Aspen

Kemadrin 5 mg Tablets

Each tablet contains Procyclidine Hydrochloride. 5 mg

Excipients-Contains Lactose Monohydrate 174.0mg and Sodium 0.5 mg

For a full list of excipients, see section 6.1.

Tablets.

White, biconvex tablets, scored, coded 'S3A' and branded 'Wellcome'.

The score line is to allow breaking for ease of swallowing

Kemadrin is indicated for the treatment of all forms of Parkinson's disease:

idiopathic (paralysis agitans), postencephalitic and arteriosclerotic.

Symptoms often responding well to Kemadrin include: rigidity, akinesia, tremor, speech and writing difficulties, gait, sialorrhoea and drooling, sweating, oculogyric crises and depressed mood.

Kemadrin is used to control troublesome extra-pyramidal symptoms induced by neuroleptic drugs including pseudo-parkinsonism, acute dystonic reactions and akathisia.

The variation in optimum dosage from one patient to another should be taken into consideration by the physician.

Treatment is usually started at 2.5 mg three times a day, increasing by 2.5 mg daily until the level of optimal control is reached.

The usual maximum total daily dose is 30 mg. However, at the discretion of the attending physician where appropriate this total may be as high as 60 mg.

In general, young and postencephalitic patients may require a somewhat higher dosage than older patients and those with arteriosclerosis.

The daily dose used in the control of neuroleptic-induced extrapyramidal symptoms is usually not more than 20mg daily.

After a period of 3-4 months, Kemadrin should be stopped and the patient observed to see if the neurolepticinduced extrapyramidal symptoms recur. Cessation of treatment periodically is to be recommended even in patients who appear to require the drug for longer periods.

Tardive dyskinesias.

As with all anticholinergics such as Kemadrin, cautious prescribing is indicated in the elderly, in patients either predisposed to glaucoma or with existing angle-closure (narrow angle) glaucoma, obstructive disease of the gastro-intestinal tract including pyloric stenosis and paralytic ileus, with urinary symptoms associated with prostatic hypertrophy and in patients with disorders characterised by tachycardia, e.g. thyrotoxicosis.

In a proportion of patients undergoing neuroleptic treatment, tardive dyskinesias will occur. While anticholinergic agents do not cause or control this syndrome, when given in combination with neuroleptics they may reduce the threshold at which dyskinesias appear in patients predisposed to this abnormality. In such individuals subsequent adjustment of neuroleptic therapy is indicated.

In rare instances, Kemadrin administered for the treatment of neuroleptic induced symptoms was associated with an apparent worsening of the patient's state.

Dosage should only be introduced gradually, sudden withdrawal of the product should be avoided.

High dosage may induce dizziness, mental confusion and hallucinations.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Monoamine oxidase inhibitors or drugs with anticholinergic properties, such as amantadine, antihistamines, phenothiazines, and tricyclic antidepressants, may increase the anticholinergic action of procyclidine.

The use of drugs with cholinergic properties, such as tacrine, may reduce the therapeutic response to Kemadrin.

The concomitant use of procyclidine with some neuroleptics for the treatment of extrapyramidal symptoms has been associated with a reduction in neuroleptic plasma concentrations. However this reduction is unlikely to be associated with a significant reduction in clinical effect.

Anticholinergics, including procyclidine, may reduce the efficacy of levodopa by increasing gastric emptying time, resulting in enhanced gastric degradation.

The effect of anticholinergics such as procyclidine may antagonise the gastrointestinal effects of cisapride and metoclopramide.

Procyclidine may potentiate the vagolytic effects of quinidine.

Anticholinergics may reduce the absorption of ketoconazole.

Exposure to high environmental temperature and humidity in association with a phenothiazine/anticholinergic drug regimen has rarely resulted in hyperpyrexia.

Daily administration of paroxetine increases significantly the plasma levels of procyclidine. If anticholinergic effects are seen, the dose of procyclidine should be reduced.

Fertility and Embryo-Foetal Development:-

In studies in rats, procyclidine did not affect fertility or cause foetal abnormalities.

Pregnancy:-

The safety of using Kemadrin during pregnancy has not been established. However, extensive clinical use has not given any evidence that it in any way compromises the normal course of pregnancy. Nevertheless, as with all drugs, use should be considered only when the expected clinical benefit of treatment for the mother outweighs any possible risk to the developing foetus.

Lactation:-

No information is available on the passage of procyclidine into human breast milk following administration of Kemadrin.

Adverse events of a neurological character such as blurred vision, dizziness, confusion and disorientation have been reported with procyclidine. Therefore if affected patients should be advised not to drive or operate machinery.

For this preparation there is no modern clinical documentation which can be used as support for determining the frequency of adverse reactions.

The main undesirable effects are those to be expected from any anticholinergic agent, these are generally reversible on reducing the dosage.

With high doses of procyclidine dizziness, mental confusion, impaired cognition and memory, disorientation, anxiety, agitation and hallucinations may occur.

Symptoms and signs:-

Symptoms of overdosage include stimulant effects such as agitation, restlessness and confusion with severe sleeplessness lasting up to 24 hours or more. Visual and auditory hallucinations have been reported. Most subjects are euphoric but the occasional patient may be anxious and aggressive. The pupils are widely dilated and unreactive to light. In recorded cases, the disorientation has lasted 1 to 4 days and ended in a recuperative sleep.

Signs of CNS depression including somnolence, reduced consciousness, and occasionally coma have been reported usually following very large overdoses.

Tachycardia has also been reported in association with cases of Kemadrin overdose.

Treatment:-

If procyclidine has been ingested within the previous hour or two (or possibly longer in view of its likely effects on gastric motility), activated charcoal should be used to reduce absorption. Further management should be as clinically indicated or as recommended by the national poisons centre, where available.

Procyclidine is a synthetic anticholinergic agent which blocks the excitatory effects of acetylcholine at the muscarinic receptor.

Idiopathic Parkinson's disease is now thought to result from degeneration of neurones in the substantia nigra whose axons project and inhibit cells in the corpus striatum. Blockade by neuroleptic drugs of the dopamine released by these terminals produces a similar clinical picture. The cell bodies in the corpus striatum also receive cholinergic innervation which is excitatory. Relief of the Parkinsonian syndrome can be achieved either by potentiation of the dopaminergic system or blockade of the cholinergic input by anticholinergics. It is by a central action of this latter type by which procyclidine exerts its effect.

Procyclidine is adequately absorbed from the gastro-intestinal tract and disappears rapidly from the tissues. It has an elimination half-life of 12 hours. After intravenous administration it acts within 5 to 20 minutes with a duration of up to 4 hours. No information is available on its metabolic fate and excretion.

Mutagenicity, Carcinogenicity:

Procyclidine was not genotoxic in in-vitro bacterial mutation or mouse lymphoma assays.

Lactose monohydrate,

Sodium starch glycollate Type A

Povidone K30

Magnesium stearate.

Not applicable.

5 years

Do not store above 25°C.

Amber glass bottles with polyethylene snap-fit closure containing either 100 or 500 tablets.

Not all pack sizes may be marketed

No special requirements.

Aspen Pharma Trading Limited

12/13 Exchange Place

I.F.S.C.

Dublin 1, Ireland

PA 1691/5/1

Date of first authorisation: 1st April 1979

Date of last renewal: 1st April 2009

January 2011