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chlordiazepoxide (Librium)
Tradename: Librium. DEA-controlled substance: class 4.
Indications:
1) anxiety, apprehension
2) alcohol withdrawal [6]
3) tension headache
4) peptic ulcer
5) irritable bowel syndrome
Contraindications: Caution:
1) not drug of choice in the elderly
2) abrupt discontinuation may cause withdrawal
3) avoid alcohol & other CNS depressants
Dosage:
- anxiety, apprehension
- 5-25 mg PO TID/QID [1].
- 15-100 mg/24 hours in divided doses [2]
- alcohol withdrawal: 25-100 mg IV/IM every 2-4 hours (symptom-triggered) [6]
- maximum: up to 300 mg IM or IV in 6 hour period & no more than 300 mg in 24 hours
Tabs: 5, 10, 25 mg.
Powder for injection: 100 mg
Dosage adjustment in renal failure:
- for creatinine clearance < 10 mL/min, use 50% of dose
Pharmacokinetics:
1) peak effect after oral dose: < 2 hours
2) protein binding: 95%
3) metabolized by liver
4) 1/2life 6-30 hours
5) 1/2life prolonged in patients with liver disease
Adverse effects:
1) common (> 10%)
- drowsiness, fatigue, impaired coordination, lightheadedness, memory impairment, insomnia, dysarthria, anxiety, decreased libido, depression, headache, dry mouth, decreased salivation, constipation, nausea/vomiting, diarrhea, tachycardia, chest pain, blurred vision, sweating, rash, increased or decreased appetitite
2) less common (1-10%)
- confusion, nervousness, syncope, dizziness, akathisia, increased salivation, hypotension, rigidity, tremor, dermatitis, nasal congestion, weight gain or weight loss, hyperventilation, tinnitus, muscle cramps
3) uncommon (< 1%)
- menstrual irregularities, blood dyscrasias, reflex slowing, drug dependence & withdrawal
4) other
- depression
- agitation
- anterograde amnesia
- hiccups
Drug interactions:
1) disulfiram, nefazodone, fluoxetine, fluvoxamine, cimetidine, erythromycin, estrogens & grapefruit juice increase chlordiazepoxide levels
2) CNS depressants including tricyclic antidepressants (TCA) increase CNS depressive effects of chlordiazepoxide
3) anti-epileptic agents & rifampin increase the metabolism of chlordiazepoxide
4) flumazenil (Romazicon) antagonizes the effects of benzodiazepines
5) carbamazepine may increase metabolism
Laboratory:
1) specimen:
a) serum, plasma (EDTA)
b) collect at trough concentration
2) methods: HPLC, GLC, RIA
3) laboratories with Loincs
- chlordiazepoxide in specimen
- chlordiazepoxide in hair
- chlordiazepoxide in tissue
- chlordiazepoxide in body fluid
- chlordiazepoxide in blood
- chlordiazepoxide in gastric fluid
- chlordiazepoxide in meconium
- chlordiazepoxide in serum/plasma
- chlordiazepoxide in stool
- chlordiazepoxide in urine
- chlordiazepoxide in vitreous fluid
Mechanism of action:
- potentiates inhibitory effects of GABA by increasing neuronal membrane permeability to chloride
Interactions
drug interactions
drug adverse effects (more general classes)
General
benzodiazepine
Properties
MISC-INFO: elimination route LIVER
1/2life 6-30 HOURS
therapeutic-range 700-1000 NG/ML
toxic-range >5000 NG/ML
protein-binding 95%
elimination by hemodialysis -
pregnancy-category D
safety in lactation -
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996.
- Manual of Medical Therapeutics, 28th ed, Ewald &
McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 7
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed.,
W.B. Saunders, 1995
- Medical Knowledge Self Assessment Program (MKSAP) 19.
American College of Physicians, Philadelphia 2021
Component-of
amitriptyline/chlordiazepoxide (Limbitrol)
chlordiazepoxide/clidinium (Librax)
chlordiazepoxide/methscopolamine (Librax refomulated)
Librax