DEMETRIN Tablet Ref.[50581] Active ingredients: Prazepam

Duration of treatment

The duration of treatment should be as short as possible (see section 4.2). 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 6–8 weeks, including a tapering-off process. Extension beyond these periods should not take place without re-evaluation of the patient’s status.

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 DEMETRIN is being discontinued.

Patients taking DEMETRIN for prolonged periods should have blood counts and liver function tests periodically.

Paradoxical reactions such as acute hyperexcitable states with rage may occur. If these occur, DEMETRIN should be discontinued. Such reactions are more frequent in children and in the elderly.

Caution should be exercised when DEMETRIN is given to porphyric patients.

Particular caution should be exercised:

• with the elderly and debilitated – who are at particular risk of over sedation, respiratory depression and ataxia. The initial oral dosage should be reduced in these patients.
• in patients with pulmonary disease and limited pulmonary reserve.
• in patients suffering from impairment of renal or hepatic function.
• in patients suffering from anxiety accompanied by an underlying depressive disorder.
• 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. Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Limit dosages and durations to the minimum required.
• in patients with glaucoma or myasthenia gravis because of possible deleterious effects attributed to the benzodiazepines in such patients.

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.

Tolerance

Tolerance to benzodiazepines may develop from continued therapy. Some loss of efficacy to the hypnotic effects of benzodiazepines may develop after repeated use for some weeks.

Lactose intolerance

DEMETRIN contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Benzodiazepines, including DEMETRIN, produce additive CNS depressant effects, including respiratory depression, when co-administered with other CNS depressants such as opioids, phenothiazines, narcotics, barbiturates, monoamine oxidase inhibitors and other antidepressants (see section 4.4).

CYP3A4 inhibitors may reduce the metabolism of DEMETRIN and increase the potential for toxicity.

Combinations containing any of the following may also interact with DEMETRIN: Erythromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice.

Oral contraceptives can increase the effects of DEMETRIN because oral contraceptives inhibit oxidative metabolism, thereby increasing serum concentrations of concomitantly administered benzodiazepines that undergo oxidation. Patients receiving oral contraceptive therapy should be observed for evidence of increased effects of DEMETRIN.

DEMETRIN should be combined cautiously with clozapine because this could cause additive CNS depressant effects. Severe confusion, hypotension and respiratory depression have occurred rarely in those patients receiving clozapine concurrently or following benzodiazepine therapy. In patients receiving concomitant clozapine, the starting doses of DEMETRIN should be approximately one-half of the usual dose until experience with the patient has been gained.

Pregnancy

DEMETRIN is contraindicated during pregnancy and in women of childbearing potential not using contraception. When DEMETRIN is prescribed to a woman of child-bearing age, the woman should be advised to inform her medical practitioner if she wishes to become or is already pregnant, so that the medical practitioner can take the decision to discontinue treatment.

When DEMETRIN is administered for medical reasons during the third trimester of pregnancy or 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) and withdrawal syndrome (tremors, irritability, hypertonicity, diarrhoea/vomiting and vigorous sucking) in the new-born.

Breastfeeding

DEMETRIN should not be administered to lactating mothers.

Fertility

Studies in animals have shown reproductive toxicity. The use of DEMETRIN in high doses decreased male fertility in rats possibly due to a decrease in spermatogenesis. A decrease in fertility and female mating have also been observed in rats.

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.

The administration of DEMETRIN is restricted to adults only (18 and above).

Tabulated summary of adverse reactions

The table below contains side effects categorised as follows utilising the incidence rates: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1000); very rare (<1/10 000).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the “6.04 Adverse Drug Reactions Reporting Form”, found online under SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8

Not applicable.