CLOBAZAM MARTINDALE PHARMA

Posology If low doses are required, the 5mg/5ml strength product is the most suitable presentation. If high doses are required, the 10mg/5ml strength product is the most suitable presentation. For patients who require only small doses of less than 1ml, the 150ml pack size of the 5mg/5ml strength should be used, which is provided with a 1ml oral syringe.

Treatment of anxiety Adults The usual anxiolytic dose for adults is 20-30 mg daily in divided doses or as a single dose given at night. Doses up to 60mg daily have been used in the treatment of adult in-patients with severe anxiety.

The lowest dose that can control symptoms should be used. After improvement of the symptoms, the dose may be reduced. It should not be used for longer than 4 weeks. Long term chronic use as an anxiolytic is not recommended. In certain cases, extension beyond the maximum treatment period may be necessary; treatment must not be extended without re-evaluation of the patient's status using special expertise.

It is strongly recommended that prolonged periods of uninterrupted treatment be avoided, since they may lead to dependence. Treatment should always be withdrawn gradually. Patients who have taken clobazam for a long time may require a longer period during which doses are reduced.

Elderly:

Doses of 10-20 mg daily in anxiety may be used in the elderly, who are more sensitive to the effects of psychoactive agents. Treatment requires low initial doses and gradual dose increments under careful observation. Treatment of epilepsy in association with one or more other anticonvulsants The oral suspension is suitable for any epilepsy patient in whom the clinician feels an oral suspension is preferable to clobazam tablets.

In all cases, treatment should be initiated at the lowest effective dose with gradual dose increments under careful observation. Adults In epilepsy a starting dose of 20-30 mg/day is recommended, increasing as necessary up to a maximum of 60 mg daily.

Elderly Treatment requires low initial doses and gradual dose increments under careful observation.

Paediatric population aged 6 years and above:

When prescribed for children treatment requires low initial doses and gradual dose increments under careful observation. It is recommended that normally treatment should be started at 5mg daily. 3 to 1mg/kg body weight daily is usually sufficient.

1 mg/kg/day for younger patients. 2 mg/kg/day at 7 days intervals, until the required clinical effect is achieved or side effects occur. 3 to 1 mg/kg/day . The daily dose can be taken in divided doses or as single dose at night.

Paediatric population aged 6 month-2 years:

Clobazam oral suspension should only be used in children from 6 months to 2 years old, under exceptional situations, when there is a clear epilepsy indication. 1mg/kg/day and titrate upwards very slowly (increasing not more often than every 5 days) to achieve required clinical effect, in divided doses twice daily.

The patient must be re-assessed after a period not exceeding 4 weeks and regularly thereafter in order to evaluate the need for continued treatment. A break in therapy may be beneficial if drug exhaustion develops, recommencing therapy at a low dose.

At the end of treatment (including in poor-responding patients), since the risk of withdrawal phenomena/rebound phenomena is greater after abrupt discontinuation of treatment, it is recommended to gradually decrease the dosage. Method of administration For oral use only Once titrated to an effective dose of clobazam, patients should remain on their treatment and care should be exercised when changing between different formulations.

The following CIOMS frequency rating is used, when applicable:

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). 4), initial insomnia, anger, hallucination, psychotic disorder, poor sleep quality, suicidal ideation Nervous system disorders Very common: somnolence, especially at the beginning of treatment and when higher doses are used Common: sedation, dizziness, disturbance in attention, slow speech/dysarthria/speech disorder (particularly with high doses or in long-term treatment, and is reversible), headache, tremor, ataxia Uncommon: emotional poverty, amnesia (may be associated with abnormal behaviour), memory impairment, anterograde amnesia (in the normal dose range, but especially at higher dose levels) Not known: cognitive disorder, altered state of consciousness (particularly in elderly patients, may be combined with respiratory disorders), nystagmus (particularly with high doses or in long-term treatment), gait disturbance (particularly with high doses or in long-term treatment, and is reversible).

g. 4) Gastrointestinal disorders Common: dry mouth, nausea, constipation Skin and subcutaneous tissue disorders Uncommon: rash Not known: photosensitivity reaction, urticaria, Stevens-Johnson syndrome, toxic epidermal necrolysis (including some cases with fatal outcome) Musculoskeletal and connective tissue disorders Not known: muscle spasms, muscle weakness General disorders and administration site conditions Very common: fatigue, especially at the beginning of treatment and when higher doses are used Not known: slow response to stimuli, hypothermia Uncommon: weight increased (particularly with high doses or in long-term treatment, and is reversible) Injury, poisoning and procedural complications Uncommon: fall 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. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Amnesia Amnesia may occur with benzodiazepines. In case of loss or bereavement psychological adjustment may be inhibited by benzodiazepines. Special caution is necessary if clobazam is used in patients with pre-existing muscle weakness, spinal or cerebellar ataxia or sleep apnoea.

A dose reduction may be necessary. Clobazam is contraindicated in patients with myasthenia gravis. Suicidal ideation, suicide attempt, suicide and depression Some epidemiological studies suggest an increased incidence of suicidal ideation, suicide attempt and suicide in patients with or without depression and treated with benzodiazepines and other hypnotics, including clobazam.

8). Personality disorders Disinhibiting effects may be manifested in various ways. Suicide may be precipitated in patients who are depressed and aggressive behaviour towards self and others may be precipitated. Extreme caution should therefore be used in prescribing benzodiazepines in patients with personality disorders.

Dependence Use of benzodiazepines - including clobazam - may lead to the development of physical and psychological dependence upon these products. 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.

; Once physical dependence has developed, abrupt termination of treatment will be accompanied by withdrawal symptoms (or rebound phenomena). Rebound phenomena are characterised by a recurrence in enhanced form of the symptoms which originally led to clobazam treatment.

This may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness. A withdrawal syndrome may also occur when abruptly changing over from a benzodiazepine with a long duration of action (for example, clobazam) to one with a short duration of action.

Respiratory depression Respiratory function should be monitored in patients with chronic or acute severe respiratory insufficiency and a dose reduction of clobazam may be necessary. Renal and hepatic impairment In patients with impairment of renal or hepatic function, responsiveness to clobazam and susceptibility to adverse effects are increased, and a dose reduction may be necessary.

In long-term treatment renal and hepatic function must be checked regularly. Serious skin reactions Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with clobazam in both children and adults during the post-marketing period.

A majority of the reported cases involved the concomitant use of other drugs, including anti-epileptic drugs that are associated with serious skin reactions. SJS/TEN could be associated with a fatal outcome. Patients should be closely monitored for signs or symptoms of SJS/TEN, especially during the first 8 weeks of treatment.

Clobazam should be immediately discontinued when SJS/TEN is suspected. 8). Elderly patients In the elderly, due to the increased sensitivity to adverse reactions such as drowsiness, dizziness, muscle weakness,there is an increased risk of fall that may result in serious injury.

A dose reduction is recommended. Tolerance in epilepsy In the treatment of epilepsy with benzodiazepines - including clobazam - consideration must be given to the possibility of a decrease in anti-convulsant efficacy (development of tolerance) in the course of treatment.

CYP2C19 poor metabolisers In patients who are CYP2C19 poor metabolisers, levels of the active metabolite N- desmethylclobazam are expected to be increased as compared to extensive metabolisers. g. 2). 5). Concomitant use of opioids and benzodiazepines Concomitant use of clobazam and opioids may result in sedation, respiratory depression, coma and death.

Because of these risks, concomitant prescribing of benzodiazepines such as clobazam with opioids should be reserved for patients for whom alternative treatment options are not possible. 2). The patients should be followed closely for signs and symptoms of respiratory depression and sedation.

5). In the treatment of epilepsy with benzodiazepines - including clobazam - consideration must be given to the possibility of a decrease in anticonvulsant efficacy (development of tolerance) in the course of treatment. Concomitant use of cannabidiol The concomitant use of clobazam with cannabidiol-containing medicinal and non- medicinal products may result in increased exposure to N-desmethylclobazam, leading to increased incidence of somnolence and sedation.

Dosage adjustment of clobazam may be necessary. 2). Excipients in the formulation Tapclob Oral Suspension contains sorbitol. Patients with a rare hereditary problems of fructose intolerance should not take this medicine. The […]

1 − In patients with any history of drug or alcohol dependence (increased risk of development of dependence). − In patients with myasthenia gravis (risk of aggravation of muscle weakness). − In patients with severe respiratory insufficiency (risk of deterioration).

− In patients with sleep apnoea syndrome (risk of deterioration). − In patients with severe hepatic insufficiencies (risk of precipitating encephalopathy). − In breast-feeding women. 6). Benzodiazepines must not be given to children without careful assessment of the need for their use.

Clobazam must not be used in children between the ages of 6 month to 2 years old, other than in exceptional cases for anticonvulsant treatment where there is a compelling indication.