Chlordiazepoxide


Generic Medicine Info
Indications and Dosage
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.

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).

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).

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.
Special Patient Group
Debilitated patients: 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.
Administration
May be taken with or without food.
Contraindications
Myasthenia gravis, severe pulmonary insufficiency, respiratory depression, phobic or obsessional states, chronic psychosis, sleep apnoea syndrome. Severe hepatic impairment.
Special Precautions
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.
Adverse Reactions
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.
Patient Counseling Information
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.
Overdosage
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.
Drug Interactions
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.
Food Interaction
May enhance sedative effect with alcohol; avoid concomitant use.
Action
Description: 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.
Pharmacokinetics:
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).
Chemical Structure

Chemical Structure Image
Chlordiazepoxide

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 2712, Chlordiazepoxide. https://pubchem.ncbi.nlm.nih.gov/compound/Chlordiazepoxide. Accessed July 29, 2020.

Storage
Store between 15-30°C. Protect from light.
MIMS Class
Anxiolytics
ATC Classification
N05BA02 - chlordiazepoxide ; Belongs to the class of benzodiazepine derivatives anxiolytics. Used in the management of anxiety, agitation or tension.
References
Anon. Chlordiazepoxide (Briggs Drugs in Pregnancy and Lactation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/02/2022.

Anon. Chlordiazepoxide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 16/03/2022.

Anon. Chlordiazepoxide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 21/02/2022.

Buckingham R (ed). Chlordiazepoxide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/02/2022.

Chlordiazepoxide 5 mg Tablets (Genethics Europe Limited). MHRA. https://products.mhra.gov.uk. Accessed 21/02/2022.

Chlordiazepoxide Capsules BP 10 mg (Crescent Pharma Limited). MHRA. https://products.mhra.gov.uk. Accessed 21/02/2022.

Chlordiazepoxide Hydrochloride Capsule (Bryant Ranch Prepack). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 21/02/2022.

Joint Formulary Committee. Chlordiazepoxide Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/02/2022.

Preston CL (ed). Chlordiazepozide - Sodium Oxybate - Levodopa Drug Interaction. Stockley’s Drug Interactions [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 21/02/2022.

Disclaimer: This information is independently developed by MIMS based on Chlordiazepoxide from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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