Clorazepate

Oral
Alcohol withdrawal syndrome, Epilepsy

Oral
Anxiety

Initiate at lower dose and adjust slowly.

Hypersensitivity (cross-sensitivity with other benzodiazepines may occur); narrow-angle glaucoma. Patients with depressive or psychotic disorders. child <9 yr. Pregnancy; lactation.

Elderly, debilitated patients; hepatic disease, alcoholics; renal impairment; resp disease; impaired gag reflex; patients experiencing apnoea during sleep; operating machines or driving; patients on CNS depressant or psychoactive drug therapy; depression, esp those with suicidal tendencies; history of drug-dependence.

Jaundice, hepatic necrosis; extrapyramidal disorders; acute attacks of porphyria in porphyric patients, hypotension; drowsiness, fatigue, ataxia, lightheadedness, memory impairment, insomnia, anxiety, headache, depression, slurred speech, confusion, nervousness, dizziness, irritability; rash; decreased libido; xerostomia, constipation, diarrhoea, decreased salivation, nausea, vomiting, increased or decreased appetite; dysarthria, tremor; blurred vision, diplopia.

PO: D

Somnolence, impaired coordination, slurred speech, confusion, coma, and diminished reflexes, hypotension, seizures, respiratory depression and apnea also may occur. Treatment is symptomatic and supportive. Flumazenil, a benzodiazepine antagonist, may be used after evaluating the benefits and risks. If recent ingestion, emesis or gastric lavage followed by activated charcoal and a saline cathartic to remove any remaining drug. Monitor pulse, respiration and blood pressure. Admin IV fluids and maintain an adequate airway. IV norepinephrine or metaraminol may be used for hypotension. Haemodialysis is not likely to be useful.

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.

Description: 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.
Pharmacokinetics:
Absorption: Following oral administration, complete absorption of the dose from the small intestine.
Distribution: Crosses the placenta and small amounts appear in the urine.
Metabolism: Rapidly activated to desmethyldiazepam via decarboxylation prior to absorption at low stomach pH; hepatic (as active oxazepam).
Excretion: Via urine.

Store at 15-30°C.

Hypnotics & Sedatives / Anticonvulsants