Chlordiazepoxide + Clidinium bromide

Oral
Irritable bowel syndrome, Peptic ulcer

Debilitated patients:

Available preparation:
Chlordiazepoxide 5 mg and clidinium bromide 2.5 mg capsule/tablet

Initially, 2 caps/tabs daily, may be increased gradually as needed and tolerated. Use the lowest effective dose.

Should be taken on an empty stomach. Take 30 min-1 hr before meals.

Glaucoma, myasthenia gravis, obstructive gastrointestinal diseases, paralytic ileus, ulcerative colitis, benign bladder neck obstruction, prostatic hyperplasia.

Patient with a history of drug abuse or acute alcoholism, depression, CV disease (e.g. CHF, coronary heart disease), respiratory disease. Patient subjected to heat exposure, strenuous exercise and dehydration, or receiving anticholinergic drugs. Elderly and debilitated patients. Renal and hepatic impairment. Avoid abrupt withdrawal (prolonged therapy).

Significant: Paradoxical reactions (e.g. hyperactive or aggressive behaviour), impaired core body temperature regulation, sleep-related activities (e.g. sleep-driving, cooking, and eating; making phone calls while asleep), falls, withdrawal symptoms, anticholinergic effects (e.g. xerostomia, blurred vision, urinary retention); drug tolerance or psychological and physical dependence.
Blood and lymphatic system disorders: Blood dyscrasias (e.g. agranulocytosis, leucopenia).
Gastrointestinal disorders: Nausea, constipation.
Hepatobiliary disorders: Hepatic dysfunction, jaundice.
Investigations: Changes in EEG.
Metabolism and nutrition disorders: Oedema.
Nervous system disorders: Ataxia, confusion, drowsiness, extrapyramidal reaction, anterograde amnesia.
Reproductive system and breast disorders: Menstrual irregularities, increased and decreased libido.
Skin and subcutaneous tissue disorders: Skin eruption.
Vascular disorders: Syncope.

This drug may impair physical or mental abilities, if affected, do not drive or operate machinery.

Monitor mental status, anticholinergic effects (e.g. CNS, bowel and bladder function); CBC, liver and renal function (as needed); respiratory and CV status (including orthostasis). Evaluate for history of addiction. Assess for signs and symptoms of CNS depression and paradoxical reactions (e.g. excitement, stimulation, acute rage).

Symptoms: Somnolence, confusion, coma, diminished reflexes; excessive dryness of mouth, blurring of vision, urinary hesitancy, and constipation. Management: Supportive treatment. Monitor respiration, pulse and blood pressure. Perform gastric lavage immediately. Administer IV fluids and maintain adequate airway. Administer physostigmine 0.5-2 mg at a rate of ≤1 mg/min and may repeat in 1-4 mg doses in the recurrence of arrhythmias, convulsions or deep coma. In case of hypotension, may administer levarterenol or metaraminol. Administer methylphenidate or caffeine and sodium benzoate to decrease the CNS-depressive effects.

Chlordiazepoxide may increase risk of CNS effect with other CNS depressants.
Potentially Fatal: Concomitant use of chlordiazepoxide with opioids may result in profound sedation, respiratory depression, and coma.

Increased CNS depressant effect with alcohol.

Description:
Mechanism of Action: Chlordiazepoxide and clidinium bromide can control some somatic and emotional factors related to gastrointestinal diseases.
Chlordiazepoxide is a long acting benzodiazepine that binds to receptors on the postsynaptic gamma-aminobutyric acid (GABA) neuron, particularly GABA-A receptor, at several sites within the CNS including the limbic system.
Clidinium bromide is a synthetic anticholinergic agent. It is a competitive inhibitor at the autonomic postganglionic cholinergic receptors located in many tissues including the gastrointestinal tract. Its action results in decrease motility in the gastrointestinal, urinary and biliary tracts.
Onset: Clidinium bromide: Antisecretory effect: Within 1 hour.
Duration: Clidinium bromide: Antisecretory effect: Up to 3 hours.
Pharmacokinetics:
Absorption: Chlordiazepoxide: Completely absorbed from the gastrointestinal tract. Bioavailability: 100%. Time to peak plasma concentrations: 1-2 hours.
Clidinium bromide: Absorbed in the intestine while incompletely absorbed from the gastrointestinal tract.
Distribution: Chlordiazepoxide: Distributed throughout the body. Crosses the CSF and placenta, enters breast milk. Volume of distribution: 3.3 L/kg. Plasma protein binding: Approx 96%.
Metabolism: Chlordiazepoxide: Extensively metabolised in the liver into its primary active metabolite, desmethyldiazepam, and other metabolites (desmethylchlordiazepoxide, demoxepam).
Clidinium bromide: Metabolised in the liver into 3-hydroxy-1-methylquinuclidinium bromide.
Excretion: Chlordiazepoxide: Mainly via urine (1-2% as unchanged drug; 3-6% as active metabolites). Elimination half-life: Approx 5-30 hours.
Clidinium bromide: Via urine (90% within the 1st day; approx 36% within 7 days); faeces (approx 20-46%). Elimination half-life: 2.4 hours (initial), 20 hours (terminal).

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.

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.

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

Thuốc chống co thắt

A03CA02 - clidinium and psycholeptics ; Belongs to the class of synthetic anticholinergic antispasmodics, in combination with psycholeptics. Used in the treatment of functional gastrointestinal disorders.

Anon. Chlordiazepoxide. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 11/06/2020.

Anon. Chlordiazepoxide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/06/2020.

Anon. Clidinium and Chlordiazepoxide. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 11/06/2020.

Anon. Clidinium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 11/06/2020.

Buckingham R (ed). Chlordiazepoxide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/06/2020.

Buckingham R (ed). Clidinium Bromide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 11/06/2020.

Chlordiazepoxide Hydrochloride and Clidinium Bromide Capsule (Bi-Coastal Pharma International Limited Liability Company). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 11/06/2020.

Chlordiazepoxide Hydrochloride and Clidinium Bromide Capsule (Sunrise Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 14/07/2020.

Chlordiazepoxide; Clidinium. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com/. Accessed 14/07/2020.

Liblan Film Coated Tablet (Y.S.P. Industries M Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 11/06/2020.

Librax Capsules (Valeant Pharmaceuticals North America LLC). U.S. FDA. https://www.fda.gov/. Accessed 14/07/2020.