Ubretid

1. Name Of The Medicinal Product

Ubretid^TM.

2. Qualitative And Quantitative Composition

Active ingredient Distigmine bromide 5mg.

3. Pharmaceutical Form

Tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

Anticholinesterase. Post-operative urinary retention. Post operative ileus and intestinal atony. To assist emptying of the neurogenic bladder. As an adjunct in the treatment of myasthenia gravis.

4.2 Posology And Method Of Administration

Adults

In prevention of urinary retention, ileus or intestinal atony following surgery:

One Ubretid tablet daily, half an hour before breakfast.

In neurogenic bladder:

One Ubretid tablet daily or on alternate days, half an hour before breakfast, on an empty stomach.

In myasthenia gravis:

Dosage to be individualised for each patient, dependent upon the severity of the condition, the degree and duration of response and the side effects encountered. The tablets should always be taken on an empty stomach half an hour before breakfast. Dosage should commence at 1 tablet daily and may be adjusted at intervals of three to four days to a total not exceeding 4 tablets daily.

Children

Up to 2 tablets daily according to age.

Elderly

No dosage adjustment is necessary for elderly patients.

Ubretid tablets are for oral administration.

4.3 Contraindications

Ubretid is contraindicated in cases of severe post operative shock, serious circulatory insufficiency, severe constipation, serious spastic and mechanical ileus, asthma and mechanical urinary obstruction.

4.4 Special Warnings And Precautions For Use

Caution should be taken in conditions where the potentiation of the effects of acetylcholine is undesirable, eg cardiac dysfunction, bronchospasm, peptic ulcer, oesophagitis, epilepsy and Parkinsonism. The patient should be supervised in the early stages of dosage titration to guard against the possibility of myasthenic crisis or cholinergic crisis.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Use with caution in patients receiving concomitantly drugs acting on the cardiovascular system, e.g. beta blockers, drugs with local anaesthetic properties and muscle relaxants. In myasthenia gravis, where short acting cholinergic drugs are taken concurrently, their dosage should be reduced to the minimum required to control symptoms.

4.6 Pregnancy And Lactation

Ubretid should be avoided during pregnancy. No information is available on lactation.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

The following side effects may occur infrequently: bradycardia, AV block, hypotension, bronchospasm, dyspnoea, increased bronchial secretions, sweating, salivation and lacrimation, muscle twitching, abdominal cramps, diarrhoea, urinary frequency and miosis. These effects of Ubretid may be controlled with atropine, giving 2mg intramuscularly; atropinisation should be maintained for at least 24 hours.

4.9 Overdose

Overdosage of Ubretid may also produce skeletal muscle fatigue, weakness and eventually paralysis. The muscarinic effects of overdosage may be controlled with atropine 2mg intramuscularly repeated at intervals indicated by the clinical response until signs of mild atropinisation (dry mouth, mydriasis) appear. The patient should be kept fully atropinised for at least 24 hours.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Distigmine is an inhibitor of cholinesterase by the formation of complexes with the enzyme. This process is reversible. Specific cholinesterase or acetylcholinesterase is inhibited more strongly than pseudo or plasma cholinesterase.

5.2 Pharmacokinetic Properties

Maximum inhibition of plasma cholinesterase occurs 9 hours after a single intramuscular dose and persists for about 24 hours.

Tritium labelled Ubretid was used to determine the urinary and biliary excretion of the drug in the rat. Activity in the urine was demonstrated quickly, amounting to 43% after 8 hours. Biliary excretion was shown to be insignificant. In man, results suggested that about 50% of a 0.5mg 1ml dose was excreted in 24 hours.

5.3 Preclinical Safety Data

There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose

Maize starch

Purified talc

Magnesium stearate

6.2 Incompatibilities

None stated.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store in a dry place below 25^oC.

6.5 Nature And Contents Of Container

Blisters of 20μm aluminium foil and 250μm UPVC/PVdC opaque white film containing 30 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS, UK

8. Marketing Authorisation Number(S)

PL 04425/0617

9. Date Of First Authorisation/Renewal Of The Authorisation

7 February 2009

10. Date Of Revision Of The Text

February 2009

11 LEGAL CLASSIFICATION

POM