CHLORDIAZEPOXIDE HYDROCHLORIDE

CHLORDIAZEPOXIDE HYDROCHLORIDE (klor-dye-az-e-pox'ide) Librium, Solium  Classifications: anxiolytic; sedative-hypnotic; benzodiazepine; Therapeutic: antianxiety; sedative-hypnotic Prototype: Lorazepam Pregnancy Category: D Controlled Substance: Schedule IV

Availability

5 mg, 10 mg, 25 mg capsules

Action

Benzodiazepine derivative that acts on the limbic, thalamic, and hypothalamic areas of the CNS. Has long-acting hypnotic properties. Causes mild suppression of REM sleep and of deeper phases, particularly stage 4, while increasing total sleep time.

Therapeutic Effect

Produces mild anxiolytic (reduces anxiety), sedative, anticonvulsant, and skeletal muscle relaxant effects.

Uses

Relief of various anxiety and tension states, preoperative apprehension and anxiety, and for management of alcohol withdrawal.

Unlabeled Uses

Essential, familial, and senile action tremors.

Contraindications

Hypersensitivity to chlordiazepoxide and other benzodiazepines; narrow angle glaucoma, prostatic hypertrophy, shock, comatose states, primary depressive disorder or psychoses, pregnancy (category D), lactation, oral use in children <6 y, parenteral use in children <12 y, acute alcohol intoxication.

Cautious Use

Anxiety states associated with impending depression, history of impaired hepatic or renal function; addiction-prone individuals, blood dyscrasias; in the older adult, debilitated patients, children; hyperkinesis, COPD.

Route & Dosage

Mild Anxiety, Preoperative Anxiety Adult: PO 5–10 mg t.i.d. or q.i.d. Geriatric: PO 5 mg b.i.d. to q.i.d. Child: PO 5 mg b.i.d. to q.i.d.; may be increased to 10 mg t.i.d. Severe Anxiety and Tension Adult: PO 20–25 mg t.i.d. or q.i.d. Alcohol Withdrawal Syndrome Adult: PO 50–100 mg prn up to 300 mg/d

Administration

Oral

• Give with or immediately after meals or with milk to reduce GI distress. If an antacid is prescribed, it should be taken at least 1 h before or after chlordiazepoxide to prevent delay in drug absorption.
• Supervise drug ingestion to prevent "cheeking" pills, a maneuver that leads to hoarding or omission of drug.

• Store in tight, light-resistant containers at room temperature unless otherwise specified by manufacturer.

Adverse Effects (≥1%)

Body as a Whole: Edema, pain in injection site, jaundice, hiccups, respiratory depression. CV: Orthostatic hypotension, tachycardia, changes in ECG patterns seen with rapid IV administration. GI: Nausea, dry mouth, vomiting, constipation, increased appetite. CNS: Drowsiness, dizziness, lethargy, changes in EEG pattern; vivid dreams, nightmares, headache, vertigo, syncope, tinnitus, confusion, hallucinations, parodoxic rage, depression, delirium, ataxia. Skin: Photosensitivity, skin rash. Urogenital: Urinary frequency.

Diagnostic Test Interference

Chlordiazepoxide increases serum bilirubin, AST and ALT; decreases radioactive iodine uptake; and may falsely increase readings for urinary 17-OHCS (modified Glenn-Nelson technique).

Interactions

Drug: Alcohol, cns depressants, anticonvulsants potentiate CNS depression; cimetidine increases chlordiazepoxide plasma levels, thus increasing toxicity; may decrease antiparkinson effects of levodopa; may increase phenytoin levels; smoking decreases sedative and antianxiety effects. Herbal: Kava, valerian may potentiate sedation.

Pharmacokinetics

Absorption: Well absorbed from GI tract. Peak: 1–4 h. Distribution: Widely distributed throughout body; crosses placenta. Metabolism: In liver via CYP3A4 to long-acting active metabolite. Elimination: Slowly excreted in urine (may last several days); excreted in breast milk. Half-Life: 5–30 h.

Nursing Implications

Assessment & Drug Effects

• Monitor for S&S of orthostatic hypotension and tachycardia, which occur more frequently with parenteral administration. Patient should stay recumbent 2–3 h after IM or IV injection; observe closely and monitor vital signs.
• Check BP and pulse before giving benzodiazepine in early part of therapy. If blood pressure falls 20 mm Hg or more or if pulse rate is above 120 bpm, delay medication and consult physician.
• Lab tests: Periodic blood cell counts and liver function tests are recommended during prolonged therapy.
• Monitor for S&S of agranulocytosis: sore throat or mouth, upper respiratory infection, fever, and malaise. Total and differential WBC counts should be ordered immediately, and protective isolation instituted.
• Monitor I&O until drug dosage is stabilized. Report changes in I&O ratio and dysuria to physician. Cumulative (overdosage) effects can result in renal dysfunction. Older adults are especially vulnerable.
• Monitor for S&S of paradoxic reactions—excitement, stimulation, disturbed sleep patterns, acute rage—which may occur during first few weeks of therapy in psychiatric patients and in hyperactive and aggressive children receiving chlordiazepoxide. Withhold drug and report to physician.
• Assess patient's sleep pattern. If dreams or nightmares interfere with rest, notify physician. A change in the dosing schedule, dose, or an alternate drug may be prescribed.
• Supervision of ambulation especially with older adults & debilitated patients.
• Observe for signs of developing physical or psychologic dependency such as requests for change in drug regimen (dose and dose interval), diminishing favorable response (e.g., disturbed sleep pattern, increase in psychomotor activity), withdrawal symptoms. Investigate the symptoms of ataxia, vertigo, slurred speech; the patient may be taking more than the prescribed dose.
• Abrupt discontinuation of drug in patients receiving high doses for long periods (≥4 mo) has precipitated withdrawal symptoms, but not for at least 5–7 d because of slow elimination.

Patient & Family Education

• Take drug specifically as prescribed: do not skip, increase, or decrease doses, change intervals, or terminate therapy without physician's advice and do not lend or offer any of drug to another person.
• Do not take OTC drugs unless prescribed.
• Long-term use of this drug may cause xerostomia. Good oral hygiene can alleviate the discomfort.
• Avoid activities requiring mental alertness until reaction to the drug has been evaluated.
• Avoid drinking alcoholic beverages. When combined with chlordiazepoxide, effects of both are potentiated.
• If pregnant during therapy or intending to become pregnant, communicate with physician about continuing therapy.
• Avoid excessive sunlight. Photosensitivity has been reported. Use sunscreen lotion (SPF 12 or above) if allowed.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug