BRAND NAMES
 MECHANISM OF ACTION
Clorazepate, like other Benzodiazepines bind to specific sites on the gamma-aminobutyric acid-A (GABAA) receptors. This enhances the effects of GABA by increasing its affinity for the GABAA receptor.
Activation of the GABAA receptor, which is linked to a chloride channel (Cl-), results in an influx of Cl- into the neurone causing hyperpolarisation, which results in inhibitory effects on the central nervous system.
Benzodiazepines action on GABAA receptors appears to produce their anxiolytic, sedative, muscle relaxant, hypnotic and anticonvulsant actions.
Clorazepate is a long-acting benzodiazepine. After oral administration clorazepate is rapidly decarboxylated to form the active metabolite desmethyldiazepam (nordiazepam). Nordiazepam quickly appears in the blood and is eliminated from the plasma with an apparent half-life of about 40 to 50 hours.
- Anxiety disorders: Clorazepate is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
- Epilepsy: Adjunctive therapy in the management of partial seizures
- Alcohol withdrawal: symptomatic relief of acute alcohol withdrawal
- Symptomatic relief of anxiety: The duration of treatment should be as short as possible. Usual daily dosage is 10 to 30 mg; higher doses may be used depending on clinical requirements. Drowsiness may occur at the initiation of treatment and with dosage increment.
- As an Adjunct to Antiepileptic Drugs:
- Adults: The maximum recommended initial dose in patients over 12 years old is 7.5 mg three times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 90 mg/day.
- Children (9-12 years): The maximum recommended initial dose is 7.5 mg two times a day. Dosage should be increased by no more than 7.5 mg every week and should not exceed 60 mg/day.
- For the symptomatic relief of acute alcohol withdrawal, the following dosage schedule is recommended:
- Day 1: 30 mg initially; followed by 30 to 60 mg in divided doses
- Day 2: 45 to 90 mg in divided doses
- Day 3: 22.5 to 45 mg in divided doses
- Day 4: 15 to 30 mg in divided doses
Thereafter, gradually reduce the daily dose to 7.5 to 15 mg. Discontinue drug therapy as soon as patient’s condition is stable.
- Hypersensitivity to Clorazepate
- Acute narrow angle glaucoma.
- Severe liver failure
- Pregnancy and lactation
- Myasthenia gravis (Clorazepate could increase the muscle weakness)
- Severe respiratory failure or sleep apnea syndrome
 WARNINGS AND PRECAUTIONS
- Do not drive or do other dangerous activities after taking Clorazepate until you feel fully awake.
- Do not drink alcohol
- Use of benzodiazepines can lead to dependence. This risk increases with dose and duration of treatment.
- Amnesia: Benzodiazepines may induce anterograde amnesia leading to a partial or complete inability to recall the recent past. Anterograde amnesia may occur using higher therapeutic dosages, the risk increasing at higher dosages.
- Withdrawal symptoms : Withdrawal symptoms associated with the abrupt discontinuation of benzodiazepines have included convulsions, delirium, tremor, abdominal and muscle cramps, vomiting, sweating, nervousness, insomnia, irritability, diarrhea, and memory impairment. The more severe withdrawal symptoms have usually been limited to those patients who had received excessive doses over an extended period of time. Generally milder withdrawal symptoms have been reported following abrupt discontinuance of benzodiazepines taken continuously at therapeutic levels for several months. Consequently, after extended therapy, clorazepate should be discontinued gradually
- Risk of Fetal Harm: Benzodiazepines can potentially cause fetal harm when administered to pregnant women
Benzodiazepines, including Clorazepate , produce additive CNS depressant effects when co-administered with other medications which themselves produce CNS depression (e.g. barbiturates, alcohol, sedatives, tricyclic antidepressants, antipsychotics, skeletal muscle relaxants, antihistamines or narcotic analgesics and anesthetics)
 PREGNANCY AND LACTATION
- Pregnancy Category D (US). An increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam and meprobamate) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided. The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered. Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.
- Nursing mothers: Benzodiazepines are known to be excreted in human milk. It should be assumed that alprazolam is as well. Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight. As a general rule, nursing should not be undertaken by mothers who must use Clorazepate.
 SIDE EFFECTS
Possible adverse effects include: most common: drowsiness. Less common (in descending order of occurrence): dizziness, various gastrointestinal complaints, nervousness, blurred vision, dry mouth, headache, and mental confusion. Other side effects included insomnia, transient skin rashes, fatigue, ataxia, genitourinary complaints, irritability, diplopia, depression, tremor, and slurred speech.
See also WARNINGS AND PRECAUTIONS section
 RELATED LINKS
|Sedatives / Hypnotics / Anxiolytics|
|Benzodiazepines||Benzodiazepines (Anxiolytics)||Alprazolam (Xanax) • Bromazepam (Lexotan, Lexotanil) • Chlordiazepoxide (Librium) • Clobazam (Frisium) • Clorazepate (Tranxene) • Clotiazepam (Rizen, Tienor) • Delorazepam (EN) • Diazepam (Valium) • Etizolam (Depas) • Ketazolam • Lorazepam (Ativan, Control, Lorans, Tavor, Temesta) • Lormetazepam (Noctamid) • Nordazepam (Nordaz) • Oxazepam (Serepax) • Prazepam (Demetrin, Lysanxia)|
|Benzodiazepines (Hypnotics)||Brotizolam (Lendormin, Bondormin, Dormex, Sintonal, Noctilan) • Clobazam (Frisium) • Estazolam (Esilgan, ProSom) • Etizolam (Depas, Pasaden, Etilaam, Etizest) • Flunitrazepam (Rohypnol) • Flurazepam (Dalmadorm, Dalmane, Felison, Flunox, Valdorm) • Ketazolam (Anseren, Anxon) • Lorazepam (Ativan, Control, Lorans, Tavor, Temesta) • Lormetazepam (Loramet, Minias, Noctamid, Pronoctan, Evamyl) • Midazolam (Dormicum, Hypnovel) • Nitrazepam (Mogadon, Nitrados, Numbon, Radedorm, Alodorm) • Nordazepam (Madar, Nordaz, Stilny, Tranxilium N) • Temazepam (Normison, Restoril, Tenox, Temaze) • Triazolam (Halcion, Hypam, Rilamir)|
|Non-Benzodiazepine Hypnotics||Eszopiclone (Lunesta) • Zolpidem (Ambien, Stilnox, Hypnogen, Sanval, Stilnoct, Zoldem, Zolsana) • Zopiclone (Imovane, Zimovane)|
|Melatonin agonists||Melatonin (Circadin) • Ramelteon (Rozerem)|
|Orexin agonists||Suvorexant (Belsomra)|