WARNINGMIXING OR WITHDRAWAL CAN BE DANGEROUS
Ordinary doses in combination with other depressants can fatally stop breathing. After prolonged dependency, stopping suddenly can also cause seizures or delirium; seek medical help.
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Clorazepate
Clorazepate is a 1,4-benzodiazepine and depressant medication1. It is a prodrug rapidly converted to desmethyldiazepam, the active metabolite responsible for most of its therapeutic effects. After oral administration, clorazepate dipotassium is rapidly decarboxylated to nordiazepam, whose apparent plasma half-life is about 40 to 50 hours1. Clorazepate is classified as habit-forming, although the excerpts do not specify particular adverse outcomes.
Dosage & Duration
Dosage
Doses are population estimates that vary widely between individuals.
Duration
Subjective Effects
Pharmacology
Pharmacodynamics
Orally administered clorazepate dipotassium is rapidly decarboxylated to nordiazepam, its primary metabolite, with essentially no circulating parent drug2. Desmethyldiazepam acts as a partial agonist at the GABA-A receptor, enhancing GABA-mediated inhibition by increasing the frequency of chloride channel opening; this benzodiazepine effect requires GABA. After oral administration of clorazepate dipotassium, essentially no parent drug circulates; its active metabolite, nordiazepam, has an apparent plasma half-life of about 40 to 50 hours2.
Pharmacokinetics
After oral administration, clorazepate dipotassium is rapidly decarboxylated to nordiazepam, with essentially no circulating parent drug2. After oral administration, peak plasma levels of desmethyldiazepam occur within 30 minutes to 2 hours. Desmethyldiazepam has a half-life of 20–179 hours. Clorazepate has a primary metabolite, nordiazepam, with high plasma protein binding (97 to 98%)2 and crosses the placenta and enters breast milk.2
Interactions
An unlisted combination is an unknown one, not a safe one. Check a dedicated combination chart before mixing.
Tolerance
Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.
Benzodiazepines
Harm Potential
Addiction & Dependence
Psychological
HighClorazepate is classified as habit-forming with significant psychological dependence potential. Regular use leads to tolerance to therapeutic effects, and withdrawal can cause anxiety, apprehension, insomnia, and irritability.
Physical
HighAbout one in three people taking benzodiazepines beyond 4 weeks develop physical dependence. Withdrawal can range from mild anxiety and insomnia to severe effects such as seizures, toxic psychosis, and a delirium-tremens-like syndrome. Stopping high doses abruptly may produce confusion and convulsions, while sudden discontinuation from lower doses may cause depression, nervousness, rebound insomnia, sweating, and diarrhea.
Psychosis Risk
Withdrawal from clorazepate can cause toxic psychosis, and delirium has been noted from discontinuation. Paradoxical effects including excitement can sometimes occur during use, with higher risk in children, the elderly, and individuals with a history of alcohol use disorder or aggressive behavior.
Seizure Risk
Withdrawal seizures are a documented risk, particularly with abrupt or over-rapid discontinuation. When used for seizure control, tolerance may manifest with an increased rate of seizures as well as increased risk of withdrawal seizures. Convulsions may occur with abrupt withdrawal from high doses.
History & Culture
Clorazepate was patented in 1965 and approved for medical use in 1967. In September 2020, the U.S. Food and Drug Administration announced a requirement to update the…
Legality
References
Citations
Article Status
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