Methenamine Tablets is indicated in the prophylaxis of uncomplicated lower urinary tract infections:

1. As long-term prophylactic therapy after initial treatment with appropriate chemotherapeutic agent of recurrent urinary infections.

2. As long-term therapy in the prevention of recurrent cystitis.

3. To provide prophylaxis in patients with indwelling catheters, urine collector etc. and to reduce the incidence of catheter blockage.

4. To provide prophylaxis against the introduction of infection into urinary tract during instrumental procedures.

5. Asymptomatic bacteriuria.

Posology

Adults: 1 g 2 times a day.

In patients with catheters the dosage may be increased to 1 g three times daily.

Paediatric population:

Children 6-12 years: 0.5 g twice daily.

Children over 12 years: 1 g twice daily.

In cases of alkaline urine pH, supply of acidifying agent could be needed.

Method of administration

For oral administration.

The tablets may be halved or crushed and taken with water if the patient is unable to swallow whole tablets.

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

• Intolerance or allergic reactions to formalin.

• Renal insufficiency, severe dehydration and gout.

• Hepatic impairment.

• Metabolic acidosis.

• Infection of the kidney.

Methenamine Tablets should not be given concurrently with sulphonamides because of the possibility of crystalluria.

Alkaline agents reduce the effect of methenamine and should be avoided, antacids might cause an increase of urine pH and hence decrease the effect of methenamine.

None

Sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

Alkaline agents reduce the effect of methenamine and should be avoided, antacids might cause an increase of urine pH and hence decrease the effect of methenamine.

Concurrent use with sulphonamides increases the risk of crystalluria.

Depending on analytical procedure, methenamine might affect the determination of steroid, catecholamine and 5-hydroxyindole acetic acid leading to incorrect results.

Pregnancy

A moderate amount of data on pregnant women (between 300-1000 pregnancies) has not shown signs of malformations or fetal/neonatal toxicity. Animal studies do not indicate reproductive toxicity (see section 5.3). The use of Methenamine Tablets may be considered during pregnancy, if necessary.

Breast-feeding

Methenamine Hippurate is excreted in human milk, but at therapeutic doses of Methenamine Tablets no effects on the breastfed newborns/infants are anticipated.

Fertility

There are no human studies regarding fertility and Methenamine Hippurate.

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Methenamine Tablets has no or negligible influence on the ability to drive and use machines.

Adverse events frequencies are defined as:

Very common (≥ 1/l0)

Common (≥ 1/100 to <1/10)

Uncommon (≥ 1/1000 to <1/100)

Rare (≥ 1/10 000 to <1/1000)

Very rare (<1/10 000)

Not known (cannot be estimated from the available data).

Occasionally superinfection with yeast may occur. At high dosage, chemical cystitis leading to dysuria may occur.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Toxicity: 8 g to a 2½ -year old child resulted in moderate intoxication.

Symptoms: Nausea, vomiting, vertigo, tinnitus and metabolic acidosis may occur. Irritating effect on the urinary tract with albuminuria and haematuria.

Treatment: The treatment is symptomatic and supportive, the use of an anti-emetic and drinking copious quantities of water. Bladder symptoms can be treated by the consumption of copious quantities of water and 2-3 teaspoonfuls of bicarbonate of soda.

Pharmacotherapeutic group: urinary antibacterial agent, ATC code: J01XX05

Mechanism of action

Methenamine Tablets contain Methenamine Hippurate, a salt of methenamine and hippuric acid, which is absorbed and excreted rapidly. In acidic environment, methenamine is hydrolyzed to formaldehyde, which, together with hippuric acid mediates the antibacterial effect in urine. Bacteriological studies have shown that the urine has antibacterial effect already 30 minutes after intake of the drug.

Pharmacodynamic effects

Methenamine Tablets is active against microorganisms, which usually causes urinary tract infection, e.g. Eschericha coli and Aerobacter aerogenes. The substance has decreased effect on urea-degrading bacteria, e.g. Pseudomonas and some strains of Proteus. Urea-degrading bacteria hydrolyze the urea to ammonium hydroxide which is basic and increase urinary pH. This results in reduced hydrolysis of methenamine to formaldehyde.

Absorption

Methenamine Tablets is readily absorbed from the gastro-intestinal tract and excreted via the kidney.

Distribution

Plasma concentrations of Methenamine Hippurate reach maximum 1-2 hours after a single dose and decline with a half-life of about 4 hours. The antibacterial effect is noticed 30 minutes after administration of the drug as mentioned in section 5.1. Methenamine recovered in the urine corresponds to about 80% of the dose given.

Preclinical studies reveal no special hazard for humans.

Colloidal silica

Povidone

Magnesium stearate

Croscarmellose sodium

Not applicable

3 years.

Store in the original package in order to protect from moisture.

20, 21, 60, 100 and 105 tablets in coloured glass bottles with a white opaque polypropylene screw cap.

Not all pack sizes may be marketed.

Any unused medicinal product or waste should be disposed in accordance with local requirements.