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Clorazepate: Pediatric drug information

Clorazepate: Pediatric drug information
2025© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Clorazepate: Drug information" and "Clorazepate: Patient drug information"

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

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

Abuse, misuse, and addiction:

The use of benzodiazepines, including clorazepate, 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 clorazepate and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.

Dependence and withdrawal reactions:

The continued use of benzodiazepines, including clorazepate, 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 clorazepate 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 clorazepate or reduce the dosage.

Brand Names: US
  • Tranxene-T [DSC]
Therapeutic Category
  • Antiseizure Agent, Benzodiazepine;
  • Benzodiazepine;
  • Sedative
Dosing: Pediatric
Partial seizures, adjunctive therapy

Partial seizures, adjunctive therapy:

Children <9 years: Limited data available: Oral: Initial: 0.3 to 0.75 mg/kg/day in 1 to 3 divided doses or 3.75 mg once to three times daily; maximum initial daily dose: 1 mg/kg/day. Titrate weekly as needed; maximum daily dose: 3 mg/kg/day or 60 mg/day, whichever is less. In trials, subjects observed as having an excellent response reported a mean dose range of 0.79 to 1.33 mg/kg/day (Ref).

Children 9 to 12 years: Oral: Initial: Up to 7.5 mg twice daily; increase in ≤7.5 mg increments at weekly intervals, maximum daily dose: 60 mg/day.

Adolescents: Oral: Initial: Up to 7.5 mg 3 times daily; increase in ≤7.5 mg increments at weekly intervals; usual dose range: 0.5 to 1 mg/kg/day; maximum daily dose: 90 mg/day.

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 dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Liver Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Adult

(For additional information see "Clorazepate: Drug information")

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).

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, 3.75 mg) may be considered in select patients only when other treatments are ineffective or poorly tolerated (Ref). Use with caution in patients with comorbid posttraumatic stress disorder; benzodiazepines may cause cognitive changes (Ref).

Initial: Oral: 7.5 to 15 mg at bedtime or 7.5 mg 2 to 3 times daily; if needed, may increase daily dose gradually (eg, in 7.5 mg increments every 3 to 4 days) based on response and tolerability up to 60 mg/day in 3 to 4 divided doses (Ref). Usual dosage: 30 mg/day in divided doses.

Focal onset seizures

Focal (partial) onset seizures (adjunctive therapy):

Note: FDA-approved for focal (partial) onset seizures; however, also used off label in other seizure types, including myoclonic and atonic seizures (Ref).

Initial: Ora l: Up to 7.5 mg 3 times daily; increase daily dose in ≤7.5 mg increments at weekly intervals; maximum dose: 90 mg/day.

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 ~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. Use with caution; clorazepate is primarily excreted in urine.

Dosing: Liver Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; clorazepate undergoes hepatic metabolism.

Adverse Reactions

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

Frequency not defined:

Cardiovascular: Systolic hypotension

Dermatologic: Skin rash

Gastrointestinal: Gastrointestinal signs and symptoms, xerostomia

Genitourinary: Genitourinary signs and symptoms

Hematologic & oncologic: Decreased hematocrit

Hepatic: Abnormal hepatic function tests

Nervous system: Ataxia, confusion, depression, dizziness, drowsiness, drug abuse, drug dependence, fatigue, headache, insomnia, irritability, nervousness, slurred speech, suicidal ideation, suicidal tendencies, tremor

Ophthalmic: Blurred vision, diplopia

Renal: Renal function test abnormality

Contraindications

Hypersensitivity to clorazepate or any component of the formulation; acute narrow-angle glaucoma

Canadian labeling: Additional contraindications (not in US labeling): Myasthenia gravis.

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 that 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).

• Suicidal ideation: Pooled analysis of trials involving various antiseizure medications (regardless of indication) showed an increased risk of suicidal thoughts/behavior (incidence rate: 0.43% treated patients compared to 0.24% of patients receiving placebo); risk observed as early as 1 week after initiation and continued through duration of trials (most trials ≤24 weeks). Monitor all patients for notable changes in behavior that might indicate suicidal thoughts or depression; notify health care provider immediately if symptoms occur.

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.

• 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 patients who are debilitated (eg, patients with organ dysfunction, comorbid conditions); dosage adjustment recommended.

• Older adult: Avoid or use with extreme caution in older adult patients. 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).

Other warnings/precautions:

• Abuse, misuse, and substance use disorder: Counsel patients at increased risk on proper use and monitoring 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.

• Appropriate use: Does not have analgesic, antidepressant, or antipsychotic properties. Not recommended for use in psychotic reactions.

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

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral, as dipotassium:

Tranxene-T: 7.5 mg [DSC] [contains fd&c yellow #6 (sunset yellow)]

Generic: 3.75 mg, 7.5 mg, 15 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Clorazepate Dipotassium Oral)

3.75 mg (per each): $1.19 - $4.03

7.5 mg (per each): $1.67 - $5.02

15 mg (per each): $2.75 - $5.45

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:

Generic: 3.75 mg, 7.5 mg, 15 mg

Controlled Substance

C-IV

Administration: Pediatric

Oral: May administer with food or water to decrease GI upset

Administration: Adult

May administer with food or water to decrease GI upset.

Storage/Stability

Store at 20°C to 25°C (68°F to 77°F). Protect from moisture and light.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/017105s085lbl.pdf#page=14, must be dispensed with this medication.

Use

Adjunct antiseizure medication in the management of partial seizures (FDA approved in ages ≥9 years and adults); treatment of anxiety disorders (FDA approved in adults); management of alcohol withdrawal (FDA approved in adults). Note: Although included as an FDA-approved use in the manufacturer's prescribing information for the symptomatic relief of acute alcohol withdrawal, guidelines do not mention clorazepate as a therapeutic option (ASAM 2020; WFSBP [Soyka 2017]).

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

Clorazepate may be confused with clofibrate, clonazepam, KlonoPIN

Older Adult: High-Risk Medication:

Beers Criteria: Clorazepate 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. Older adults also have slower metabolism of long-acting benzodiazepines (eg, clorazepate). 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 (Minor); 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.

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

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

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

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

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

Fosamprenavir: May increase serum concentration of Clorazepate. Risk C: Monitor

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

Nirmatrelvir and Ritonavir: May increase serum concentration of Clorazepate. 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

Ritonavir: May increase serum concentration of Clorazepate. 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

Saquinavir: May increase serum concentration of Clorazepate. 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

Tobacco (Smoked): May decrease active metabolite exposure of Clorazepate. 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

Clorazepate is not a first-line medication to treat anxiety disorders prior to conception in patients who are treatment naïve 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]).

Manage epilepsy in patients who could become pregnant based on a shared decision-making process that optimizes seizure control and considers the possibility of pregnancy during treatment (Pack 2024). Regularly discuss age-specific and developmental needs, including pregnancy planning and contraceptive options during the patient's reproductive lifespan (ACOG 806 2020; NICE NG217 2022).

Pregnancy Considerations

Nordiazepam, the active metabolite of clorazepate, crosses the placenta and is measurable in cord blood and amniotic fluid (Rey 1979).

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 clorazepate 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 2024; Wang 2022).

Epilepsy is associated with adverse maternal and fetal outcomes (Kuang 2024; Mazzone 2023). Convulsive seizures should be minimized to reduce risks to the fetus and pregnant patient. Use caution if removing or replacing an effective seizure medication in patients who become pregnant during therapy. Folic acid supplementation prior to and during pregnancy minimizes the risk of congenital malformations and poor neurodevelopment (Pack 2024).

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 clorazepate 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 is ongoing. Encourage pregnant patients to enroll in the National Pregnancy Registry for Psychiatric Medications (1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/).

Monitoring Parameters

Excessive CNS depression, respiratory rate, and cardiovascular status; with prolonged use: CBC, liver enzymes, renal function; signs and symptoms of suicidality (eg, anxiety, depression, behavior changes)

Mechanism of Action

Long-acting benzodiazepine (Griffin 2013). Binds to stereospecific benzodiazepine receptors on the postsynaptic GABA neuron at several sites within the central nervous system, including the limbic system and 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 (Nelson 1999).

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: Nordiazepam: Vd: 0.7 to 2.2 L/kg (Riss, 2008)

Protein binding: Nordiazepam: 97% to 98%

Metabolism: Rapidly decarboxylated to nordiazepam (active) in acidic stomach prior to absorption; nordiazepam is hepatically hydroxylated by CYP 2C19 and CYP3A4 to oxazepam (active) and undergoes glucuronidation to form a glucuronide conjugate (Riss, 2008)

Half-life elimination: Nordiazepam: 20 to 160 hours; Oxazepam: 6 to 24 hours (Riss, 2008)

Time to peak, serum: ~0.5 to 2 hours (Carrigan, 1977; Riss, 2008)

Excretion: Urine (62% to 67%; primarily metabolites of conjugated oxazepam); feces (15% to 19%)

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

  • (AE) United Arab Emirates: Tranxene;
  • (AR) Argentina: Justum | Moderane | Modiur Disgrelent | Tencilan | Tranxilium;
  • (AT) Austria: Tranxilium;
  • (BE) Belgium: Tranxene | Uni-tranxene;
  • (BG) Bulgaria: Tranxene;
  • (BR) Brazil: Tranxilene;
  • (CH) Switzerland: Clorazepate zentiva | Tranxilium;
  • (CL) Chile: Calner | Modival | Tranxilium;
  • (CZ) Czech Republic: Tranxene;
  • (DE) Germany: Tranxilium;
  • (DO) Dominican Republic: Nansius | Tranxene;
  • (EC) Ecuador: Tranxene;
  • (EE) Estonia: Tranxene;
  • (EG) Egypt: Tranxene;
  • (ES) Spain: Clorazepato Normon | Nansius | Tranxilium;
  • (FI) Finland: Anxidin | Tranxilen;
  • (FR) France: Clorazepate dipota | Tranxene;
  • (GB) United Kingdom: Tranxene;
  • (GR) Greece: Tranxene;
  • (HK) Hong Kong: Tranxene;
  • (ID) Indonesia: Tranxene;
  • (IE) Ireland: Tranxene;
  • (IL) Israel: Tranxal;
  • (IT) Italy: Transene;
  • (JO) Jordan: Tranxene;
  • (JP) Japan: Mendon;
  • (KR) Korea, Republic of: Tranxene | Trisan;
  • (LB) Lebanon: Tranxene;
  • (LT) Lithuania: Tranxene;
  • (LU) Luxembourg: Tranxene;
  • (LV) Latvia: Tranxene;
  • (MA) Morocco: Tranxene | Tranxilium;
  • (MX) Mexico: Tranxene;
  • (MY) Malaysia: Apo-clorazepate | Sanor | Tranxene;
  • (NL) Netherlands: Clorazepaat | Clorazepaatdik | Clorazepaatdikalium pch | Tranxene | Tranxilium;
  • (PE) Peru: Ansiopaz | Tranxene;
  • (PH) Philippines: Tranxene;
  • (PK) Pakistan: Tranconil | Tranxene;
  • (PL) Poland: Cloranxen | Tranxene;
  • (PT) Portugal: Medipax | Tranxene;
  • (RU) Russian Federation: Tranxene;
  • (SA) Saudi Arabia: Tranxene;
  • (SE) Sweden: Tranxilen;
  • (SG) Singapore: Tranxene;
  • (SI) Slovenia: Tranxene;
  • (SK) Slovakia: Tranxene;
  • (TH) Thailand: Anxielax | Cexene | Chloraze | Cloramed | Cloraxene | Clozene | Deda | Diposep | Dipot | Dipotassium chlorazepate | Flulium | Frexene | Gaxene | Manotran | Polizep | Pomadom | Posene | Sanor | Serene | Trancap | Tranclor | Trancon | Tranmed | Tranpate | Tranpon | Transon | Tranxene | Tranzep | Uptran | Zetran-5;
  • (TN) Tunisia: Tranxene;
  • (TR) Turkey: Anksen | Tranxilene;
  • (TW) Taiwan: Clozene | Tranxene | Tranxilium;
  • (UA) Ukraine: Tranxene;
  • (UY) Uruguay: Ansiopax | Tranxene;
  • (VE) Venezuela, Bolivarian Republic of: Tranxen;
  • (ZA) South Africa: Tranxene
  1. 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372 [PubMed 37139824]
  2. American College of Obstetricians and Gynecologists (ACOG). Gynecologic management of adolescents and young women with seizure disorders: ACOG Committee Opinion, Number 806. Obstet Gynecol. 2020;135(5):e213-e220. doi:10.1097/AOG.0000000000003827 [PubMed 32332416]
  3. American College of Obstetricians and Gynecologists (ACOG). Treatment and management of mental health conditions during pregnancy and postpartum: ACOG Clinical Practice Guideline No. 5. Obstet Gynecol. 2023;141(6):1262-1288. doi:10.1097/AOG.0000000000005202 [PubMed 37486661]
  4. American Society of Addiction Medicine (ASAM). The ASAM clinical practice guideline on alcohol withdrawal management. J Addict Med. 2020;14(3S)(suppl 1):1-72. doi:10.1097/ADM.0000000000000668 [PubMed 32511109]
  5. Andrade C, Varadharajan N, Bascarane S, Menon V. Gestational exposure to benzodiazepines or z-hypnotics and neurodevelopmental disorders in offspring: systematic review and meta-analysis. Acta Psychiatr Scand. 2024;150(2):65-77. doi:10.1111/acps.13696 [PubMed 38751163]
  6. Bandelow B, Allgulander C, Baldwin DS, et al. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for treatment of anxiety, obsessive-compulsive and posttraumatic stress disorders - version 3. Part I: anxiety disorders. World J Biol Psychiatry. 2023;24(2):79-117. doi:10.1080/15622975.2022.2086295 [PubMed 35900161]
  7. Bellantuono C, Tofani S, Di Sciascio G, Santone G. Benzodiazepine exposure in pregnancy and risk of major malformations: a critical overview. Gen Hosp Psychiatry. 2013;35(1):3-8. doi:10.1016/j.genhosppsych.2012.09.003 [PubMed 23044244]
  8. Carrigan PJ, Chao GC, Barker WM, Hoffman DJ, Chun AH. Steady-state bioavailability of two clorazepate dipotassium dosage forms. J Clin Pharmacol. 1977;17(1):18-28. [PubMed 13089]
  9. Chen VC, Wu SI, Lin CF, et al. Association of prenatal exposure to benzodiazepines with development of autism spectrum and attention-deficit/hyperactivity disorders. JAMA Netw Open. 2022;5(11):e2243282. doi:10.1001/jamanetworkopen.2022.43282 [PubMed 36413366]
  10. Chuang HM, Meng LC, Lin CW, et al. Concomitant use of antidepressants and benzodiazepines during pregnancy and associated risk of congenital malformations: a population-based cohort study in Taiwan. Lancet Psychiatry. 2024;11(8):601-610. doi:10.1016/S2215-0366(24)00176-7 [PubMed 38968942]
  11. Clorazepate [product monograph]. Vaughan, Ontario, Canada: AA Pharma Inc; December 2021.
  12. Clorazepate dipotassium tablets, USP [prescribing information]. East Windsor, NJ: Novitium Pharma LLC; February 2023.
  13. Clorazepate dipotassium tablets, USP [prescribing information]. Hawthrone, NY: Taro Pharmaceuticals USA Inc; November 2023.
  14. Craske M, Bystritsky A. Generalized anxiety disorder in adults: management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 19, 2022.
  15. Currow DC, Agar MR. Benzodiazepine prescribing in people with chronic obstructive pulmonary disease: clinical considerations. Drugs Aging. 2020;37(4):263-270. doi:10.1007/s40266-020-00756-z [PubMed 32107742]
  16. Dolder CR, Nelson MH. Hypnosedative-induced complex behaviours: incidence, mechanisms and management. CNS Drugs. 2008;22(12):1021-1036. doi:10.2165/0023210-200822120-00005. [PubMed 18998740]
  17. Eleftheriou G, Zandonella Callegher R, et al. Consensus panel recommendations for the pharmacological management of breastfeeding women with postpartum depression. Int J Environ Res Public Health. 2024;21(5):551. doi:10.3390/ijerph21050551 [PubMed 38791766]
  18. Freeman MP, Góez-Mogollón L, McInerney KA, et al. Obstetrical and neonatal outcomes after benzodiazepine exposure during pregnancy: results from a prospective registry of women with psychiatric disorders. Gen Hosp Psychiatry. 2018;53:73-79. doi:10.1016/j.genhosppsych.2018.05.010 [PubMed 29958100]
  19. Fujii T, Okuno T, Go T, et al, “Clorazepate Therapy for Intractable Epilepsy,” Brain Dev, 1987, 9(3):288-91. [PubMed 2889387]
  20. Grigoriadis S, Graves L, Peer M, et al. Benzodiazepine use during pregnancy alone or in combination with an antidepressant and congenital malformations: systematic review and meta-analysis. J Clin Psychiatry. 2019;80(4):18r12412. doi:10.4088/JCP.18r12412 [PubMed 31294935]
  21. Griffin CE 3rd, Kaye AM, Bueno FR, Kaye AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013;13(2):214-223. [PubMed 23789008]
  22. Iqbal MM, Sobhan T, Ryals T. Effects of commonly used benzodiazepines on the fetus, the neonate, and the nursing infant. Psychiatr Serv. 2002;53(1):39-49. [PubMed 11773648]
  23. Jennum P, Baandrup L, Ibsen R, et al. Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study. Eur Neuropsychopharmacol. 2015;25(11):1906-1913. doi: 10.1016/j.euroneuro.2015.08.014. [PubMed 26342397]
  24. Katzman MA, Bleau P, Blier P, et al; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles anxieux and McGill University. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(suppl 1):S1. doi:10.1186/1471-244X-14-S1-S1 [PubMed 25081580]
  25. Kuang H, Li Y, Lu Y, Zhang L, Wei L, Wu Y. Reproductive and fetal outcomes in women with epilepsy: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2024;37(1):2351196. doi:10.1080/14767058.2024.2351196 [PubMed 38735863]
  26. Lader M. Benzodiazepines revisited--will we ever learn? Addiction. 2011;106(12):2086‐2109. doi:10.1111/j.1360-0443.2011.03563.x [PubMed 21714826]
  27. Mancuso CE, Tanzi MG, Gabay M. Paradoxical reactions to benzodiazepines: literature review and treatment options. Pharmacotherapy. 2004;24(9):1177-1185. [PubMed 15460178]
  28. Mazzone PP, Hogg KM, Weir CJ, Stephen J, Bhattacharya S, Chin RFM. Comparison of perinatal outcomes for women with and without epilepsy: a systematic review and meta-analysis. JAMA Neurol. 2023;80(5):484-494. doi:10.1001/jamaneurol.2023.0148 [PubMed 36912826]
  29. McAllister-Williams RH, Baldwin DS, Cantwell R, et al. British Association for Psychopharmacology consensus guidance on the use of psychotropic medication preconception, in pregnancy and postpartum 2017. J Psychopharmacol. 2017;31(5):519-552. doi:10.1177/0269881117699361 [PubMed 28440103]
  30. Menninger JA. Assessment and treatment of alcoholism and substance-related disorders in the elderly. Bull Menninger Clin. 2002;66(2):166-183. [PubMed 12141383]
  31. Mimaki T, Tagawa T, Ono J, et al. Antiepileptic effect and serum levels of clorazepate on children with refractory seizures. Brain Dev. 1984;6(6):539-544. [PubMed 6152517]
  32. Naidu S, Gruener G, Brazis P. Excellent results with clorazepate in recalcitrant childhood epilepsies. Pediatr Neurol. 1986;2(1):18-22. [PubMed 2907857]
  33. National Institute for Health and Care Excellence (NICE). Epilepsies in children, young people and adults. https://www.nice.org.uk/guidance/ng217. Published April 27, 2022. Accessed June 19, 2024.
  34. Nelson J, Chouinard G. Guidelines for the clinical use of benzodiazepines: pharmacokinetics, dependency, rebound and withdrawal. Canadian Society for Clinical Pharmacology. Can J Clin Pharmacol. 1999;6(2):69-83. [PubMed 10519733]
  35. Pack AM, Oskoui M, Williams Roberson S, et al. Teratogenesis, perinatal, and neurodevelopmental outcomes after in utero exposure to antiseizure medication: practice guideline from the AAN, AES, and SMFM. Neurology. 2024;102(11):e209279. doi:10.1212/WNL.0000000000209279 [PubMed 38748979]
  36. Park TW. Benzodiazepine use disorder. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 12, 2022.
  37. Patel DA and Patel AR, “Clorazepate and Congenital Malformations,” JAMA, 1980, 244(2):135-6. [PubMed 6103970]
  38. Radojčić MR, El Marroun H, Miljković B, et al. Prenatal exposure to anxiolytic and hypnotic medication in relation to behavioral problems in childhood: a population-based cohort study. Neurotoxicol Teratol. 2017;61:58-65. doi:10.1016/j.ntt.2017.02.005 [PubMed 28259732]
  39. Refer to manufacturer's labeling.
  40. Rey E, Giraux P, d'Athis P, Turquais JM, Chavinie J, Olive G. Pharmacokinetics of the placental transfer and distribution of clorazepate and its metabolite nordiazepam in the feto-placental unit and in the neonate. Eur J Clin Pharmacol. 1979;15(3):181-185. doi:10.1007/BF00563103 [PubMed 37090]
  41. Rickels K, Schweizer E, Csanalosi I, Case WG, Chung H. Long-term treatment of anxiety and risk of withdrawal. Prospective comparison of clorazepate and buspirone. Arch Gen Psychiatry. 1988;45(5):444-450. doi:10.1001/archpsyc.1988.01800290060008 [PubMed 2895993]
  42. Riss J, Cloyd J, Gates J, Collins S. Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008;118(2):69-86. doi:10.1111/j.1600-0404.2008.01004.x [PubMed 18384456]
  43. Saarelainen L, Tolppanen AM, Koponen M, et al. Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study. Int J Geriatr Psychiatry. 2018;33(4):583-590. doi: 10.1002/gps.4821. [PubMed 29143367]
  44. Soyka M, Kranzler HR, Hesselbrock V, Kasper S, Mutschler J, Möller HJ; WFSBP Task Force on Treatment Guidelines for Substance Use Disorders. Guidelines for biological treatment of substance use and related disorders, part 1: alcoholism, first revision. World J Biol Psychiatry. 2017;18(2):86-119. doi:10.1080/15622975.2016.1246752 [PubMed 28006997]
  45. Sugai K. Clobazam as a new antiepileptic drug and clorazepate dipotassium as an alternative antiepileptic drug in Japan. Epilepsia. 2004;45 (Suppl 8):20-25. [PubMed 15610190]
  46. Sundbakk LM, Wood M, Gran JM, Nordeng H. Prenatal exposure to benzodiazepine and z-hypnotics and fifth-grade scholastic skills - emulating target trials using data from the Norwegian Mother, Father and Child Cohort Study. Am J Epidemiol. 2025;194(1):73-84. doi:10.1093/aje/kwae159 [PubMed 38944758]
  47. Szpunar MJ, Freeman MP, Kobylski LA, et al. Risk of major malformations in infants after first-trimester exposure to benzodiazepines: results from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications. Depress Anxiety. 2022;39(12):751-759. doi:10.1002/da.23280 [PubMed 35909254]
  48. Tinker SC, Reefhuis J, Bitsko RH, et al; National Birth Defects Prevention Study. Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997-2011. Birth Defects Res. 2019;111(10):613-620. doi:10.1002/bdr2.1497 [PubMed 30891943]
  49. Tranxene (clorazepate) [prescribing information]. Bristol, TN: UPM Pharmaceuticals; January 2023.
  50. US Department of Veterans Affairs/US Department of Defense. VA/DoD clinical practice guideline for management of posttraumatic stress disorder and acute stress disorder. https://www.healthquality.va.gov/guidelines/MH/ptsd/VA-DoD-CPG-PTSD-Full-CPG.pdf. Published 2023. Accessed November 27, 2023.
  51. US Department of Veterans Affairs/US Department of Defense. VA/DoD clinical practice guideline for the management of substance use disorders. https://www.healthquality.va.gov/guidelines/MH/sud/VADoDSUDCPG.pdf. Published August 2021. Accessed May 12, 2022.
  52. Vinkers CH, Olivier B. Mechanisms underlying tolerance after long-term benzodiazepine use: a future for subtype-selective gaba(a) receptor modulators? Adv Pharmacol Sci. 2012;2012:1-19. [PubMed 22536226]
  53. Wang X, Zhang T, Ekheden I, et al. Prenatal exposure to benzodiazepines and Z-drugs in humans and risk of adverse neurodevelopmental outcomes in offspring: a systematic review. Neurosci Biobehav Rev. 2022;137:104647. doi:10.1016/j.neubiorev.2022.104647 [PubMed 35367514]
  54. Webster LR, Karan S. The physiology and maintenance of respiration: a narrative review. Pain Ther. 2020;9(2):467-486. doi:10.1007/s40122-020-00203-2 [PubMed 33021707]
  55. Wlodarczyk BJ, Palacios AM, George TM, et al, "Antiepileptic Drugs and Pregnancy Outcomes," Am J Med Genet A, 2012, 158A(8):2071-90. [PubMed 22711424]
  56. Wu HN, Liang Y, Li LL, Jiang HY, Xu LL. The safety of benzodiazepines and related drugs during pregnancy: an updated meta-analysis of cohort studies. Arch Gynecol Obstet. 2024;310(1):45-54. doi:10.1007/s00404-024-07557-4 [PubMed 38806942]
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