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Chlordiazepoxide: Drug information

Chlordiazepoxide: Drug information
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For additional information see "Chlordiazepoxide: Patient drug information" and "Chlordiazepoxide: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
ALERT: US Boxed Warning
Risks from concomitant use of benzodiazepines and opioids:

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

Abuse, misuse, and addiction:

The use of benzodiazepines, including chlordiazepoxide, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing chlordiazepoxide and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.

Dependence and withdrawal reactions:

The continued use of benzodiazepines, including chlordiazepoxide, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of chlordiazepoxide after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide or reduce the dosage.

Pharmacologic Category
  • Benzodiazepine
Dosing: Adult

Dosage guidance:

Safety: Reduce dose or avoid use in patients receiving opioids or with significant chronic disease (eg, respiratory compromise) (Ref). Avoid use in patients with a history of substance use, misuse of medications, or depression (Ref).

Alcohol withdrawal syndrome, treatment

Alcohol withdrawal syndrome, treatment:

Note: Withdrawal will progress at different rates in some patients; flexibility in dosing and duration is warranted (Ref). Regimens vary and depend on withdrawal history, degree of current withdrawal symptoms, blood alcohol concentration, and whether the patient is treated inpatient or in the ambulatory setting. Many facilities only treat alcohol withdrawal in the ambulatory setting if Clinical Institute Withdrawal Assessment for Alcohol (CIWA-AR) score is ≤15 and there is no history of withdrawal seizures or delirium tremens (Ref). The following are 2 suggested regimens.

Symptom-triggered regimen:

Note: Some experts recommend symptom-triggered dosing for patients who score >15 on the CIWA-AR, revised scale (Ref).

Oral: 25 to 100 mg as needed per institution-specific protocol until appropriate sedation achieved; dose and frequency determined by withdrawal symptom severity using a validated severity assessment scale, such as the CIWA-AR (Ref).

Example regimen (Holt 2023):

Day 1: Oral: 50 mg every 6 hours.

Day 2: Oral: 50 mg every 8 hours.

Day 3: Oral: 50 mg every 12 hours.

Day 4: Oral: 50 mg once at bedtime.

Fixed regimen:

Note: Some experts recommend fixed-dose regimens for patients at risk for mild withdrawal (CIWA-AR ≤15), particularly in an ambulatory setting where CIWA-AR scores cannot be reliably administered (Ref). In addition to scheduled doses shown in the example regimen below, provide up to 5 additional as-needed 50 mg doses to be used over the 4-day treatment period for breakthrough symptoms (Ref).

Day 1: Oral: 50 mg every 4 to 6 hours.

Day 2: Oral: 50 mg every 8 to 12 hours.

Day 3: Oral: 50 mg every 12 to 24 hours.

Day 4: Oral: 25 mg every 12 to 24 hours, then discontinue chlordiazepoxide (Ref).

Anxiety disorders

Anxiety disorders (adjunctive therapy or monotherapy) (alternative agent):

Note: Generally used short-term for symptom relief until preferred therapy (eg, serotonin reuptake inhibitor) is effective (eg, 4 to 6 weeks, followed by tapering). Long-term low-dose therapy (eg, 5 mg/day) may be considered in select patients when other treatments are ineffective or poorly tolerated (Ref). Use with caution in patients with posttraumatic stress disorder; benzodiazepines may cause cognitive changes (Ref).

Usual range: Oral: 5 to 25 mg 2 to 4 times daily; increase gradually based on response and tolerability; patients with mild to moderate symptoms generally respond to total daily doses ≤40 mg. Maximum dose: 100 mg/day in divided doses.

Discontinuation of therapy: Unless safety concerns require a more rapid withdrawal, gradually taper to detect reemerging symptoms and minimize rebound and withdrawal symptoms (Ref).

Low or moderate dose, no concerns for benzodiazepine use disorder : Taper total daily dose by 20% to 25% every week based on response and tolerability (taper increments will be limited by available dosage forms) (Ref).

Extended or high-dose therapy, or suspected benzodiazepine use disorder: Taper total daily dose by approximately 25% every 1 to 2 weeks based on response, tolerability, and individual patient factors (taper increments will be limited by available dosage forms) (Ref). Reduce dose more rapidly in the beginning, and slow the dose reduction as the taper progresses because earlier stages of withdrawal are easier to tolerate (Ref). The optimal duration and taper increment will vary; up to 6 months may be necessary for some patients on higher doses, and a taper rate of 50% every week may be tolerated in some patients (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; however, the following recommendations have been used by some clinicians:

Adults:

CrCl ≥10 mL/minute: No dosage adjustment necessary (Ref).

CrCl <10 mL/minute: Administer 50% of dose (Ref).

Peritoneal dialysis: Administer 50% of dose (Ref).

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; however, chlordiazepoxide undergoes hepatic metabolism and should be used with caution.

Dosing: Older Adult

Alcohol withdrawal syndrome: Refer to adult dosing.

Anxiety disorders: Oral: Use lower initial doses of 5 mg 2 to 4 times daily and titrate slowly; refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Chlordiazepoxide: Pediatric drug information")

Anxiety

Anxiety: Note: Use of chlordiazepoxide as an anxiolytic has been replaced by newer agents (Ref). Children ≥6 years and Adolescents: Oral: Usual dose: 5 mg 2 to 4 times daily; may increase to 10 mg 2 to 3 times daily in some patients. Pediatric patients may have variable response; begin with the lowest dose and slowly titrate.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific dosage adjustments provided in the manufacturer’s labeling; in adult patients, dosage adjustment suggested.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, chlordiazepoxide undergoes hepatic metabolism and should be used with caution.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined

Cardiovascular: Edema, syncope

Central nervous system: Abnormal electroencephalogram, ataxia, confusion, drowsiness, drug-induced extrapyramidal reaction

Dermatologic: Skin rash

Endocrine & metabolic: Change in libido, menstrual disease

Gastrointestinal: Constipation, nausea

Hematologic & oncologic: Agranulocytosis, bone marrow depression

Hepatic: Hepatic insufficiency, jaundice

Miscellaneous: Paradoxical reaction

Contraindications

Hypersensitivity to chlordiazepoxide or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Anterograde amnesia: Benzodiazepines have been associated with anterograde amnesia (Nelson 1999).

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Paradoxical reactions: Paradoxical reactions, including hyperactive or aggressive behavior, have been reported with benzodiazepines; risk may be increased in adolescent/pediatric patients, geriatric patients, or patients with a history of alcohol use disorder or psychiatric/personality disorders (Mancuso 2004).

• Sleep-related activities: Hazardous sleep-related activities such as sleep-driving, cooking and eating food, and making phone calls while asleep have been noted with benzodiazepines (Dolder 2008).

Disease-related concerns:

• Depression: Avoid use in patients with depression because of concerns about worsening mood symptoms, particularly if suicidal risk may be present, except for acute or emergency situations (eg, acute agitation, status epilepticus) (Craske 2022).

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Porphyria: Use with caution in patients with porphyria.

• Renal impairment: Use with caution in patients with renal impairment.

• Respiratory disease: Reduce dose or avoid use in patients with respiratory disease, including chronic obstructive pulmonary disease or sleep apnea. Benzodiazepines may cause significant respiratory depression.

Special populations:

• Debilitated patients: Use with caution in debilitated patients; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects, including ataxia and over-sedation.

• Older adult: Avoid use; if used, use with caution in older adults; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects, including ataxia and over-sedation. Older adult patients may be at an increased risk of death with use; risk has been found highest within the first 4 months of use in older adult dementia patients (Jennum 2015; Saarelainen 2018).

• Fall risk: Use with extreme caution in patients who are at risk of falls; benzodiazepines have been associated with falls and traumatic injury (Nelson 1999).

• Pediatric: Use with caution in children; active metabolites with extended half-lives may lead to delayed accumulation and adverse effects, including ataxia and over-sedation.

Other warnings/precautions:

• Abuse, misuse, and substance use disorder: Counsel patients at increased risk on proper use and monitor for signs and symptoms of abuse, misuse, and substance use disorder. Institute early treatment or refer patients in whom substance use disorder is suspected. Limit dosages and durations to the minimum required.

• Dependence and withdrawal reactions: Some patients may develop a protracted withdrawal syndrome lasting >12 months; may be difficult to differentiate withdrawal symptoms from reemergence or continuation of symptoms for which benzodiazepines were prescribed. Flumazenil may cause withdrawal in patients receiving long-term benzodiazepine therapy.

• Tolerance: Chlordiazepoxide is a long half-life benzodiazepine. Duration of action after a single dose is determined by redistribution rather than metabolism. Tolerance does not develop to the anxiolytic effects (Vinkers 2012). Chronic use of this agent may increase the perioperative benzodiazepine dose needed to achieve desired sedative effect.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Generic: 5 mg, 10 mg, 25 mg

Generic Equivalent Available: US

Yes

Pricing: US

Capsules (chlordiazePOXIDE HCl Oral)

5 mg (per each): $0.35 - $19.90

10 mg (per each): $0.40 - $21.08

25 mg (per each): $0.43 - $22.33

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral, as hydrochloride:

Generic: 5 mg, 10 mg, 25 mg

Controlled Substance

C-IV

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/012249s049lbl.pdf#page=8, must be dispensed with this medication.

Use: Labeled Indications

Alcohol withdrawal syndrome: Management of acute alcohol withdrawal symptoms.

Anxiety disorders: Management of anxiety disorders or short-term relief of anxiety symptoms.

Medication Safety Issues
Sound-alike/look-alike issues:

ChlordiazePOXIDE may be confused with chlorproMAZINE or chlorothiazide

Librium may be confused with Librax

Older Adult: High-Risk Medication:

Beers Criteria: Chlordiazepoxide is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older due to risk of abuse, misuse, physical dependence, and addiction. In addition, older adults have an increased risk of impaired cognition, delirium, falls, fractures, and motor vehicle accidents with benzodiazepine use and slower metabolism of long-acting benzodiazepines (eg, chlordiazepoxide). However, benzodiazepines may be appropriate in the elderly when used for seizure disorders, rapid eye movement sleep behavior disorder, benzodiazepine or ethanol withdrawal, severe generalized anxiety disorder, or periprocedural anesthesia (Beers Criteria [AGS 2023]).

Metabolism/Transport Effects

Substrate of CYP3A4 (Major with inhibitors), CYP3A4 (Minor with inducers); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor

Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

ARIPiprazole Lauroxil: May increase CNS depressant effects of Benzodiazepines. ARIPiprazole Lauroxil may increase hypotensive effects of Benzodiazepines. Specifically, the risk of orthostatic hypotension may be increased. Risk C: Monitor

ARIPiprazole: May increase CNS depressant effects of Benzodiazepines. ARIPiprazole may increase hypotensive effects of Benzodiazepines. Specifically, orthostatic hypotension may be increased. Risk C: Monitor

Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification

Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Beta-Acetyldigoxin: Benzodiazepines may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor

Blonanserin: CNS Depressants may increase CNS depressant effects of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider Therapy Modification

Brexanolone: CNS Depressants may increase CNS depressant effects of Brexanolone. Risk C: Monitor

Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromopride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Buprenorphine: CNS Depressants may increase CNS depressant effects of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider Therapy Modification

BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor

Certoparin: May increase serum concentration of Benzodiazepines. Risk C: Monitor

Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification

Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification

Chlormethiazole: May increase CNS depressant effects of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider Therapy Modification

Chlorphenesin Carbamate: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Cimetidine: May increase serum concentration of ChlordiazePOXIDE. Risk C: Monitor

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

CloZAPine: Benzodiazepines may increase adverse/toxic effects of CloZAPine. Management: Consider decreasing the dose of (or possibly discontinuing) benzodiazepines prior to initiating clozapine. Monitor for respiratory depression, hypotension, and other toxicities if these agents are combined. Risk D: Consider Therapy Modification

CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Corticosteroids (Orally Inhaled): Benzodiazepines may increase adverse/toxic effects of Corticosteroids (Orally Inhaled). Specifically, the risk of pneumonia may be increased. Risk C: Monitor

CYP3A4 Inhibitors (Strong): May increase serum concentration of ChlordiazePOXIDE. Risk C: Monitor

Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Daridorexant: May increase CNS depressant effects of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider Therapy Modification

Difelikefalin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor

Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Disulfiram: May increase serum concentration of ChlordiazePOXIDE. Risk C: Monitor

Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor

DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification

Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor

Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid

Flunitrazepam: CNS Depressants may increase CNS depressant effects of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider Therapy Modification

Fosphenytoin-Phenytoin: ChlordiazePOXIDE may increase serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification

Ilaprazole: May increase serum concentration of Benzodiazepines. Risk C: Monitor

Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Lemborexant: May increase CNS depressant effects of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider Therapy Modification

Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification

Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Melatonin: May increase sedative effects of Benzodiazepines. Risk C: Monitor

Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Methadone: Benzodiazepines may increase CNS depressant effects of Methadone. Management: Clinicians should generally avoid concurrent use of methadone and benzodiazepines when possible; any combined use should be undertaken with extra caution. Risk D: Consider Therapy Modification

Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider Therapy Modification

Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor

Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid

OLANZapine: Benzodiazepines may increase adverse/toxic effects of OLANZapine. Management: Monitor closely for hypotension, respiratory or central nervous system depression, and bradycardia if olanzapine is combined with benzodiazepines. Use of parenteral benzodiazepines with IM olanzapine is not recommended. Risk C: Monitor

Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Opioid Agonists: CNS Depressants may increase CNS depressant effects of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid

Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid

Oxybate Salt Products: Benzodiazepines may increase CNS depressant effects of Oxybate Salt Products. Risk X: Avoid

OxyCODONE: CNS Depressants may increase CNS depressant effects of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider Therapy Modification

Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid

Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor

Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor

Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor

Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider Therapy Modification

ROPINIRole: CNS Depressants may increase sedative effects of ROPINIRole. Risk C: Monitor

Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor

Suvorexant: CNS Depressants may increase CNS depressant effects of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider Therapy Modification

Teduglutide: May increase serum concentration of Benzodiazepines. Risk C: Monitor

Thalidomide: CNS Depressants may increase CNS depressant effects of Thalidomide. Risk X: Avoid

Theophylline Derivatives: May decrease therapeutic effects of Benzodiazepines. Risk C: Monitor

Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor

Yohimbine: May decrease therapeutic effects of Antianxiety Agents. Risk C: Monitor

Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification

Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification

Reproductive Considerations

Evaluate pregnancy status prior to use. Pregnancy testing is recommended before treating acute alcohol withdrawal symptoms; however, treatment should not be delayed in symptomatic patients if pregnancy status is unknown (ASAM 2020).

Chlordiazepoxide is not a first line medication to treat anxiety disorders prior to conception in patients who are treatment naive or who do not have a history of effective treatment with a specific medication. Patients effectively treated may continue their current medication when planning a pregnancy, unless contraindications exist. Management of mental health conditions in patients who could become pregnant should be based on a shared decision-making process that considers the possibility of pregnancy during treatment (ACOG 2023; BAP [McAllister-Williams 2017]).

Pregnancy Considerations

Chlordiazepoxide crosses the human placenta and fetal serum concentrations are similar to those in the mother (Stirrat 1974).

In utero exposure to benzodiazepines has the potential to cause harm to the fetus. Teratogenic effects have been observed in some studies; however, a clear association has not been reported and additional data are needed (Bellantuono 2013; Chuang 2024; Freeman 2018; Grigoriadis 2019; Tinker 2019; Wu 2024). Exposure to a benzodiazepine late in pregnancy may cause neonatal sedation (hypotonia, lethargy, respiratory depression) and/or symptoms of neonatal withdrawal (feeding difficulties, hyperreflexia, inconsolable crying, irritability, restlessness, tremors). Monitor newborns exposed to chlordiazepoxide in utero for adverse events. Data related to long-term effects on neurodevelopment following maternal use of benzodiazepines are inconclusive (Andrade 2024; Radojčić 2017; Sundbakk 2025; Wang 2022).

Benzodiazepines are one of the preferred options for treating pregnant patients with alcohol withdrawal. Inpatient treatment is recommended during pregnancy. Agents with a shorter onset and duration of action should be used if near delivery. Monitor newborns for fetal alcohol spectrum disorder, sedative withdrawal, and intoxication (ASAM 2020).

Untreated and undertreated mental health conditions are associated with adverse pregnancy outcomes. Anxiety disorders during pregnancy are associated with low birth weight, preterm birth, and adverse behavioral outcomes in the offspring. Discontinuing effective medications during pregnancy increases the risk of relapse. Management should be made as part of a shared decision-making process. Agents other than chlordiazepoxide may be preferred when treatment for anxiety is initiated for the first time during pregnancy. The use of benzodiazepines for the treatment of perinatal anxiety should be avoided or used sparingly until preferred therapy is initiated and effective, or when preferred therapy is not effective. When medications are used, the lowest effective dose of a single agent is recommended. Optimize dosing prior to changing a medication or adding additional agents whenever possible. Monthly monitoring for symptom improvement with a validated screening tool during pregnancy is recommended. Manage side effects as needed (ACOG 2023).

Data collection to monitor pregnancy and infant outcomes following exposure to chlordiazepoxide is ongoing. Encourage pregnant patients to enroll in the National Pregnancy Registry for Psychiatric Medications (1-866-961-2388).

Breastfeeding Considerations

Benzodiazepines are present in breast milk.

Drowsiness, lethargy, or weight loss in breastfeeding infants have been observed in case reports following maternal use of some benzodiazepines (Iqbal 2002).

Due to the long half-life of chlordiazepoxide, the potential to accumulate in breast milk, and the potential for serious adverse events in a breastfed infant (eg, sedation, withdrawal), breastfeeding is not recommended by the manufacturer. A benzodiazepine with a short half-life can be considered for the treatment of anxiety in patients who are breastfeeding. Avoid benzodiazepines with long half-life or multiple active metabolites (Eleftheriou 2024).

Monitoring Parameters

Respiratory and cardiovascular status (including orthostasis); mental status; paradoxical reactions (eg, excitement, stimulation, acute rage); if used for ethanol withdrawal, signs/symptoms of ethanol withdrawal

Mechanism of Action

Long-acting benzodiazepine (Griffin 2013). Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the CNS, 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. Benzodiazepine receptors and effects appear to be linked to the GABA-A receptors. Benzodiazepines do not bind to GABA-B receptors (Vinkers 2012).

Pharmacokinetics (Adult Data Unless Noted)

Duration of action: Classified as a long-acting benzodiazepine; classification based on benzodiazepines with half-life >40 hours (Griffin 2013).

Distribution: Vd: 3.3 L/kg (Schwartz 1971)

Protein binding: 96% (Baskin 1982)

Metabolism: Extensively hepatic to desmethyldiazepam (active and long-acting), desmethylchlordiazepoxide, and demoxepam (Baskin 1982; Schwartz 1971).

Half-life elimination: Parent: 24 to 48 hours; demoxepam 14 to 95 hours (Schwartz 1971)

Time to peak, serum: 0.5 to 2 hours (Baskin 1982)

Excretion: Urine (1% to 2% unchanged; 3% to 6% as metabolite)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (CI) Côte d'Ivoire: Apo chlordiazepoxide;
  • (GB) United Kingdom: Calmoden | Chlordiazepox | Chlordiazepox aps | Chlordiazepox cox | Chlordiazepox dc | Chlordiazepox kent | Chlordiazepoxide | Chlordiazepoxide hydrochloride roche | Librium | Tropium;
  • (GR) Greece: Oasil;
  • (HK) Hong Kong: Chlordiazepoxide | Corlium | Litamin;
  • (ID) Indonesia: Librium | Tensinyl;
  • (IE) Ireland: Librium;
  • (IT) Italy: Librium | Reliberan;
  • (JP) Japan: Balance | Peast c;
  • (KR) Korea, Republic of: Clozepam | Liberty;
  • (LB) Lebanon: Psicodex;
  • (MA) Morocco: Librium;
  • (MX) Mexico: Kalmocaps;
  • (MY) Malaysia: Benpine | Chlordiazepoxide;
  • (NO) Norway: Librium;
  • (NZ) New Zealand: Nova-pam;
  • (PR) Puerto Rico: Chlordiazepox hydrochloride | Chlordiazepoxide | Chlordiazepoxide HCL | Librium;
  • (PT) Portugal: Lentotran;
  • (QA) Qatar: Librium;
  • (SG) Singapore: Apo chlordiazepoxide | Benpine | Klorpo;
  • (SR) Suriname: Apo chlordiazepoxide;
  • (TH) Thailand: Benpine | Chlordiazepoxide | Cozep | Epoxide | Lazep | Librium | Minoxide | Tranadon S | Vapine;
  • (TW) Taiwan: Anaten | Chlordiazepoxide | Dipoxido | E chun | Honcalm | Libmin | Librium | Lipolin | Livarium | Peace | Sugent | Suil | Zunchin;
  • (ZA) South Africa: Librium
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