Administration 
Clorazepate dipotassium is administered orally in 1-4 doses daily.
Dosage
Dosage of clorazepate dipotassium must be carefully individualized, and the smallest effective dosage should be used (especially in geriatric or debilitated patients and in those with liver disease or low serum albumin) to avoid oversedation. Since the metabolites of clorazepate have long elimination half-lives, time to reach steady-state plasma concentrations should be considered when dosage adjustments are made. In patients who have received prolonged (e.g., for several months) clorazepate dipotassium therapy, abrupt discontinuance of the drug should be avoided since manifestations of withdrawal can be precipitated; if the drug is to be discontinued in such patients, it is recommended that dosage be gradually tapered. It is particularly important that the drug not be discontinued abruptly in patients with a history of a seizure disorder since seizures may be precipitated.
Anxiety Disorders
For the symptomatic treatment of anxiety, the usual adult dosage of clorazepate dipotassium is 30 mg daily in divided doses. Alternatively, a single daily dose may be given at bedtime, but an initial bedtime dose should not exceed 15 mg. Dosage should be gradually adjusted to 15-60 mg daily. In geriatric or debilitated patients, clorazepate dipotassium therapy should be initiated with 7.5-15 mg daily in divided doses or as a single bedtime dose.
Acute Alcohol Withdrawal
For the management of agitation associated with acute alcohol withdrawal, 30 mg of clorazepate dipotassium is given initially, followed by an additional 30-60 mg in divided doses on day 1. The maximum dosage recommended by the manufacturer is 90 mg daily. On day 2, 45-90 mg of clorazepate dipotassium is given in divided doses; 22.5-45 mg is given in divided doses on day 3; 15-30 mg is given in divided doses on day 4. Thereafter, daily dosage should be gradually reduced to 7.5-15 mg of clorazepate dipotassium and discontinued when the patient's condition is stable.
Partial Seizures
As adjunct in the treatment of partial seizures in adults and children older than 12 years of age, clorazepate dipotassium may be given in an initial dosage of up to 7.5 mg 3 times daily; dosage should be increased by no more than 7.5 mg per week and should not exceed 90 mg/day. As an adjunct in the treatment of partial seizures in children 9-12 years of age, the drug may be given in an initial dosage of up to 7.5 mg twice daily; dosage should be increased by no more than 7.5 mg per week and should not exceed 60 mg/day.
Precautions
A boxed warning has been included in the prescribing information for all benzodiazepines describing the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions associated with all drugs in this class.900 Abuse and misuse can result in overdose or death, especially when benzodiazepines are combined with other medicines, such as opioid pain relievers, alcohol, or illicit drugs.900 Frequent follow-up with patients receiving benzodiazepines is important.900 Reassess patients regularly to manage their medical conditions and any withdrawal symptoms.900 Clinicians should assess a patient's risk of abuse, misuse, and addiction. 900 Standardized screening tools are available ([Web]).900 To reduce the risk of acute withdrawal reactions, use a gradual dose taper when reducing the dosage or discontinuing benzodiazepines.900 Take precautions when benzodiazepines are used in combination with opioid medications.900
Clorazepate dipotassium shares the toxic potentials of the benzodiazepines, and the usual precautions of benzodiazepine administration should be observed. (See Cautions in the Benzodiazepines General Statement 28:24.08.)
Pediatric Precautions
Safety and efficacy of clorazepate dipotassium in children younger than 9 years of age have not been established.
Chemistry and Stability
Chemistry
Clorazepate dipotassium is a benzodiazepine. The drug occurs as a fine, light-yellow powder and is very soluble in water and very slightly soluble in alcohol.
Stability
Clorazepate dipotassium tablets should be stored in tight, light-resistant containers at 15-30°C. Clorazepate dipotassium is unstable in water and reportedly degrades in the presence of moisture, resulting in the formation of carbon dioxide gas. Because formation of carbon dioxide may result in rapid disintegration of commercially available tablets of the drug, it has been recommended that desiccant packets be kept in original containers of clorazepate dipotassium tablets; consideration also should be given to using desiccant packets when dispensing a large number of tablets in a multiple-dose container.
Additional Information
For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, chronic toxicity, acute toxicity, drug interactions, laboratory test interferences, and dosage and administration of clorazepate, see the Benzodiazepines General Statement 28:24.08.
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