Hiprex Tablets

1. Name Of The Medicinal Product

Hiprex 1 g Tablets

2. Qualitative And Quantitative Composition

Each Hiprex tablet contains methenamine hippurate 1 g.

For excipients see 6.1.

3. Pharmaceutical Form

White, oblong tablet with breakline marked HX on one side and 3M on the other.

4. Clinical Particulars

4.1 Therapeutic Indications

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

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

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

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

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

5. Asymptomatic bacteriuria.

4.2 Posology And Method Of Administration

Adults: 1g twice daily.

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

Children under 6 years: Not recommended.

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

Elderly: No special dosage recommendations.

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

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 Special Warnings And Precautions For Use

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.

4.6 Pregnancy And Lactation

There is inadequate evidence of safety of the drug in human pregnancy but it has been in wide use for many years without apparent ill consequence, animal studies having shown no hazard.

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

4.7 Effects On Ability To Drive And Use Machines

None.

4.8 Undesirable Effects

Occasionally rashes, pruritis,gastric irritation, irritation of the bladder, may occur.

All side effects are reversible on the withdrawal of the drug.

4.9 Overdose

Vomiting and haematuria may occur. These can be treated by the use of an anti-emetic 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

Not applicable

6. Pharmaceutical Particulars

6.1 List Of Excipients

Magnesium Stearate

Povidone

Colloidal anhydrous silica

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

5 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 And Other Handling

None

7. Marketing Authorisation Holder

Meda Pharmaceuticals Ltd

Skyway House

Parsonage Road

Takeley

Bishop's Stortford

CM22 6PU

United Kingdom

8. Marketing Authorisation Number(S)

PL 15142/0099

9. Date Of First Authorisation/Renewal Of The Authorisation

12 October 1989/13 September 2005

10. Date Of Revision Of The Text

31^st March 2010