CLONAZEPAM CELIX

Posology Adults Initial dose not to exceed 1 mg/day. The maintenance dosage for adults normally falls with the range 4 – 8 mg. 5 mg/day. The elderly are particularly sensitive to the effects of centrally depressant drugs and may experience confusion.

5 mg tablets to ensure optimum dosage adjustment. 25 mg/day for infants and small children (1-5 yrs). 5 mg/day for older children. 5 – 1 mg/day Small children (1 – 5 years) 1 – 3 mg/day School children (5-12 years) 3 – 6 mg/day In some forms of childhood epilepsy, certain patients may cease to be adequately controlled by clonazepam.

Control may be re-established by increasing the dose or interrupting treatment with clonazepam for 2 or 3 weeks. During the interruption in therapy, careful observation and other drugs may be needed. Hepatic Impairment In patients with mild to moderate hepatic impairment the dose should be adjusted to individual requirements and will probably be lower.

Method of administration For oral administration. Treatment should be started with low doses. The dose may be increased progressively until the maintenance dose suited to the individual patient has been found. The cross- scored tablets facilitate the administration of lower daily doses in the initial stages of treatment.

The dosage of clonazepam must be adjusted to the needs of each individual and depends on the individual response to therapy. The maintenance dosage must be determined according to clinical response and tolerance. The daily dose should be divided into 3 or 4 doses throughout the day.

If doses are not equally divided, the largest dose should be given before retiring. Once the maintenance dose level has been reached, the daily amount may be given in a single dose in the evening. Simultaneous administration of more than one antiepileptic drug is a common practice in the treatment of epilepsy and may be undertaken with clonazepam.

The dosage of each drug may be required to be adjusted to obtain the optimum effect. If status epilepticus occurs in a patient receiving oral clonazepam, intravenous clonazepam may still control the status. Before adding clonazepam to an existing anticonvulsant regimen, it should be considered that the use of multiple anticonvulsants may result in an increase of undesired effects.

If necessary, larger doses may be given at the discretion of the physician, up to a maximum of 20 mg daily. The maintenance dose should be attained after 2-4 weeks of treatment.

Frequencies are defined according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).

The side effects marked with an asterisk (*) are usually transitory and disappear spontaneously as treatment continues or with dose 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.

Blood and the lymphatic system disorders Isolated cases of blood dyscrasias. Immune system disorders Allergic reaction and a very few cases of anaphylaxis and angioedema. Endocrine disorders Isolated cases of reversible development of premature secondary sex characteristics in children (incomplete precocious puberty) have been reported.

Psychiatric disorders and Paradoxical Reactions Anterograde amnesia (risk increases at higher dosages). Amnestic effects may be associated with inappropriate behaviour. Depression, loss of libido, impotence. Use of benzodiazepines may lead to the development of physical and psychological dependence upon these products.

4). 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 occur.

If these occur, the benefit of continuing the drug should be weighed against the adverse effect. It may be necessary to add another suitable drug to the regimen or to discontinue clonazepam therapy. Nervous system disorders Dizziness*, light-headedness*, somnolence*, fatigue*, co-ordination disturbances*, poor concentration, restlessness, confusion and disorientation, headache.

Dysarthria and ataxia* are reversible disorders and occur particularly in long-term or high-dose treatment. These undesirable effects occur relatively frequently and may disappear gradually in the course of the treatment or on reduction of the dosage.

They can be partially prevented by increasing the dose slowly at the start of treatment. Headache was observed in rare cases. Causing of generalized fits was observed very rarely. Particularly in long-term or high-dose treatment, reversible disorders such as dysarthria, reduced coordination of movements and gait disorder (ataxia) and nystagmus may occur.

Anterograde amnesia may occur using benzodiazepines at therapeutic dosages, the risk increasing at higher dosages. Amnestic effects may be associated with inappropriate behavior. Although clonazepam has been given uneventfully to patients with porphyria, rarely it may induce convulsions in these patients.

With certain forms of epilepsy, an increase in the frequency of seizures during long term treatment is possible. Rarely, convulsions may be induced in patients with porphyria. Eye disorders Double vision and nystagmus are reversible disorders and occur particularly in long term or high-dose treatment.

Common: nystagmus Cardiac Disorders Cardiac failure including cardiac arrest has been reported. Respiratory, thoracic and mediastinal disorders Rarely respiratory depression may occur with intravenous clonazepam, particularly if other depressant drugs have been administered.

This effect may be aggravated by pre- existing airways obstruction or brain damage or if other medications which depress respiration have been given. This effect can usually be avoided by careful adjustment of the dose to individual requirements.

In infants and small children, and particularly those with a degree of mental impairment, salivary or bronchial hypersecretion with drooling may occur. Supervision of the airway may be required. Gastrointestinal disorders Rarely: nausea, gastrointestinal and epigastric symptoms.

Hepato-biliary disorders Isolated cases of abnormal liver function tests have been reported. Skin and subcutaneous tissue disorders Rarely: urticaria, pruritus, rash, transient hair loss, pigmentation changes. Musculoskeletal, connective tissue and bone disorders Muscle weakness*, occasional muscular hypotonia* Renal and urinary disorders Rarely: urinary incontinence.

Reproductive System and Breast Disorders In rare cases erectile dysfunction or loss of libido may occur.

General disorders and administration site conditions Withdrawal:

Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms. During long-term treatment, withdrawal symptoms may develop, especially withdrawing from 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, discontinuation should be carried out by gradually reducing the daily dose.

Injury, Poisoning and Procedural Complications An increased risk for falls and fractures has been reported in elderly benzodiazepine users. The risk is increased in those taking concomitant sedatives (including alcoholic beverages) Investigations In rare cases decreased platelet count may occur.

As with other benzodiazepines, isolated cases of blood dyscrasias. 4). Pediatric population For pediatric specific events please refer to the information listed under headings: Endocrine […]

Suicidal behaviour:

Suicidal ideation and behaviour have been reported in patients treated with antiepileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour.

The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for clonazepam. Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered.

Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge. Patients with a history of depression and/or suicide attempts should be kept under close supervision.

Use with caution in patients with chronic pulmonary insufficiency, or with renal or hepatic function impairment, and in the elderly or debilitated. In these cases dosage should generally be reduced. g. chronic obstructive pulmonary disease) and in patients undergoing treatment with other centrally acting medications or anticonvulsant (antiepileptic) agents (see section

Known hypersensitivity to benzodiazepines. 1. Acute pulmonary insufficiency; severe respiratory insufficiency, sleep apnoea syndrome, myasthenia gravis, severe hepatic insufficiency. Clonazepam must not be used in patients in a coma, or in patients known to be abusing pharmaceuticals, drugs or alcohol.