SEDOXIL Tablet Ref.[50994] Active ingredients: Mexazolam

Dependence

Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment, and is also greater in patients with a history of drug abuse or alcoholism. Once physical dependence has developed, abrupt termination of the drug will be accompanied by withdrawal symptoms; these may consist of headaches, muscle pain, extreme anxiety, tension, restlessness, confusion and irritability. In severe cases the following symptoms may occur: derealization, depersonalization, hyperacusis, numbness and tingling of extremities, hypersensitivity to light, noise and physical contact, hallucinations or epileptic seizures.

Rebound of anxiety

A transient syndrome, whereby the symptoms that led to treatment with a benzodiazepine recur in an enhanced aggravated form, may occur on withdrawal of treatment. It may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness. Since the risk of rebound phenomena is greater after abrupt discontinuance of the drug, it is recommended that the dosage be decreased gradually.

Duration of treatment

It should be as short as possible, depending on the indication, but should not exceed 8-12 weeks in case of anxiety, including tapering off process. Extension beyond this period should not take place without revaluation 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. The patient should be aware of the possibility of rebound phenomena, thereby minimising anxiety over such symptoms should they occur.

When benzodiazepines with a long duration of action, as mexazolam, are being used it is important to warn against changing to a benzodiazepine with a short duration of action, as withdrawal symptoms might develop.

Amnesia

Benzodiazepines may induce anterograde amnesia. The condition occurs most often several hours after ingesting the product and therefore to reduce the risk patients would ensure that they would be able to have an uninterrupted sleep of 7-8 hours (see Undesirable Effects).

Paradoxical and psychiatric reactions

Reactions like restlessness, agitation, irritability, aggressiveness, delusions, rage, nightmares, hallucinations, psychosis, inappropriate behaviour and other adverse behavioural effects are known to occur when benzodiazepines are used. Should this occur, use of the drug should be discontinued. These reactions are more like to occur in children and the elderly. Paradoxical reactions were reported in schizophrenic patients.

Specific patient groups

Elderly patients should be given a reduced dose (see dosage). A lower dosage is also recommended for patients with chronic respiratory insufficiency due to the risk of respiratory depression.

Benzodiazepines are not indicated for patients with severe hepatic insufficiency as they may precipitate encephalopathy.

Benzodiazepines are not recommended for the primary treatment of psychotic illness.

Benzodiazepines should not be used alone to treat depression or anxiety associated with depression (suicide might be precipitated in such patients).

Benzodiazepines should be used with extreme caution in patients with a history of drug abuse and alcoholism.

SEDOXIL should be used with caution in patients with cardiac, renal or hepatic disorders and in patients with encephalic organic disorders.

Not recommended - concomitant intake with alcohol.

The sedative effect may be enhanced when SEDOXIL is used in combination with alcohol; this affects the ability to drive or use machines.

Take into account the association with CNS depressants.

Enhancement of the central depressive effect may occur in cases of concomitant use of SEDOXIL with antipsychotic (neuroleptics), hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anti-epileptic products, anesthetises, and antihistamine sedatives.

In the case of narcotic analgesics enhancement of the euphoria may also occur leading to an increase in psychic dependence.

In pre-clinical trails with animals the following interactions were reported:

Drugs enhancing mexazolam effects: chlorpromazine, haloperidol, diazepam, cyproheptadine, aminopyrine, phenobarbital, ethanol, sulpiride, trichlormethiazide and alpha-methyldopa.

Drugs antagonising mexazolam effects: imipramine, amitriptyline and chlorpheniramine.

Drugs, which have not shown interaction with mexazolam: diphenylhidantoin, scopolamine butylbromide, gefarnate, propranolol and pindolol.

Although pre-clinical trials on animals did not suggest any harm of mexazolam during pregnancy, its safety in humans was not established during pregnancy. Benzodiazepines may cause congenital abnormalities when administered in the first trimester of pregnancy. If for compelling reasons SEDOXIL is administered during the late phase of pregnancy or during labour at high doses, effects on the neonate such as hypothermia, hypotonia and moderate respiratory depression can be expected.

Infants born to mothers who took benzodiazepines chronically during pregnancy may have developed physical dependence and may be at some risk for developing withdrawal symptoms in the postnatal period.

Since mexazolam may be found in the breast milk, it should not be given to breast feeding mothers. Every woman of childbearing potential should contact the physician if she intends to become or suspects that she is pregnant.

Sedation, amnesia, impaired concentration and impaired muscular function resulting from the administration of SEDOXIL may adversely affect the ability to drive or use machines.

If insufficient sleep duration occurs the likelihood of impaired alertness may be increased.

The most frequent side effects of benzodiazepines are likely to be an extension of the pharmacological actions and include drowsiness during the day, numbed emotions, reduced alertness, confusion, fatigue, headache, light-headedness, muscle weakness, ataxia or double vision.

1. Rarely (<0,1%) the following adverse events were reported with mexazolam: swollen tongue, hypotension, light-headedness, nausea, vomiting, anorexia, gastric discomfort, gastric pain, abdominal pain, diarrhoea, hypersensitivity reactions (e.g. skin reactions), decreased libido, decrease of alkaline phosphatase, anaemia and leukopenia. Commonly (0.1-5%) were reported drowsiness, vertigo, dizziness, headache, ataxia, dry mouth, weakness, increases of aspartate aminotransferase, alanine aminotransferase and gamma – glutamyl transpeptidase.

Side effects occur predominantly at the start of therapy and usually disappear upon continued administration.

Amnesia: Anterograde amnesia may occur using therapeutic doses of benzodiazepines, the risk increasing when higher doses are used. Amnestic effects may be associated with inappropriate behaviour (see precautions).

Depression: Pre-existing depression may recur when benzodiazepines are used.

Psychiatric and paradoxical reactions.

Reactions like restlessness, agitation, irritability, aggressiveness, delusions, rage, nightmares, psychoses, inappropriate behaviour and other related adverse behavioural effects are known to occur and become particularly severe with benzodiazepines. They are more likely to occur in children and the elderly.

Dependence: Even at therapeutic doses, SEDOXIL may lead to the development of physical dependence – discontinuance of the therapy may result in withdrawal or rebound phenomena (see precautions). Psychic dependence may also occur. Abuse of benzodiazepines has been reported.

Not applicable.