Dipentum Capsules

1. Name Of The Medicinal Product

Dipentum Capsules.

2. Qualitative And Quantitative Composition

Each capsule contains 250 mg olsalazine sodium.

3. Pharmaceutical Form

Capsule, hard.

4. Clinical Particulars

4.1 Therapeutic Indications

Oral treatment of acute mild ulcerative colitis and the maintenance of remission.

4.2 Posology And Method Of Administration

Oral.

General

Olsalazine taken on an empty stomach may sometimes lead to loose stools or diarrhoea. By taking the drug at the end of a meal, this may be avoided.

Acute Mild Disease

Adults including the elderly:

Commence on 1 g daily in divided doses taken at the end of meals. Depending on the patient's response, the dose may be titrated upwards over a period of one week to a maximum of 3g daily.

A single dose should not exceed 1 g.

Remission

Adults including the elderly:

A dose of 0.5g should be taken twice daily, at the end of meals.

Olsalazine has been used concomitantly with gluco-cortiscosteroids.

4.3 Contraindications

Hypersensitivity to salicylates.

There is no experience of the use of olsalazine in patients with significant renal impairment. Olsalazine is contra-indicated in patients with significant renal impairment.

4.4 Special Warnings And Precautions For Use

Serious blood dyscrasias have been reported very rarely with olsalazine. Haematological investigations should be performed if the patient develops unexplained bleeding, bruising, purpura, anaemia, fever or sore throat. Treatment should be stopped if there is a suspicion or evidence of a blood dyscrasia.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Those characteristic of salicylates are a theoretical possibility, although with low blood levels of salicylate during therapy such effects have not been seen.

4.6 Pregnancy And Lactation

Reproduction studies performed in mice, rats and rabbits have revealed no evidence of impaired fertility, harm to the foetus or teratogenic effects due to olsalazine administration. However, the experience of use in pregnant women is limited.

Dipentum should not be used during pregnancy unless the clinician considers that the potential benefit outweighs the possible risk to the foetus.

4.7 Effects On Ability To Drive And Use Machines

Such effects are not theoretically likely and have not been found in practice.

4.8 Undesirable Effects

As with sulphasalazine and mesalazine gastrointestinal side-effects are the most common. The most frequently reported adverse reactions are diarrhoea, abdominal cramps, headache, nausea, dyspepsia, arthralgia and rash.

Diarrhoea is often transient, clearing in a few days. Where it does not, taking the drug at the end of a more substantial meal, dose titration or dose reduction are usually effective. Withdrawal in clinical studies when the drug was taken at the end of meals was around 3%. Where diarrhoea persists, the drug should be stopped.

Blood dyscrasias have been reported in a few patients: leucopenia, neutropenia, aplastic anaemia, pancytopenia, thrombocytopenia, anaemia and haemolytic anaemia.

4.9 Overdose

There is no specific antidote to olsalazine. Treatment should be supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Olsalazine is itself a relatively inert compound. Absorption in the small intestine is slight. On entering the colon it is split by bacteria into two molecules of 5-amino salicylate (mesalazine). 5-ASA is believed to be the principal active fragment of sulphasalazine, which has been in use for 40 years in the treatment of ulcerative colitis. 5-ASA is believed to be the active form of dipentum, as olsalazine has little benefit in in-vitro tests or on experimental animals. The clinical benefits of sulphasalazine, 5-ASA and olsalazine are evident in ulcerative colitis, but the pharmacological mechanism is not established.

5.2 Pharmacokinetic Properties

Studies in man and animals indicate a low uptake of olsalazine ane its metabolites, which is in keeping with the desired aim to deliver a high local concentration of 5-ASA to the colon.

In man an oral dose of olsalazine is negligibly absorbed in the gut. Bacteria split olsalazine in the colon into two molecules of 5-ASA. Local concentrations of 5-ASA in the colon can be 1000 times the plasma levels. Uptake by colonic mucosal cells leads to acetyl 5-ASA generation (the principal metabolite), traces of 5-ASA and olsalazine-O-SO₄ also being found in plasma. 500 mg b.d. in 6 volunteers gave a steady state level of amino salicylate of 0.8 —2.9 micrograms/ml after 6-9 days. In ileostomised patients almost all the olsalazine could be recovered in ileal fluid. Intravenous administration of olsalazine shower biliary excretion and traces of Ac-5-ASA in the urine and a half life of 56 minutes. Olsalazine given with or without food was taken up to the extent of 1.3 or 1.6% respectively. After a 1 g dose p.o. a maximum plasma level of 12.2 micrograms/ml was noted at 1 hour of olsalazine. 22-33% of an oral dose appears in the urine almost all as Ac-5-ASA. The metabolite olsalazine-O-SO₄ is 99% plasma bound and has a half life of 6-10 days.

Olsalazine does not penetrate red cells nor displace warfarin, naproxen, diazepam or digitoxin from plasma blinding.

Autoradiography in rats showed no activity in the brain, testes, placenta or foetus, some activity in the bile duct and high activity in the gut.

5.3 Preclinical Safety Data

6. Pharmaceutical Particulars

6.1 List Of Excipients

Magnesium stearate

Capsule

Gelatin

6.2 Incompatibilities

As a salicylate, interference in biochemical and other tests characteristic of salicylates may occur.

6.3 Shelf Life

60 months

6.4 Special Precautions For Storage

Store at room temperature in a dry place.

6.5 Nature And Contents Of Container

White, square, polyethylene bottles with knurled tamper-evident cap containing 112 capsules, with a label incorporating a pull—out leaflet.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Pharmacia Laboratories Limited

Davy Avenue

Milton Keynes

MK5 8PH

UK

8. Marketing Authorisation Number(S)

PL 0022/0134

9. Date Of First Authorisation/Renewal Of The Authorisation

13 May 1993/15 July 1994

10. Date Of Revision Of The Text

22 April 1999

Legal category

POM