HIPREX 1G TABLETS - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Hiprex 1 g Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each Hiprex tablet contains methenamine hippurate 1 g.

For the full list of excipients, see 6.1.

3 PHARMACEUTICAL FORM

A white to creamy-white oblong shaped tablet coded HX with break line on one face and break line on the other face with or without 3M.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Hiprex is indicated in the prophylaxis and treatment of urinary tract infections:

As maintenance therapy after successful initial treatment of acute infections with antibiotics.

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

To suppress urinary infection in patients with indwelling catheters and to reduce the incidence of catheter blockage.

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

Asymptomatic bacteriuria.

4.2 Posology and method of administration

Posology

Adults: 1g twice daily.

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

Paediatric population:

Children under 6 years: Not recommended.

Children: 6–12 years: 500mg twice daily.

Older people:

No special dosage recommendations.

Method of administration

The tablets may be halved, or they can be crushed and taken with a drink of milk or fruit juice if the patient prefers.

4.3 Contraindications

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

Hepatic dysfunction, renal parenchymal infection, severe dehydration, metabolic acidosis, severe renal failure (creatinine clearance or GFR<10 ml/min.) or gout. Hiprex may be used where mild (20–50 ml/min.) to moderate (10–20 ml/min.) renal insufficiency is present. (If the GFR is not available the serum creatinine concentration can be used as a guide.). Hiprex should not be administered concurrently with sulphonamides because of the possibility of crystalluria, or with alkalising agents, such as a mixture of potassium citrate.

4.4

None.

4.5 Interaction with other medicinal products and other forms of interaction

Methenamine hippurate should not be given/administered concurrently with sulphonamides because of the possibility of crystalluria, or with alkalising agents such as potassium citrate. Concurrent use with acetazolamide should be avoided as the desired effect of hexamine will be lost.

Depending on the type of analysing method used, methenamine can affect the determination of steroids, catecholamines and 5 hydroxyindole acetic acid from urine and give false results.

4.6 Fertility, Pregnancy and lactation

Pregnancy

There is inadequate evidence of safety of methenamine hippurate in human pregnancy, but it has been in wide use for many years without apparent ill consequence. Animal studies are insufficient with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of methenamine hippurate during pregnancy.

Breast-feeding

Methenamine is excreted in breast milk but the quantities will be insignificant to the infant. Mothers can therefore breast feed their infants.

Fertility

There are no human data available on fertility. Data from studies in rats do not indicate any effects on female fertility, effects on male fertility have not been adequately tested (see section 5.3).

4.7 Effects on ability to drive and use machines

None.

4.8 Undesirable effects

Adverse events are listed below by system organ class and frequency. Frequencies are defined as:

Very common (>1/l0)

Common (>1/100 and <1/10)

Uncommon (>1/1000 and <1/100)

Rare (> 1/10,000 and <1/1000)

Very rare (<1/10,000)

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

Gastrointestinal disorders

Uncommon: gastric irritation, irritation of the bladder, nausea, vomiting

Not known: Diarrhoea, abdominal pain

Skin and subcutaneous disorders

Uncommon: Rash, pruritus

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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Vomiting and haematuria may occur. These can be treated by the use of an antiemetic and drinking copious quantities of water respectively. Bladder symptoms can be treated by the consumption of copious quantities of water and 2–3 teaspoonfuls of bicarbonate of soda.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group G04A A01

Hiprex is a urinary antibacterial agent with a wide antibacterial spectrum covering both gram-positive and gram-negative organisms. Urinary antibacterial activity can be shown within 30 minutes of administration.

The chemical structure of methenamine hippurate is such that a two-fold antibacterial action is obtained:

1. The slow release of the bactericidal formaldehyde, from the methenamine part, in the urine; acid pH is necessary for this reaction to occur. It is obtained and maintained there by the presence of hippuric acid.

2. The bacteriostatic effect of hippuric acid itself on urinary tract pathogens.

5.2 Pharmacokinetic properties

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

Plasma concentrations of methenamine hippurate reach maximum 1–2 hours after a single dose and then decline with a half-life of about 4 hours. Methenamine recovered in the urine corresponds to about 80% of the dose given per 12 hours.

5.3 Preclinical safety data

Non- clinical data reveal no special hazard for humans based on repeated dose toxicity studies. No carcinogenicity or genotoxicity data are available for methenamine hippurate. Methenamine did not demonstrate any carcinogenic potential in long term studies in rodents.

In limited studies in pregnant rabbits with methenamine hippurate at approximately 3 times the clinical dose based on body surface area, there was increased postimplantation loss resulting in lower litter sizes and a limited occurrence of fetal deformities including shortness of tail and malrotation of limbs. No effects on development were noted at doses equivalent to the clinical dose. Methenamine hippurate, administered at approximately 3 times the clinical dose, based on body surface area, did not adversely affect the fertility of female rats. Effects on male fertility have not been adequately studied.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Magnesium Stearate

Povidone

Colloidal anhydrous silica

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Do not store above 30°C. Keep bottle tightly closed.

6.5 Nature and contents of container

Glass bottles of 60 tablets

6.6 Special precautions for disposal

No special requirements.

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

7 MARKETING AUTHORISATION HOLDER

Mylan Products Ltd.,

Station Close,

Potters Bar,

Herts,

EN6 1TL,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 46302/0200

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THEAUTHORISATION

13/09/2005