Peringatan Keamanan

The overdosage of benzodiazepines, such as clorazepate, is characterized by central nervous system (CNS) depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Paradoxical or disinhibitory reactions are rare but may occur. In severe cases, patients experiencing a benzodiazepine overdose may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants may be fatal. General supportive measures, including intravenous fluids and airway management, should be used to manage a benzodiazepine overdose. The use of flumazenil for the complete or partial reversal of benzodiazepine-sedative effects during an overdose can lead to withdrawal and adverse reactions. Refer to the product label of clorazepate for additional overdosage management recommendations.L44788

In rats, the oral LD50 of clorazepate is 1320 mg/kg, and in monkeys, it exceeds 1600 mg/kg. In animal reproduction studies, clorazepate did not affect fertility indices or the reproductive capacity of adult animals.L44788

Clorazepic acid

DB00628

small molecule approved illicit

Deskripsi

Clorazepic acid (clorazepate) is a water-soluble benzodiazepine with muscle-relaxant and anticonvulsant actions effective in the treatment of anxiety.A957,L44788 Following administration, clorazepate is rapidly converted to nordiazepam (N-desmethyldiazepam), its active metabolite, before entering systemic circulation. Similar to other benzodiazepines, the active metabolite of clorazepate enhances the binding of gamma-aminobutyric acid (GABA) to the GABA type A (GABA-A) receptor, which promotes channel opening and neuronal hyperpolarization.A256683,T883 The concomitant use of clorazepate and opioids may result in profound sedation, respiratory depression, coma, and death. Also, the use of clorazepate exposes users to users to the risks of abuse, misuse, and addiction, and its continued use may lead to significant physical dependence. In September 2020, a black box warning describing these risks was included on the product label of benzodiazepines as per FDA regulation.L44798 Clorazepate and its active metabolite, nordiazepam, are present in breast milk.A958,L44788

Struktur Molekul 2D

Berat 314.723
Wujud solid

Peta Jejaring Molekuler
Legenda: Obat • Target • Gen • Enzim • (Panah → menunjukkan arah efek / relasi) • Transporter • Carrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) The serum half-life of clorazepate is approximately 2 days. Nordiazepam, the primary metabolite, quickly appears in the blood and is eliminated from the plasma with an apparent half-life of about 40 to 50 hours.[L44788]
Volume Distribusi Following a single 20 mg intravenous dose, the volume of distribution of nordiazepam (active metabolite of clorazepate) was 1.24 L/kg.[A256608]
Klirens (Clearance) Following a single 20 mg intravenous dose, nordiazepam (the active metabolite of clorazepate) had a total clearance of 0.24 mL/min/kg.[A256608]

Absorpsi

Clorazepate is a prodrug for nordiazepam, and this conversion occurs almost entirely before entering systemic circulation. Therefore, the pharmacokinetic parameters of clorazepate are based on nordiazepam concentrations. In healthy volunteers given a 20 mg oral dose of clorazepate, nordiazepam had a peak plasma level of 356 ng/mL, which was reached approximately 0.9 h after the administration of clorazepate.A256608 The plasma levels of nordiazepam increase proportionally with the clorazepate dose and show moderate accumulation with repeated administration.L44788 The oral bioavailability of clorazepate is 91%.T238

Metabolisme

Clorazepate is metabolized in the liver and excreted mainly through urine.L44788 Following oral administration, clorazepate is decarboxylated by the gastric acid of the stomach before absorption.A256663 The primary metabolite, nordiazepam, is further metabolized by hydroxylation. The major urinary metabolite is conjugated oxazepam (3-hydroxynordiazepam), and smaller amounts of conjugated p-hydroxynordiazepam and nordiazepam are also found in the urine.L44788

Rute Eliminasi

Clorazepate is mainly excreted through urine and feces. In two volunteers given 15 mg of 14C-clorazepate, 62-67% of the radioactivity was excreted in the urine and 15-19% was eliminated in the feces within 10 days. On day 10, both subjects were still excreting about 1% of the 14C-dose in the urine.L44788

Interaksi Makanan

2 Data
  • 1. Avoid alcohol. The concomitant use of clorazepate and alcohol may lead to an increased frequency of serious adverse outcomes.
  • 2. Take with or without food. The absorption is unaffected by food.

Interaksi Obat

1486 Data
Buprenorphine Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
Doxylamine Doxylamine may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Dronabinol Dronabinol may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Droperidol Droperidol may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Hydrocodone Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
Hydroxyzine Hydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Magnesium sulfate The therapeutic efficacy of Clorazepic acid can be increased when used in combination with Magnesium sulfate.
Methotrimeprazine Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
Metyrosine Clorazepic acid may increase the sedative activities of Metyrosine.
Minocycline Minocycline may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Mirtazapine Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
Nabilone Nabilone may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Orphenadrine Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
Paraldehyde Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
Perampanel Perampanel may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Pramipexole Clorazepic acid may increase the sedative activities of Pramipexole.
Ropinirole Clorazepic acid may increase the sedative activities of Ropinirole.
Rotigotine Clorazepic acid may increase the sedative activities of Rotigotine.
Rufinamide The risk or severity of adverse effects can be increased when Rufinamide is combined with Clorazepic acid.
Suvorexant Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
Tapentadol Tapentadol may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Thalidomide Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
Zolpidem Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Clozapine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Clozapine.
Methadone Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Methadone.
Sodium oxybate Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Sodium oxybate.
Teduglutide The serum concentration of Clorazepic acid can be increased when it is combined with Teduglutide.
Yohimbine The therapeutic efficacy of Clorazepic acid can be increased when used in combination with Yohimbine.
Mefloquine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Mefloquine.
Mianserin The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Mianserin.
Orlistat Orlistat can cause a decrease in the absorption of Clorazepic acid resulting in a reduced serum concentration and potentially a decrease in efficacy.
Topotecan Clorazepic acid may increase the excretion rate of Topotecan which could result in a lower serum level and potentially a reduction in efficacy.
Saquinavir The serum concentration of Clorazepic acid can be increased when it is combined with Saquinavir.
Tetracosactide The risk or severity of liver damage can be increased when Tetracosactide is combined with Clorazepic acid.
Ethanol Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
Azelastine Clorazepic acid may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
Brimonidine Brimonidine may increase the central nervous system depressant (CNS depressant) activities of Clorazepic acid.
Zimelidine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Zimelidine.
Dapoxetine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Dapoxetine.
Seproxetine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Seproxetine.
Fluvoxamine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Fluvoxamine.
Citalopram The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Citalopram.
Duloxetine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Duloxetine.
Trazodone The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Trazodone.
Paroxetine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Paroxetine.
Sertraline The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Sertraline.
Sibutramine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Sibutramine.
Escitalopram The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Escitalopram.
Milnacipran The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Milnacipran.
Desvenlafaxine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Desvenlafaxine.
Levomilnacipran The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Levomilnacipran.
Indalpine The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Indalpine.
Ritanserin The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Ritanserin.
Alaproclate The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Alaproclate.
Benzatropine Benzatropine may decrease the excretion rate of Clorazepic acid which could result in a higher serum level.
Disopyramide Disopyramide may decrease the excretion rate of Clorazepic acid which could result in a higher serum level.
Cyproheptadine The risk or severity of CNS depression can be increased when Cyproheptadine is combined with Clorazepic acid.
Propiomazine The risk or severity of CNS depression can be increased when Clorazepic acid is combined with Propiomazine.
Propantheline Clorazepic acid may decrease the excretion rate of Propantheline which could result in a higher serum level.
Dicyclomine Clorazepic acid may decrease the excretion rate of Dicyclomine which could result in a higher serum level.
Cocaine The risk or severity of methemoglobinemia can be increased when Clorazepic acid is combined with Cocaine.
Tolterodine Clorazepic acid may decrease the excretion rate of Tolterodine which could result in a higher serum level.
Flavoxate Clorazepic acid may decrease the excretion rate of Flavoxate which could result in a higher serum level.
Tiotropium Clorazepic acid may decrease the excretion rate of Tiotropium which could result in a higher serum level.
Fesoterodine Clorazepic acid may decrease the excretion rate of Fesoterodine which could result in a higher serum level.
Aclidinium Clorazepic acid may decrease the excretion rate of Aclidinium which could result in a higher serum level.
Trimebutine Clorazepic acid may decrease the excretion rate of Trimebutine which could result in a higher serum level.
Imidafenacin Clorazepic acid may decrease the excretion rate of Imidafenacin which could result in a higher serum level.
Propiverine Clorazepic acid may decrease the excretion rate of Propiverine which could result in a higher serum level.
Nicardipine The metabolism of Clorazepic acid can be decreased when combined with Nicardipine.
Amitriptyline The risk or severity of CNS depression can be increased when Amitriptyline is combined with Clorazepic acid.
Imipramine The risk or severity of CNS depression can be increased when Imipramine is combined with Clorazepic acid.
Doxepin The risk or severity of CNS depression can be increased when Clorazepic acid is combined with Doxepin.
Desipramine The risk or severity of CNS depression can be increased when Clorazepic acid is combined with Desipramine.
Zopiclone The risk or severity of adverse effects can be increased when Clorazepic acid is combined with Zopiclone.
Caffeine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Caffeine.
Dyphylline The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Dyphylline.
Pentoxifylline The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Pentoxifylline.
Mercaptopurine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Mercaptopurine.
Oxtriphylline The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Oxtriphylline.
Theobromine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Theobromine.
Fenethylline The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Fenethylline.
8-azaguanine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with 8-azaguanine.
7,9-Dimethylguanine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with 7,9-Dimethylguanine.
Xanthine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Xanthine.
7-Deazaguanine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with 7-Deazaguanine.
Guanine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Guanine.
9-Methylguanine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with 9-Methylguanine.
Peldesine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Peldesine.
Hypoxanthine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Hypoxanthine.
9-Deazaguanine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with 9-Deazaguanine.
Propentofylline The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Propentofylline.
Valomaciclovir The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Valomaciclovir.
3-isobutyl-1-methyl-7H-xanthine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with 3-isobutyl-1-methyl-7H-xanthine.
Uric acid The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Uric acid.
Doxofylline The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Doxofylline.
6-O-benzylguanine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with 6-O-benzylguanine.
Lisofylline The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Lisofylline.
Lobucavir The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Lobucavir.
Cafedrine The therapeutic efficacy of Clorazepic acid can be decreased when used in combination with Cafedrine.

Target Protein

GABA(A) Receptor GABRA1
Translocator protein TSPO
GABA(A) Receptor Benzodiazepine Binding Site GABRA1

Referensi & Sumber

Synthesis reference: Schmitt, J. (1970). 1,4 benzodiazepine-2-ones having a carboxylic acid ester or amide group in the 3-position (U.S. Patent 3,516,988). U.S. Patent and Trademark Office. https://patentimages.storage.googleapis.com/ce/c5/88/de9de70d8e622e/US3516988.pdf
Artikel (PubMed)
  • PMID: 7388368
    Authors unspecified: Systematic review of the benzodiazepines. Guidelines for data sheets on diazepam, chlordiazepoxide, medazepam, clorazepate, lorazepam, oxazepam, temazepam, triazolam, nitrazepam, and flurazepam. Committee on the Review of Medicines. Br Med J. 1980 Mar 29;280(6218):910-2.
  • PMID: 7881198
    McElhatton PR: The effects of benzodiazepine use during pregnancy and lactation. Reprod Toxicol. 1994 Nov-Dec;8(6):461-75.
  • PMID: 6124654
    Ochs HR, Steinhaus E, Locniskar A, Knuchel M, Greenblatt DJ: Desmethyldiazepam kinetics after intravenous, intramuscular, and oral administration of clorazepate dipotassium. Klin Wochenschr. 1982 Apr 15;60(8):411-5. doi: 10.1007/BF01735933.
  • PMID: 2908106
    Frey HH, Scherkl R: Clorazepate, correlation between metabolism and anticonvulsant activity. Eur J Pharmacol. 1988 Dec 13;158(3):213-6. doi: 10.1016/0014-2999(88)90069-6.
  • PMID: 36551212
    Goldschen-Ohm MP: Benzodiazepine Modulation of GABA(A) Receptors: A Mechanistic Perspective. Biomolecules. 2022 Nov 30;12(12):1784. doi: 10.3390/biom12121784.
Textbook
  • Davies, JA (2007). Clorazepate. In XPharm: The comprehensive Pharmacology Reference (pp. 1-5). Elsevier.
  • ISBN: 9781118937006
    Trinka, E, Brigo F (2015). Benzodiazepines Used in the Treatment of Epilepsy. In The Treatment of Epilepsy, 4 (pp. 398-417). John Wiley & Sons, Ltd.

Contoh Produk & Brand

Produk: 68 • International brands: 22
Produk
  • Clorazepate
    Capsule • 15 mg • Oral • Canada • Approved
  • Clorazepate
    Capsule • 3.75 mg • Oral • Canada • Approved
  • Clorazepate
    Capsule • 7.5 mg • Oral • Canada • Approved
  • Clorazepate Dipotassium
    Tablet • 3.75 mg/1 • Oral • US • Generic • Approved
  • Clorazepate Dipotassium
    Tablet • 7.5 mg/1 • Oral • US • Generic • Approved
  • Clorazepate Dipotassium
    Tablet • 3.75 mg/1 • Oral • US • Generic • Approved
  • Clorazepate Dipotassium
    Tablet • 7.5 mg/1 • Oral • US • Generic • Approved
  • Clorazepate Dipotassium
    Tablet • 15 mg/1 • Oral • US • Generic • Approved
Menampilkan 8 dari 68 produk.
International Brands
  • Anksen — Sanovel
  • Calner — Medipharm
  • Cloranxen — Teva
  • Clorazepatum — sanofi-aventis
  • Clozene — Weidar
  • Dipot — Asian
  • Flulium — Pharmasant
  • Gen-xene — Alra
  • Justum — Sandoz
  • Manotran — March

Sekuens Gen/Protein (FASTA)

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