INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
DEMETRIN 10 mg (Tablet)

SCHEDULING STATUS:
S5

PROPRIETARY NAME
(and dosage form):

DEMETRIN 10 mg (Tablet)

COMPOSITION:
Each tablet contains 10 mg of Prazepam.

PHARMACOLOGICAL CLASSIFICATION:
A: 2.6 Tranquillizers.

PHARMACOLOGICAL ACTION:
Demetrin is a benzodiazepine derivative with anxiolytic and central muscle relaxant activity.
Benzodiazepines reportedly act as agonists at the benzodiazepine receptors, which have been shown to form a component of a functional supramolecular unit known as the benzodiazepine-GABA receptor-chloride ionophore complex.

INDICATIONS:
Symptomatic relief of anxiety-tension states resulting from stressful circumstances, anxiety associated with anxiety neurosis and other psychoneuroses, and as an adjunct in other disease states in which anxiety is manifested.
Demetrin is only indicated when the disorder is severe, disabling or subjecting the individual to extreme stress.

CONTRA-INDICATIONS:
Demetrin is contra-indicated in patients with a known hypersensitivity to prazepam or other benzodiazepines; or who have acute narrow-angle glaucoma, or acute pulmonary insufficiency.

DOSAGE AND DIRECTIONS FOR USE:
Demetrin is administered orally, usually in divided doses. The usual daily dose is 30 mg. The dose should be adjusted gradually within the range of 20 to 60 mg daily in accordance with the response of the patient. Drowsiness and fatigue may occur in some patients with moderate anxiety receiving higher doses on a daily basis. In elderly or debilitated patients, it is advisable to initiate treatment at a daily dose of 10 to 15 mg. (See Side Effects and Special Precautions.) A single, daily dose at bedtime usually ranges between 20 and 40 mg. Treatment should be started with the lowest recommended dose. The maximum dose should not be exceeded.
Treatment Period:
Treatment should be as short as possible. The patient should be reassessed regularly and the need for continued treatment should be evaluated, especially in the case of a patient being symptom free.
The overall duration of treatment should, generally, not be more than 8 - 12 weeks, including a tapering-off process. In certain cases extension beyond the maximum treatment period may be necessary; if so, it should not take place without re-evaluation of the patient’s status.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
The administration of Demetrin is restricted to adults only (18 and above).
The side-effects most commonly encountered are drowsiness and oversedation. Drowsiness is more common in elderly and debilitated patients and in patients receiving high doses.
Less common are depression of mood and affect, disorientation or confusion, lethargy and ataxia. Also reported have been headache, weakness, dizziness, lightheadedness, tremor, vivid dreams, slurred speech, palpitations, stimulation, dry mouth, diaphoresis, and various gastrointestinal complaints.
Paradoxical reactions such as acute hyperexcitable states with rage may occur. If these occur, the medication should be discontinued.
Demetrin is not recommended for the primary treatment of psychotic illness. Demetrin should not be used alone to treat depression or anxiety with depression; suicide may be precipitated in such patients.
Dependence:
As there is a potential for abuse and development of physical and psychic dependence, especially with prolonged use and high doses, extreme caution should be observed in patients who are considered to have a psychological potential for drug dependence; these would include patients with a history of alcohol or drug abuse.
Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. These may consist of headaches, tremor, abdominal and muscle pain, extreme anxiety, tension, restlessness, confusion, irritability, vomiting and sweating. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.
Rebound effects:
A transient syndrome, whereby the symptoms that led to treatment with Demetrin recur in an enhanced form, may occur on withdrawal of treatment. It may be accompanied by other reactions including mood changes, anxiety and restlessness. Since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended that the dosage is decreased gradually.
Duration of treatment:
The duration of treatment should be as short as possible (see Dosage), but should not exceed eight to twelve weeks in, including the tapering-off process. Extension beyond these periods should not take place without re-evaluation of the situation. It may be useful to inform the patient, when treatment is started, that it will be of limited duration and to explain precisely how the dosage will be progressively decreased. Moreover it is important that the patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms, should they occur while the product is being discontinued.
Particular caution should be exercised:-

(1)	With the elderly and debilitated - who are at particular risk of oversedation, respiratory depression and ataxia. The initial oral dosage should be reduced in these patients.
(2)	In patients with pulmonary disease and limited pulmonary reserve.
(3)	In patients suffering from impairment of renal or hepatic function.
(4)	In patients suffering from anxiety accompanied by an underlying depressive disorder.
(5)	In patients receiving barbiturates or other central nervous system depressants. There is an additive risk of central nervous system depression when these medicines are taken together. Patients should be cautioned against the additive effect of alcohol.
(6)	In patients with glaucoma or myasthenia gravis because of possible deleterious effects attributed to the benzodiazepines in such patients.

Patients should be advised, particularly at the initiation of therapy, not to drive a motor vehicle, climb dangerous heights or operate dangerous machinery. In these situations, impaired decision making could lead to accidents.
Patients taking benzodiazepines for prolonged periods should have blood counts and liver function tests periodically.
Some benzodiazepines, such as chlordiazepoxide, have been shown to exacerbate porphyria; therefore caution should be exercised when prazepam is given to porphyric patients.
Drug Interactions:
Phenothiazines, narcotics, barbiturates, MAO inhibitors and other antidepressants will potentiate the action of prazepam.
Demetrin is not recommended during pregnancy until such time as its safety in pregnancy has been established. Given during labour, Demetrin and its metabolites cross the placental barrier and may cause the floppy-infant syndrome characterised by central respiratory depression, hypothermia, hypotonia and poor sucking. It should not be administered to lactating mothers.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Manifestations of overdosage include somnolence, confusion, coma, respiratory and cardiovascular depression and hypotension. Vomiting should be induced. The stomach should be emptied by gastric lavage. General supportive care with close observation is indicated. Hypotension may be controlled with noradrenaline or another suitable vasoconstrictor. Flumazenil (as an adjunct to, not as a substitute for, overdosage treatment) is indicated for the complete or partial reversal of the sedative effects of the drug.

IDENTIFICATION:
A blue, slightly mottled, round, biconvex tablet scored on one side, and bearing a monogram DEM on the other.

PRESENTATION:
Securitainers of 100 and 500 tablets.

STORAGE INSTRUCTIONS:
Store in a cool, dark (below 25°C) dry place.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
G/2.6/188

NAME AND BUSINESS ADDRESS OF APPLICANT:
Pfizer Laboratories (Pty) Ltd
102 Rivonia Road
SANDTON, 2196
South Africa

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
13 October 1983.

        Revised: FEB97

Updated on this site: February 2005
Source: Pharmaceutical Industry
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