The side-effects observed consist of fatigue, muscle weakness, dizziness, ataxia, light-headedness, somnolence, occasional muscular hypotonia and co-ordination disturbances. Such effects are usually transitory and disappear spontaneously as treatment continues or with dosage reduction. They tend to occur early in treatment and can be greatly reduced, if not avoided, by commencing with low dosages followed by progressive increases. Poor concentration, restlessness, confusion and disorientation have been observed. Anterograde amnesia may occur using benzodiazepines at therapeutic dosage, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behaviour. Depression may occur in patients treated with clonazepam, but it may be also associated with the underlying disease. In rare cases, urticaria, pruritus, transient hair loss, pigmentation changes, nausea, gastrointestinal symptoms, headache, decrease in sexual drive (loss of libido), impotence and urinary incontinence may occur. Isolated cases of reversible development of premature secondary sex characteristics in children (incomplete precocious puberty) have been reported. Allergic reactions and a very few cases of anaphylaxis and angioedema have been reported to occur with benzodiazepines. Particularly in long-term or high-dose treatment, reversible disorders such as a slowing or slurring of speech (dysarthria), reduced co-ordination of movements and gait (ataxia) and disorders of vision (double vision, nystagmus) may occur. Rarely respiratory depression may occur with intravenous clonazepam, particularly if other depressant drugs have been administered. As a rule, this effect can be avoided by careful adjustment of the dose in individual requirements. Use of benzodiazepines may lead to the development of physical and psychological dependence upon these products. The risk of dependence increases with dose and duration of treatment and is particularly pronounced in predisposed patients with a history of alcoholism or drug abuse. Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. During long-term treatment, withdrawal symptoms may develop, especially with high doses or if the daily dose is reduced rapidly or abruptly discontinued. The symptoms include tremor, sweating, agitation, sleep disturbances and anxiety, headaches, muscle pain, extreme anxiety, tension, restlessness, confusion, irritability and epileptic seizures which may be associated with the underlying disease. In severe cases the following symptoms may occur: derealisation, depersonalisation, hyperacusis, numbness and tingling of the extremities, hypersensitivity to light, noise and physical contact or hallucinations. Since the risk of withdrawal symptoms is greater after abrupt discontinuation of treatment, abrupt withdrawal of the drug should therefore be avoided and treatment - even if only of short duration - should be terminated by gradually reducing the daily dose. In infants and small children, and particularly those with a degree of mental impairment, clonazepam may give rise to salivary or bronchial hypersecretion with drooling. Supervision of the airway may be required. With certain forms of epilepsy, an increase in the frequency of seizures during long-term treatment is possible. As with other benzodiazepines, isolated cases of blood dyscrasias and abnormal liver function tests have been reported. Clonazepam generally has a beneficial effect on behaviour disturbances in epileptic patients. In certain cases, paradoxical effects such as aggressiveness, excitability, nervousness, hostility, anxiety, sleep disturbances, nightmares, vivid dreams, irritability, agitation, psychotic disorders and activation of new types of seizures may be precipitated. If these occur, the benefit of continuing the drug should be weighed against the adverse effect. The addition to the regimen of another suitable drug may be necessary or, in some cases, it may be advisable to discontinue clonazepam therapy. Although clonazepam has been given uneventfully to patients with porphyria, rarely it may induce convulsions in these patients. An increased risk of falls and fractures has been recorded in elderly benzodiazepine users.
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 the national reporting systems.
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