Chlordiazepoxide (Librium® and generic) is a benzodiazepine that is used as an anxiolytic. It is a Schedule IV drug.
(Historical note: Chlordiazepoxide was the first benzodiazepine to be introduced into clinical use in 1959.)
Here is basic information about this medication.
FDA-approved indications
1. Generalized anxiety disorder
2. Short-term relief of symptoms of anxiety
3. Withdrawal symptoms of acute alcoholism
4. Preoperative apprehension and anxiety
Pharmacokinetics
Half-life
– 24 to 48 hours
– For its active metabolite N-desmethyldiazepam (also known as nordiazepam): about 100 hours (range 36 to 200 hours).
Metabolism
Primarily by oxidation in the liver.
Clinical tips
– The duration of effect of chlordiazepoxide is often less than what might be expected based on its long half-life. This is why despite its long half-life and the even longer half-life of its metabolite, it is typically given three to four times a day.
– When given orally, chlordiazepoxide, like lorazepam, has an intermediate speed of absorption and onset of action. But, when given intramuscularly, unlike lorazepam, its absorption is slow and erratic (Greenblatt et al., 1974).
Bottom line: Chlordiazepoxide does not seem to offer any advantages over other benzodiazepines. It is not commonly used in clinical practice.
Dosage
A. Adults
Relief of mild and moderate anxiety disorders and symptoms of anxiety
Usual: 5–10 mg, 3-4 times daily
Relief of severe anxiety disorders and symptoms of anxiety
Usual: 20 to 25 mg, 3 to 4 times daily
Preoperative apprehension and anxiety
On days preceding surgery, 5 to 10 mg orally, 3 or 4 times daily. If used as preoperative medication, 50 to 100 mg IM 1 hour prior to surgery.
Withdrawal symptoms of acute alcoholism
Usually parenteral form is used initially. Alternatively, initial dose of 50 to 100 mg orally, repeated as needed until agitation is controlled, up to 300 mg/day may be prescribed. Dosage should then be reduced to maintenance levels.
B. Geriatric patients, or in the presence of debilitating disease
Usual: 5 mg, 2-4 times daily
C. Pediatric Patients (6 years or older)
Initiate with the lowest possible dose and increase as required
Usual: 5 mg, 2-4 times daily or 10 mg, 2-3 times daily
D. Dosage in patients with hepatic or renal impairment: See Prescribing Information
Dosage forms and strengths
Capsules: 5 mg, 10 mg, 25 mg
Also available for intramuscular injection (but see Clinical tips above).
Drug interactions
Respiratory depression, possibly serious, may occur when any benzodiazepine is used along with opioids.
Boxed (“Black box”) warning
Quoted from the official Prescribing Information: “Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.”
Potential adverse effects
As noted above, respiratory depression, possibly serious, may occur when any benzodiazepine is used along with opioids.
Other potential adverse effects: drowsiness, ataxia, confusion, skin rash, edema, menstrual irregularities, nausea, constipation, extrapyramidal symptoms, increased libido, decreased libido, changes in EEG patterns (low-voltage fast activity).
Rarely, blood dyscrasias (including agranulocytosis) and hepatic impairment have been reported. The Prescribing Information recommends periodically checking blood counts and hepatic function tests in patients on longer-term treatment with chlordiazepoxide.
Important! Please refer to the Prescribing Information for a complete discussion of dosage, administration, warnings and precautions, contraindications, and use in special populations.
Related Pages
Important facts about benzodiazepines
Psychiatric medications with a long half-life
References
Chlordiazepoxide Prescribing Information
Greenblatt DJ, Shader RI, Koch-Weser J. Slow absorption of intramuscular chlordiazepoxide. N Engl J Med. 1974 Nov 21;291(21):1116-8. PubMed PMID: 4416981.
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