Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
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 (243)
- 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.
- acrivastine
acrivastine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
- 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.
- amisulpride
amisulpride 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.
- asenapine
asenapine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
- asenapine transdermal
asenapine transdermal and chlordiazepoxide both increase sedation. 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.
- ceritinib
ceritinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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 (29)
- acetazolamide
acetazolamide will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
- cyclophosphamide
cyclophosphamide will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 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.
- larotrectinib
larotrectinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 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.
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
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
Pregnancy & Lactation
Pregnancy
Neonates born to mothers using benzodiazepines during later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal (
Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects
Over decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
Neonates born to mothers using benzodiazepines during the later stages of pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal
Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association with benzodiazepines and major birth defects
Over decades of use, there is an absence of published data on orally administered clidinium bromide in pregnant women, including an absence of any reports of a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
Lactation
There are no data on presence of chlordiazepoxide in either human or animal milk, effects on breastfed infant, or on milk production; there are reports of sedation, poor feeding and poor weight gain in infants exposed to other benzodiazepines through breast milk
There are no data on presence of clidinium in either human or animal milk, effects on breastfed infant, or on milk production; as with other anticholinergic drugs, clidinium may cause suppression of lactation
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for this drug combination and any potential adverse effects on breastfed infant from
Infants exposed to this drug combination through breast milk should be monitored for sedation, poor feeding, and poor weight gain
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.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
Images
Formulary
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