Anxiety Disorders, Preoperative Anxiolysis, and Alcohol Withdrawal 
Chlordiazepoxide shares the actions of other benzodiazepines and is used for the management of anxiety disorders or for short-term relief of symptoms of anxiety, preoperatively to relieve anxiety and tension, and for the management of agitation associated with acute alcohol withdrawal. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic. The efficacy of chlordiazepoxide for long-term use (i.e., for longer than 4 months) has not been established, and the need for continued therapy with the drug should be periodically reassessed.
Chlordiazepoxide hydrochloride, as the fixed-combination with amitriptyline, also has been used in the management of depression associated with severe anxiety.
Peptic Ulcer Disease, Irritable Bowel Syndrome, Acute Enterocolitis
Chlordiazepoxide hydrochloride, as the fixed-combination with clidinium bromide, has been used as an adjunct in the treatment of peptic ulcer disease and in the treatment of functional disturbances of GI motility such as irritable bowel syndrome and acute enterocolitis. For further information on the treatment of these disorders, see Uses in Clidinium 12:08.08.
Administration
Chlordiazepoxide and its hydrochloride salt are usually administered orally in 3 or 4 doses daily. After dosage has been stabilized, most clinicians believe that the drug may be administered in 1 or 2 doses daily. Although chlordiazepoxide hydrochloride also has been administered parenterally†, a parenteral dosage form of the drug is no longer commercially available in the US.101
Dosage
On the basis of molecular weight, 89 mg of chlordiazepoxide is equivalent to 100 mg of chlordiazepoxide hydrochloride; however, the manufacturer of chlordiazepoxide base claims that chlordiazepoxide and its hydrochloride salt may be used interchangeably on a milligram-for-milligram basis.
Dosage must be 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 chlordiazepoxide and its metabolites have long elimination half-lives, time to reach steady-state plasma concentrations should be considered when dosage adjustments are made.
Commercially available preparations containing chlordiazepoxide or its hydrochloride salt in fixed combination with an anticholinergic (clidinium) or an antidepressant (amitriptyline) generally should not be used as initial therapy in patients who require both drugs. Dosage should first be adjusted by administering each drug separately. If it is determined that the optimum maintenance dosage corresponds to the ratio in a commercial combination preparation, such a product may be used. When dosage adjustment is necessary, the drugs should be administered separately.
In patients who have received prolonged (e.g., for several months) chlordiazepoxide hydrochloride 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.
Adult Dosage
Anxiety Disorders
For the management of mild to moderate anxiety, the usual adult oral dosage of chlordiazepoxide hydrochloride is 5-10 mg 3 or 4 times daily. For severe anxiety, 20-25 mg may be given orally 3 or 4 times daily.
Preoperative Anxiolysis
To relieve anxiety and tension preoperatively in adults, the manufacturer recommends that 5-10 mg of chlordiazepoxide hydrochloride be given orally 3 or 4 times daily for several days preceding surgery.
Acute Alcohol Withdrawal
For the management of agitation associated with acute alcohol withdrawal, the initial oral dose is 50-100 mg; doses are repeated until agitation is controlled.
The manufacturers state that in acute alcohol withdrawal, oral dosage should not exceed 300 mg daily; however, some clinicians have used chlordiazepoxide hydrochloride dosages of 600-800 mg daily to control symptoms without adverse effects. After agitation is controlled, the drug should be withdrawn slowly.
Peptic Ulcer Disease, Irritable Bowel Syndrome, Acute Enterocolitis
When chlordiazepoxide hydrochloride is used in fixed combination with clidinium bromide, the usual adult maintenance dosage of chlordiazepoxide hydrochloride is 5 or 10 mg given orally 3 or 4 times daily, administered before meals and at bedtime.
Pediatric Dosage
Because of the unpredictable response of children to CNS drugs, chlordiazepoxide therapy should be initiated with the lowest dosage and increased as required.
Anxiety Disorders, Preoperative Anxiolysis, and Alcohol Withdrawal
The usual oral dosage of chlordiazepoxide hydrochloride in children older than 6 years of age is 5 mg 2-4 times daily; the initial dosage should not exceed 10 mg daily. If necessary, dosage for children may be increased to 10 mg 2 or 3 times daily. Alternatively, some clinicians have recommended a pediatric oral dosage of 0.5 mg/kg daily or 15 mg/m2 daily, given in 3 or 4 divided doses.
Dosage in Geriatric or Debilitated Patients
Geriatric or debilitated patients may receive 5 mg of chlordiazepoxide hydrochloride orally 2-4 times daily; the initial dose should not exceed 10 mg daily. When chlordiazepoxide hydrochloride is used in fixed combination with clidinium bromide, the recommended initial geriatric dosage of chlordiazepoxide hydrochloride is 10 mg daily, which may be increased gradually as needed and tolerated. (See Cautions: Geriatric Precautions.)
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
Chlordiazepoxide shares the toxic potentials of the benzodiazepines, and the usual precautions of benzodiazepine administration should be observed. (See Cautions in the Benzodiazepines General Statement.) The precautions and contraindications associated with antimuscarinics or tricyclic antidepressants also should be considered when commercially available preparations containing chlordiazepoxide or its hydrochloride salt in fixed combination with clidinium or amitriptyline are used. (See Cautions in the Antimuscarinics/Antispasmodics General Statement 12:08.08 and also see Cautions in the Tricyclic Antidepressants General Statement 28:16.04.28.)
Pediatric Precautions
Safety and efficacy of orally administered chlordiazepoxide or chlordiazepoxide hydrochloride in children younger than 6 years of age have not been established.
Safety and efficacy of the fixed-combination preparation containing chlordiazepoxide hydrochloride and clidinium bromide in pediatric patients have not been established.
Geriatric Precautions
Although safety and efficacy of chlordiazepoxide in geriatric patients have not been studied specifically to date, one manufacturer states that geriatric adults may be especially prone to adverse effects such as drowsiness, ataxia, and confusion when receiving chlordiazepoxide hydrochloride in fixed combination with clidinium bromide. These adverse effects usually can be prevented by proper dosage adjustment. Therefore, it is recommended that the initial dosage of this combination in geriatric patients be selected carefully and gradually increased if needed and tolerated. However, these adverse effects occasionally have been observed in geriatric patients receiving the lower range of the usual dosage of this combination.
Chemistry and Stability
Chemistry
Chlordiazepoxide is a benzodiazepine. Chlordiazepoxide occurs as a yellow, practically odorless, crystalline powder and has solubilities of less than 0.1 mg/mL in water and approximately 20 mg/mL in alcohol at 25°C. Chlordiazepoxide hydrochloride occurs as a white or practically white, odorless, crystalline powder and is soluble in water and in alcohol and slightly soluble in propylene glycol. Chlordiazepoxide has a pKa of 4.8.
Stability
Chlordiazepoxide tablets and chlordiazepoxide hydrochloride capsules must be protected from light.
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 chlordiazepoxide, see the Benzodiazepines General Statement 28:24.08.
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