors that can affect this medication’s effectiveness, as described below.

Formaldehyde’s bactericidal activity is effective for both gram-positive and gram-negative bacteria. However, formaldehyde generation solely depends on the acidic environment of the urine. The below factors can affect the urine’s acidity, interfering with the effects of methenamine hippurate:

Diet: If you consume a lot of vegetables, legumes, and citrus fruits, you will keep your urine more alkaline, which is the opposite of being acidic. On the other hand, meat and cranberry juice will keep your urine acidic. With that said, depending on your daily diet, methenamine hippurate can be less effective if you consume food that can make your urine more alkaline.
Certain bacteria reducing urine acid: While the formaldehyde generated from methenamine doesn't discriminate whether it’s Gram-positive or Gram-negative bacteria, certain bacteria in the urine can also make it more alkaline, which is not ideal for the generation of formaldehyde. Those bacteria include Proteus and Pseudomonas.
Certain bacteria resistant to methenamine: This drug is active against certain bacteria that can cause urinary tract infections, such as E. coli, Enterococci, and Staphylococci. It can protect you against a recurrent urinary tract infection caused by these bacteria. However, other types of bacteria, such as Enterobacter aerogenes, tend to be resistant to methenamine.

In older adults and people with renal impairment (reduced kidney function due to kidney disease), enough methenamine may not reach the urine to be effective in preventing recurrent infections.

Methenamine may not work well in people with certain health conditions, such as known renal tract abnormalities, neurogenic bladder, long-term catheters, severe hepatic impairment (liver disease), severe renal impairment (kidney disease), severe dehydration, gout, and metabolic acidosis. Therefore, this antibiotic is only recommended for UTI prevention in patients without renal tract abnormalities and the above-listed conditions. Pregnant women should discuss the pros and cons of taking prophylactic antibiotics for UTIs with their healthcare provider.

What is the advantage of taking methenamine for recurrent UTIs?

Indiscriminate or repeated use of antibiotics can lead to antibiotic resistance in bacteria, making future bacterial infections harder to treat. Daily low-dose antibiotics can help prevent recurrent UTIs but may lead to antibiotic resistance. Methenamine reduces antibiotic resistance by preventing recurrent urinary tract infections that would require antibiotic treatment.

To reduce the incidence of antibiotic-resistant bacteria and maintain the effectiveness of methenamine hippurate and other antibiotics, you should only use methenamine or other antibiotic treatment for urinary tract infections that are proven or strongly suspected to be bacterial infections.

Your doctor may give you another antibiotic from an antibiotic group tested positive on your urine culture and sensitivity test. An antibiotic being “tested positive” means the bacteria being treated is not resistant to that antibiotic, which is very important to have a successful treatment to clear an active urinary tract infection. If you have an active UTI, keep in mind that you need to be treated with an antibiotic before starting on methenamine for the prevention of recurrent UTIs. This is to make sure your urine is clear of bacteria before starting methenamine.

What is the recommended dose of Hiprex?

The recommended dose of methenamine hippurate (Hiprex) is 1 gram by mouth twice daily. In clinical trials, the treatment duration for the prevention of recurrent urinary tract infections was up to 6 months. However, the duration of treatment may be individualized based on response and side effect tolerability. Your doctor will tell you exactly how long you will need to take methenamine hippurate for UTI prevention.

Methenamine comes in the form of an oral tablet (1 gram) and oral suspension (500 milligrams/5 milliliters) to take by mouth. Swallow the tablets whole with a full glass of water, milk, or food.

Do not cut, crush, or chew the tablets.

Shake the bottle of liquid medicine well before use. You should use an oral syringe or medicine-measuring device instead of household or kitchen tools like tablespoons or teaspoons to ensure dosing accuracy.

What are the side effects of methenamine?

Common side effects of methenamine (Hiprex) include nausea, vomiting, diarrhea, upset stomach, abdominal pain, stomach cramps, and loss of appetite. Taking the medicine with food can help reduce these adverse effects.

What are the risks of taking methenamine?

Rarely, methenamine can cause a serious allergic reaction. Tell your provider if you have had allergic reactions in the past to methenamine, aspirin, tartrazine (FD&C Yellow No. 5), or any other medications. Seek immediate medical attention if you develop signs and symptoms of an allergic reaction, such as skin rash, hives, itching, swelling, or difficulty breathing.

The methenamine group of medicines can cause a temporary increase in liver enzymes. These adverse reactions are more likely in people with a history of liver disease. Your doctor may not prescribe methenamine to you if you have severe liver dysfunction. Keep all your medical and lab appointments during methenamine therapy. Your doctor may want to order liver function tests from time to time.

Taking high doses of the methenamine hippurate group for long periods of time (more than 8 grams daily for 3 to 4 weeks or longer) can lead to increased frequency, painful urination, bladder irritation, blood in urine, and protein in urine.

What precautions should I take while on Hiprex?

Do not change the dose, dosage frequency, or treatment period of methenamine without your doctor’s approval.

Continue taking methenamine even if you feel well or don’t have UTI symptoms. Do not stop antibiotic therapy without talking to your doctor. Call your doctor if you develop symptoms of an acute UTI while on methenamine.

If you miss a dose of methenamine, take it as soon as you remember. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take a double dose or extra medicine to make up for a missed dose.

Check with your healthcare provider before taking any other over-the-counter medicines, prescription medications, or alternative treatments. Drug interactions between methenamine and your other medications can affect how the medicines work or cause serious adverse effects. Methenamine may have drug interactions with sulfamethizole antibiotic group, antacids, diuretics (water pills), and supplements, including vitamins.

References: