Clobazam

Usage

  • Clobazam is a benzodiazepine.
  • Clobazam is usually used as an adjunctive therapy in patients with focal and Lennox-Gastaut Epilepsies.
  • It has also been used in generalised seizures not controlled by first line drugs.

Resources

Side effects

Possible side effects:

  • 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 anticonvulsants are potentially teratogenic and this is often dose-related (see section: AED Prescribing - Pregnancy). 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

Dosing

  • The below initiation and escalation doses are only a guide and need to be individualised based on patient (age, weight, co-morbidities), disease (seizure type, frequency, duration) and medication (metabolism, interactions, side-effect profile) characteristics.

 

  • Situations that require more careful consideration include children with higher weights, polytherapy, or multiple co-morbidities. Consultation with appropriate formularies or a paediatric neurologist may be required in specific circumstances.

Commonly used regime

  • Initially 0.1 to 0.2mg/kg/day in 1 to 2 doses. Slowly increase initially at weekly intervals up to a total of 0.8mg/kg/day (beyond weight of 30-40kg this guideline does not apply). Doses above 0.3mg/kg/day are better split into 2 divided doses across the day.
  • The dose of 0.8mg/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 5mgs to a total daily dose of 10-20mg 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: 10mg scored
  • Syrup: Can be compounded by a pharmacy.

Interactions | Precautions

  • 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 and cannabidiol interact to increase each other’s active metabolites. Concurrent use often results in excessive sedation and a reduction in the dose of clobazam is usually required.
  • Stiripentol increases the blood levels of clobazam and its active metabolites.
  • Clobazam also interacts with multiple other anti-epileptic 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 metabolizers), individuals with liver disease, or if there is simultaneous use of CYP2C19 inhibitors such as fluconazole, fluvoxamine, and omeprazole.

 

Information last reviewed: 3/05/2023.