clorazepate

General Information

Clorazepate dipotassium is a benzodiazepine prodrug indicated for the management of anxiety disorders or short-term relief of anxiety symptoms, adjunctive therapy in partial seizures, and symptomatic relief of acute alcohol withdrawal (label; product-dependent).

Clorazepate is rapidly decarboxylated to nordiazepam, a long-acting benzodiazepine metabolite (half-life ~40–50 hours) (label). Long duration can provide smoother coverage but increases next-day impairment, falls, and cognitive slowing risk—especially in older adults and with polypharmacy.

Benzodiazepine risks include abuse/misuse, addiction, and clinically significant physical dependence with withdrawal reactions; these risks support defined duration and taper planning rather than open-ended use (label / safety guidance).

Boxed warning: Concomitant use with opioids can cause profound sedation, respiratory depression, coma, and death; avoid co-prescribing when possible (label).

The clorazepate compare view, clorazepate evidence feed, and clorazepate print page can support counseling about duration, taper planning, and alternatives.

Clorazepate is best thought of as a long-acting benzodiazepine (via nordiazepam). That can be helpful when smoother coverage is desired, but it increases accumulation and carryover impairment. When used, teams often pair it with explicit duration, follow-up, and taper planning, and avoid it in high fall-risk settings when safer alternatives exist.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Converted to nordiazepam, which acts as a positive allosteric modulator of GABA-A receptors, increasing inhibitory neurotransmission.

Sedation and cognitive slowing scale with dose and co-administered CNS depressants; total sedative burden drives harm.

Repeated use can lead to tolerance and physical dependence; withdrawal reactions can be severe after abrupt discontinuation.

• GABA-A receptor positive allosteric modulation (via nordiazepam).

Metabolism and Pharmacokinetics

• Orally administered clorazepate is rapidly decarboxylated to nordiazepam; essentially no circulating parent drug is present (label).
• Nordiazepam has an apparent elimination half-life of about 40–50 hours and shows moderate accumulation with repeated dosing (label).
• Metabolized in the liver and excreted primarily in urine (label).
• Long half-life increases next-day impairment and interaction persistence, especially in older adults and polypharmacy (label/class).

Dosing and Administration

• Anxiety: administered in divided doses; usual daily dose is 30 mg, adjusted gradually within 15–60 mg/day based on response (label).
• Older or debilitated patients: initiate at 7.5–15 mg/day to reduce oversedation and falls (label).
• Acute alcohol withdrawal: label includes structured schedules with a maximum of 90 mg/day; monitoring of vitals and sedation is typical in practice.
• To reduce withdrawal reactions, gradual tapering is used when discontinuing after regular use (label).

Monitoring & Labs

• Daytime sedation, driving safety, falls, and cognitive impairment, especially during dose changes.
• Substance use risk, opioid co-prescribing, alcohol use, and other sedative co-prescriptions.
• Withdrawal monitoring when tapering or discontinuing after prolonged use.
• Mood/behavior changes when used as seizure adjunct therapy (AED class warning).

Sources: FDA/DailyMed label; anxiety and alcohol-withdrawal guideline context; benzodiazepine safety guidance.

Adverse Effects

Interactions

• Additive CNS/respiratory depression occurs with alcohol, opioids, antihistamines, sedating antipsychotics, and other sedatives; total sedative burden drives harm.
• Long half-life increases interaction persistence; new sedatives or alcohol use can change risk for days.
• Avoid combining with multiple benzodiazepines or hypnotics except in exceptional, closely monitored situations.

Other Useful Information

• For chronic anxiety disorders, guidelines typically prioritize psychotherapy and SSRIs/SNRIs; benzodiazepines are commonly time-limited as bridges for severe symptoms.
• Long-acting benzodiazepines can play a role in structured tapers from shorter-acting agents, but they still require close monitoring for misuse, impairment, and withdrawal risk.
• When used for alcohol withdrawal, coordination with medical teams and structured monitoring of vitals and sedation is typical.
• Documenting indication, duration, and taper strategy helps prevent inadvertent long-term use and withdrawal risk.

References

1. Clorazepate dipotassium tablets prescribing information — DailyMed (2025)
2. ASAM guideline on benzodiazepines — Journal of Addiction Medicine (2020)
3. The ASAM Clinical Practice Guideline on Alcohol Withdrawal Management — Journal of Addiction Medicine (2020)
4. Evidence Based Pharmacological Treatment OF Anxiety Disorders — Depression and Anxiety (2014)
5. Guidelines FOR THE Pharmacological Treatment OF Anxiety Disorders, Obsessive Compulsive Disorder AND Posttraumatic Stress Disorder IN Primary Care — International Journal of Psychiatry in Clinical Practice (2012)