More information about Chlordiazepoxide
Pronunciation(klor dye az e POKS ide)
U.S. Brand NamesLibrium®
Generic AvailableYes: Capsule
Canadian Brand NamesApo-Chlordiazepoxide®
UseManagement of anxiety disorder or for the short-term relief of symptoms of anxiety; withdrawal symptoms of acute alcoholism; preoperative apprehension and anxiety
Pregnancy Risk FactorD
LactationEnters breast milk/not recommended
ContraindicationsHypersensitivity to chlordiazepoxide or any component of the formulation (cross-sensitivity with other benzodiazepines may also exist); narrow-angle glaucoma; pregnancy
Warnings/PrecautionsActive metabolites with extended half-lives may lead to delayed accumulation and adverse effects. Use with caution in elderly or debilitated patients, pediatric patients, patients with hepatic disease (including alcoholics) or renal impairment. Use with caution in patients with respiratory disease or impaired gag reflex. Use with caution in patients with porphyria.
Parenteral administration should be avoided in comatose patients or shock. Adequate resuscitative equipment/personnel should be available, and appropriate monitoring should be conducted at the time of injection and for several hours following administration. The parenteral formulation should be diluted for I.M. administration with the supplied diluent only. This diluent should not be used when preparing the drug for intravenous administration.
Causes CNS depression (dose-related) resulting in sedation, dizziness, confusion, or ataxia which may impair physical and mental capabilities. Patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Use with caution in patients receiving other CNS depressants or psychoactive agents (lithium, phenothiazines). Effects with other sedative drugs or ethanol may be potentiated. Benzodiazepines have been associated with falls and traumatic injury and should be used with extreme caution in patients who are at risk of these events (especially the elderly).
Use caution in patients with depression, particularly if suicidal risk may be present. Use with caution in patients with a history of drug dependence. Benzodiazepines have been associated with dependence and acute withdrawal symptoms on discontinuation or reduction in dose. Acute withdrawal, including seizures, may be precipitated in patients after administration of flumazenil to patients receiving long-term benzodiazepine therapy.
Benzodiazepines have been associated with anterograde amnesia. Paradoxical reactions, including hyperactive or aggressive behavior have been reported with benzodiazepines, particularly in adolescent/pediatric or psychiatric patients. Does not have analgesic, antidepressant, or antipsychotic properties.
Central nervous system: Drowsiness, fatigue, ataxia, lightheadedness, memory impairment, dysarthria, irritability
Endocrine & metabolic: Decreased libido, menstrual disorders
Gastrointestinal: Xerostomia, decreased salivation, increased or decreased appetite, weight gain/loss
Genitourinary: Micturition difficulties
1% to 10%:
Central nervous system: Confusion, dizziness, disinhibition, akathisia, increased libido
Gastrointestinal: Increased salivation
Genitourinary: Sexual dysfunction, incontinence
Neuromuscular & skeletal: Rigidity, tremor, muscle cramps
Respiratory: Nasal congestion
Overdosage/ToxicologySymptoms of overdose include hypotension, respiratory depression, coma, hypothermia, and cardiac arrhythmias. Treatment for benzodiazepine overdose is supportive. Flumazenil has been shown to selectively block the binding of benzodiazepines to CNS receptors, resulting in a reversal of benzodiazepine-induced CNS depression. Respiratory depression may not be reversed.
Drug InteractionsSubstrate of CYP3A4 (major)
CNS depressants: Sedative effects and/or respiratory depression may be additive with CNS depressants; includes ethanol, barbiturates, narcotic analgesics, and other sedative agents; monitor for increased effect
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of chlordiazepoxide. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of chlordiazepoxide. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.
Levodopa: Therapeutic effects may be diminished in some patients following the addition of a benzodiazepine; limited/inconsistent data
Oral contraceptives: May decrease the clearance of some benzodiazepines (those which undergo oxidative metabolism); monitor for increased benzodiazepine effect
Theophylline: May partially antagonize some of the effects of benzodiazepines; monitor for decreased response; may require higher doses for sedation
Ethanol: Avoid ethanol (may increase CNS depression).
Food: Serum concentrations/effects may be increased with grapefruit juice, but unlikely because of high oral bioavailability of chlordiazepoxide.
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
StabilityInjection: Prior to reconstitution, store under refrigeration and protect from light. Solution should be used immediately following reconstitution.
I.M. use: Reconstitute by adding 2 mL of provided diluent; agitate gently until dissolved. Provided diluent is not for I.V. use.
I.V. use: Reconstitute by adding 5 mL NS or SWFI; agitate gently until dissolved; do not administer this dilution I.M.
CompatibilityStable in D5W; incompatible (consult detailed reference) in Ringer's injection, NS
Y-site administration: Compatible: Heparin, hydrocortisone sodium succinate, potassium chloride, vitamin B complex with C. Incompatible: Cefepime
Mechanism of ActionBinds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system, reticular formation. Enhancement of the inhibitory effect of GABA on neuronal excitability results by increased neuronal membrane permeability to chloride ions. This shift in chloride ions results in hyperpolarization (a less excitable state) and stabilization.
Distribution: Vd: 3.3 L/kg; crosses placenta; enters breast milk
Protein binding: 90% to 98%
Metabolism: Extensively hepatic to desmethyldiazepam (active and long-acting)
Half-life elimination: 6.6-25 hours; End-stage renal disease: 5-30 hours; Cirrhosis: 30-63 hours
Time to peak, serum: Oral: Within 2 hours; I.M.: Results in lower peak plasma levels than oral
Excretion: Urine (minimal as unchanged drug)
<6 years: Not recommended
>6 years: Anxiety: Oral, I.M.: 0.5 mg/kg/24 hours divided every 6-8 hours
Oral: 15-100 mg divided 3-4 times/day
I.M., I.V.: Initial: 50-100 mg followed by 25-50 mg 3-4 times/day as needed
Preoperative anxiety: I.M.: 50-100 mg prior to surgery
Ethanol withdrawal symptoms: Oral, I.V.: 50-100 mg to start, dose may be repeated in 2-4 hours as necessary to a maximum of 300 mg/24 hours
Note: Up to 300 mg may be given I.M. or I.V. during a 6-hour period, but not more than this in any 24-hour period.
Dosing adjustment in renal impairment: Clcr<10 mL/minute: Administer 50% of dose
Hemodialysis: Not dialyzable (0% to 5%)
Dosing adjustment/comments in hepatic impairment: Avoid use
I.M.: Administer by deep I.M. injection slowly into the upper outer quadrant of the gluteus muscle; use only the diluent provided for I.M. use; solutions made with SWFI or NS cause pain with I.M. administration
I.V.: Administer slowly over at least 1 minute; do not use the diluent provided for I.M. use; air bubbles form during reconstitution
Monitoring ParametersRespiratory and cardiovascular status, mental status, check for orthostasis
Reference RangeTherapeutic: 0.1-3 mcg/mL (SI: 0-10
Patient EducationOral: Take exactly as directed; do not increase dose or frequency. Drug may cause physical and/or psychological dependence. Do not use alcohol or other prescription or OTC medications (especially pain medications, sedatives, antihistamines, or hypnotics) without consulting prescriber. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. You may experience drowsiness, lightheadedness, impaired coordination, dizziness, or blurred vision (use caution when driving or engaging in tasks requiring alertness until response to drug is known); dry mouth (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, fruit, or fiber may help); or altered sexual drive or ability (reversible). Report persistent CNS effects (eg, euphoria, confusion, increased sedation, depression); chest pain, palpitations, or rapid heartbeat; muscle cramping, weakness, tremors, rigidity, or altered gait; or worsening of condition. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication; use appropriate contraceptive measures. Breast-feeding is not recommended.
Nursing ImplicationsRaise bed rails; initiate safety measures; aid with ambulation
Additional InformationAbrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms.
Anesthesia and Critical Care Concerns/Other ConsiderationsChronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired effect. Abrupt discontinuation after sustained use (generally >10 days) may cause withdrawal symptoms.
Dental Health: Effects on Dental TreatmentKey adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).
Dental Health: Vasoconstrictor/Local Anesthetic PrecautionsNo information available to require special precautions
Capsule, as hydrochloride: 5 mg, 10 mg, 25 mg
Injection, powder for reconstitution, as hydrochloride: 100 mg [diluent contains benzyl alcohol, polysorbate 80, and propylene glycol]
Bailey DN, "Blood Concentrations and Clinical Findings Following Overdose of Chlordiazepoxide Alone and Chlordiazepoxide Plus Ethanol,"Clin Toxicol, 1984, 22(5):433-46.
Burkhart KK and Kulig KW, "The Diagnostic Utility of Flumazenil (A Benzodiazepine Antagonist) in Coma of Unknown Etiology,"Ann Emerg Med, 1990, 19(3):319-21.
Hicks R, Dysken MW, Davis JM, et al, "The Pharmacokinetics of Psychotropic Medication in the Elderly: A Review,"J Clin Psychiatry, 1981, 42(10):374-85.
Minder EI, "Toxicity in a Case of Acute and Massive Overdose of Chlordiazepoxide and Its Correlation to Blood Concentration,"J Toxicol Clin Toxicol, 1989, 27(1-2):117-27.
Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.
Reidenberg MM, Levy M, Warner H, et al, "Relationship Between Diazepam Dose, Plasma Level, Age, and Central Nervous System Depression,"Clin Pharmacol Ther, 1978, 23(4):371-4.
International Brand NamesApo-Chlordiazepoxide® (CA); Benpine® (SG, TH); Cetabrium® (ID); Chlordiazepoxide® (GB); Chlordiazepoxid-LFM.® (HU); Clordiazepoxido L.CH.® (CL); Clorodiazepoxido® (CL); Defobin® (CZ); Elenium® (CZ, HU, PL); Epoxide® (TH); Equilibrium® (IN); Huberplex® (ES); Iremal® (CY); Kalmocaps® (DO, GT, HN, SV); Klopoxid Dak® (DK); Klorpo® (SG); Librium® (DE, GB, HU, IE, IN, IT, RO, ZA); Multum® (DE); Napoton® (RO); Neo Gnostoride® (GR); Novapam® (NZ); Oasil® (GR); O.C.M.® (AR); Omnalio® (ES); Paxium® (PT); Psico Blocan® (ES); Psicosedin® (BR); Radepur® (CZ, DE); Reliberan® (IT); Risolid® (DK, FI); Tensinyl® (ID); Tropium® (GB)