Clobazam

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Clobazam.jpg

[edit] MECHANISM OF ACTION

Clobazam, like other Benzodiazepines bind to specific sites on the gamma-aminobutyric acid-A (GABAA) receptors. This enhances the effects of GABA by increasing its affinity for the GABAA receptor.

Activation of the GABAA receptor, which is linked to a chloride channel (Cl-), results in an influx of Cl- into the neurone causing hyperpolarisation, which results in inhibitory effects on the central nervous system.

Benzodiazepines action on GABAA receptors appears to produce their anxiolytic, sedative, muscle relaxant, hypnotic and anticonvulsant actions.

[edit] INDICATIONS

  • Short-term, symptomatic relief of tension, anxiety and agitation. Note that anxiety or tension associated with the normal stress of everyday life usually does not require treatment with benzodizepines.
  • Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in adults and children 2 years of age or older.

[edit] DOSAGE

  • Anxiety Disorder: The usual anxiolytic dose for adults is 20-30 mg daily in divided doses or as a single dose given at night. in the elderly, 10-20 mg daily may be used.
    The lowest dose that can control symptoms should be used. After improvement of the symptoms, the dose may be reduced. Clobazam should not be used for longer than 4 weeks. Long term chronic use as an anxiolytic is not recommended ( prolonged periods of uninterrupted treatment may lead to dependence).
  • Adjunctive treatment of seizures associated with Lennox-Gastaut syndrome:
    • Patients ≤30 kg: Initiate at 5 mg daily and titrate as tolerated up to 20 mg daily.
    • Patients >30 kg: Initiate at 10 mg daily and titrate as tolerated up to 40 mg daily.
    • For doses above 5 mg/day administer in two divided doses
    • Dosage adjustment needed in following groups: geriatric patients, known CYP2C19 poor metabolizers, and in mild or moderate hepatic impairment.
    • Reduce dose, or discontinue drug gradually.

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Clobazam or to other benzodiazepines
  • Narrow angle glaucoma.
  • Pregnancy and breastfeeding
  • Myasthenia gravis (risk of aggravation of muscle weakness)
  • Severe respiratory failure or sleep apnea syndrome
  • Severe liver failure

[edit] WARNINGS AND PRECAUTIONS

  • Do not drive or do other dangerous activities after taking Clobazam until you feel fully awake.
  • Avoid drinking alcohol
  • Respiratory depression may occur in benzodiazepine overdose
  • Use of benzodiazepines can lead to dependence. This risk increases with dose and duration of treatment and in patients with a history of alcohol or drug abuse.
  • Withdrawal symptoms: Stopping Clobazam quickly may lead to seizures or withdrawal symptoms, such as headaches, trouble sleeping, anxiety, confusion, irritability. Clobazam should be discontinued gradually.
  • Paradoxical reactions like restlessness, agitation, irritability, aggressiveness, increased muscle spasticity, insomnia have been reported when using benzodiazepines. Should this occur, the use of the drug should be discontinued.
  • Amnesia: Benzodiazepines may induce anterograde amnesia leading to a partial or complete inability to recall the recent past. Anterograde amnesia may occur using higher therapeutic dosages, the risk increasing at higher dosages.
  • In the treatment of epilepsy with benzodiazepines including clobazam, consideration must be given to the possibility of a decrease in anticonvulsant efficacy (development of tolerance) in the course of treatment.
  • Serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been reported with Clobazam in both children and adults during the post-marketing period. Patients should be closely monitored for signs or symptoms of SJS/TEN, especially during the first 8 weeks of treatment initiation or when re-introducing therapy. Clobazam should be discontinued at the first sign of rash, unless the rash is clearly not drug-related.
  • Risk of Fetal Harm: Benzodiazepines can potentially cause fetal harm when administered to pregnant women.

[edit] METABOLISM

Clobazam is extensively metabolized in the liver primarly by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6 mainly to to the active N-desmethylclobazam. N-desmethylclobazam is further metabolized mainly by CYP2C19. The estimated mean elimination half-life is 36–42 hr for clobazam and 71–82 hr for N-desmethylclobazam. Clearance is lower in the elderly.

[edit] INTERACTIONS

  • Drugs metabolized by CYP2D6 (CYP2D6 substrates) like dextromethorphan: Lower doses of these drugs may be required when used concomitantly with Clobazam.
  • Strong or Moderate CYP2C19 Inhibitors (e.g., fluconazole, fluvoxamine, omeprazole, ticlopidine) can potentiate the effect of Clobazam. Dosage adjustment of Clobazam may be necessary
  • Alcohol: Increases blood levels of clobazam by about 50%. Avoid concomitant use
  • Benzodiazepines, including Clobazam, produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression (e.g. barbiturates, alcohol, sedatives, tricyclic antidepressants, antipsychotics, skeletal muscle relaxants, antihistamines or narcotic analgesics and anesthetics).

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category C (US). Clobazam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
  • Since benzodiazepines are found in the breast milk, benzodiazepines should not be given to breast feeding mothers.

[edit] SIDE EFFECTS

Most Common: constipation, somnolence or sedation, pyrexia, lethargy (lack of energy, apathy), and drooling.

See also WARNINGS AND PRECAUTIONS section

[edit] RELATED LINKS

[edit] REFERENCES

Sedatives / Hypnotics / Anxiolytics
Benzodiazepines Benzodiazepines (Anxiolytics)‎ Alprazolam (Xanax)   Bromazepam (Lexotan, Lexotanil)   Chlordiazepoxide (Librium)   Clobazam (Frisium)   Clorazepate (Tranxene)   Clotiazepam (Rizen, Tienor)   Delorazepam (EN)   Diazepam (Valium)   Etizolam (Depas)   Ketazolam   Lorazepam (Ativan, Control, Lorans, Tavor, Temesta)   Lormetazepam (Noctamid)   Nordazepam (Nordaz)   Oxazepam (Serepax)   Prazepam (Demetrin, Lysanxia)
Benzodiazepines (Hypnotics) Brotizolam (Lendormin, Bondormin, Dormex, Sintonal, Noctilan)   Clobazam (Frisium)   Estazolam (Esilgan, ProSom)   Etizolam (Depas, Pasaden, Etilaam, Etizest)   Flunitrazepam (Rohypnol)   Flurazepam (Dalmadorm, Dalmane, Felison, Flunox, Valdorm)   Ketazolam (Anseren, Anxon)   Lorazepam (Ativan, Control, Lorans, Tavor, Temesta)   Lormetazepam (Loramet, Minias, Noctamid, Pronoctan, Evamyl)   Midazolam (Dormicum, Hypnovel)   Nitrazepam (Mogadon, Nitrados, Numbon, Radedorm, Alodorm)   Nordazepam (Madar, Nordaz, Stilny, Tranxilium N)   Temazepam (Normison, Restoril, Tenox, Temaze)   Triazolam (Halcion, Hypam, Rilamir)
Non-Benzodiazepine Hypnotics Eszopiclone (Lunesta)   Zolpidem (Ambien, Stilnox, Hypnogen, Sanval, Stilnoct, Zoldem, Zolsana)   Zopiclone (Imovane, Zimovane)
Melatonin agonists Melatonin (Circadin)   Ramelteon (Rozerem)
Orexin agonists Suvorexant (Belsomra)