CLOBAZAM ESSENTIAL PHARMACEUTICALS

Posology Treatment of epilepsy in association with one or more other anticonvulsants Adults A starting dose of 5–15 mg/day is recommended. 8). The dose may be divided in 1–3 doses with the largest dose to be taken in the evening. A single dose up to 30 mg can be taken in the evening.

Paediatric population When prescribed for children, treatment requires low initial doses and gradual dose increments under careful observation since there may be an increased or paradoxical response to the treatment. Plasma drug concentrations may be measured where there is worsening seizures, status epilepticus, suspected noncompliance or suspected toxicity.

Paediatric population aged 6 months–2 years Data are limited about the use of Clobazam Essential Pharmaceuticals 1 mg/ml Oral Suspension under 2 years of age and it should only be used under the supervision of a paediatrician with experience in the treatment of severe childhood epileptic syndromes.

1 mg/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. 1 mg/kg/day. 8). 3 to 1 mg/kg/day. Maximum daily dose is 30 mg per day for children aged 2–5 years.

The daily dose can be taken in divided doses 2–3 times a day or as a single dose at night. The largest dose should be taken at night. Single doses should not exceed 1 mg/kg. Children aged ≥6 years Initial dose: 5 mg/day. 8). 3 to 1 mg/kg/day.

The daily dose can be divided in 2–3 doses or as a single dose at night. The largest dose should be taken at night. Single doses should not exceed 1 mg/kg or 30 mg. Maximum daily dose is 60 mg per day for children aged ≥6 years. 8). The daily dose can be taken in divided doses or as single dose at night.

The largest dose (which should not exceed 30 mg) should be taken at night. Hepatic impairment There is no experience of treatment with clobazam in patients with mild and moderate hepatic impairment. 3). 8). For long-term treatment, hepatic function should be checked regularly.

Renal impairment Clobazam Essential Pharmaceuticals 1 mg/ml Oral Suspension can be used for patients with mild and moderate renal impairment without any dose adjustment. The product is not recommended to be used for patients with severe renal failure.

8). For long-term treatment, renal function should be checked regularly. Duration 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.

This product may settle during storage. Shake the bottle well for approximately 15 seconds and turn the bottle upside down. Observe the transparency of the bottom. No precipitation sediment or caked sediment should be visible on the bottom of the bottle.

Summary of the safety profile In clinical studies the overall incidence of adverse reactions was 33%, of which the most common adverse reactions were related to the CNS and include fatigue, somnolence, restlessness, irritability and aggression.

Serious adverse reactions to clobazam include respiratory depression, hallucinations, Stevens-Johnson syndrome and toxic epidermal necrolysis. Drug dependence has been reported and discontinuation of the therapy may result in withdrawal or rebound phenomena.

1%). Tabulated summary of adverse reactions The frequencies of adverse events are ranked according to the following: 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).

g. 4) Gastrointestinal disorders Common • dryness of the mouth • constipation • nausea 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 Rare • muscle weakness Not known • muscle spasm General disorders and administration site conditions Very common • fatigue4 Uncommon • weight increased2,3 Not known • slow response to stimuli • hypothermia Injury, poisoning and procedural complications Uncommon • fall 1.

4) 2. Particularly with high doses or in long-term treatment Is reversible 3. Especially at the beginning of treatment and when higher doses are used 4. In the normal dose range, but especially at higher dose levels

Switching between formulations When taking Clobazam Essential Pharmaceuticals 1 mg/ml Oral Suspension, clobazam reaches higher peak plasma levels than the same dose as a tablet. This may lead to an increased risk of respiratory depression and sedation which may be most noticeable when switching to this medicine from tablets.

Moreover, the minimum plasma level at steady state (Cmin,ss) may be lower compared to tablet formulation, which can lead to an increased risk of reduced seizure control. Therefore, caution must be taken when switching between different formulations of clobazam, as the doses are not equivalent.

As with other anti-epileptic drugs, some patients may experience an increase in seizure frequency or the onset of new types of seizures with clobazam. These phenomena may be the consequence of an overdose, a decrease in plasma concentrations of concomitantly used anti-epileptics, progress of the disease, or a paradoxical effect.

8). 3). Amnesia Benzodiazepines can cause anterograde amnesia when used in the normal dose range, but especially at high doses. In case of loss or bereavement psychological adjustment may be inhibited by benzodiazepines. Muscle weakness Clobazam can cause muscle weakness.

Special caution is necessary if clobazam is used in patients with pre-existing muscle weakness, spinal or cerebellar ataxia. A dose reduction may be necessary. 3). Dependence Use of benzodiazepines such as 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. 2). g. agitation, seizures). This may be accompanied by other reactions including mood changes, anxiety or sleep disturbances and restlessness.

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.

g. “withdrawal delirium”), numbness of the limbs, tingling, muscle pain, tremor, sweating, nausea, hyperacusis, sensitivity to light, noise and physical contact, as well as epileptic seizures. g. 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. 3). 3). In long-term treatment renal and hepatic function must be checked regularly.

3). 8), often with serious consequences in this population. 2). 8). 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. If signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered.

Depression and 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.

Suicidal ideation and 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 antiepileptic medicinal products has also shown a small increased risk of suicidal ideation and behaviour.

The mechanism of […]

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. - In patients with acute intoxication with alcohol and CNS-active substances.