Chlordiazepoxide Hydrochloride – Librax® – Libriumv® – Limbitrol®

• Librax®, Librium®, Limbitrol®

• Benzodiazepines
• Anxiolytic
• Sedative

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

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

• 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.

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

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

1. Antacids (aluminum- and magnesium-containing): Possible decrease in rate chlordiazepoxide absorption
2. Anticoagulants
3. Cimetidine: Decreased clearance and increased plasma concentrations of chlordiazepoxide
4. CNS depressants (e.g., alcohol, anticonvulsants, psychotropic drugs, sedatives)
5. Psychotropic agents: Concomitant use is not recommended.
6. Disulfiram: Reduce chlordiazepoxide dosage
7. Levodopa: decreased control of parkinsonian symptoms
8. Test for pregnancy (Gravindex test): Possible false-positive reaction
9. Tests for urinary alkaloids: falsely elevated readings
10. Tests for urinary 17-ketosteroids: falsely elevated or decreased concentrations

>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

1. Hypersensitivity to chlordiazepoxide, other benzodiazepines, or any ingredient in the formulation.
2. Acute angle-closure glaucoma

• Pregnancy: Category D
• Lactation: not recommended in nursing mothers.

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.