Commonly used regime

In children 2-12 years: 

• Initially 0.1 to 0.2 mg/kg/day in 1 to 2 doses.
• Slowly increase initially at weekly intervals up to a total of 0.8mg/kg/day (usual max 20 mg; beyond weight of 30-40 kg this guideline does not apply).
• Doses above 0.3 mg/kg/day are better split into 2 divided doses across the day.
• The dose of 0.8 mg/kg/day is a high dose.
• Dosages of this level should be done in conjunction with a neurologist. Efficacy and side-effect profile must be monitored and slow escalation is emphasised.

In children > 12 years: 

• a reasonable starting dose is 5 mg. It is often helpful to start with a nocte dose.

In children with difficult epilepsy: 

• increasing at weekly increments of 5 mgs to a total daily dose of 10-20 mg if tolerated is reasonable. Rarely there may be a need to increase to higher doses.
• If the patient is unable to swallow the tablets whole, the tablet may be crushed and mixed with a small amount of food such as apple sauce, yoghurt, ice cream.
• When discontinuing, withdraw very slowly. Sudden cessation of benzodiazepines can cause seizures. The withdrawal plan is dependent on total daily dosage and duration of treatment but should be done very gradually.

Preparations

• Tablets: 10 mg scored
• Syrup: Can be compounded by a pharmacy.

Formularies

• Australian Medicines Handbook (AMH)
• eMIMS

• Sedation, tiredness, or drowsiness.

Other notable side effects

• Less commonly, headache and dry mouth.
• Be aware of paradoxical reactions which can lead to restlessness, difficulty in falling asleep and agitation, hyperactivity, and aggressive outbursts.
• All anti-seizure medications are potentially teratogenic and this is often dose-related.
• Clobazam use during pregnancy can result in ‘floppy infant syndrome’ or withdrawal symptoms in the newborn.
• For a complete list of adverse effects, appropriate formularies should be consulted

• Clobazam may cause drowsiness or sedation, particularly in the context of polytherapy.
• Clobazam should be used with extreme caution in patients with severe respiratory insufficiency or sleep apnoea. Caution should be taken if used in conjunction with other potentially sedating drugs.
• Great care is required when using clobazam in conjunction with opioids as respiratory depression may occur.
• Clobazam has pharmacokinetic interactions with some of the anti-seizure medications that are usually used in refractory epilepsies such as Dravet and Lennox-Gastaut Syndromes - these include cannabidiol, stiripentol and fenfluramine. This needs to be taken into account to guide dosing.
• Clobazam also interacts with multiple other anti-seizure medications (both pharmacokinetic and pharmacodynamic – valproate, carbamazepine, phenytoin, phenobarbitone) – In practice, this requires careful clinical observation and adjustment of dosage based on side-effect profile.
• Monitoring of clobazam levels is only helpful in the context of toxicity, but not to measure therapeutic effect. However, monitoring of levels of some of the other medications being used alongside clobazam, such as carbamazepine, phenytoin and phenobarbitone may be helpful.
• You need to adjust the dose in patients who are known to slowly metabolize medications through the liver (known CYP2C19 slow metabolisers), individuals with liver disease, or if there is simultaneous use of CYP2C19 inhibitors such as fluconazole, fluvoxamine, and omeprazole.