Chlordiazepoxide

Oral
Anxiety
Adult: For the management of anxiety disorders or the short-term relief of anxiety symptoms: Usual dose range: 5-25 mg 2-4 times daily; may increase gradually. Max: 100 mg daily in divided doses. For the relief of preoperative anxiety and apprehension: 5-10 mg 3-4 times daily for several days preceding surgery. Individualise dosage and treatment duration according to patient response and severity of the disorder. Use the lowest effective dose for the shortest possible duration. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).
Elderly: Dose reduction may be required. Dosage recommendations may vary among countries and individual products (refer to detailed product guidelines).
Renal impairment: Dose reduction may be required.
Hepatic impairment: Mild to moderate: Dose reduction may be required. Severe: Contraindicated.

Oral
Acute symptoms of alcohol withdrawal
Adult: 25-100 mg, may be repeated, if necessary, after 2-4 hours. Max: 300 mg daily. Dosage recommendations may vary among countries and individual products (refer to specific product guidelines).
Elderly: Dose reduction may be required. Dosage recommendations may vary among countries and individual products (refer to detailed product guidelines).
Renal impairment: Dose reduction may be required.
Hepatic impairment: Mild to moderate: Dose reduction may be required. Severe: Contraindicated.

Oral
Insomnia associated with anxiety
Adult: 10-30 mg before bedtime. Individualise dosage and treatment duration according to patient response and severity of the disorder. Use the lowest effective dose for the shortest possible duration. Treatment duration: Few days to 2 weeks; Max of 4 weeks, including a tapering off process.
Elderly: Dose reduction may be required.
Renal impairment: Dose reduction may be required.
Hepatic impairment: Mild to moderate: Dose reduction may be required. Severe: Contraindicated.

Oral
Muscle spasms
Adult: 10-30 mg daily in divided doses. Individualise dosage and treatment duration according to patient response and severity of the disorder. Use the lowest effective dose for the shortest possible duration.
Elderly: Dose reduction may be required.
Renal impairment: Dose reduction may be required.
Hepatic impairment: Mild to moderate: Dose reduction may be required. Severe: Contraindicated.

Special Populations: Debilitated patients: Dose reduction may be required. Dosage recommendations may vary among countries and individual products (refer to detailed product guidelines).

May be taken with or without food.

Myasthenia gravis, severe pulmonary insufficiency, respiratory depression, phobic or obsessional states, chronic psychosis, sleep apnoea syndrome. Severe hepatic impairment.

Patient with depression (particularly if with suicidal risk), porphyria, respiratory disease, history of alcohol or drug abuse; marked personality disorder; at risk of falls. Debilitated patients. Avoid abrupt withdrawal. Not indicated for use alone to treat depression or anxiety associated with depression. Renal and mild to moderate hepatic impairment. Elderly. Pregnancy and lactation. Concomitant use with opioids. Patient Counselling This drug may cause sedation, amnesia, impaired concentration, dizziness, drowsiness, and impaired muscular function; if affected, do not drive or operate machinery. Monitoring Parameters Monitor respiratory, CV (including orthostasis), and mental status. Evaluate for paradoxical reactions (e.g. acute rage, stimulation, excitement). If indicated for alcohol withdrawal, monitor for signs and symptoms of alcohol withdrawal. Assess the patient's risk for abuse, misuse, and addiction prior to initiation and during treatment.

Significant: Anterograde amnesia, paradoxical reactions (including hyperactive or aggressive behaviour), sleep-related activities (e.g. sleep-driving, making phone calls, cooking, and eating food while asleep); physical dependence and withdrawal reactions (prolonged use; high doses), tolerance (prolonged use). Blood and lymphatic system disorders: Rarely, blood dyscrasias (e.g. agranulocytosis). Eye disorders: Rarely, visual impairment (including diplopia). Gastrointestinal disorders: Nausea, constipation, changes in salivation. General disorders and administration site conditions: Fatigue. Hepatobiliary disorders: Jaundice. Investigations: Increased serum bilirubin, transaminases, and alkaline phosphatase; changes in EEG patterns. Metabolism and nutrition disorders: Increased appetite. Musculoskeletal and connective tissue disorders: Muscle weakness. Nervous system disorders: Somnolence, sedation, dizziness, unsteadiness, ataxia, dysarthria, gait disturbance, extrapyramidal symptoms (e.g. tremor, dyskinesia). Psychiatric disorders: Confusion, hallucinations, restlessness, agitation, delusion, irritability, nightmares, emotional disturbances, psychotic disorder, abnormal behaviour. Reproductive system and breast disorders: Rarely, changes in libido, minor menstrual irregularities. Skin and subcutaneous tissue disorders: Rarely, skin eruptions.

Symptoms: Drowsiness, mental confusion, lethargy. Severe cases may lead to ataxia, hypotonia, hypotension, respiratory depression, and rarely, coma. Management: Symptomatic and supportive treatment. Initiate IV fluids administration and maintain an adequate airway. Administration of activated charcoal may be given within 1 hour of ingestion, provided that the airway is protected. If hypotension occurs, administer norepinephrine or metaraminol. Flumazenil may be considered as an adjunctive agent for proper overdose management; it is indicated for the complete or partial reversal of the sedative effects. Necessary measures must be instituted to secure airway, ventilation, and IV access prior to flumazenil use.

Potentiated central depressive effects with other centrally-acting agents (e.g. antipsychotics, hypnotics, anxiolytics, antidepressants, analgesics, sedative antihistamines, anaesthetics). Side effects and toxicity may be more evident when used concomitantly with antiepileptic drugs (e.g. phenytoin, barbiturates). May enhance respiratory depression with sodium oxybate. May decrease clearance with CYP450 inhibitors (e.g. cimetidine, erythromycin, omeprazole). May increase clearance with CYP450 inducers (e.g. rifampicin). Increased sedative effect with lofexidine, nabilone, baclofen, tizanidine, and disulfiram. May antagonise the effect of levodopa. Reduced therapeutic effect with theophylline.
Potentially Fatal: Concomitant use with opioids may result in profound sedation, respiratory depression, and coma.

May enhance sedative effect with alcohol; avoid concomitant use.

Chlordiazepoxide, a benzodiazepine, has antianxiety, sedative, appetite-stimulating, and weak analgesic actions. It binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron. It enhances the inhibitory effect of GABA in different parts of the CNS by increasing the permeability of neuronal membrane to chloride ions, thus resulting in hyperpolarisation and stabilisation.
Absorption: Almost completely absorbed. Time to peak plasma concentration: 0.5-2 hours.
Distribution: Crosses the placenta and passes into CSF; enters breast milk. Volume of distribution: 3.3 L/kg. Plasma protein binding: Approx 96%.
Metabolism: Extensively metabolised in the liver to desmethylchlordiazepoxide, desmethyldiazepam (active and long-acting metabolite), and demoxepam.
Excretion: Via urine (1-2% as unchanged drug; 3-6% as metabolite). Elimination half-life: 24-48 hours (chlordiazepoxide); 14-95 hours (demoxepam).

Oral: Store between 15-30°C. Protect from light.

Anxiolytics

N05BA02 - chlordiazepoxide ; Belongs to the class of benzodiazepine derivatives anxiolytics. Used in the management of anxiety, agitation or tension.