Chlordiazepoxide

Pronunciation

Pronunciation: klor-DIE-aze-ee-POX-ide
Class: Benzodiazepine

Trade Names

Chlordiazepoxide
- Capsules 5 mg
- Capsules 10 mg
- Capsules 25 mg

Apo-Chlordiazepoxide (Canada)

Pharmacology

Potentiates action of GABA to produce CNS depression.

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Pharmacokinetics

Absorption

T max is 0.5 to 4 h.

Distribution

96% protein bound.

Metabolism

Metabolized in the liver to the major metabolite desmethylchlordiazepoxide and to several inactive intermediate metabolites.

Elimination

The t ½ is 5 to 30 h. Excreted in the urine, with 1% to 2% as unchanged drug and 3% to 6% as a conjugate.

Indications and Usage

Management of anxiety disorders; relief of acute alcohol withdrawal symptoms; relief of preoperative apprehension and anxiety.

Unlabeled Uses

Treatment of irritable bowel syndrome.

Contraindications

Hypersensitivity to benzodiazepines; psychoses; acute narrow-angle glaucoma; shock; coma.

Dosage and Administration

Individualize dosage. Acute symptoms may be rapidly controlled IM or IV, with subsequent oral treatment (max, 300 mg/day).

Children older than 6 yr of age

PO 5 mg 2 to 4 times daily; may be increased to 10 mg 2 to 3 times daily.

Mild to Moderate Anxiety
Adults

PO 5 to 10 mg 3 or 4 times daily.

Severe Anxiety
Adults

PO 20 to 25 mg 3 or 4 times daily.

Elderly or Debilitated Patients

PO 5 mg 2 to 3 times daily.

Preoperative Apprehension/Anxiety
Adults

PO 5 to 10 mg 3 or 4 times daily on days preceding surgery.

Acute Alcohol Withdrawal
Adults

PO 50 to 100 mg, repeat as needed (max oral or parenteral dose is 300 mg/day).

General Advice

Administer prescribed dose without regard to meals but administer with food if GI upset occurs.

Storage/Stability

Store capsules at controlled room temperature (59° to 86°F).

Drug Interactions

Alcohol and CNS depressants

Additive CNS depressant effects are possible.

Azole antifungal agents (eg, itraconazole, ketoconazole), fluvoxamine, isoniazid, nefazodone, protease inhibitors (eg, indinavir)

May increase chlordiazepoxide plasma concentrations.

Cigarette smoking, theophyllines

May antagonize sedative effects.

Cimetidine, oral contraceptives, disulfiram, omeprazole

May increase effects of chlordiazepoxide with excessive sedation and impaired psychomotor function.

Digoxin

May increase serum digoxin concentrations.

Rifamycins

May decrease chlordiazepoxide plasma concentrations.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

CV collapse; hypotension; hypertension; tachycardia; bradycardia; edema; phlebitis or thrombosis at IV sites.

CNS

Drowsiness; confusion; ataxia; dizziness; fatigue; apathy; memory impairment; disorientation; anterograde amnesia; restlessness; headache; slurred speech; loss of voice; stupor; coma; euphoria; irritability; vivid dreams; psychomotor retardation; paradoxical reactions (eg, anger, hostility, mania, insomnia, muscle spasms); syncope; extrapyramidal symptoms.

Dermatologic

Rash.

EENT

Visual or auditory disturbances; depressed hearing; blurred vision.

GI

Constipation; diarrhea; dry mouth; coated tongue; nausea; anorexia; vomiting.

Genitourinary

Menstrual irregularities; increase or decrease in libido.

Hematologic

Blood dyscrasias including agranulocytosis; anemia; thrombocytopenia; leukopenia; neutropenia.

Hepatic

Abnormal LFTs; hepatic function impairment including hepatitis and jaundice.

Miscellaneous

Dependency/withdrawal syndrome.

Precautions

Monitor

CBC

Ensure that CBC with differential and liver enzymes are evaluated periodically in patient on prolonged therapy.

Periodic therapy review

Ensure that therapy is periodically reviewed to determine if therapy needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated.

Response to treatment

Frequently assess patient for response to treatment. Notify health care provider if condition does not appear to improve or worsens.

Withdrawal

If treatment is to be discontinued, or the dose reduced, gradually taper the dose and monitor patient for withdrawal symptoms. If significant withdrawal symptoms develop (eg, increased anxiety, tremor, muscle or abdominal cramps, sweating) reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.


Pregnancy

Category D . Avoid especially in first trimester because of possible increased risk of congenital malformations.

Lactation

Excreted in breast milk.

Children

Initial dose should be small and gradually increased. Oral form not recommended in children younger than 6 yr of age.

Elderly

Initial dose should be small and gradually increased. Use with caution in patients with limited pulmonary reserve.

Renal Function

Observe caution to avoid accumulation of drug.

Hepatic Function

Observe caution to avoid accumulation of drug.

Debilitated patients

Initial dose should be small and gradually increased. Use with caution in patients with limited pulmonary reserve.

Drug dependency

Prolonged use can lead to dependency. Withdrawal syndrome has occurred within 4 to 6 wk of treatment, especially if drug is abruptly discontinued. For discontinuation after long-term treatment, use caution and taper dosage.

Psychiatric disorders

Not intended for patients with primary depressive disorder, psychosis, or disorders in which anxiety is not prominent.

Suicide

Use with caution in patients with suicidal tendencies; do not allow access to large quantities of drug.

Overdosage

Symptoms

Drowsiness, confusion, somnolence, impaired coordination, diminished reflexes, lethargy, ataxia, hypotonia, hypotension, hypnosis, coma, death.

Patient Information

  • Advise patient or caregiver to read the patient information leaflet before starting therapy and with each refill.
  • Advise patient that medication is usually started at a low dose and then gradually increased until max benefit is obtained.
  • Caution patient that medication may be habit forming and to take as prescribed and not to stop taking or change the dose unless advised to do so by health care provider.
  • Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
  • Advise patient that if a dose is missed to skip that dose and take the next dose at the regularly scheduled time. Caution patient to never take 2 doses at the same time.
  • Advise patient that if medication needs to be discontinued it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
  • Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Advise patient with anxiety to take medication as needed and to seek alternative methods for controlling or preventing anxiety (eg, stress reduction, counseling).
  • Instruct patient to contact health care provider if symptoms do not appear to be getting better, are getting worse, or if bothersome adverse reactions (eg, drowsiness, memory impairment) occur.
  • Advise patient that drug may cause drowsiness or impair judgment, thinking, or reflexes and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.

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