Epilepsy clobazam

Canadian Study Group for Childhood Epilepsy. Clobazam has equivalent efficacy to carbamazepine and phenytoin as monotherapy for childhood epilepsy. Epilepsia 1998 39(9) 952-9. 

In cases where fits are liable to occur at a particular time, e.g. the menstrual period, dosage should be adjusted to achieve maximal drug effect at that time or drug treatment can be confined to this time. For example, in catamenial epilepsy, clobazam can be useful given only at period time. 

Benzodiazepines used to treat epilepsy include diazepam, clonazepam, clobazam and lorazepam. Of these, diazepam and lorazepam have been most widely used to control status epilepticus, while use of clonazepam is usually restricted to the chronic treatment of severe mixed types of seizures (e.g. Lennox-Gastaut syndrome and infantile spasm). The major problem with most of the benzodiazepines, with the possible exception of clobazam, is sedation. 

Clonazepam is the most potent of the benzodiazepine anticonvulsants and is particularly indicated in the treatment of the more difficult cases of epilepsy, especially those of the multiple seizure type. More recently, clobazam, which at therapeutic doses has the advantage of causing little... 

This fivefold clinical activity is possessed, to a greater or lesser extent, by all benzodiazepines in current clinical use. The properties of benzodiazepines make them ideally useful for managing anxiety (e.g. diazepam, chlordiazepoxide, lorazepam) insomnia (e.g. diazepam, temazepam, nitrazepam, loprazolam, flurazepam, lormetazepam) epilepsy (e.g. clobazam, diazepam, lorazepam) sports injuries where muscle relaxation is required (e.g. diazepam) and as premedications prior to surgery (e.g. midazolam, lorazepam). The benzodiazepines have a number of other uses, including management of alcohol withdrawal syndrome (chlordiazepoxide, diazepam) and restless legs (clonazepam). Short... 

In an open study 25 patients with new-onset focal and primary generalized epilepsy were treated with clobazam at a single centre (2). After a mean follow-up of 16 months (range 7-24), 16 patients were seizure free, while five had more than a 50% reduction in seizure frequency. Sedation was the most common adverse event, reported by four patients however it was always mild and did not require withdrawal of clobazam. Other adverse effects, reported in one patient each, were weight gain, ataxia, loss of shortterm memory, and breakthrough seizures. 

Clobazam is better tolerated than other benzodiazepines used in epilepsy (5). Its most common adverse effects are mild and transient drowsiness, dizziness, or fatigue rather less common are muscle weakness, restlessness, aggressiveness, weight increase, ataxia, mood disorders, psychotic and behavioral disturbances, vertigo, hypotonia, hypersalivation, and edema (SED-13, 152). There may be a loss of therapeutic response over time. 

Of 63 children with refractory epilepsy given add-on clobazam (mean dosage 0.8 mg/kg/day) and followed for 15-64 months, 15 (24%) had to discontinue treatment owing to adverse effects, which included severe aggressive outbursts, hyperactivity, insomnia, and depression with suicidal ideation (6). Likewise, there were behavioral or mood problems in 38 of 119 children taking clobazam... 

Toxic epidermal necrolysis has been associated with clobazam (SEDA-21, 48). Bullae with sweat gland necrosis rarely complicate coma, but have recently been reported in association with clobazam, used as adjunctive therapy for resistant epilepsy in a 4-year-old girl (9). 

Clobazam has similar effects on anxiety to other benzodiazepines, but may be better tolerated (SEDA-20, 31). Used as an anticonvulsant, clobazam is generally well tolerated in epileptic patients, many showing little evidence of tolerance (5). On the other hand, children with epilepsy appear unusually prone to adverse behavioral reactions when taking clobazam (SEDA-19, 34). 

These findings explain some pharmacokinetic interactions of clobazam with ketoconazole (which inhibits the demethy-lation of clobazam by 70%) and omeprazole (which inhibits the hydroxylation of N-desmethylclobazam by 26%). In addition, in 22 patients with epilepsy who were genotyped for CYP2C19, there was a higher plasma metabolic ratio of N-desmethylclobazam clobazam in patients with one CYP2C19 2 mutated allele than in those with the wild-type genotype. 

Mehndiratta MM, Krishnamurthy M, Rajesh KN, Singh G. Clobazam monotherapy in drug naive adult patients with epilepsy. Seizure 2003 12 226-8. 

Bawden HN, Camfield CS, Camfield PR, Cunningham C, Darwish H, Dooley JM, Gordon K, Ronen G, Stewart J, van Mastrigt RCanadian Study Group for Childhood Epilepsy. The cognitive and behavioural effects of clobazam and standard monotherapy are comparable. Epilepsy Res 1999 33(2-3) 133-43. 

Remy C. Clobazam in the treatment of epilepsy a review of the literature. Epilepsia 1994 35(Suppl 5) S88-91. 

Sheth RD, Ronen GM, Goulden KJ, Penney S, Bodensteiner JB. Clobazam for intractable pediatric epilepsy. J Child Neurol 1995 10(3) 205-8. 

Sheth RD, Goulden KJ, Ronen GM. Aggression in children treated with clobazam for epilepsy. Clin Neuropharmacol 1994 17(4) 332-7. 

Rey E, Tran A, D Athis P, Chiron C, Dulac O, Vincent J, Pons G. Stiripentol potentiates clobazam in childhood epilepsy a pharmacological study. Epilepsia 1999 40(Suppl 7) 112-3. 

Contin RivaR, Albani F, Baruzzi A. Effect of felbamate on clobazam and its metabolite kinetics in patients with epilepsy. Ther Drug Monit ( 999)2, 604-8. 

Stiripentol was given marketing authorization in the European Union on 4 January 2007 for use in conjunction with clobazam and valproate as adjunctive therapy of refractory generalized tonic-clonic seizures in patients with severe myoclonic epilepsy in infancy (Dravet s syndrome) whose seizures are not adequately controlled with clobazam and valproate [284 ]. 

Epilepsy Treatment-emergent adverse events of clobazam were studied in an open-label trial in 267 patients with Lennox-Gastaut syndrome who received clobazam at dosages <80 mg per day [6 ]. In total, 82% of patients experienced treatment-emergent adverse event. The most common adverse events were upper respiratory tract infection (18.4%), fall (14.2%), pneumonia (13.9%), somnolence (12.7%), otitis media (12.0%), pyrexia (10.5%) and constipation (10.1%). The upper respiratory tract infection and pneumonia events occurred predominantly in paediatric patients. 

Ng YT, Conry J, PaoHcchi J, Kernitsky L, Mitchell W, Drummond R, et al. Long-term safety and efficacy of clobazam for Lennox-Gastaut syndrome interim results of an open-label extension study. Epilepsy Behav December 2012 25(4) 687-94. 

A 60-year-old male with known cerebral palsy and epilepsy on phenytoin and clobazam, presented to emergency department with a community-acquired pneumonia which was treated with levofloxacin. Phenytoin levels on admission were high and therefore phenytoin was omitted until levels were in the therapeutic range. Ten days into admission, he developed status epilepticus that necessitated intubation and ventilation for airway protection. Continuous EEC monitoring showed nonconvulsive status epilepticus. 

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