Category : CNS AGENTS

Name : CHLORDIAZEPOXIDE     Type & Dosage : F.C. Tab. ; 10 mg Package : 100

Pharmacologic Category Benzodiazepine ; Antianxiety agent , sedative – hypnotic , Antitremor agent Mechanism Of Action In general, benzodiazepines act as depressants of the CNS, producing all levels of CNS depression from mild sedation to hypnosis to coma , depending on dose . It is believed that benzodiazepines enhance or facilitate the action of gamma – aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS, by causing it to bind more tightly to the GABA type A receptor . By stimulation of GABA receptor in the ascending reticular activating system , benzodiazepines increase inhibition and block both cortical and limbic arousal following stimulation of the brain stem reticular formation. Indications Anxiety – Chlordiazepoxide is indicated for the management of anxiety disorders or for the short – term relief of the symptoms of anxiety .Chlordiazepoxide is indicated for treatment of preoperative apprehension and anxiety. Alcohol withdrawal – Chlordiazepoxide is indicated for the relief of acute alcohol withdrawal symptoms such as acute agitation , tremor , impending or acute delirium tremens , and hallucinosis . Tension headache and tremors – Chlordiazepoxide is used in the treatment of tension headache and familial , senile , or essential action tremors. Side Adverse Effects Psychological or physical dependence and tolerance may occur with benzodiazepine use , especially with high – dose or prolonged use . Geriatric and debilitated patients, children (especially the very young ) , and patients with hepatic disease or low serum albumin are usually more sensitive to the CNS effects of benzodiazepines. a-Those indicating need for medical attention: Antegrade amnesia ; Anxiety ; Confusion ; Mental depression ; Tachycardia/Palpitation ; Abnormal thinking including delusions , depersonalization or disorientation; Allergic reaction ; Behavior changes including bizarre behavior or decreased inhibition ; Blood dyscrasias including agranulocytosis , anemia, leukopenia , neutropenia or thrombocytopenia ; Extrapyramidal effects, dystonic ; Hepatic dysfunction ; Hypotension ; Muscle weakness ; Paradoxical reactions including agitation , aggressive behavior , hallucinations , hostility or rage , insomnia , unusual excitement , irritability or nervousness ; Seizures. b-Those indicating need for medical attention only if they continue or are bothersome: Ataxia ; Dizziness or lightheadedness ; Drowsiness including residual daytime drowsiness when used as a hypnotic; Slurred speech ; Abdominal or stomach cramps or pain ; Blurred vision ; Changes in libido ; Constipation ; Diarrhea ; Dryness of mouth or increased thirst ; Euphoria ; Headache ; Increased bronchial secretion or excessive salivation ; Muscle spasm ; Nausea or vomiting ; Problems with urination ; Tremor; Unusual tiredness or weakness. c–Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued: Insomnia ; Irritability ; Nervousness ; Abdominal or stomach cramps ; Confusion ; Depersonalization ; Increased sweating ; Mental depression ; Muscle cramps ; Nausea or vomiting ; Perceptual disturbances including hyperacusis , hypersensitivity to touch and pain , paresthesia or photophobia ; Tachycardia ; Tremor ; Convulsions ; Delirium ; Hallucinations ; Paranoid symptoms. Contraindications Hypersensitivity to chlordiazepoxide or any component of the formulation (cross- sensitivity with other benzodiazepines may also exist) ; Narrow – angle glaucoma ; Pregnancy Warnings Precautions Risk – benefit should be considered when the following medical problems exist:Acute alcohol intoxication with depressed vital signs ; History of drug abuse or dependence ; Hepatic function impairment ; Hyperkinesis ; Hypoalbuminemia ; Severe mental depression ; Myasthenia gravis ; Organic brain disorders ; Psychoses ; Severe chronic obstructive pulmonary disease ; Renal function impairment ; Established or suspected sleep apnea ; Swallowing abnormality in children. Patients must be cautioned about performing tasks which require mental alertness (eg , operating machinery or driving) . Benzodiazepines have been associated with falls and traumatic injury and should be used with extreme caution in patients who are at risk of these events (especially the elderly ). Pregnancy FDA pregnancy category D. Chlordiazepoxide crosses the placenta and has been reported to increase the risk of congenital malformations when used during the first trimester of pregnancy . Therefore, chlordiazepoxide should be avoided during pregnancy , especially during the first trimester. Breast Feeding Chlordiazepoxide is distributed into breast milk . Since neonates metabolize benzodiazepine more slowly than adults and accumulation of the benzodiazepines and/or its metabolite may occur , use by nursing mothers may cause sedation, feeding difficulties , and/or weight loss in the infant . Therefore , chlordiazepoxide is not recommended during breast – feeding period. Drug Interactions Prolonged concurrent use with addictive medications , especially CNS depressants with habituating potential may increase the risk of habituation ; caution is recommended . Use of alcohol during treatment with a benzodiazepine is not recommended because potentiation of CNS depressant effects and increasing of the risk of apnea . Caution is recommended when another CNS depression- producing medication is used with a benzodiazepine , and dosage of one or both agents should be reduced . When a benzodiazepine is used with an opioid analgesic , the dosage of the opioid analgesic should be reduced by at least one third and administered in small increments . Concurrent use of antacids with chlordiazepoxide may delay , but not reduce , the absorption of chlordiazepoxide. Carbamazepine concentrarions may be increased during concurrent use with a benzodiazepine ; monitoring of carbamazepine blood concentration as a guide to dosage is recommended. Concurrent use of cimetidine , oral estrogen –containing contraceptive , diltiazem , erythromycin , fluxetine , fluvoxamine , grapefruit juice , itraconazole , ketoconazole , nefazodone , propoxyphene , ranitidine and verapamil may inhibit the hepatic metabolism of benzodiazepines , resulting in increased plasma concentrations. Collapse , sometimes accompanied by respiratory depression or arrest , has been reported in a few patients receiving clozapine concurrently with benzodiazepines .Concurrent use with benzodiazepines may decrease the therapeutic effects of levodopa . Concurrent use with benzodiazepines may decrease the clearance of zidovudine ; the toxicity of zidovudine potentially could be increased .Aminoglutethimide , carbamazepine, nafcilin , nevirapine , phenobarbital , phenytoin , and rifamycins may decrease the levels/effects of chlordiazepoxide . Theophylline may partially antagonize some of the effects of benzodiazepines. Monitoring Parameters Respiratory and cardiovascular status , mental status , check for orthostasis. Dietary Considerations Serum concentrations/effects may be increased with grapefruit juice . Avoid ethanol ( may increase CNS depression). Administration And Dosage Usual adult dose: Antianxiety agent – Oral , 5 to 25 mg 3 or 4 times a day. Sedative – hypnotic ; Alcohol withdrawal – Oral , initially 50 to 100 mg, repeated as needed , up to 400 mg per day , the dosage then reduced to maintenance levels. Usual pediatric dose: Antianxiety agent– children younger than 6 years of age: Safety and efficacy have not been established. Children 6 years of age and older: Oral , 5 mg 2 to 4 times a day , the dosage being increased , to 10 mg 2 or 3 times a day. Usual geriatric dose: Antianxiety agent – Oral , 5 mg 2 to 4 times a day , the dosage being increased gradually as needed and tolerated How Supplied Tablet 5 and 10 mg Storage Store below 30°C. Protect from light and moisture. References USP DI, 2004 Up To Date, Vol. 13.1 (2005) Martindale, The Complete Drug Reference, 33 rd edition 2002