Clorazepate

Brand names: GenXene®Tranxene®Tranxene® SD

Chemical formula:

Drug Forms:
• Clorazepate Dipotassium Oral tablet (below)
• Clorazepate Dipotassium Oral tablet, extended-release

Español:
• Clorazepato Dipotasico, Tableta oral
• Clorazepato Dipotásico, Tableta oral de liberación prolongada

Clorazepate Dipotassium Oral tablet

What is this medicine?

CLORAZEPATE (klor AZ e pate) is a benzodiazepine. It is used to treat anxiety. It also used to treat alcohol withdrawal and certain types of seizures.
 
This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:
•an alcohol or drug abuse problem
•bipolar disorder, depression, psychosis or other mental health condition
•glaucoma
•kidney or liver disease
•lung or breathing disease
•myasthenia gravis
•Parkinson's disease
•seizures or a history of seizures
•suicidal thoughts
•an unusual or allergic reaction to clorazepate, other benzodiazepines, other medicines, foods, dyes, or preservatives
•pregnant or trying to get pregnant
•breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Follow the directions on the prescription label. Take your doses at regular intervals. Do not take your medicine more often than directed. If you have been taking this medicine regularly for some time, do not suddenly stop taking it. You must gradually reduce the dose or you may get severe side effects. Ask your doctor or health care professional for advice. Even after you stop taking this medicine it can still affect your body for several days.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed. While this drug may be prescribed for children as young as 9 years for selected conditions, precautions do apply.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.
NOTE: This medicine is only for you. Do not share this medicine with others.

What may interact with this medicine?

Do not take this medicine with any of the following medications:
•itraconazole

This medicine may also interact with the following medications:
•medicines for depression, mental problems or psychiatric disturbances
•prescription pain medicines
•some medicines for seizures like carbamazepine, phenobarbital, phenytoin, primidone

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress. Your body can become dependent on this medicine. Ask your doctor or health care professional if you still need to take it.
 
You may get drowsy or dizzy. Do not drive, use machinery, or do anything that needs mental alertness until you know how this medicine affects you. To reduce the risk of dizzy and fainting spells, do not stand or sit up quickly, especially if you are an older patient. Alcohol may increase dizziness and drowsiness. Avoid alcoholic drinks.
 
Do not treat yourself for coughs, colds or allergies without asking your doctor or health care professional for advice. Some ingredients can increase possible side effects.
 
The use of this medicine may increase the chance of suicidal thoughts or actions. Pay special attention to how you are responding while on this medicine. Any worsening of mood, or thoughts of suicide or dying should be reported to your health care professional right away.
 
Women who become pregnant while using this medicine may enroll in the North American Antiepileptic Drug Pregnancy Registry by calling 1-888-233-2334. This registry collects information about the safety of antiepileptic drug use during pregnancy.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:
•allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
•confusion
•feeling faint or lightheaded, falls
•mood changes, depression, excitability or aggressive behavior
•movement difficulty, staggering or jerky movements
•muscle cramps
•restlessness
•tremors
•unusually weak or tired

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):
•changes in vision
•dizziness, drowsiness, clumsiness, or unsteadiness, a hangover effect
•dry mouth
•headache
•stomach upset

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children. This medicine can be abused. Keep your medicine in a safe place to protect it from theft. Do not share this medicine with anyone. Selling or giving away this medicine is dangerous and against the law.

Store at room temperature below 25 degrees C (77 degrees F). Protect from moisture and light. Keep bottle tightly closed. Throw away any unused medicine after the expiration date.

Last updated: 7/1/2002

Important Disclaimer: The drug information provided here is for educational purposes only. It is intended to supplement, not substitute for, the diagnosis, treatment and advice of a medical professional. This drug information does not cover all possible uses, precautions, side effects and interactions. It should not be construed to indicate that this or any drug is safe for you. Consult your medical professional for guidance before using any prescription or over the counter drugs.

A benzodiazepine compound used in the treatment of seizures in dogs.

Clorazepate
Systematic (IUPAC) name
7-chloro-2,3-dihydro-2-oxo-5-phenyl- 1H-1,4-benzodiazepine-3-carboxylic acid
Identifiers
CAS number	23887-31-2 57109-90-7 (potassium salt)
ATC code	N05BA05
PubChem	2809
DrugBank	APRD00881
ChemSpider	10617010
Chemical data
Formula	C16H11ClN2O3
Mol. mass	314.72
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	91%
Metabolism	Hepatic
Half life	48 hours
Excretion	Renal
Therapeutic considerations
Pregnancy cat.	D(US)
Legal status	Schedule IV(US)
Routes	Oral
Y(what is this?)  (verify)

Clorazepate (marketed under the brand names Tranxene and Novo-Clopate), is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Clorazepate was discontinued in February 2006 in the United Kingdom.^[1] Clorazepate is a prodrug for desmethyldiazepam which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.^[2]

Contents 1 Indications 2 Pharmacology 3 Interactions 4 Tolerance, dependence and withdrawal 5 Pregnancy 6 Legal status 7 See also 8 References 9 External links

Indications

Clorazepate is used in the treatment of anxiety disorders and insomnia. It may also be prescribed as an anticonvulsant or muscle relaxant.^[3]

Clorazepate is principally prescribed in the treatment of alcohol withdrawal and epilepsy, although it is also a useful anxiolytic because of its long half-life. The normal starting dosage range of Clorazepate is 15 to 60 mg per day. The drug is to be taken two to four times per day. Dosages as high as 90 to 120 mg per day may be used in the treatment of acute alcohol withdrawal. In the United States and Canada, Clorazepate is available in 3.75, 7.5, and 15 mg capsules or tablets. In Europe, tablet formations are 5 mg, 10 mg, 20 mg and 50 mg.^[4] Clorazepate SD (controlled release) is available in 11.25 and 22.5 mg tablets. Clorazepate SD is only prescribed when the patient has become adjusted to a certain dosage, and is taken once a day. Clorazepate is available in generic form. Clorazepate begins to act on the central nervous system within one or two hours, and its effects may be felt for an entire day or longer in some individuals. It is contraindicated for those with impaired renal or hepatic function.

Pharmacology

Clorazepate is a "classical" benzodiazepine. Other classical benzodiazepines include alprazolam, diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam and flurazepam.^[5] Clorazepate is a long acting benzodiazepine drug.^[6] Clorazepate produces the metabolite desmethyl-diazepam which has a half life of 36 - 200 hours.^[7]

Interactions

All sedatives or hypnotics eg other benzodiazepines, alcohol, antihistamines, opiates, neuroleptics, sleep aids are likely to magnify the effects of clorazepate on the central nervous system. Drugs which may interact with clorazepate include, digoxin, disulfiram, fluoxetine, isoniazid, ketoconazole, levodopa, metoprolol, hormonal contraceptives, probenecid, propranolol, rifampin, theophylline, valproic acid.^[3]

Cimetidine, trade name Tagamet, inhibits breakdown of Clorazepate, and leads to increased levels of the drug in the system.^[8]

Tolerance, dependence and withdrawal

Main article: Benzodiazepine withdrawal syndrome

In humans tolerance to the anticonvulsant effects of clorazepate occurs frequently with regular use.^[9] Regular use of benzodiazepines causes the development of dependence characterised by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremor, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal from benzodiazepines should be gradual as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhoea.^[10]

Pregnancy

Chlorazepate if used late in pregnancy, the third trimester, causes a definite risk a severe benzodiazepine withdrawal syndrome in the neonate with symptoms including hypotonia, and reluctance to suck, to apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the new born may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth.^[11]

Legal status

Clorazepate is listed under Schedule IV of the Controlled Substances Act.

See also

• Benzodiazepine
• Benzodiazepine dependence
• Benzodiazepine withdrawal syndrome
• Long term effects of benzodiazepines

References

1. ^ National electronic Library for Medicines. "SPC (Product Licence) Changes". E-Communications Team at the London and South East Medicines Information Service based at Guy’s Hospital London. http://www.nelm.nhs.uk/en/NeLM-Area/Other-Lib-Updates/SPC-Changes/502132. Retrieved 19 December 2008. 
2. ^ Ochs HR, Greenblatt DJ, Verburg-Ochs B, Locniskar A (October 1984). "Comparative single-dose kinetics of oxazolam, prazepam, and clorazepate: three precursors of desmethyldiazepam". J Clin Pharmacol 24 (10): 446–51. PMID 6150943. http://jcp.sagepub.com/cgi/content/abstract/24/10/446. 
3. ^ ^{a b} National Institutes of Health (2003). "Clorazepate". National Library of Medicine. http://www.nlm.nih.gov/medlineplus/druginfo/medmaster/a682052.html. Retrieved 19 July 2008. 
4. ^ Tranxene prescribing information in the Netherlands (Dutch language); accessed 2007-03-08
5. ^ Braestrup C; Squires RF. (1 April 1978). "Pharmacological characterization of benzodiazepine receptors in the brain". Eur J Pharmacol 48 (3): 263–70. doi:10.1016/0014-2999(78)90085-7. PMID 639854. 
6. ^ The Committee on the Review of Medicines (CRM) (March 29, 1980). "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. 280 (6218): 910–2. doi:10.1136/bmj.280.6218.910. PMID 7388368. 
7. ^ Professor heather Ashton (April 2007). "BENZODIAZEPINE EQUIVALENCY TABLE". http://www.bcnc.org.uk/equivalence.html. Retrieved September 23 2007. 
8. ^ Divoll M; Greenblatt DJ, Abernethy DR, Shader RI (November 1982). "Cimetidine impairs clearance of antipyrine and desmethyldiazepam in the elderly". J Am Geriatr Soc 30 (11): 684–9. PMID 6813365. 
9. ^ Loiseau P (1983). "[Benzodiazepines in the treatment of epilepsy]". Encephale 9 (4 Suppl 2): 287B–292B. PMID 6373234. 
10. ^ Committee on the Review of Medicines (March 29, 1980). "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" (pdf). Br Med J. 280 (6218): 910–2. doi:10.1136/bmj.280.6218.910. PMID 7388368. http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1601049&blobtype=pdf. 
11. ^ McElhatton PR. (Nov-December 1994). "The effects of benzodiazepine use during pregnancy and lactation". Reprod Toxicol. 8 (6): 461–75. doi:10.1016/0890-6238(94)90029-9. PMID 7881198. 

External links

• Rx-List.com - Clorazepate
• Inchem.org - Clorazepate

v • d • e Benzodiazepines (N05BA, N05CD) 1,4-Benzodiazepines Bromazepam • Camazepam • Chlordiazepoxide • Cinolazepam • Clonazepam • Clorazepate • Cyprazepam • Delorazepam • Diazepam • Doxefazepam • Elfazepam • Ethyl carfluzepate • Ethyl dirazepate • Ethyl loflazepate • Fletazepam • Fludiazepam • Flunitrazepam • Flurazepam • Flutemazepam • Flutoprazepam • Fosazepam • Gidazepam • Halazepam • Iclazepam • Lopirazepam • Lorazepam • Lormetazepam • Meclonazepam • Medazepam • Menitrazepam • Metaclazepam • Nimetazepam • Nitrazepam • Nitrazepate • Nordazepam • Oxazepam • Phenazepam • Pinazepam • Pivoxazepam • Prazepam • Proflazepam • Quazepam • QH-II-66 • Reclazepam • Sulazepam • Temazepam • Tetrazepam • Uldazepam 1,5-Benzodiazepines Arfendazam • Clobazam • Lofendazam • Triflubazam 2,3-Benzodiazepines Girisopam • GYKI-52466 • GYKI-52895 • Nerisopam • Tofisopam Triazolobenzodiazepines Adinazolam • Alprazolam • Estazolam • Triazolam  Imidazobenzodiazepines Bretazenil • Climazolam • Flumazenil • Imidazenil • L-655,708 • Loprazolam • Midazolam • PWZ-029 • Ro15-4513 • Ro48-6791 • Sarmazenil • SH-053-R-CH3-2′F Oxazolobenzodiazepines Cloxazolam • Flutazolam • Haloxazolam • Mexazolam • Oxazolam Thienodiazepines Brotizolam • Ciclotizolam • Clotiazepam • Etizolam Pyridodiazepines Zapizolam • Lopirazepam Pyrazolodiazepines Ripazepam • Zolazepam • Zomebazam Pyrrolodiazepines Premazepam Benzodiazepine Prodrugs Avizafone • Rilmazafone Others Bentazepam • Devazepide • Ketazolam • Razobazam • Tifluadom

v • d • e Anticonvulsants (N03) GABAA receptor agonist Barbiturates Barbexaclone · Metharbital · Methylphenobarbital · Pentobarbital · Phenobarbital · Primidone Benzodiazepines Clobazam · Clonazepam · Clorazepate · Diazepam · Flutoprazepam · Lorazepam · Midazolam · Nimetazepam · Nitrazepam · Temazepam Other GABA agents Aromatic allylic alcohols Stiripentol Carbonic anhydrase inhibitor Sulfa drugs Acetazolamide · Ethoxzolamide · Sultiame · Zonisamide Channel blockers Primarily sodium Hydantoins Ethotoin · Fosphenytoin · Mephenytoin · Phenytoin Carboxamides Carbamazepine · Eslicarbazepine acetate · Oxcarbazepine · Rufinamide Primarily calcium Succinimides Ethosuximide · Mesuximide · Phensuximide Unknown/ungrouped Phenyltriazines Lamotrigine Oxazolidinediones Ethadione · Paramethadione · Trimethadione Ureas Phenacemide · Pheneturide Monosaccharides Topiramate Indirect GABA agents Carboxylic acids/ Fatty acid derivatives GABA transaminase inhibitor: Valproic acid (Sodium valproate & Valproate semisodium) · Valpromide · Valnoctamide GABA reuptake inhibitor: Tiagabine GABA analogs Gabapentin · Pregabalin · Progabide · Vigabatrin Unknown/multiple/ unsorted Carbamates Emylcamate · Felbamate · Meprobamate · Carisbamate Pyrrolidines Brivaracetam · Levetiracetam · Nefiracetam · Seletracetam Propionates Beclamide · Lacosamide Aldehydes Paraldehyde Bromides Potassium bromide · Sodium bromide

v • d • e Psycholeptics: Anxiolytics (N05B) GABAA PAMs Benzodiazepines: Adinazolam • Alprazolam • Bretazenil • Bromazepam • Camazepam • Chlordiazepoxide • Clobazam • Clonazepam • Clorazepate • Clotiazepam • Cloxazolam • Diazepam • Ethyl Loflazepate • Etizolam • Fludiazepam • Halazepam • Imidazenil • Ketazolam • Lorazepam • Medazepam • Nordazepam • Oxazepam • Pinazepam • Prazepam • Tofisopam; Carbamates: Emylcamate • Carisoprodol • Mebutamate • Meprobamate • Phenprobamate • Procymate • Tybamate; Nonbenzodiazepines: Abecarnil • Adipiplon • Alpidem • CGS-9896 • CGS-20625 • Divaplon • ELB-139 • Etifoxine • GBLD-345 • Gedocarnil • ICI-190,622 • L-838,417 • NS-2664 • NS-2710 • Ocinaplon • Pagoclone • Panadiplon • Pipequaline • RWJ-51204 • SB-205,384 • SL-651,498 • TP-003 • TP-13 • TPA-023 • Tracazolate • Y-23684 • ZK-93423; Others: Chlormezanone • Etazolate • Ethanol (Alcohol) • Kavalactones (Kava Kava) • Skullcap • Valerenic Acid (Valerian) 5-HT1A Agonists Azapirones: Buspirone • Gepirone • Tandospirone; Others: Flesinoxan • PRX-00023 H1 Antagonists Diphenylmethanes: Captodiame • Hydroxyzine; Others: Brompheniramine • Chlorpheniramine • Pheniramine CRF1 Antagonists Antalarmin • CP-154,526 • Pexacerfont NK2 Antagonists GR-159,897 • Saredutant MCH1 antagonists ATC-0175 • SNAP-94847 mGluR2/3 Agonists Eglumegad mGluR5 NAMs Fenobam TSPO agonists DAA-1097 • DAA-1106 • Emapunil • FGIN-127 • FGIN-143 Others Benzoctamine • Carbetocin • Demoxytocin • Mephenoxalone • Oxytocin • Promoxolane • Trimetozine • WAY-267,464

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)