CHLORDIAZEPOXIDE CAPSULES 10MG

Indications

• Anxiety disorders
• Alcohol withdrawal syndrome
• Preoperative sedation
• Muscle spasms

Dosage

Children: Refer to the BNF for Children for appropriate pediatric dosing information.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Chlordiazepoxide exerts its effects by binding to the benzodiazepine site on the GABA-A receptor. This results in an increase in the frequency of chloride channel opening in response to GABA, which enhances the inhibitory effects of GABA in the central nervous system. The resultant hyperpolarization of neuronal membranes leads to the anxiolytic, sedative, muscle relaxant, and anticonvulsant effects associated with this drug.

Pharmacodynamics

Chlordiazepoxide has a rapid onset of action, with effects typically observed within 30 minutes to 1 hour after oral administration. It exhibits dose-dependent effects, where lower doses primarily provide anxiolytic effects, while higher doses can lead to sedation or muscle relaxation. Tolerance may develop with prolonged use, necessitating dose adjustments or cessation of therapy.

Pharmacokinetics

Chlordiazepoxide is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 2 hours after oral administration. It is extensively metabolized in the liver, primarily through oxidation, and has active metabolites that contribute to its therapeutic effects. The elimination half-life of chlordiazepoxide ranges from 5 to 30 hours, with an average of about 24 hours. The drug and its metabolites are excreted mainly in the urine.

Contra-indications

• Myasthenia gravis
• Severe respiratory insufficiency
• Severe hepatic impairment
• Sleep apnoea syndrome
• Known hypersensitivity to chlordiazepoxide or other benzodiazepines

Adverse effects

• Drowsiness
• Dizziness
• Confusion
• Ataxia
• Dependence
• Withdrawal symptoms
• Paradoxical reactions (e.g., increased anxiety, agitation)

Interactions

• Chlordiazepoxide with antiepileptics may affect their concentration, though the specific effects are unknown
• Co-administration with fosphenytoin may affect concentration, details unknown
• Phenytoin may also interact with chlordiazepoxide, affecting its concentration
• Rifampicin may decrease the exposure of chlordiazepoxide

Precautions

• Caution in patients with a history of substance abuse
• Use with caution in elderly patients due to increased sensitivity
• Monitor for signs of dependence and withdrawal
• Caution in patients with a history of depression or suicidal ideation

Pregnancy

Chlordiazepoxide is not recommended during pregnancy due to potential risks to the fetus, including the possibility of congenital malformations and neonatal withdrawal syndrome.

Breast-feeding

Chlordiazepoxide is excreted in breast milk and may affect a nursing infant; caution is advised if used while breastfeeding.

Storage

Store in a cool, dry place, away from direct light. Keep out of reach of children.

Formulations

• Oral tablets

Indications

• Short-term management of anxiety disorders
• Treatment of alcohol withdrawal symptoms
• Management of muscle spasms
• Adjunctive treatment in certain mental health disorders

Dosage

Children: Refer to BNF for Children for appropriate dosing information.

Adults: For anxiety: 10 mg three times a day, increased if necessary to 60-100 mg daily in divided doses. For alcohol withdrawal: 10-50 mg four times a day, with dose adjustments based on clinical response.

Mechanism of action

Chlordiazepoxide enhances the action of GABA, the primary inhibitory neurotransmitter in the brain. By binding to the GABA-A receptor, it increases the frequency of chloride channel opening, leading to hyperpolarization of the neuron. This reduces neuronal excitability, contributing to its anxiolytic, sedative, muscle relaxant, and anticonvulsant effects.

Pharmacodynamics

Chlordiazepoxide exhibits anxiolytic, sedative, muscle relaxant, anticonvulsant, and amnesic properties. Its effects are dose-dependent, with higher doses leading to increased sedation and risk of respiratory depression. The onset of action is typically within 1-2 hours, with a duration of effect ranging from several hours to a day, depending on the dose and individual metabolism.

Pharmacokinetics

Chlordiazepoxide is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring about 1-2 hours after oral administration. It undergoes extensive hepatic metabolism, primarily through cytochrome P450 enzymes, resulting in active metabolites. The drug has a half-life ranging from 5 to 30 hours, depending on individual factors, and is excreted primarily in the urine. The pharmacokinetics may be altered in individuals with hepatic impairment, necessitating dose adjustments.

Contra-indications

• Chronic psychosis
• Severe respiratory depression

Adverse effects

• Menstruation irregularities
• Urinary incontinence
• Decreased alertness
• Anxiety
• Ataxia (more common in elderly)
• Confusion
• Gastrointestinal disorders
• Hepatic disorders (common in elderly)
• Depression
• Dizziness
• Drowsiness
• Hyperprolactinaemia
• Peripheral oedema
• Dysarthria
• Fatigue
• Headache
• Hypotension
• Altered mood
• Photosensitivity reaction
• Suicidal thoughts
• Muscle weakness
• Nausea
• Respiratory depression (particularly with high doses)
• Anterograde amnesia
• Abnormal behavior
• Hallucinations
• Libido disorder
• Rash
• Aggression (more common in children and elderly)
• Blood disorders
• Delusions
• Jaundice
• Paradoxical drug reactions
• Restlessness
• Urinary retention

Interactions

• Increased effects when used with other CNS depressants
• Alcohol may enhance sedation and drowsiness

Precautions

• Caution in patients with muscle weakness
• Caution in organic brain changes
• Risk of dependence and withdrawal symptoms
• Use with caution in hepatic impairment
• Use with caution in renal impairment

Pregnancy

Avoid regular use during pregnancy. Use only if there is a clear indication, such as seizure control. High doses during late pregnancy or labour may cause neonatal hypothermia, hypotonia, and respiratory depression.

Breast-feeding

Benzodiazepines are present in breast milk and should be avoided if possible during breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets