chlordiazepoxide hydrochloride

Apo-Chlordiazepoxide (CA)

Pharmacologic class: Benzodiazepine

Therapeutic class: Anxiolytic, sedative-hypnotic

Controlled substance schedule IV Pregnancy risk category D

Action

Unknown. May potentiate effects of gamma-aminobutyric acid (an inhibitory neurotransmitter) by increasing neuronal membrane permeability; may depress CNS at limbic and subcortical levels of brain. Anxiolytic effect occurs at doses well below those that cause sedation or ataxia.

Availability

Capsules: 5 mg, 10 mg, 25 mg

Injection: 100-mg ampules

Indications and dosages

➣ Mild to moderate anxiety

Adults: 5 to 10 mg P.O. three to four times daily

➣ Severe anxiety

Adults: Initially, 50 to 100 mg I.M. or I.V.; then 25 to 50 mg P.O. three to four times daily as needed

➣ Preoperative apprehension or anxiety

Adults: 5 to 10 mg P.O. three to four times daily for several days before surgery or 50 to 100 mg I.M. 1 hour before surgery

➣ Acute alcohol withdrawal

Adults: Initially, 50 to 100 mg I.V. or I.M. Repeat dose as needed up to 300 mg/day.

Dosage adjustment

• Hepatic impairment

• Age 65 or older

Contraindications

• Hypersensitivity to drug, other benzodiazepines, or tartrazine

• CNS depression

• Uncontrolled severe pain

• Porphyria

• Pregnancy or breastfeeding

• Children younger than age 6

Precautions

Use cautiously in:

• hepatic dysfunction, severe renal impairment

• debilitated or elderly patients.

Administration

• Dilute I.V. preparation with 5 ml of normal saline solution. Administer slowly over at least 1 minute.

• When giving I.M., use 2 ml of special I.M. diluent. Inject slowly and deeply into gluteus muscle.

• Don't use I.M. diluent for I.V. preparation.

• After I.V. or I.M. administration, observe patient closely and enforce bedrest for at least 3 hours.

Adverse reactions

CNS: dizziness, drowsiness, hangover, headache, depression, paradoxical stimulation

EENT: blurred vision

GI: nausea, vomiting, constipation, diarrhea

Hematologic: agranulocytosis

Hepatic: jaundice

Skin: rash

Other: physical or psychological drug dependence, drug tolerance, pain at I.M. site

Interactions

Drug-drug. Antidepressants, antihistamines, opioids: additive CNS depression

Barbiturates, rifampin: decreased chlordiazepoxide efficacy

Cimetidine, disulfiram, fluoxetine, hormonal contraceptives, isoniazid, ketoconazole, metoprolol, propoxyphene, propranolol, valproic acid: enhanced chlordiazepoxide effect

Levodopa: decreased levodopa efficacy

Drug-diagnostic tests. Alanine aminotransferase, aspartate aminotransferase, bilirubin: increased levels

Granulocytes: decreased count

Metyrapone test: decreased response

Radioactive iodine uptake test (¹²³I or ¹³¹I): decreased uptake

Urine 17-ketogenic steroids, urine 17-ketosteroids: altered test results

Drug-herbs. Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Drug-behaviors. Alcohol use: increased CNS depression

Patient monitoring

• Monitor CBC and hepatic enzyme levels in prolonged therapy.

• Monitor renal and hepatic studies.

• Assess patient for apnea, bradycardia, and hypotension.

Patient teaching

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Advise patient to avoid alcohol during therapy.

• Tell patient not to stop taking drug abruptly. Instruct him to discuss dosage-tapering schedule with prescriber.

• Caution female patient not to take drug if she's pregnant or might become pregnant during therapy. Advise her to use reliable contraception.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.