22316-47-8

Hazard Information

Questions And Answer

• Description

  Clobazam is a first-generation AED known under the proprietary brand name of Frisium® (Sanofi, Paris) in the UK and Onfi® (Lundbeck, Copenhagen) in the USA. ;

• Generic formulation

  MHRA/ CHM advice to minimize risk when switching patients with epilepsy between different manufacturers’ products (including generic products):
  • The need for continued supply of a particular manufacturer’s product should be based on clinical judgment, and consultation with the patient and/ or carer, taking into account factors such as seizure frequency and treatment history.
  ;

• Indications

  Epilepsy: adjunctive therapy of focal and generalized seizures.
  
  Recommendations summarized from NICE (2012)
  • Seizure types: adjunctive (generalized tonic- clonic seizures, focal seizures), on referral to tertiary care (absence seizures, myoclonic seizures).
  • Epilepsy types: adjunctive (epilepsy with generalized tonic- clonic seizures only), on referral to tertiary care (absence syndromes, juvenile myoclonic epilepsy, idiopathic generalized epilepsy): 
  • Psychiatry— short-term relief (2–4 weeks) of severe, disabling, or unacceptably distressing anxiety, occurring alone or in association with insomnia, or shortterm psychosomatic, organic, or psychotic illness (adjunctive treatment in patients with psychotic illness).
  ;

• Dose titration

  • Epilepsy—adjunctive therapy: 20– 30 mg daily (max. 60 mg daily in divided doses).
  • Anxiety (short-term use): 20– 30 mg nocte or in divided doses (max. 60 mg daily, in divided doses).
  The effectiveness of clobazam may decrease significantly after weeks or months of continuous therapy. ;

• Cautions

  • Patients with dependent/ avoidant/ obsessive– compulsive personality disorder (may increase risk of dependence).
  • Patients with organic brain damage.
  • Patients with muscle weakness.
  ;

• Interactions

  With AEDs
  Phenytoin and carbamazepine may cause an increase in the metabolic conversion of clobazam to the active metabolite N- desmethyl clobazam.
  
  With other drugs
  • With administration of clobazam (especially at higher doses), an enhancement of the central depressive effect may occur in cases of concomitant use with antipsychotics, hypnotics, anxiolytics/sedatives, antidepressant agents, narcotic analgesics, anticonvulsant drugs, anaesthetics, and sedative antihistamines.
  • If clobazam is used concomitantly with narcotic analgesics, possible euphoria may be enhanced (possibly leading to increased psychological dependence).
  • The effects of muscle relaxants, analgesics and nitrous oxide may be enhanced by concomitant use of clobazam.
  • Dosage adjustment of clobazam may be necessary when co- administered with strong (e.g. fluconazole, fluvoxamine, ticlopidine) or moderate (e.g. omeprazole) CYP2C9 inhibitors, which may result in increased exposure to N- desmethyl clobazam, the active metabolite of clobazam.
  • Dose adjustment of drugs metabolized by CYP2D6 (e.g. dextromethorphan, nebivolol, paroxetine, and pimozide) may be necessary, as clobazam is a weak CYP2D6 inhibitor.
  With alcohol/food
  There is an increased sedative effect when clonazepam or clobazam are given with alcohol, and it is recommended that patients abstain from drinking alcohol during treatment with these drugs. ;

• Special populations

  Hepatic impairment
  • Start with smaller initial dose or reduce maintenance dose.
  • Avoid in severe impairment.
  
  Renal impairment
  Start with smaller dose in significant impairment.
  
  Pregnancy
  • As a precautionary measure, it is preferable to avoid the use of Clobazam during pregnancy. Clobazam should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
  • Administration Clobazam in the last trimester of pregnancy or during labour can result in hypothermia, hypotonia, respiratory depression, and feeding difficulties in the neonate.
  • Infants born to mothers who have taken Clobazam during the later stages of pregnancy may develop physical dependence, and may be at risk for developing withdrawal symptoms in the postnatal period.
  • Clobazam, like all benzodiazepines, are present in milk and should be avoided if possible during breastfeeding.
  ;

• Behavioural and cognitive effects in patients with epilepsy

  Behavioural effects include sleepiness, poor coordination, and agitation with paradoxical aggression/ disinhibition (usually dose- dependent). Long- term use may result in tolerance, dependence, and withdrawal symptoms if stopped abruptly. In addition to seizure exacerbation, abrupt discontinuation of benzodiazepines can be accompanied by changes in mental status, including anxiety, agitation, confusion, depression, psychosis, and delirium. Benzodiazepines are more frequently associated with adverse cognitive effects than most other AEDs. Among cognitive domains, attention and language appear to be more significantly affected in patients treated with clobazam (mainly at high doses). ;

• Psychiatric use

  In addition to its role as an AED, clobazam has an indication for short-term relief (2– 4 weeks) of acute anxiety in patients who have not responded to other drugs, with or without insomnia, and without uncontrolled clinical depression. ;

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