Clobazam

Introduction

Clobazam is a long-acting benzodiazepine with antiepileptic properties. It may be used as an adjunct with other antiepileptics in the treatment of epilepsy including seizzures associated with the Lennox-Gastaut syndrome, although its use may be limited by the development of tolerance or sedation. It is also used in the short-term treatment of acute anxiety.

Mechanism of Action

• Clobazam is a benzodiazepine.
• Gama-Aminobutyric acid (GABA) is an inhibitory neurotransmitter, acting on the GABA receptors in the central nervous system (CNS), thus inhibiting the nerve impulses.
• It acts on the benzodiazepine receptors in the brain and the spinal cord. Benzodiazepine receptors in the CNS are linked with GABA receptors as a complex.
• Clobazam by binding to the benzodiazepine receptors results in activation of the GABA-benzodiazepine receptor complex, resulting in inhibition of nerve impulses, overall depression of brain and spinal cord.
• Thus Clobazam use helps to promote muscle relaxation, reduce anxiety, control of convulsions and promote sleep.

Generic Name 藥名	HA Code 藥物代碼	Classification藥物分類
Clobazam Tablet 10 mg	CLOB01	P1S1S3 & Part 1 Dangerous Drug
Alprazolam Tablet 0.5 mg	ALPR02	DDA

Dosage

Epilepsy and myoclonus

By mouth ADULT: initially 1 mg at night for 4 nights, Dose to be increased over 2 to 4 weeks usual dose 4 to 8 mg daily, adjusted according to response ELDERLY: initially 500 micrograms at night for 4 nights dose to be increased over 2 – 4 weeks, usual dose 4 – 8 mg daily, adjusted according to response ADMINISTRATION IN CHILDREN: The following usual maintenance doses according to age: 1 to 5 years: 1 to 3 mg daily in 3 divided doses 5 to 12 years: 3 to 6 mg daily in 3 divided doses Older children may be given the usual adult dose

Side Effects

Sedative drugs, including alprazolam, have been associated with an increased risk of death.

Possible side effects include:

Very common (>10% of incidence) or Common (1-10% of incidence)	Amnesia and concentration problems Ataxia (especially in the elderly) Confusion (especially in the elderly) Dizziness Drowsiness Muscle weakness
Infrequent(0.1 -1% of incidence)	Dysphoria煩躁不安 Increased frequency of seizures Personality changes Behavioral disturbances
Rare (<0.1% of incidence)	Dysarthria Blood disorders Jaundice Respiratory depression hypersensitivity reactions Paradoxical reactions Suicidal ideation Visual disturbances on long-term treatment

Overdosage can produce CNS depression and coma.

Paradoxical reactions

Although unusual, the following paradoxical reactions have been shown to occur:

• aggression, rage
• mania, agitation, and restlessness
• hallucinations, inappropriate behavior
• twitches and tremor

Pharmacokinetics

Oral bioavailability	Clonazepam is well absorbed after oral doses.
Onset of action	Peak plasma concentrations occur within 1 to 4 hours of a dose.
Metabolism	Clonazepam is metabolized in the liver
Elimination half-life	Clonazepam is eliminated in the urine. Its elimination half-life ranges from about 20 to 40 hours, and occasionally more.

Drug Management

Monitoring

• Changes in mood, the development or worsening depression, and/or any thoughts or *Behaviour of suicide.
• Blood pressure and respiratory rate should be monitored
• An increased risk of falls and fractures in elderly, so fall prevention is needed
• Some patients develop blood dyscrasias, and have raised liver enzymes, so periodic blood counts and liver function tests are recommended

Dependence and Withdrawal

• One-third of individuals treated with benzodiazepines for longer than 4 weeks develop a dependence on the drug and experience a withdrawal syndrome upon dose reduction.
• Tolerance develops to the anticonvulsant effects of clonazepam.
• Clonazepam should therefore be withdrawn by tapering the dose to minimize occurrence of withdrawal symptoms.

Drug interaction

• Enhanced sedation effects may occur if clonazepam is given with other drugs that have CNS-depressant properties; these include alcohol, antidepressants, sedative antihistamines, antipsychotics, and opioid analgesics.
• Clonazepam decreases the level of carbamazepine, and likewise, clonazepam’s level is reduced by carbamazepine.
• Clonazepam may affects levels of phenytoin. In turn, phenytoin may lower clonazepam plasma levels by increasing the speed if clonazepam clearance by about 50% and decreasing its half-life by 31%.
• Antifungals, such as ketoconazole, may inhibit the metabolism of clonazepam, and increase its side-effect.