Brand name
- Librax®, Librium®, Limbitrol®
Drug Class
- Benzodiazepines
- Anxiolytic
- Sedative
Preparations
Chlordiazepoxide Hydrochloride Capsules:
- 5 mg, 10 mg, 25 mg
Chlordiazepoxide and Amitriptyline Hydrochloride film-coated Tablets:
- 5 mg Chlordiazepoxide and 12.5 mg Amitriptyline Hydrochloride
- 10 mg Chlordiazepoxide and 25 mg Amitriptyline Hydrochloride
Chlordiazepoxide Hydrochloride and Clidinium Bromide Capsules:
- 5 mg Chlordiazepoxide Hydrochloride and 2.5 mg Clidinium Bromide
Indications
1. Alcohol Withdrawal:
- Relief of agitation and tremor and prevention or symptomatic relief of delirium tremens and hallucinations associated with acute alcohol withdrawal.
2. Anxiety and Depressive Disorders:
3. Preoperative Anxiolytics:
4. Peptic Ulcer Disease, Irritable Bowel Syndrome, and Acute Enterocolitis
Pharmacology
- Inhibition of GABA neurotransmitter action in CNS
- Site and mechanism of action within the CNS: Appear to involve a macromolecular complex that includes GABAA receptors, high-affinity benzodiazepine receptors, and chloride channels.
Metabolism
Absorption
- Bioavailability: GI tract
Distribution
- Extent:
- Widely distributed into body tissues & cross the blood-brain barrier
- Excrete into milk and crosses the placenta
- Plasma Protein Binding: highly bound to plasma proteins
Elimination
- Metabolism: Mainly in the liver
- Elimination Route: principally in urine
- Half-life: 5–30 hours
Special Populations
- Half-lives of chlordiazepoxide is prolonged in:
- Geriatric patients
- Patients with liver disease
- Patients on hemodialysis
Dosing
Pediatric Patients
1. Anxiety Disorders in children ≥6 years of age:
- Usual dosage: 5 mg 2–4 times daily or 0.5 mg/kg daily or 15 mg/m2 daily in 3 or 4 divided doses.
- Maximum initial dosage: 10 mg daily
Adults
1. Alcohol Withdrawal:
- Initial dose: 50-100 mg dose (repeat dose until agitation is controlled)
- Max dose: 300 mg daily
2. Anxiety and Depressive Disorders:
- Monotherapy:
- Maximum initial dose: 10 mg daily
- Mild to moderate anxiety: 5–10 mg 3 or 4 times daily
- Severe anxiety: 20–25 mg 3 or 4 times daily
- Chlordiazepoxide/Amitriptyline Combination Therapy:
- Initial dose: 30 or 40 mg/75 or 100 mg daily in divided doses.
3. Preoperative Anxiolytic:
- 5–10 mg 3 or 4 times daily (for several days preceding surgery.)
4. Peptic Ulcer Disease, Irritable Bowel Syndrome, and Acute Enterocolitis:
- Maintenance dosage: 5 or 10 mg 3 or 4 times daily
Special Populations
- Hepatic Impairment: Reduce dosage to the smallest effective dosage
- Renal Impairment: No specific dosage recommendations
- Geriatric or Debilitated Patients: Reduce initial dosage and use the smallest effective dosage
Drug Interactions
- Antacids (aluminum- and magnesium-containing): Possible decrease in rate chlordiazepoxide absorption
- Anticoagulants
- Cimetidine: Decreased clearance and increased plasma concentrations of chlordiazepoxide
- CNS depressants (e.g., alcohol, anticonvulsants, psychotropic drugs, sedatives)
- Psychotropic agents: Concomitant use is not recommended.
- Disulfiram: Reduce chlordiazepoxide dosage
- Levodopa: decreased control of parkinsonian symptoms
- Test for pregnancy (Gravindex test): Possible false-positive reaction
- Tests for urinary alkaloids: falsely elevated readings
- Tests for urinary 17-ketosteroids: falsely elevated or decreased concentrations
Adverse Effects
>10%:
- Ataxia, drowsiness, memory impairment, sedation, muscle weakness, rash, decreased libido, menstrual disorders, xerostomia, salivation decreased, increased/decreased appetite, weight gain/loss, micturition difficulties
1-10%:
- Confusion, dizziness, disinhibition, akathisia, dermatitis, hypotension, increased salivation, sexual dysfunction, incontinence, rigidity, tremor, muscle cramps, tinnitus, nasal congestion
Contraindications
- Hypersensitivity to chlordiazepoxide, other benzodiazepines, or any ingredient in the formulation.
- Acute angle-closure glaucoma
Pregnancy and Breastfeeding
- Pregnancy: Category D
- Lactation: not recommended in nursing mothers.
Precautions
1. CNS Effects:
- Performance of activities requiring mental alertness and physical coordination may be impaired.
- Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.
- Paradoxical reactions (e.g., excitement, stimulation, acute rage) reported in psychiatric patients and in hyperactive aggressive children.
2. Fetal/Neonatal Morbidity: Increase risk of congenital malformations in infants of mothers receiving chlordiazepoxide during the first trimester of pregnancy >>> Usage during the first trimester almost always should be avoided.
3. Usage in patients with Psychiatric problems: should not be used in patients with depressive neuroses or psychotic reactions in which anxiety is not prominent.
4. Abuse Potential:
- Tolerance, psychologic dependence, and physical dependence might occur following prolonged use
- Patients with a history of drug or alcohol dependence or abuse are at risk of habituation or dependence
5. Withdrawal Syndrome:
- Abrupt discontinuance may result in symptoms of withdrawal
- Symptoms may be relieved by tapering the dosage.
6. Suicide possibility: Use with caution in depressed patients; potential for suicidal tendencies.
7. Use of Fixed Combinations: When used in fixed combination with clidinium bromide or amitriptyline hydrochloride, consider the cautions, precautions, and contraindications associated with the concomitant agent.
8. Usage in Porphyria: because of exacerbation of porphyria use with caution
9. Laboratory Testing: Blood dyscrasias (including agranulocytosis), jaundice, and hepatic dysfunction might occur occasionally >>> Monitor blood counts and liver function tests periodically during prolonged therapy.
10. Caution in Pediatric Usage:
- Not recommended in children <6 years
- Response of children to CNS drugs is unpredictable >>>initiate therapy at low dosage and increase as required.
- Monitor hyperactive, aggressive children for paradoxical reactions (e.g., excitement, stimulation, acute rage)
11. Caution in Geriatric Usage: Prolonged elimination of chlordiazepoxide and its metabolites >>> possibility of increased risk of drowsiness, ataxia, and confusion; generally preventable by proper dosage adjustment
12. Hepatic Impairment: Prolonged elimination of chlordiazepoxide and its metabolites >>> Use with caution.
13. Renal Impairment: Use with caution.
14. Alcohol usage: Advice to patients about importance of not consuming alcoholic beverages.
Section
This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.