chlordiazepoxide
Libritabs

chlordiazepoxide hydrochloride
Librium, Mitran, Reposans-10

Pharmacologic classification: benzodiazepine
Therapeutic classification: anxiolytic, anticonvulsant, sedative-hypnotic
Pregnancy risk category D
Controlled substance schedule IV

Available forms
Available by prescription only
Capsules: 5 mg, 10 mg, 25 mg
Powder for injection: 100 mg/ampule
Tablets: 10 mg, 25 mg

Indications and dosages
 Mild to moderate anxiety and tension. Adults: 5 to 10 mg P.O. t.i.d. or q.i.d.
Children older than age 6 and geriatric or debilitated patients: 5 mg P.O. b.i.d. to q.i.d. Maximum dose is 10 mg P.O. b.i.d. or t.i.d.
 Severe anxiety and tension. Adults: 20 to 25 mg P.O. t.i.d. or q.i.d.
 Withdrawal symptoms of acute alcoholism. Adults: 50 to 100 mg P.O., I.M., or I.V. Maximum dose is 300 mg daily.
 Preoperative apprehension and anxiety. Adults: 5 to 10 mg P.O. t.i.d. or q.i.d. on day before surgery. Or, 50 to 100 mg I.M. 1 hour before surgery.

Pharmacodynamics
Anxiolytic action: Chlordiazepoxide depresses the CNS at the limbic and subcortical levels of the brain. It produces an antianxiety effect by influencing the effect of the neurotransmitter gamma-aminobutyric acid on its receptor in the ascending reticular activating system, which increases inhibition and blocks cortical and limbic arousal after stimulation of the reticular formation.
Anticonvulsant action: Drug suppresses the spread of seizure activity produced by the epileptogenic foci in the cortex, thalamus, and limbic structures by enhancing presynaptic inhibition.
Sedative-hypnotic action: Drug causes CNS depression and sedation only at doses beyond those needed for anxiolytic effect.

Pharmacokinetics
Absorption: When given orally, drug is absorbed well through the GI tract. I.M. administration results in erratic absorption.
Distribution: Distributed widely throughout the body; 90% to 98% is protein-bound.
Metabolism: Metabolized in the liver to several active metabolites.
Excretion: Most metabolites are excreted in urine as glucuronide conjugates. Half-life of drug is 5 to 30 hours.

Route Onset Peak Duration
P.O. Unknown 1/2-4 hr Unknown
I.V. 1-5 min Unknown 15-60 min
I.M. 15-30 min Unknown Unknown


Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with impaired renal or hepatic function, mental depression, or porphyria.

Interactions
Drug-drug. Antacids: May delay chlordiazepoxide absorption. Monitor patient closely.
Antidepressants, antihistamines, barbiturates, general anesthetics, MAO inhibitors, narcotics, phenothiazines: Potentiates CNS depressant effects. Avoid use together.
Cimetidine, possibly disulfiram: Reduces hepatic metabolism of chlordiazepoxide, which increases its plasma levels. Monitor patient carefully.
Digoxin, phenytoin: May increase levels of these drugs. Monitor patient for toxicity.
Levodopa: May decrease levodopa effects. Avoid use together.
Oral contraceptives: May impair chlordiazepoxide absorption. Avoid use together.
Drug-lifestyle. Alcohol use: Potentiates CNS depressant effects. Discourage alcohol use.
Heavy smoking: Accelerates chlordiazepoxide metabolism and reduces effectiveness. Discourage smoking.

Adverse reactions
CNS: drowsiness, lethargy, ataxia, confusion, extrapyramidal symptoms, EEG changes.
CV: edema.
GI: nausea, constipation.
GU: menstrual irregularities.
Hematologic: agranulocytosis.
Hepatic: jaundice.
Skin: swelling,pain at injection site, skin eruptions.
Other: altered libido.

Effects on lab test results
• May increase liver function test values. May decrease granulocyte count.

Overdose and treatment
Overdose may cause somnolence, confusion, coma, hypoactive reflexes, dyspnea, labored breathing, hypotension, bradycardia, slurred speech, and unsteady gait or impaired coordination.
 Support blood pressure and respiration until drug effects subside; monitor vital signs. Flumazenil, a specific benzodiazepine antagonist, may be useful. Mechanical ventilatory assistance via endotracheal tube may be required to maintain a patent airway and support adequate oxygenation. Use I.V. fluids and vasopressors, such as dopamine and phenylephrine, to treat hypotension as needed. Use gastric lavage if ingestion was recent, but only if an endotracheal tube is in place to prevent aspiration. Induce emesis if the patient is conscious. After emesis or lavage, administer activated charcoal with a cathartic as a single dose. Don’t administer barbiturates if excitation occurs. Dialysis is of limited value.

Special considerations
• I.M. administration isn’t recommended because of erratic and slow absorption. However, if I.M. route is used, reconstitute with special diluent only. Don’t use diluent if hazy. Discard unused portion. Inject I.M. deep into large muscle mass.
• For I.V. administration, reconstitute drug with sterile water or normal saline solution and infuse slowly, directly into a large vein, at a rate not exceeding 50 mg/minute for adults. Don’t infuse chlordiazepoxide into small veins. Avoid extravasation into S.C. tissue. Observe infusion site for phlebitis. Keep resuscitation equipment nearby in case of an emergency.
• Prepare solutions for I.V. or I.M. use immediately before administration. Discard unused portions.
• Lower doses are effective in patients with renal or hepatic dysfunction.
• Minor changes in EEG patterns, usually low-voltage, fast activity, may occur during and after chlordiazepoxide therapy.
• Chlordiazepoxide may cause a false-positive pregnancy test, depending on method used. It may also alter urinary 17-ketosteroids (Zimmerman reaction), urine alkaloid determination (Frings thin layer chromatography method), and urinary glucose determinations (with Chemstrip uG and Diastix, but not glucose enzymatic test strip).
• Patient should remain in bed under observation for at least 3 hours after parenteral administration of chlordiazepoxide.
• Closely monitor renal and hepatic studies for signs of dysfunction.
Breast-feeding patients
• The breast-fed infant of a woman who receives chlordiazepoxide may become sedated, have feeding difficulties, or lose weight. Don’t give drug to breast-feeding women.
Pediatric patients
• Safety of oral form hasn’t been established in children younger than age 6. Safety of parenteral form hasn’t been established in children younger than age 12.
Geriatric patients
• Elderly patients demonstrate a greater sensitivity to the CNS depressant effects of drug. Some may require supervision with walking and activities of daily living at start of therapy or after an increase in dose.
• Lower doses are usually effective in elderly patients because of decreased elimination.
• Parenteral administration of drug is more likely to cause apnea, hypotension, and bradycardia in elderly patients.

Patient education
• Warn patient that sudden changes in position may cause dizziness. Advise patient to dangle legs a few minutes before getting out of bed to prevent falls and injury.
• Warn patient not to abruptly stop using drug because withdrawal symptoms may occur.
• Tell patient to avoid hazardous activities until the CNS effects of the drug are known.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use