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4.2 Posology and method of administration
The patient should be checked regularly at the start of treatment in order to minimise the dosage and/or the frequency of administration to prevent overdose due to accumulation.
Elderly and/or debilitated patients
Elderly patients require lower doses because of individual variations in sensitivity and pharmacokinetics; doses should not exceed half those normally recommended (see section 5.2
Pharmacokinetics in special populations).
4.4 Special warnings and precautions for use
Some loss of efficacy to the effects of
benzodiazepines may develop after repeated use for a few weeks.
Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products, (see section 4.8). The risk of dependence increases with dose and duration of treatment; it is also greater in patients with a history of alcohol or drug abuse.
Benzodiazepines may induce anterograde amnesia. Anterograde amnesia may occur using higher therapeutic dosages (documented at 6mg), the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients should ensure that they will be able to have an uninterrupted sleep of 7 – 8 hours (see section 4.8).
Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide may be precipitated in such patients).
Patients with known or presumed dependence on alcohol, medicines or drugs should not take benzodiazepines, except in rare situations under medical supervision.
4.5 Interaction with other medicinal products and other forms of interaction
Not recommended: Concomitant intake with alcohol.
The sedative effect may be enhanced when the product is used in combination with alcohol. This affects the ability to drive or use machines.
Take into account: Combinations with CNS depressants
Enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic drugs, anaesthetics and sedative antihistamines.
In the case of narcotic analgesics, enhancement of the euphoria may also occur leading to an increase in psychic dependence.
4.8 Undesirable effects
Drowsiness (when the product is used as a hypnotic it should be stated explicitly, drowsiness during the day), numbed emotions, reduced alertness, confusion, fatigue, headache, dizziness, muscle weakness, ataxia or double vision. These phenomena occur predominantly at the start of therapy and usually disappear with repeated administration.
Other side-effects like gastrointestinal disturbances, changes in libido or skin reactions have been reported occasionally.
Anterograde amnesia may occur using therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour (see section 4.4 Special warnings and special precautions for use).
Pre-existing depression may be unmasked during benzodiazepine use.
Psychiatric and “paradoxical” reactions
Reactions like restlessness, agitation, irritability, aggressiveness, delusion, rages, nightmares, hallucinations, psychoses, inappropriate behaviour and other adverse behavioural effects are known to occur when using benzodiazepines or benzodiazepine-like agents, see section 4.4 Special warnings and special precautions for use. They may be quite severe with this product. Should this occur, the use of the drug should be discontinued. They are more likely to occur in children and the elderly than in other patients.
Use (even at therapeutic doses) may lead to the development of physical dependence: discontinuation of the therapy may result in withdrawal or rebound phenomena (see section 4.4 Special warnings and special precautions for use). Psychic dependence may occur. Abuse of benzodiazepines has been reported.
Benzodiazepines commonly cause drowsiness, ataxia, dysarthria and nystagmus.
Coma, hypotension and respiratory depression occasionally occur but are seldom serious if these drugs are taken alone. Coma, if it occurs, usually lasts only a few hours but it may be more protracted and cyclical, particularly in elderly patients. Benzodiazepine respiratory depressant effects are more serious in patients with respiratory disease.
If CNS depression is severe consider the use of flumazenil (Anexate®), a benzodiazepine antagonist. This should only be administered under closely monitored conditions. It has a short half-life (about an hour), therefore patients administered flumazenil will require monitoring after its effects have worn off. Flumazenil is
contraindicated in the presence of drugs that reduce seizure threshold (e.g. tricyclic antidepressants). Refer to the prescribing information for flumazenil (Anexate®), for further information on the correct use of this drug.
10. DATE OF REVISION OF THE TEXT