CLORAZEPATE

Mechanism of Action :

Clorazepate binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron within the central nervous system, limbic system, reticular formation resulting to an increase in chloride ion permeability which further leads to hyperpolarisation and stabilisation.
Onset: 1-2 hrs.
Duration: 8-24 hrs.

Indication, Dosage and Frequency

Oral
ANXIETY
Adult: 7.5 mg tid.
Elderly: and debilitated patients: Initiate at lower dose and adjust slowly.
ALCOHOL WITHDRAWAL SYNDROME
Adult: 90 mg daily in divided doses.
Child: 9-12 yr old: 60 mg in divided doses.
Elderly: and debilitated patients: Initiate at lower dose and adjust slowly.
EPILEPSY
Adult: 90 mg daily in divided doses.
Child: 9-12 yr old: 60 mg in divided doses.
Elderly: and debilitated patients: Initiate at lower dose and adjust slowly.

Interactions :

Potentiates CNS effects of narcotic analgesics, barbiturates, phenothiazines, ethanol, antihistamines, MAO Inhibitors, sedative-hypnotics, cyclic antidepressants. CYP3A4 inhibitors eg, amprenavir, cimetidine, ciprofloxacin, clarithromycin may increase serum conc and toxicity of clorazepate. Carbamazepine, rifampin and rifabutin may decrease clorazepate therapeutic effects by enhancement of clorazepate metabolism.
Grapefruit juice increases serum conc or toxicity risk of clorazepate. Herbs or nutraceuticals eg, valerian, St. John's wort, kava kava and gotu kola may increase CNS depression upon concomitant admin with clorazepate.