Clonazepam

Class: anticonvulsant – benzodiazepine

Indications (NB some may be unlicensed): epilepsy, convulsions, sedation, agitation, restless leg syndrome, neuropathic pain, dyspnoea, hiccups, panic disorder (with or without agoraphobia) resistant to antidepressant therapy (unapproved); generalised anxiety disorder (unapproved) but see notes; prevention of seizures in palliative care; treatment of prolonged grand mal seizures or status epilepticus in palliative care; myoclonus (unapproved); agitation or confusion in the last days of life (usually in conjunction with an antipsychotic) (unapproved)

Contraindications/cautions: avoid sudden withdrawal, respiratory depression; acute pulmonary insufficiency; sleep apnoea syndrome; marked neuromuscular respiratory weakness including unstable myasthenia gravis

Adverse reactions: common: fatigue, drowsiness (at higher doses); less common: respiratory depression, incontinence, co-ordination problems, disinhibition, increase in salivation, confusion

Metabolism/clearance: metabolised by enzyme CYP3A mainly in the liver

Interactions:

• increased clinical effect/toxicity of clonazepam (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. clarithromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole
• decreased clinical effect/toxicity of clonazepam (due to decreased blood concentrations) may occur with some CYP metabolism enzyme inducers (see above) e.g. carbamazepine, phenobarbitone, phenytoin, rifampicin, St John’s wort
• additive CNS effects with other CNS depressants e.g. opioids (e.g. morphine), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline), alcohol

Mechanism of action: Benzodiazepines act on GABA receptors in the central nervous system (CNS) to enhance activity of the inhibitory neurotransmitter GABA resulting in CNS depression

Onset: oral (seizure control): 20 to 40 minutes

Half life: > 30 hours (18 to 45 hours)

Notes:

• a long acting benzodiazepine so difficult to titrate to response
• benzodiazepines may reduce dyspnoea by anxiolytic and sedative effects
• approximate equivalent oral anxiolytic/sedative doses:

Pharmacological properties of benzodiazepines