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{{Drugbox|
{{DrugProjectFormSinglePage
| IUPAC_name = ''9-chloro-5-hydroxy-N-methyl-6-phenyl-<BR>2,5-diazabicyclo[5.4.0]undeca-<BR>1,6,8,10-tetraen-3-imine''
|authorTag=
| image = Chlordiazepoxide.png
 
| width = 150
{{VP}}
| image2 = Chlordiazepoxide3d.png
 
| width = 150
<!--Overview-->
 
|genericName=
 
 
 
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a
 
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Yes
 
|adverseReactions=
 
 
 
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Title
 
|blackBoxWarningBody=
<i><span style="color:#FF0000;">ConditionName: </span></i>
 
* Content
 
<!--Adult Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Adult)-->
 
|fdaLIADAdult=
 
Chlordiazepoxide HCI Capsules are indicated for the management of anxiety disorders or for the short-term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.
 
The effectiveness of chlordiazepoxide in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.
 
<!--Off-Label Use and Dosage (Adult)-->
 
<!--Guideline-Supported Use (Adult)-->
 
|offLabelAdultGuideSupport=
 
=====Condition1=====
 
* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
 
|offLabelAdultNoGuideSupport=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
 
|fdaLIADPed=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Off-Label Use and Dosage (Pediatric)-->
 
<!--Guideline-Supported Use (Pediatric)-->
 
|offLabelPedGuideSupport=
 
=====Condition1=====
 
* Developed by:
 
* Class of Recommendation:
 
* Strength of Evidence:
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Non–Guideline-Supported Use (Pediatric)-->
 
|offLabelPedNoGuideSupport=
 
=====Condition1=====
 
* Dosing Information
 
:* Dosage
 
=====Condition2=====
 
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
 
<!--Contraindications-->
 
|contraindications=
 
* Chlordiazepoxide HCI Capsules are contraindicated in patients with known hypersensitivity to the drug.
 
<!--Warnings-->
 
|warnings=
 
*Chlordiazepoxide may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a vehicle or operating machinery. Similarly, it may impair mental alertness in children. The concomitant use of alcohol or other central nervous system depressants may have an additive effect. PATIENTS SHOULD BE WARNED ACCORDINGLY.
 
*Usage in Pregnancy: 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.
 
*Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines. (See DRUG ABUSE AND DEPENDENCE section.)
 
====Precautions====
 
*In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (10 mg or less per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of chlordiazepoxide HCI and other psychotropic agents is not recommended. If such combination therapy seems indicated, careful consideration should be given to the pharmacology of the agents to be employed — particularly when the known potentiating compounds such as the MAO inhibitors and phenothiazines are to be used. The usual precautions in treating patients with impaired renal or hepatic function should be observed.
 
*Paradoxical reactions, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and in hyperactive aggressive children, and should be watched for during chlordiazepoxide therapy. The usual precautions are indicated when chlordiazepoxide HCI capsules are used in the treatment of anxiety states where there is any evidence of impending depression; it should be borne in mind that suicidal tendencies may be present and protective measures may be necessary. Although clinical studies have not established a cause and effect relationship, physicians should be aware that variable effects on blood coagulation have been reported very rarely in patients receiving oral anticoagulants and chlordiazepoxide. In view of isolated reports associating chlordiazepoxide with exacerbation of porphyria, caution should be exercised in prescribing chlordiazepoxide to patients suffering from this disease.
 
<!--Adverse Reactions-->
 
<!--Clinical Trials Experience-->
 
|clinicalTrials=
 
*The necessity of discontinuing therapy because of undesirable effects has been rare. Drowsiness, ataxia and confusion have been reported in some patients —particularly the elderly and debilitated. While these effects can be avoided in almost all instances by proper dosage adjustment, they have occasionally been observed at the lower dosage ranges. In few instances syncope has been reported.
 
*Other adverse reactions reported during therapy include isolated instances of skin eruptions, edema, minor menstrual irregularities, nausea and constipation, extrapyramidal symptoms, as well as increased and decreased libido. Such side effects have been infrequent and are generally controlled with reduction of dosage. Changes in EEG patterns (low-voltage fast activity) have been observed in patients during and after chlordiazepoxide treatment.
 
*Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When chlordiazepoxide treatment is protracted, periodic blood counts and liver function tests are advisable.
 
<!--Postmarketing Experience-->
 
|postmarketing=
 
There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
 
<!--Drug Interactions-->
 
|drugInteractions=
 
<!--Use in Specific Populations-->
 
|useInPregnancyFDA=
* '''Pregnancy Category'''
 
|useInPregnancyAUS=
* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
 
|useInLaborDelivery=
There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
 
|useInNursing=
There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
 
|useInPed=
There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
 
|useInGeri=
There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
 
|useInGender=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
 
|useInRace=
There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
 
|useInRenalImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with renal impairment.
 
|useInHepaticImpair=
There is no FDA guidance on the use of {{PAGENAME}} in patients with hepatic impairment.
 
|useInReproPotential=
There is no FDA guidance on the use of {{PAGENAME}} in women of reproductive potentials and males.
 
|useInImmunocomp=
There is no FDA guidance one the use of {{PAGENAME}} in patients who are immunocompromised.
 
<!--Administration and Monitoring-->
 
|administration=
 
* Oral
 
|monitoring=
 
There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
 
<!--IV Compatibility-->
 
|IVCompat=
 
There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
 
<!--Overdosage-->
 
|overdose=
 
===Acute Overdose===
 
====Signs and Symptoms====
 
*Manifestations of chlordiazepoxide overdosage includes somnolence, confusion, coma and diminished reflexes.
 
====Management====
 
*Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following chlordiazepoxide overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. There have been occasional reports of excitation in patients following chlordiazepoxide overdosage; if this occurs barbiturates should not be used. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.
 
*Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation, and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression, and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use.
 
===Chronic Overdose===
 
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
 
<!--Pharmacology-->
 
<!--Drug box 2-->
 
|drugBox=
 
{{Drugbox2
| Watchedfields = changed
| verifiedrevid = 477165694
| IUPAC_name = 7-chloro-2-methylamino-5-phenyl-3''H''-1,4-benzodiazepine-4-oxide''
| image = Chlordiazepoxide00.png
| width = 200
| image2 = Chlordiazepoxide000.gif
| width2 = 250
 
<!--Clinical data-->
| tradename = Librium
| Drugs.com = {{drugs.com|monograph|chlordiazepoxide}}
| MedlinePlus = a682078
| pregnancy_US = D
| legal_AU = S4
| legal_US = Schedule IV
| legal_UK = PoM
| routes_of_administration = oral <br> intramuscular
 
<!--Pharmacokinetic data-->
| metabolism = [[Liver|Hepatic]]
| elimination_half-life = 5&ndash;30 hours (Active metabolite [[desmethyldiazepam]] 36-200 hours: other active metabolites include [[oxazepam]].)
| excretion = [[Kidney|Renal]]
 
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 58-25-3
| CAS_number = 58-25-3
| ATC_prefix = N05
| ATC_prefix = N05
| ATC_suffix = BA02
| ATC_suffix = BA02
| ATC_supplemental =
| PubChem = 2712
| PubChem = 2712
| DrugBank = APRD00682
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00475
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10248513
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 6RZ6XEZ3CR
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00267
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 3611
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 451
 
<!--Chemical data-->
| C=16 | H=14 | Cl=1 | N=3 | O=1
| C=16 | H=14 | Cl=1 | N=3 | O=1
| molecular_weight = 299.8
| molecular_weight = 299.75 g/mol
| bioavailability = well absorbed
| smiles = ClC1=CC2=C(N=C(NC)C[N+]([O-])=C2C3=CC=CC=C3)C=C1
| metabolism = [[Liver|Hepatic]]
| InChI = 1/C16H14ClN3O/c1-18-15-10-20(21)16(11-5-3-2-4-6-11)13-9-12(17)7-8-14(13)19-15/h2-9H,10H2,1H3,(H,18,19)
| elimination_half-life = 5-30 hours
| InChIKey = ANTSCNMPPGJYLG-UHFFFAOYAM
| excretion = [[Kidney|Renal]]
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_US = D
| StdInChI = 1S/C16H14ClN3O/c1-18-15-10-20(21)16(11-5-3-2-4-6-11)13-9-12(17)7-8-14(13)19-15/h2-9H,10H2,1H3,(H,18,19)
| legal_US = Schedule IV
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration = oral <br> intramuscular
| StdInChIKey = ANTSCNMPPGJYLG-UHFFFAOYSA-N
}}
}}
'''Chlordiazepoxide''' (pronounced [ˈklɔːrˌdaɪəzepˈoksaɪd], marketed under the trade name '''Librium®''') is a sedative/hypnotic drug which is a [[benzodiazepine]] derivative. It has a medium to long [[half life]].


==History==
<!--Mechanism of Action-->
''See the main article [[benzodiazepine]] for the history of Librium.''
 
|mechAction=


The correct IUPAC name is: 7-chloro-2(methylamine)-5-phenyl-3H-1,4-benzodiazepine-4-oxide-hydrochloride and you have to include HCL
* Chlordiazepoxide HCI has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The precise mechanism of action is not known. The drug blocks EEG arousal from stimulation of the brain stem reticular formation. It takes several hours for peak blood levels to be reached and the half-life of the drug is between 24 and 48 hours. After the drug is discontinued plasma levels decline slowly over a period of several days. Chlordiazepoxide is excreted in the urine, with 1 to 2% unchanged and 3 to 6% as a conjugate.


==Pharmacology==
<!--Structure-->
Chlordiazepoxide acts on benzodiazepine subreceptors of the main GABA<sub>A</sub> receptor and this results in an increased binding of the inhibitory neurotransmitter [[GABA]] to the GABA<sub>A</sub> receptor thereby producing inhibitory effects on the [[central nervous system]] and body similar to the effects of other [[benzodiazepines]].<ref>{{cite journal | author = Skerritt JH | coauthors = Johnston GA. | year = 1983 | month = May | date = 6 | title = Enhancement of GABA binding by benzodiazepines and related anxiolytics. | journal = Eur J Pharmacol. | volume = 89 | issue = 3-4 | pages = 193-8 | pmid = 6135616 }}</ref> Chlordiazepoxide at high doses decreases histamine turnover via it's action at the benzodiazepine-GABA receptor complex.<ref>{{cite journal | author = Oishi R | coauthors = Nishibori M, Itoh Y, Saeki K. | year = 1986 | month = May | date = 27 | title = Diazepam-induced decrease in histamine turnover in mouse brain. | journal = Eur J Pharmacol. | volume = 124 | issue = 3
| pages = 337-42 | pmid = 3089825 }}</ref> Chlordiazepoxide is molecularly related to [[quinazolines]] and is a [[hapten]].<ref>{{cite journal | author = Earley JV | coauthors = Fryer RI, Ning RY. | year = 1979 | month = Jul | title = Quinazolines and 1,4-benzodiazepines. LXXXIX: Haptens useful in benzodiazepine immunoassay development. | journal = J Pharm Sci. | volume = 68 | issue = 7 | pages = 845-50 | pmid = 458601 }}</ref>
There is preferential storage of chlordiazepoxide in some organs including the heart. Absortion by any administered route and the risk of accumulation is significantly increased in the neonate and there are clinical justification to recommend the withdrawal of chlordiazepoxide during pregnancy and breast feeding as chlordiazepoxide rapidly crosses the placenta and also is excreted in breast milk.<ref>{{cite journal | author = Olive G | coauthors = Dreux C. | year = 1977 | month = Jan | title = Pharmacologic bases of use of benzodiazepines in peréinatal medicine. | journal = Arch Fr Pediatr. | volume = 34(1) | pages = 74-89 | pmid = 851373 }}</ref>


Chlordiazepoxide is a long acting benzodiazepine drug. The half life of Chlordiazepoxide is 5-30 hours but has an active benzodiazepine metabolite which has a half life of 36 - 200 hours.<ref>{{cite web | url = http://www.bcnc.org.uk/equivalence.html | title = BENZODIAZEPINE EQUIVALENCY TABLE | accessmonthday = Sept 23 | accessyear = 2007 | author = Ashton CH. | year = 2007 | month = April }}</ref> The half life of chlordiazepoxide increases significantly in the elderly which may result in prolonged action as well as accumulation of the drug during repeated administration. Delayed body clearance of the long half life active metabolite also occurs in those over 60 years of age which further prolongs the effects of the drugs with additional accumulation after repeated dosing.<ref>{{cite journal | author = Vozeh S. | coauthors = | year = 1981 | month = Nov | date = 21 | title = [Pharmacokinetic of benzodiazepines in old age] | journal = Schweiz Med Wochenschr. | volume = 111 | issue = 47 | pages = 1789-93 | pmid = 6118950 }}</ref>
|structure=


==Tolerance==
* Chlordiazepoxide hydrochloride is the prototype for the benzodiazepine compounds.


Tolerance to the [[anxiolytic]] effects develops rapidly and a stimulating effect develops after repeated daily administration.<ref>{{cite journal | author = Nowakowska E | coauthors = Chodera A, Cenajek-Musiał D, Szczawińska K. | year = 1987 | month = May-Jun | title = Differences in the development of tolerance to various benzodiazepines. | journal = Pol J Pharmacol Pharm. | volume = 39 | issue = 3 | pages = 245-52 | pmid = 2894019 }}</ref> In mice tolerance to the anticonvulsant properties of chlordiazepoxide developed slowly over 15 days, although some anticonvulsant effects were still apparent after 15 days of continued administration.<ref>{{cite journal | author = Garratt JC | coauthors = Gent JP, Feely M, Haigh JR. | year = 1988 | month = Jan | date = 5 | title = Can benzodiazepines be classified by characterising their anticonvulsant tolerance-inducing potential? | journal = Eur J Pharmacol. | volume = 145 | issue = 1 | pages = 75-80 | pmid = 2894998 }}</ref>
*Chlordiazepoxide hydrochloride is 7-chloro-2-(methylamino)-5-phenyl-3 H-1, 4-benzodiazepine 4-oxide hydrochloride. A white to practically white crystalline substance, it is soluble in water. It is unstable in solution and the powder must be protected from light. The structural formula of chlordiazepoxide hydrochloride is as follows:


==Dependence==
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]


Chlordiazepoxide can cause [[physical dependence]], [[addiction]] and what is known as the [[benzodiazepine withdrawal syndrome]]. Withdrawal from chlordiazepoxide or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen with alcohol and [[barbiturates]]. The higher the dose and the longer the drug is taken the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can however occur at standard dosages and also after short term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regime.<ref>{{cite journal | author = MacKinnon GL | coauthors = Parker WA. | year = 1982 | month = | title = Benzodiazepine withdrawal syndrome: a literature review and evaluation. | journal = The American journal of drug and alcohol abuse. | volume = 9 | issue = 1 | pages = 19-33 | pmid = 6133446 }}</ref>
*Available as capsules for oral administration containing either 5 mg, 10 mg or 25 mg of chlordiazepoxide hydrochloride.


===The Committee on the Review of Medicines===
<!--Pharmacodynamics-->


The Committee on the Review of Medicines (UK) carried out a review into benzodiazepines due to significant concerns of tolerance, [[drug dependence]] and [[benzodiazepine withdrawal]] problems and other adverse effects. The committee found that benzodiazepines do not have any [[antidepressant]] or [[analgesic]] properties and are therefore unsuitable treatments for conditions such as depression, [[tension headaches]] and [[dysmenorrhoea]]. Benzodiazepines are also not beneficial in the treatment of [[psychosis]] due to a lack of efficacy. The committee also recommended against benzodiazepines being used in the treatment of [[anxiety]] or [[insomnia]] in children. The committee was in agreement with the [[Institute of Medicine]] (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the [[National Institute on Drug Abuse]] (USA) that there was little evidence that long term use of benzodiazepine hypnotics were benefitial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tended to lose their sleep promoting properties within 3 - 14 days of continuous use and in the treatment of anxiety the committee found that there was little convincing evidence that benzodiazepines retained efficacy in the treatment of anxiety after 4 months continuous use due to the development of tolerance. The committee found that the regular use of benzodiazepines caused 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 symptoms tended to develop within 24 hours on the cessation of a short acting benzodiazepine and within 3 - 10 days after the cessation of a more short acting benzodiazepine. Withdrawal effects could occur after treatment lasting only 2 weeks at therapeutic dose levels however withdrawal effects tended to occur with habitual use beyond 2 weeks and were more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition. The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short term use only. It was noted in the review that alcohol can potentiate the [[central nervous system]] depressant effects of benzodiazepines and should be avoided. The central nervous system depressant effects of benzodiazepines may make driving or operating machinery dangerous and the elderly are more prone to these adverse effects. In the [[neonate]] high single doses or repeated low doses have been reported to produce [[hypotonia]], poor sucking, and [[hypothermia]] in the [[neonate]] and irregularities in the [[fetal]] heart. Benzodiazepines should be avoided in [[lactation]]. 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]].<ref>{{cite journal | author = Committee on the Review of Medicines | year = 1980 | month = Mar | date  = 29 | title = 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. | journal = Br Med J. | volume = 280 | issue = 6218 | pages = 910-2 | pmid = 7388368 | url = http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1601049&blobtype=pdf | format = pdf }}</ref>
|PD=


==Abuse Potential==
There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
Chlordiazepoxide is frequently detected in urine samples of drug abusers who have not been prescribed the drug suggesting a high misuse potential for chlordiazepoxide.<ref>{{cite journal | author = Garretty DJ | coauthors = Wolff K, Hay AW, Raistrick D. | year = 1997 | month = Jan | title = Benzodiazepine misuse by drug addicts. | journal = Annals of clinical biochemistry. | volume = 34 | issue = Pt 1 | pages = 68-73 | pmid = 9022890 }}</ref>
Chlordiazepoxide in animal studies has been shown to increase reward seeking behaviours which may suggest an increased risk of addictive behavioural patterns.<ref>{{cite journal | author = Thiébot MH | coauthors = Le Bihan C, Soubrié P, Simon P. | year = 1985 | month = | title = Benzodiazepines reduce the tolerance to reward delay in rats. | volume = 86 | issue = 1-2 | pages = 147-52 | pmid = 2862657 | journal = Psychopharmacology (Berl).}}</ref>


==Indications==
<!--Pharmacokinetics-->
Chlordiazepoxide is indicated for the short term (2 - 4 weeks) treatment of severe and distressing insomnia, anxiety and panic attacks. It has also been used as a treatment for acute alcohol or opiate withdrawal, as well as relief from Crohn's and ulcerative colitis.


==Dosage==
|PK=
Chlordiazepoxide is available in 5mg, 10mg and 25mg strengths.


==Side effects==
There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
Common side effects of chlordiazepoxide include:
* Drowsiness
* [[depression (mood)|Depression]]
* Impaired motor function
** Impaired coordination
** Impaired balance
** [[Dizziness]]
* [[Nervousness]]
* [[Anterograde amnesia]] (especially pronounced in higher doses)
* Impaired learning


Chloridazepoxide in laboratory studies impairs latent learning. Benzodiazepines impair learning and memory via their action on benzodiazepine receptors which causes a dysfunction in the cholinergic neuronal system.<ref>{{cite journal | author = Nabeshima T | coauthors = Tohyama K, Ichihara K, Kameyama T. | year = 1990 | month = Nov | title = Effects of benzodiazepines on passive avoidance response and latent learning in mice: relationship to benzodiazepine receptors and the cholinergic neuronal system. | journal = J Pharmacol Exp Ther. | volume = 255 | issue = 2 | pages = 789-94 | pmid = 2173758 }}</ref> In tests of various benzodiazepine compounds Chlordiazepoxide was found to cause the most profound reduction in the turn over of 5HT which is the building block of serotonin. Serotonin is closely involved in regulating mood and may be one of the causes of feelings of depression in users of Chlordiazepoxide or other benzodiazepines.<ref>{{cite journal | author = Antkiewicz-Michaluk L | coauthors = Grabowska M, Baran L, Michaluk J. | year = 1975 | month = | title = Influence of benzodiazepines on turnover of serotonin in cerebral structures in normal and aggressive rats. | journal = Arch Immunol Ther Exp (Warsz). | volume = 23 | issue = 6 | pages = 763-7 | pmid = 1241268 }}</ref>
<!--Nonclinical Toxicology-->


[[Image:chlordiazepoxide_DOJ.jpg|right|frame]]
|nonClinToxic=


==Contraindications==
*The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses.
Use of chlordiazepoxide should be avoided in individuals with the following conditions:
* [[Myasthenia gravis]]
* Acute intoxication with alcohol, narcotics, or other psychoactive substances
* [[Ataxia]]
* Severe [[hypoventilation]]
* Acute narrow-angle [[glaucoma]]
* Severe liver deficiencies ([[hepatitis]] and liver [[cirrhosis]] decrease elimination by a factor of 2)
* Severe [[sleep apnea]]
* Hypersensitivity or allergy to any drug in the [[benzodiazepine]] class


==Interactions==
*Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide revealed a “taming” action with the elimination of fear and aggression. The taming effect of chlordiazepoxide was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.
Oral contraceptive pills, reduce the clearance of chlordiazepoxide which may lead to increased plasma levels of chlordiazepoxide and accumulation.<ref>{{cite journal | author = Back DJ | coauthors = Orme ML. | year = 1990 | month = Jun | title = Pharmacokinetic drug interactions with oral contraceptives. | journal = Clin Pharmacokinet. | volume = 18 | issue = 6 | pages = 472-84 | pmid = 2191822 }}</ref> Chlordiazepoxide interacts with contraceptives resulting in increased bleeding.<ref>{{cite journal |author=Somos P. |coauthors= |title= Interaction between certain psychopharmaca and low-dose oral contraceptives. |volume=38 |issue=1 |pages=37-40 |year=1990 |pmid=1971733 }}</ref>


==Overdose==
*The LD50 of parenterally administered chlordiazepoxide HCI was determined in mice (72 hours) and rats (5 days), and calculated according to the method of Miller and Tainter, with the following results: mice, I.V., 123 ± 12 mg/kg; mice, I.M., 336 ± 7 mg/kg; rats, I.V., 120 ± 7 mg/kg; rats, I.M., >160 mg/kg.
An individual who has consumed too much chlordiazepoxide will display one or more of the following symptoms:
* [[Somnolence]] (difficulty staying awake)
* Mental confusion
* [[Hypotension]]
* [[Hypoventilation]]
* Impaired motor functions
** Impaired reflexes
** Impaired coordination
** Impaired balance
** [[Dizziness]]
** Muscle Weakness
* [[Coma]]


In animal models, the oral LD<sub>50</sub> of chlordiazepoxide is 537 mg/kg.  
*Effects on Reproduction:
:*Reproduction studies in rats fed 10, 20, and 80 mg/kg daily and bred through one or two mating showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. However, in another study at 100 mg/kg daily there was noted a significant decrease in the fertilization rate and a marked decrease in the viability and body weight of offspring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened maternal nursing and care of the young. One neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. Further studies are in progress to determine the significance of these findings.


Chlordiazepoxide is a drug which is very frequently involved in drug intoxication, including overdose.<ref>{{cite journal | author = Zevzikovas A | coauthors = Kiliuviene G, Ivanauskas L, Dirse V. | year = 2002 | month = | date  = | title = [Analysis of benzodiazepine derivative mixture by gas-liquid chromatography] | journal = Medicina (Kaunas). | volume = 38 | issue = 3 | pages = 316-20 | pmid = 12474705 }}</ref> Chlordiazepoxide overdose is considered a medical emergency and generally requires the immediate attention of medical personnel. The [[antidote]] for an overdose of chlordiazepoxide (or any other benzodiazepine) is [[flumazenil]] (Anexate®).
<!--Clinical Studies-->


==Legal status==
|clinicalStudies=
Internationally, chlordiazepoxide is a Schedule IV drug under the [[Convention on Psychotropic Substances]][http://www.incb.org/pdf/e/list/green.pdf].


==Toxicity==
There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
Laboratory tests assessing the toxicity of chlordiazepoxide, [[nitrazepam]] and [[diazepam]] on mice [[spermatozoa]] found that chlordiazepoxide produced toxicities in sperm including abnormalities involving both the shape and size of the sperm head. Nitrazepam however caused more profound abnormalities than chlordiazepoxide.<ref>{{cite journal | author = Kar RN | coauthors = Das RK. | year = 1983 | month = | title = Induction of sperm head abnormalities in mice by three tranquilizers. | journal = Cytobios. | volume = 36 | issue = 141 | pages = 45-51 | pmid = 6132780 }}</ref>


==Alternative trade names==
<!--How Supplied-->


* Librocol
|howSupplied=
* Librelease
* Libritabs
* Limbitrol
* Menrium
* Novo-Poxide
* Poxidium
* Risolid
* Defobin


==Combination Drugs==
*Chlordiazepoxide Hydrochoride Capsules USP, 5 mg are available as a two-piece hard gelatin capsule with an aqua green opaque cap and a yellow opaque body filled with white powder, imprinted in black ink barr 158. They are available as follows:
* Librax - chlordiazepoxide and [[clidinium]]
:*NDC 51079-374-20 - Unit dose blister packages of 100 (10 cards of 10 capsules each).


==External links==
*Chlordiazepoxide Hydrochloride Capsules USP, 10 mg are available as a two-piece hard gelatin capsule with a black opaque cap and a green opaque body filled with white powder, imprinted in white ink barr 033. They are available as follows:
* [http://www.rxlist.com/cgi/generic/chlordia.htm Rx-List.com - Chlordiazepoxide]
:*NDC 51079-375-20 - Unit dose blister packages of 100 (10 cards of 10 capsules each).
* [http://www.inchem.org/documents/pims/pharm/pim321.htm Inchem.org - Chlordiazepoxide]


==References==
*Chlordiazepoxide Hydrochloride Capsules USP, 25 mg are available as a two-piece hard gelatin capsule with an aqua green opaque cap and a white opaque body filled with white powder, imprinted in black ink barr 159. They are available as follows:
<references/>
:*NDC 51079-141-20 - Unit dose blister packages of 100 (10 cards of 10 capsules each).


{{Benzodiazepines}}
*Store at 20° to 25°C (68° to 77°F) in a dry place.
 
*Protect from light.
 
<!--Patient Counseling Information-->
 
|fdaPatientInfo=
 
*To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing the drug.
 
<!--Precautions with Alcohol-->
 
|alcohol=
 
* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
 
<!--Brand Names-->
 
|brandNames=
 
* ®<ref>{{Cite web | title =  | url =  }}</ref>
 
<!--Look-Alike Drug Names-->
 
|lookAlike=
 
* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>
 
<!--Drug Shortage Status-->
 
|drugShortage=
}}
 
<!--Pill Image-->
 
{{PillImage
|fileName=No image.jpg|This image is provided by the National Library of Medicine.
|drugName=
|NDC=
|drugAuthor=
|ingredients=
|pillImprint=
|dosageValue=
|dosageUnit=
|pillColor=
|pillShape=
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<!--Label Display Image-->
 
{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
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{{LabelImage
|fileName={{PAGENAME}}11.png|This image is provided by the National Library of Medicine.
}}


[[Category:Benzodiazepines]]
<!--Category-->
[[Category:Hypnotics]]


[[es:Clordiazepóxido]]
[[Category:Drug]]
[[gl:Chlordiazepoxide]]
[[nl:Chloordiazepoxide]]
[[ja:クロルジアゼポキシド]]
[[pl:Chlordiazepoksyd]]
[[pt:Clorodiazepóxido]]
[[ru:Хлозепид]]
[[sv:Klordiazepoxid]]
{{WikiDoc Help Menu}}

Revision as of 19:29, 22 December 2014

Chlordiazepoxide
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]

Disclaimer

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Black Box Warning

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content

Overview

Chlordiazepoxide is a that is FDA approved for the {{{indicationType}}} of . There is a Black Box Warning for this drug as shown here. Common adverse reactions include .

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Chlordiazepoxide HCI Capsules are indicated for the management of anxiety disorders or for the short-term relief of symptoms of anxiety, withdrawal symptoms of acute alcoholism, and preoperative apprehension and anxiety. Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic.

The effectiveness of chlordiazepoxide in long-term use, that is, more than 4 months, has not been assessed by systematic clinical studies. The physician should periodically reassess the usefulness of the drug for the individual patient.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Chlordiazepoxide in adult patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Chlordiazepoxide in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding FDA-Labeled Use of Chlordiazepoxide in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

Condition1
  • Developed by:
  • Class of Recommendation:
  • Strength of Evidence:
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Guideline-Supported Use of Chlordiazepoxide in pediatric patients.

Non–Guideline-Supported Use

Condition1
  • Dosing Information
  • Dosage
Condition2

There is limited information regarding Off-Label Non–Guideline-Supported Use of Chlordiazepoxide in pediatric patients.

Contraindications

  • Chlordiazepoxide HCI Capsules are contraindicated in patients with known hypersensitivity to the drug.

Warnings

Title
See full prescribing information for complete Boxed Warning.
ConditionName:
  • Content
  • Chlordiazepoxide may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a vehicle or operating machinery. Similarly, it may impair mental alertness in children. The concomitant use of alcohol or other central nervous system depressants may have an additive effect. PATIENTS SHOULD BE WARNED ACCORDINGLY.
  • Usage in Pregnancy: 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.
  • Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines. (See DRUG ABUSE AND DEPENDENCE section.)

Precautions

  • In elderly and debilitated patients, it is recommended that the dosage be limited to the smallest effective amount to preclude the development of ataxia or oversedation (10 mg or less per day initially, to be increased gradually as needed and tolerated). In general, the concomitant administration of chlordiazepoxide HCI and other psychotropic agents is not recommended. If such combination therapy seems indicated, careful consideration should be given to the pharmacology of the agents to be employed — particularly when the known potentiating compounds such as the MAO inhibitors and phenothiazines are to be used. The usual precautions in treating patients with impaired renal or hepatic function should be observed.
  • Paradoxical reactions, e.g., excitement, stimulation and acute rage, have been reported in psychiatric patients and in hyperactive aggressive children, and should be watched for during chlordiazepoxide therapy. The usual precautions are indicated when chlordiazepoxide HCI capsules are used in the treatment of anxiety states where there is any evidence of impending depression; it should be borne in mind that suicidal tendencies may be present and protective measures may be necessary. Although clinical studies have not established a cause and effect relationship, physicians should be aware that variable effects on blood coagulation have been reported very rarely in patients receiving oral anticoagulants and chlordiazepoxide. In view of isolated reports associating chlordiazepoxide with exacerbation of porphyria, caution should be exercised in prescribing chlordiazepoxide to patients suffering from this disease.

Adverse Reactions

Clinical Trials Experience

  • The necessity of discontinuing therapy because of undesirable effects has been rare. Drowsiness, ataxia and confusion have been reported in some patients —particularly the elderly and debilitated. While these effects can be avoided in almost all instances by proper dosage adjustment, they have occasionally been observed at the lower dosage ranges. In few instances syncope has been reported.
  • Other adverse reactions reported during therapy include isolated instances of skin eruptions, edema, minor menstrual irregularities, nausea and constipation, extrapyramidal symptoms, as well as increased and decreased libido. Such side effects have been infrequent and are generally controlled with reduction of dosage. Changes in EEG patterns (low-voltage fast activity) have been observed in patients during and after chlordiazepoxide treatment.
  • Blood dyscrasias (including agranulocytosis), jaundice and hepatic dysfunction have occasionally been reported during therapy. When chlordiazepoxide treatment is protracted, periodic blood counts and liver function tests are advisable.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Chlordiazepoxide in the drug label.

Drug Interactions

There is limited information regarding Chlordiazepoxide Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Chlordiazepoxide in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Chlordiazepoxide during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Chlordiazepoxide with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Chlordiazepoxide with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Chlordiazepoxide with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Chlordiazepoxide with respect to specific gender populations.

Race

There is no FDA guidance on the use of Chlordiazepoxide with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Chlordiazepoxide in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Chlordiazepoxide in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Chlordiazepoxide in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Chlordiazepoxide in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Oral

Monitoring

There is limited information regarding Monitoring of Chlordiazepoxide in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Chlordiazepoxide in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

  • Manifestations of chlordiazepoxide overdosage includes somnolence, confusion, coma and diminished reflexes.

Management

  • Respiration, pulse and blood pressure should be monitored, as in all cases of drug overdosage, although, in general, these effects have been minimal following chlordiazepoxide overdosage. General supportive measures should be employed, along with immediate gastric lavage. Intravenous fluids should be administered and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. There have been occasional reports of excitation in patients following chlordiazepoxide overdosage; if this occurs barbiturates should not be used. As with the management of intentional overdosage with any drug, it should be borne in mind that multiple agents may have been ingested.
  • Flumazenil, a specific benzodiazepine receptor antagonist, is indicated for the complete or partial reversal of the sedative effects of benzodiazepines and may be used in situations when an overdose with a benzodiazepine is known or suspected. Prior to the administration of flumazenil, necessary measures should be instituted to secure airway, ventilation, and intravenous access. Flumazenil is intended as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. Patients treated with flumazenil should be monitored for resedation, respiratory depression, and other residual benzodiazepine effects for an appropriate period after treatment. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use.

Chronic Overdose

There is limited information regarding Chronic Overdose of Chlordiazepoxide in the drug label.

Pharmacology

Template:Px
Template:Px
Chlordiazepoxide
Systematic (IUPAC) name
7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide
Identifiers
CAS number 58-25-3
ATC code N05BA02
PubChem 2712
DrugBank DB00475
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 299.75 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability ?
Metabolism Hepatic
Half life 5–30 hours (Active metabolite desmethyldiazepam 36-200 hours: other active metabolites include oxazepam.)
Excretion Renal
Therapeutic considerations
Pregnancy cat.

D(US)

Legal status

Prescription Only (S4)(AU) ?(UK) Schedule IV(US)

Routes oral
intramuscular

Mechanism of Action

  • Chlordiazepoxide HCI has antianxiety, sedative, appetite-stimulating and weak analgesic actions. The precise mechanism of action is not known. The drug blocks EEG arousal from stimulation of the brain stem reticular formation. It takes several hours for peak blood levels to be reached and the half-life of the drug is between 24 and 48 hours. After the drug is discontinued plasma levels decline slowly over a period of several days. Chlordiazepoxide is excreted in the urine, with 1 to 2% unchanged and 3 to 6% as a conjugate.

Structure

  • Chlordiazepoxide hydrochloride is the prototype for the benzodiazepine compounds.
  • Chlordiazepoxide hydrochloride is 7-chloro-2-(methylamino)-5-phenyl-3 H-1, 4-benzodiazepine 4-oxide hydrochloride. A white to practically white crystalline substance, it is soluble in water. It is unstable in solution and the powder must be protected from light. The structural formula of chlordiazepoxide hydrochloride is as follows:
This image is provided by the National Library of Medicine.
  • Available as capsules for oral administration containing either 5 mg, 10 mg or 25 mg of chlordiazepoxide hydrochloride.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Chlordiazepoxide in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Chlordiazepoxide in the drug label.

Nonclinical Toxicology

  • The drug has been studied extensively in many species of animals and these studies are suggestive of action on the limbic system of the brain, which recent evidence indicates is involved in emotional responses.
  • Hostile monkeys were made tame by oral drug doses which did not cause sedation. Chlordiazepoxide revealed a “taming” action with the elimination of fear and aggression. The taming effect of chlordiazepoxide was further demonstrated in rats made vicious by lesions in the septal area of the brain. The drug dosage which effectively blocked the vicious reaction was well below the dose which caused sedation in these animals.
  • The LD50 of parenterally administered chlordiazepoxide HCI was determined in mice (72 hours) and rats (5 days), and calculated according to the method of Miller and Tainter, with the following results: mice, I.V., 123 ± 12 mg/kg; mice, I.M., 336 ± 7 mg/kg; rats, I.V., 120 ± 7 mg/kg; rats, I.M., >160 mg/kg.
  • Effects on Reproduction:
  • Reproduction studies in rats fed 10, 20, and 80 mg/kg daily and bred through one or two mating showed no congenital anomalies, nor were there adverse effects on lactation of the dams or growth of the newborn. However, in another study at 100 mg/kg daily there was noted a significant decrease in the fertilization rate and a marked decrease in the viability and body weight of offspring which may be attributable to sedative activity, thus resulting in lack of interest in mating and lessened maternal nursing and care of the young. One neonate in each of the first and second matings in the rat reproduction study at the 100 mg/kg dose exhibited major skeletal defects. Further studies are in progress to determine the significance of these findings.

Clinical Studies

There is limited information regarding Clinical Studies of Chlordiazepoxide in the drug label.

How Supplied

  • Chlordiazepoxide Hydrochoride Capsules USP, 5 mg are available as a two-piece hard gelatin capsule with an aqua green opaque cap and a yellow opaque body filled with white powder, imprinted in black ink barr 158. They are available as follows:
  • NDC 51079-374-20 - Unit dose blister packages of 100 (10 cards of 10 capsules each).
  • Chlordiazepoxide Hydrochloride Capsules USP, 10 mg are available as a two-piece hard gelatin capsule with a black opaque cap and a green opaque body filled with white powder, imprinted in white ink barr 033. They are available as follows:
  • NDC 51079-375-20 - Unit dose blister packages of 100 (10 cards of 10 capsules each).
  • Chlordiazepoxide Hydrochloride Capsules USP, 25 mg are available as a two-piece hard gelatin capsule with an aqua green opaque cap and a white opaque body filled with white powder, imprinted in black ink barr 159. They are available as follows:
  • NDC 51079-141-20 - Unit dose blister packages of 100 (10 cards of 10 capsules each).
  • Store at 20° to 25°C (68° to 77°F) in a dry place.
  • Protect from light.

Storage

There is limited information regarding Chlordiazepoxide Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

{{#ask: Label Page::Chlordiazepoxide |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

  • To assure the safe and effective use of benzodiazepines, patients should be informed that, since benzodiazepines may produce psychological and physical dependence, it is advisable that they consult with their physician before either increasing the dose or abruptly discontinuing the drug.

Precautions with Alcohol

  • Alcohol-Chlordiazepoxide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ Empty citation (help)
  2. ↑ "http://www.ismp.org". External link in |title= (help)


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