chlordiazepoxide/clidinium (Rx)

Brand and Other Names:Librax
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

chlordiazepoxide/clidinium

capsule

  • 5mg/2.5mg

Peptic Ulcer, IBS, & Enterocolitis

1-2 cap PO q6-8hr ac and hs

Possibly effective

  • Based on a review by the National Academy of Sciences – National Research Council and/or other information, FDA as classified the indications as follows:
  • “Possibly” effective: as adjunctive therapy in the treatment of peptic ulcer and in the treatment of the irritable bowel syndrome (irritable colon, spastic colon, mucous colitis), and acute enterocolitis
  • Final classification of the less-than-effective indications requires further investigation

Safety and efficacy not established

Avoid; high incidence of anticholinergic effects and uncertain effectiveness; avoid except in short-term situations to decrease secretions (Beers Criteria)

Use smallest effective dose

Not to exceed 2 capsules PO per day initially; may increase gradually as needed and tolerated

Ataxia, oversedation, or confusion may occur more frequently in elderly patients

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Interactions

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              Serious - Use Alternative (21)

              • abametapir

                abametapir will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

              • apalutamide

                apalutamide will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

              • benzhydrocodone/acetaminophen

                benzhydrocodone/acetaminophen, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              • calcium/magnesium/potassium/sodium oxybates

                chlordiazepoxide, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              • conivaptan

                conivaptan will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • dacomitinib

                dacomitinib will increase the level or effect of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

              • enzalutamide

                enzalutamide will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • fexinidazole

                fexinidazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              • hydrocodone

                hydrocodone, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              • idelalisib

                idelalisib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

              • ivosidenib

                ivosidenib will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

              • lonafarnib

                lonafarnib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

              • metoclopramide intranasal

                chlordiazepoxide, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              • nefazodone

                nefazodone will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • olopatadine intranasal

                chlordiazepoxide and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

              • selinexor

                selinexor, chlordiazepoxide. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

              • sodium oxybate

                chlordiazepoxide, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              • sufentanil SL

                sufentanil SL, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              • tucatinib

                tucatinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              • valerian

                valerian and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug.

              • voxelotor

                voxelotor will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

              Monitor Closely (238)

              • abiraterone

                abiraterone increases levels of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

              • albuterol

                chlordiazepoxide increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • alfentanil

                chlordiazepoxide and alfentanil both increase sedation. Use Caution/Monitor.

              • alprazolam

                alprazolam and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • amitriptyline

                chlordiazepoxide and amitriptyline both increase sedation. Use Caution/Monitor.

              • amobarbital

                amobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

                amobarbital will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • amoxapine

                chlordiazepoxide and amoxapine both increase sedation. Use Caution/Monitor.

              • apomorphine

                chlordiazepoxide and apomorphine both increase sedation. Use Caution/Monitor.

              • arformoterol

                chlordiazepoxide increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • aripiprazole

                chlordiazepoxide and aripiprazole both increase sedation. Use Caution/Monitor.

              • armodafinil

                chlordiazepoxide increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • atazanavir

                atazanavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              • azelastine

                azelastine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • baclofen

                chlordiazepoxide and baclofen both increase sedation. Use Caution/Monitor.

              • belladonna and opium

                chlordiazepoxide and belladonna and opium both increase sedation. Use Caution/Monitor.

              • belzutifan

                belzutifan will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

              • benperidol

                chlordiazepoxide and benperidol both increase sedation. Use Caution/Monitor.

              • benzphetamine

                chlordiazepoxide increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • bosentan

                bosentan will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • brexanolone

                brexanolone, chlordiazepoxide. Either increases toxicity of the other by sedation. Use Caution/Monitor.

              • brompheniramine

                brompheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • buprenorphine

                chlordiazepoxide and buprenorphine both increase sedation. Use Caution/Monitor.

              • buprenorphine buccal

                chlordiazepoxide and buprenorphine buccal both increase sedation. Use Caution/Monitor.

              • buprenorphine subdermal implant

                chlordiazepoxide increases toxicity of buprenorphine subdermal implant by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Studies have shown that the combination of benzodiazepines and buprenorphine altered the usual ceiling effect on buprenorphine-induced respiratory depression, making the respiratory effects of buprenorphine appear similar to those of full opioid agonists. There have been postmarketing reports of coma and death with coadministration of buprenorphine and benzodiazepines. In many, but not all of these cases, buprenorphine was misused by self-injection. If a benzodiazepine must be used for an indication other than seizures, lower the benzodiazepine initial dose and cautiously titrate to clinical response.

              • buprenorphine, long-acting injection

                chlordiazepoxide increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

              • butabarbital

                butabarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • butalbital

                butalbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • butorphanol

                chlordiazepoxide and butorphanol both increase sedation. Use Caution/Monitor.

              • caffeine

                chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • carbamazepine

                carbamazepine will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • carbinoxamine

                carbinoxamine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • carisoprodol

                chlordiazepoxide and carisoprodol both increase sedation. Use Caution/Monitor.

              • cenobamate

                cenobamate, chlordiazepoxide. Either increases effects of the other by sedation. Use Caution/Monitor.

              • chloral hydrate

                chlordiazepoxide and chloral hydrate both increase sedation. Use Caution/Monitor.

              • chlorpheniramine

                chlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • chlorpromazine

                chlordiazepoxide and chlorpromazine both increase sedation. Use Caution/Monitor.

              • chlorzoxazone

                chlordiazepoxide and chlorzoxazone both increase sedation. Use Caution/Monitor.

              • cimetidine

                cimetidine increases levels of chlordiazepoxide by decreasing metabolism. Use Caution/Monitor.

              • cinnarizine

                cinnarizine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • clarithromycin

                clarithromycin will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • clemastine

                clemastine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • clobazam

                chlordiazepoxide, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

              • clomipramine

                chlordiazepoxide and clomipramine both increase sedation. Use Caution/Monitor.

              • clonazepam

                chlordiazepoxide and clonazepam both increase sedation. Use Caution/Monitor.

              • clonidine

                clonidine, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.

              • clorazepate

                chlordiazepoxide and clorazepate both increase sedation. Use Caution/Monitor.

              • clozapine

                chlordiazepoxide and clozapine both increase sedation. Use Caution/Monitor.

              • cobicistat

                cobicistat will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • codeine

                chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.

              • crofelemer

                crofelemer increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

              • cyclizine

                cyclizine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • cyclobenzaprine

                chlordiazepoxide and cyclobenzaprine both increase sedation. Use Caution/Monitor.

              • cyproheptadine

                cyproheptadine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • dabrafenib

                dabrafenib will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              • dantrolene

                chlordiazepoxide and dantrolene both increase sedation. Use Caution/Monitor.

              • daridorexant

                chlordiazepoxide and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

              • darunavir

                darunavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              • desflurane

                desflurane and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • desipramine

                chlordiazepoxide and desipramine both increase sedation. Use Caution/Monitor.

              • deutetrabenazine

                chlordiazepoxide and deutetrabenazine both increase sedation. Use Caution/Monitor.

              • dexchlorpheniramine

                dexchlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • dexfenfluramine

                chlordiazepoxide increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • dexmedetomidine

                chlordiazepoxide and dexmedetomidine both increase sedation. Use Caution/Monitor.

              • dexmethylphenidate

                chlordiazepoxide increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • dextroamphetamine

                chlordiazepoxide increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • dextromoramide

                chlordiazepoxide and dextromoramide both increase sedation. Use Caution/Monitor.

              • diamorphine

                chlordiazepoxide and diamorphine both increase sedation. Use Caution/Monitor.

              • diazepam

                chlordiazepoxide and diazepam both increase sedation. Use Caution/Monitor.

              • diazepam intranasal

                diazepam intranasal, chlordiazepoxide. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

              • diethylpropion

                chlordiazepoxide increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • difelikefalin

                difelikefalin and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • difenoxin hcl

                chlordiazepoxide and difenoxin hcl both increase sedation. Use Caution/Monitor.

              • dimenhydrinate

                dimenhydrinate and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • diphenhydramine

                diphenhydramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • diphenoxylate hcl

                chlordiazepoxide and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

              • dipipanone

                chlordiazepoxide and dipipanone both increase sedation. Use Caution/Monitor.

              • dobutamine

                chlordiazepoxide increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • dopamine

                chlordiazepoxide increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • dopexamine

                chlordiazepoxide increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • dosulepin

                chlordiazepoxide and dosulepin both increase sedation. Use Caution/Monitor.

              • doxepin

                chlordiazepoxide and doxepin both increase sedation. Use Caution/Monitor.

              • doxylamine

                chlordiazepoxide and doxylamine both increase sedation. Use Caution/Monitor.

              • droperidol

                chlordiazepoxide and droperidol both increase sedation. Use Caution/Monitor.

              • duvelisib

                duvelisib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. will increase the level or effect of

              • efavirenz

                efavirenz will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • elagolix

                elagolix will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

              • eliglustat

                eliglustat increases levels of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; consider benzodiazepine dose reduction.

              • encorafenib

                encorafenib, chlordiazepoxide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

              • ephedrine

                chlordiazepoxide increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • epinephrine

                chlordiazepoxide increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • epinephrine racemic

                chlordiazepoxide increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • esketamine intranasal

                esketamine intranasal, chlordiazepoxide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

              • estazolam

                chlordiazepoxide and estazolam both increase sedation. Use Caution/Monitor.

              • ethanol

                chlordiazepoxide and ethanol both increase sedation. Use Caution/Monitor.

              • etomidate

                etomidate and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • etravirine

                etravirine will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • fedratinib

                fedratinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              • fenfluramine

                chlordiazepoxide increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • flibanserin

                chlordiazepoxide and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

              • fluphenazine

                chlordiazepoxide and fluphenazine both increase sedation. Use Caution/Monitor.

              • flurazepam

                chlordiazepoxide and flurazepam both increase sedation. Use Caution/Monitor.

              • formoterol

                chlordiazepoxide increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • fosamprenavir

                fosamprenavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              • gabapentin

                gabapentin, chlordiazepoxide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

              • gabapentin enacarbil

                gabapentin enacarbil, chlordiazepoxide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

              • ganaxolone

                chlordiazepoxide and ganaxolone both increase sedation. Use Caution/Monitor.

              • haloperidol

                chlordiazepoxide and haloperidol both increase sedation. Use Caution/Monitor.

              • hydromorphone

                chlordiazepoxide and hydromorphone both increase sedation. Use Caution/Monitor.

              • hydroxyzine

                hydroxyzine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • iloperidone

                chlordiazepoxide and iloperidone both increase sedation. Use Caution/Monitor.

                iloperidone increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

              • imipramine

                chlordiazepoxide and imipramine both increase sedation. Use Caution/Monitor.

              • indinavir

                indinavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              • isoproterenol

                chlordiazepoxide increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • istradefylline

                istradefylline will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              • itraconazole

                itraconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ketamine

                ketamine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • ketoconazole

                ketoconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ketotifen, ophthalmic

                chlordiazepoxide and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

              • lasmiditan

                lasmiditan, chlordiazepoxide. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

              • lemborexant

                lemborexant, chlordiazepoxide. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

              • letermovir

                letermovir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • levalbuterol

                chlordiazepoxide increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • levoketoconazole

                levoketoconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • levorphanol

                chlordiazepoxide and levorphanol both increase sedation. Use Caution/Monitor.

              • lisdexamfetamine

                chlordiazepoxide increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • lofepramine

                chlordiazepoxide and lofepramine both increase sedation. Use Caution/Monitor.

              • lofexidine

                chlordiazepoxide and lofexidine both increase sedation. Use Caution/Monitor.

              • lopinavir

                lopinavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available. Consider lowering benzodiazepine dose.

              • loprazolam

                chlordiazepoxide and loprazolam both increase sedation. Use Caution/Monitor.

              • lorazepam

                chlordiazepoxide and lorazepam both increase sedation. Use Caution/Monitor.

              • lorlatinib

                lorlatinib will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lormetazepam

                chlordiazepoxide and lormetazepam both increase sedation. Use Caution/Monitor.

              • loxapine

                chlordiazepoxide and loxapine both increase sedation. Use Caution/Monitor.

              • loxapine inhaled

                chlordiazepoxide and loxapine inhaled both increase sedation. Use Caution/Monitor.

              • lurasidone

                lurasidone, chlordiazepoxide. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

              • maprotiline

                chlordiazepoxide and maprotiline both increase sedation. Use Caution/Monitor.

              • marijuana

                chlordiazepoxide and marijuana both increase sedation. Use Caution/Monitor.

              • melatonin

                chlordiazepoxide and melatonin both increase sedation. Use Caution/Monitor.

              • meperidine

                chlordiazepoxide and meperidine both increase sedation. Use Caution/Monitor.

              • meprobamate

                chlordiazepoxide and meprobamate both increase sedation. Use Caution/Monitor.

              • metaproterenol

                chlordiazepoxide increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • metaxalone

                chlordiazepoxide and metaxalone both increase sedation. Use Caution/Monitor.

              • methadone

                chlordiazepoxide and methadone both increase sedation. Use Caution/Monitor.

              • methamphetamine

                chlordiazepoxide increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • methocarbamol

                chlordiazepoxide and methocarbamol both increase sedation. Use Caution/Monitor.

              • methylenedioxymethamphetamine

                chlordiazepoxide increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • midazolam

                chlordiazepoxide and midazolam both increase sedation. Use Caution/Monitor.

              • midazolam intranasal

                midazolam intranasal, chlordiazepoxide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

              • midodrine

                chlordiazepoxide increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • mirtazapine

                chlordiazepoxide and mirtazapine both increase sedation. Use Caution/Monitor.

              • mitotane

                mitotane decreases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

              • modafinil

                chlordiazepoxide increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • morphine

                chlordiazepoxide and morphine both increase sedation. Use Caution/Monitor.

              • motherwort

                chlordiazepoxide and motherwort both increase sedation. Use Caution/Monitor.

              • moxonidine

                chlordiazepoxide and moxonidine both increase sedation. Use Caution/Monitor.

              • nabilone

                chlordiazepoxide and nabilone both increase sedation. Use Caution/Monitor.

              • nafcillin

                nafcillin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • nalbuphine

                chlordiazepoxide and nalbuphine both increase sedation. Use Caution/Monitor.

              • nelfinavir

                nelfinavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

              • norepinephrine

                chlordiazepoxide increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • nortriptyline

                chlordiazepoxide and nortriptyline both increase sedation. Use Caution/Monitor.

              • olanzapine

                chlordiazepoxide and olanzapine both increase sedation. Use Caution/Monitor.

              • oliceridine

                oliceridine, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

              • opium tincture

                chlordiazepoxide and opium tincture both increase sedation. Use Caution/Monitor.

              • orphenadrine

                chlordiazepoxide and orphenadrine both increase sedation. Use Caution/Monitor.

              • oxazepam

                chlordiazepoxide and oxazepam both increase sedation. Use Caution/Monitor.

              • oxycodone

                chlordiazepoxide and oxycodone both increase sedation. Use Caution/Monitor.

              • oxymorphone

                chlordiazepoxide and oxymorphone both increase sedation. Use Caution/Monitor.

              • paliperidone

                chlordiazepoxide and paliperidone both increase sedation. Use Caution/Monitor.

              • papaveretum

                chlordiazepoxide and papaveretum both increase sedation. Use Caution/Monitor.

              • papaverine

                chlordiazepoxide and papaverine both increase sedation. Use Caution/Monitor.

              • pentazocine

                chlordiazepoxide and pentazocine both increase sedation. Use Caution/Monitor.

              • pentobarbital

                pentobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • perampanel

                perampanel and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • perphenazine

                chlordiazepoxide and perphenazine both increase sedation. Use Caution/Monitor.

              • phendimetrazine

                chlordiazepoxide increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • phenobarbital

                phenobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

                phenobarbital will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • phentermine

                chlordiazepoxide increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • phenylephrine

                chlordiazepoxide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • phenylephrine PO

                chlordiazepoxide increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              • phenytoin

                phenytoin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              • pholcodine

                chlordiazepoxide and pholcodine both increase sedation. Use Caution/Monitor.

              • pimozide

                chlordiazepoxide and pimozide both increase sedation. Use Caution/Monitor.

              • pirbuterol

                chlordiazepoxide increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • posaconazole

                posaconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pregabalin

                pregabalin, chlordiazepoxide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

              • primidone

                primidone and chlordiazepoxide both increase sedation. Use Caution/Monitor.

                primidone will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • prochlorperazine

                chlordiazepoxide and prochlorperazine both increase sedation. Use Caution/Monitor.

              • promethazine

                promethazine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • propofol

                propofol and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • propylhexedrine

                chlordiazepoxide increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • protriptyline

                chlordiazepoxide and protriptyline both increase sedation. Use Caution/Monitor.

              • quazepam

                chlordiazepoxide and quazepam both increase sedation. Use Caution/Monitor.

              • quetiapine

                chlordiazepoxide and quetiapine both increase sedation. Use Caution/Monitor.

              • ramelteon

                chlordiazepoxide and ramelteon both increase sedation. Use Caution/Monitor.

              • remimazolam

                remimazolam, chlordiazepoxide. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

              • ribociclib

                ribociclib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • rifabutin

                rifabutin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • rifampin

                rifampin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • risperidone

                chlordiazepoxide and risperidone both increase sedation. Use Caution/Monitor.

              • ritonavir

                ritonavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available. Potential for increased toxicity. Consider lowering benzodiazepine dose.

              • rolapitant

                rolapitant will increase the level or effect of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

              • rucaparib

                rucaparib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

              • salmeterol

                chlordiazepoxide increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • saquinavir

                saquinavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available. Consider lowering benzodiazepine dose.

              • scullcap

                chlordiazepoxide and scullcap both increase sedation. Use Caution/Monitor.

              • secobarbital

                secobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.

                secobarbital will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. May also enhance CNS depressant effect of chlordiazepoxide

              • sevoflurane

                sevoflurane and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • shepherd's purse

                chlordiazepoxide and shepherd's purse both increase sedation. Use Caution/Monitor.

              • stiripentol

                stiripentol, chlordiazepoxide. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

                stiripentol, chlordiazepoxide. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

              • sufentanil

                chlordiazepoxide and sufentanil both increase sedation. Use Caution/Monitor.

              • suvorexant

                suvorexant and chlordiazepoxide both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

              • tapentadol

                chlordiazepoxide and tapentadol both increase sedation. Use Caution/Monitor.

              • tazemetostat

                tazemetostat will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tecovirimat

                tecovirimat will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

              • teduglutide

                teduglutide increases levels of chlordiazepoxide by Other (see comment). Use Caution/Monitor. Comment: Teduglutide may increase absorption of concomitant PO medications; caution with with drugs requiring titration or those with a narrow therapeutic index; dose adjustment may be necessary.

              • temazepam

                chlordiazepoxide and temazepam both increase sedation. Use Caution/Monitor.

              • terbinafine

                terbinafine will increase the level or effect of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

              • terbutaline

                chlordiazepoxide increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • thioridazine

                chlordiazepoxide and thioridazine both increase sedation. Use Caution/Monitor.

              • thiothixene

                chlordiazepoxide and thiothixene both increase sedation. Use Caution/Monitor.

              • tipranavir

                tipranavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available. Consider lowering benzodiazepine dose.

              • topiramate

                chlordiazepoxide and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              • tramadol

                chlordiazepoxide and tramadol both increase sedation. Use Caution/Monitor.

              • trazodone

                chlordiazepoxide and trazodone both increase sedation. Use Caution/Monitor.

              • triazolam

                chlordiazepoxide and triazolam both increase sedation. Use Caution/Monitor.

              • triclofos

                chlordiazepoxide and triclofos both increase sedation. Use Caution/Monitor.

              • trifluoperazine

                chlordiazepoxide and trifluoperazine both increase sedation. Use Caution/Monitor.

              • trimipramine

                chlordiazepoxide and trimipramine both increase sedation. Use Caution/Monitor.

              • triprolidine

                triprolidine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

              • voriconazole

                voriconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • xylometazoline

                chlordiazepoxide increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • yohimbine

                chlordiazepoxide increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              • ziconotide

                chlordiazepoxide and ziconotide both increase sedation. Use Caution/Monitor.

              • ziprasidone

                chlordiazepoxide and ziprasidone both increase sedation. Use Caution/Monitor.

              • zotepine

                chlordiazepoxide and zotepine both increase sedation. Use Caution/Monitor.

              Minor (25)

              • brimonidine

                brimonidine increases effects of chlordiazepoxide by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

              • ciprofloxacin

                ciprofloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • clotrimazole

                clotrimazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • disulfiram

                disulfiram increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • esomeprazole

                esomeprazole will increase the level or effect of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • eucalyptus

                chlordiazepoxide and eucalyptus both increase sedation. Minor/Significance Unknown.

              • fleroxacin

                fleroxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • fluconazole

                fluconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • gemifloxacin

                gemifloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • green tea

                green tea decreases effects of chlordiazepoxide by pharmacodynamic antagonism. Minor/Significance Unknown. Caffeine component of green tea may decrease sedative effects of benzodiazepines.

              • ketoconazole

                ketoconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • levofloxacin

                levofloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • levoketoconazole

                levoketoconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • metyrapone

                chlordiazepoxide decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

              • miconazole vaginal

                miconazole vaginal increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • moxifloxacin

                moxifloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • ofloxacin

                ofloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • omeprazole

                omeprazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • posaconazole

                posaconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • rifabutin

                rifabutin decreases levels of chlordiazepoxide by increasing metabolism. Minor/Significance Unknown.

              • rifampin

                rifampin decreases levels of chlordiazepoxide by increasing metabolism. Minor/Significance Unknown.

              • sage

                chlordiazepoxide and sage both increase sedation. Minor/Significance Unknown.

              • vinpocetine

                chlordiazepoxide increases effects of vinpocetine by unspecified interaction mechanism. Minor/Significance Unknown. Desirable interaction enhanced memory improvement (based on preliminary trial).

              • voriconazole

                voriconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

              • zolpidem

                zolpidem, chlordiazepoxide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

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              Adverse Effects

              Frequency Not Defined

              Drowsiness

              Ataxia

              Confusion

              Skin eruptions,

              Edema

              Menstrual irregularities

              Nausea

              Constipation

              Xerostomia

              Extrapyramidal symptoms

              Libido, increased/decreased

              Agranulocytosis

              Jaundice

              Hepatic dysfunction

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              Warnings

              Black Box Warnings

              Concomitant use of benzodiazepines and opioids may result in profound respiratory depression, coma, and death; administer concomitantly when there are no alternative options; limit dosages and durations to minimum required; monitor for signs and symptoms of respiratory depression and sedation

              Addiction, abuse, and misuse

              • On September 2020, FDA addressed serious risks of benzodiazepine addiction, abuse, and misuse, which can lead to overdose and death
              • Physical dependence can occur when taken steadily for several days to weeks, even as prescribed
              • Stopping abruptly or reducing dosage too quickly can result in withdrawal reactions, including seizures, which can be life-threatening
              • Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes; before prescribing and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction
              • Assess each patient’s risk prior to prescribing and monitor regularly for the development of these conditions
              • Risks of dependence and withdrawal increase with longer treatment duration and higher daily dose; although injection is indicated only for intermittent use, if used more frequently than recommended, abrupt discontinuation or rapid dosage reduction may precipitate acute withdrawal reactions, including seizures, which can be life-threatening; use gradual taper when discontinuing therapy to reduce withdrawal reactions risk

              Contraindications

              Hypersensitivity

              Glaucoma

              Prostatic hypertrophy

              Benign bladder neck obstruction

              Severe respiratory depression

              Cautions

              Decrease dose in debilitated or elderly patients

              Concomitant administration with other psychotropic agents not recommended; if such combination seems indicated, give careful consideration to pharmacology of agents to be employed, particularly when known potentiating compounds such as MAO inhibitors and phenothiazines are to be used; usual precautions in treating patients with impaired renal or hepatic function should be observed

              Paradoxical reactions to chlordiazepoxide have occurred (eg, excitement, stimulation, acute rage)

              Anterograde amnesia reported with benzodiazepine use

              May cause anticholinergic effects

              May cause CNS depression, which may impair ability to perform hazardous tasks, including operating heavy machinery, driving

              Although clinical studies have not established a cause and effect relationship, variable effects on blood coagulation have been reported very rarely in patients receiving oral anticoagulants and chlordiazepoxide hydrochloride

              Use caution in hot weather; may cause heat prostration

              Use of drug, particularly in patients at elevated risk of abuse, necessitates counseling about risks and proper use of drug along with monitoring for signs and symptoms of abuse, misuse, and addiction; do not exceed recommended dosing frequency

              Avoid or minimize concomitant use of CNS depressants and other substances associated with abuse, misuse, and addiction (eg, opioid analgesics, stimulants); advise patients on proper disposal of unused drug; if a substance use disorder is suspected, evaluate patient and institute (or refer them for) early treatment, as appropriate

              For patients using treated more frequently than recommended, to reduce risk of withdrawal reactions, use a gradual taper to discontinue therapy (a patient-specific plan should be used to taper the dose)

              Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use

              In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months

              Usual precautions are indicated when chlordiazepoxide hydrochloride is used to treat 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

              Caution in patients with impaired gag reflex or respiratory disease

              Concomitant use of opioid analgesics and benzodiazepines increases risk of drug-related mortality compared to use of opioids alone; if decision made to prescribe drug concomitantly with opioids, prescribe lowest effective dosages and minimum durations of concomitant use; follow patients closely for signs and symptoms of respiratory depression and sedation; advise both patients and caregivers about risks of respiratory depression and sedation when drug is used with opioids

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              Pregnancy & Lactation

              Pregnancy Category: D; increased risk of congenital malformations associated with use of benzodiazepines during 1st trimester

              Lactation: Distributed in breast milk, avoid use; anticholinergic agents are known to inhibit lactation

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Chlordiazepoxide: Benzodiazepine; depresses all levels of CNS, including limbic and reticular formation, possibly by increasing gamma-aminobutyric acid (GABA) activity, a major inhibitory neurotransmitter

              Clidinium: Anticholinergic agent; elicits antispasmodic and antisecretory effects on GI tract

              Pharmacokinetics

              Half-Life: 6-24 h (chlordiazepoxide)

              Metabolites: Metabolized in liver to active metabolites; demoxepam, desmethylchlordiazepoxide, desmethyldiazepam, oxazepam

              Excretion: Urine

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              Images

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
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              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.