1. Name Of The Medicinal Product
Dipentum Tablets 500 mg
2. Qualitative And Quantitative Composition
Olsalazine sodium HSE 500.0mg
3. Pharmaceutical Form
Tablet
4. Clinical Particulars
4.1 Therapeutic Indications
Oral treatment of mild active ulcerative colitis and maintenance of remission.
4.2 Posology And Method Of Administration
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 elderly
Commence on 1 g daily in divided doses and depending upon the patient response, titrate the dose upwards to a maximum of 3 g daily over one week.
Single doses should not exceed 1 g.
Olsalazine should be taken with food.
Remission
Adults including the elderly one tablet (0.5 g) twice daily, taken with food.
Olsalazine has been used concomitantly with gluco-corticosteroids.
4.3 Contraindications
Hypersensitivity to salicylates. There is not 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 dyscrasias.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Those characteristic of salicylates are a theoretical possibility, although with the 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, plastic anaemia, pancytopenia, thrombocytopenia, anaemia and haemolytic anaemia.
4.9 Overdose
There is not specific antidote to olsalazine. Treatment should be supportive. As a salicylate, interference in biochemical and other tests characteristic of salicylates may occur.
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 (5-ASA, mesalazine). 5-ASA is believed to be 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 effect 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 and 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 principle 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 mcg/ml after 6-9 days. In ileostomised patients almost all the olsalazine could be recovered in ileal fluid. Intravenous administration of olsalazine showed bilary excretion and traces of Ac-5-ASA in the urine and a half life of 56 minutes. Olsalazine given both 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 mcg/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, diazepam or digitoxin from plasma binding.
Autoradiography in rats showed no activity in the brain, testes, placenta or foetus, some activity in the bile duct and kidney and high activity in the gut.
5.3 Preclinical Safety Data
None stated.
6. Pharmaceutical Particulars
6.1 List Of Excipients
Magnesium stearate* Ph. Eur.
Colloidal silicon dioxide Ph. Eur.
Polyvidone 30 Ph. Eur.
Crospovidone NF
Ethanol 99.5% BP
* Quantity may be between 2.0 and 3.0 mg according to granulate and equipment.
6.2 Incompatibilities
As a salicylate, interference in biochemical and other tests characteristics of salicylates may occur.
6.3 Shelf Life
48 months, unopened.
6.4 Special Precautions For Storage
Store in a dry place.
6.5 Nature And Contents Of Container
HD polyethylene securitainers with cap,
or
HD polyethylene square section pots with child or tamper resistant cap.
Packs of 60 tablets
Packs of 100 tablets (not marketed)
6.6 Special Precautions For Disposal And Other Handling
None stated.
7. Marketing Authorisation Holder
Pharmacia Laboratories Limited
Davy Avenue
Milton Keynes
MK5 8PH
8. Marketing Authorisation Number(S)
PL 0022/0135
9. Date Of First Authorisation/Renewal Of The Authorisation
9 January 1995
10. Date Of Revision Of The Text
September 1999Legal Category
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