Kemadrin Tablets

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2.         QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Each tablet contains Procyclidine Hydrochloride 5 mg

 

Excipients with known effect:

 

For the full list of excipients, see section 6.1.

 

 

 

4.2       Posology and method of administration

 

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

 

Posology

 

 

Parkinson’s disease

 

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. Addition of a fourth dose before retiring has been seen to be beneficial in some patients.

 

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.

 

Kemadrin may be combined with levodopa or amantadine in patients who are inadequately controlled on a single agent.

 

Neuroleptic-induced extrapyramidal symptoms

 

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

 

After a period of three to four months, Kemadrin should be stopped and the patient observed to see if the neuroleptic-induced extrapyramidal symptoms recur. If this is the case Kemadrin should be reintroduced to avoid debilitating extra-pyramidal symptoms. Cessation of treatment periodically is to be recommended even in patients who appear to require the drug for longer periods.

 

Paediatric population

 

Safety and efficacy have not been established in the paediatric age group; therefore, the use of procyclidine in this age group requires that the potential benefits be weighed against the possible risk to the child.

 

Elderly patients

 

Elderly patients may be more susceptible than younger adults to the anticholinergic effects of Kemadrin and a reduced dosage may be required (see section 4.4).

 

Method of administration

 

For oral use.

 

Pharmacokinetic studies have indicated that the mean plasma elimination half-life of Kemadrin is sufficient to allow twice daily administration orally, if more convenient.

 

Oral administration may be better tolerated if associated with a meal.

 

 

4.3       Contraindications

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Kemadrin is contraindicated in individuals with known hypersensitivity to any component of the preparation, and in patients with Tardive dyskinesias.

 

 

4.4       Special warnings and precautions for use

 

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 anti-cholinergic agents do not cause or control this syndrome, when given in combination with neuroleptics they may exacerbate the symptoms of tardive dyskinesia or reduce the threshold at which dyskinesias appear in patients predisposed to this abnormality. In such individuals subsequent adjustment of neuroleptic therapy or reduction in anticholinergic treatment should be considered.

 

 

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

 

Patients with mental disorders occasionally experience a precipitation of a psychotic episode when procyclidine is administered for the treatment of the extrapyramidal side effects of neuroleptics.

 

Elderly patients, especially those on high doses of anticholinergics may be more susceptible to the adverse events associated with such therapy (see section 4.8). Specifically, the elderly patients may be particularly vulnerable to Central Nervous System (CNS) disturbances such as confusion, impairment of cognitive function and memory, disorientation and hallucinations. These effects are usually reversible on reduction or discontinuation of anticholinergic therapy.

 

There is no specific information available concerning the use of Kemadrin in patients with impaired renal or hepatic function. However, since procyclidine is metabolised in the liver and excreted via urine care should be exercised when administering Kemadrin to patients with impaired kidney or liver function.

 

Dosage should only be introduced gradually. Sudden withdrawal of the product should be avoided, as rebound of parkinsonian symptoms may occur.

High dosage may induce dizziness, mental confusion and hallucinations.

 

Kemadrin, along with other anticholinergic drugs, has the potential to be abused. Although the cases of abuse are rare, physicians should exercise caution in prescribing Kemadrin to patients with symptoms that may not be genuine.

 

4.6       Fertility, pregnancy and lactation

 

Fertility and Embryo-Foetal Development

See section 5.3.

 

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

 

Breast‑feedingLactation

 

 

4.8       Undesirable effects

 

Undesirable effects are listed below by system organ class and frequency.  For this preparation there is no modern clinical documentation which can be used as support for determining the frequency of adverse reactions.

The frequency was determined based on literature data and defined as follows:

Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).

 

 

Reporting of suspected adverse reactions

 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:

 

HPRA Pharmacovigilance,Earlsfort Terrace, IRL - Dublin 2. Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: medsafety@hpra.ie .

 

 

5.         PHARMACOLOGICAL PROPERTIES

 

5.1       Pharmacodynamic properties

 

Pharmacotherapeutic group: Anticholinergic agents, ATC code: N04A A04.

 

Mechanism of action

 

 

 

 

5.2       Pharmacokinetic properties

 

Absorption

 

Procyclidine is adequately absorbed from the gastro-intestinal tract with a bioavailability of 75%

 

Distribution

 

Procyclidine disappears rapidly from the tissues.

 

Biotransformation

 

The relatively low clearance of 68 ml/min represents a predominantly metabolic change with a small first pass effect.

 

  er intravenous administration it acts within 5 to 20 minutes with a duration of up to 4 hours.  No detailed information is available on the metabolic fate of procyclidine  but very little of the parent compound is excreted in the urine unchanged. When given orally about one fifth of the dose is known to be metabolised in the liver, principally by cytochrome P₄₅₀ and then conjugated with glucuronic acid. This conjugate has been detected in the urine.

 

Elimination

 

The mean plasma elimination half-life after both oral and intravenous administration is approximately  12 hours.

 

 

 

 

 

5.3       Preclinical safety data

 

Fertility

 

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

 

 

 

6.6        Special precautions for disposal of a used medicinal product or waste materials derived from such medicinal product and other handling of the product

 

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

No special requirements

 

 

 

10.       DATE OF REVISION OF THE TEXT

 

April 2016 April 2014March September 2015

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7.         MARKETING AUTHORISATION HOLDER

 

3016 Lake Drive

Citywest Business Campus

Dublin 24

Ireland

12/13 Exchange Place

I.F.S.C

Dublin 1

Ireland

10.       DATE OF REVISION OF THE TEXT

 

March 2014September 2013

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3.         PHARMACEUTICAL FORM

 

Tablets

White, round, biconvex tablets, one face with a break-line and coded KT above the break-line and 05 below the break-line, with a score-line on the other face.scored, coded ‘S3A’ and branded ‘WELLCOME’.

The score line is to allow breaking for ease of swallowing.

The tablet can be divided into equal doses.

 

4.2       Posology and method of administration

Method of administration

 

For oral use.

 

5.1       Pharmacodynamic properties

 

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

 

Idiopathic Parkinson's disease is notw 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.

10.       DATE OF REVISION OF THE TEXT

 

February 2011September 2013

Improved electronic presentation

Product ownership changed from GSK to Aspen

Section 1. NAME OF THE MEDICINAL PRODUCT

·         Inserted space between ‘5’ and ‘mg’

 

Section 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

·         Changed wording from ‘Tablet containing’ to ‘Each tablet contains’

·         Where quantities are detailed, inserted space between quantity and unit, e.g. between ‘5’ and ‘mg’

 

Section 4.2 Posology and Method of Administration

·         Where quantities are detailed, inserted space between quantity and unit, e.g. between ‘2.5’ and ‘mg’

 

Section 9 DATE OF FIRST AUTHORISATION/RENEWAL OF AUTHORISATION

·         Included the texts ‘Date of first authorisation’ and ‘Date of last renewal’

·         Corrected the date of last renewal to ‘2009’

Kemadrin 5mg Renewal:  Amended Text Highlighted in Red:

 

 

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

 

Tablets containing Procyclidine Hydrochloride. 5mg

 

Excipients-Contains Lactose Monohydrate 174.0mg and Sodium0.5mg

 

            For a full list of excipients, see section 6.1.

3.       PHARMACEUTICAL FORM

 

Tablets.

White, biconvex tablets, scored, coded ‘S3A’ and branded ‘Wellcome’.

The score line is to allow breaking for ease of swallowing

 

6.5     Nature and Contents of Containers

 

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

 

Not all pack sizes may be marketed

 

5.3       Preclinical Safety Data

 

Mutagenicity, Carcinogenicity:

 

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