by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.butalbitalMonitor Closely (4)butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. butalbital and chlordiazepoxide both increase sedation. Use Caution/Monitor. butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. butalbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.butorphanolMonitor Closely (2)chlordiazepoxide and butorphanol both increase sedation. Use Caution/Monitor. butorphanol and amitriptyline both increase sedation. Use Caution/Monitor.caffeineMonitor Closely (2)amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.calcium/magnesium/potassium/sodium oxybatesSerious - Use Alternative (2)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. amitriptyline, 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.carbacholMonitor Closely (1)carbachol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.carbamazepineMonitor Closely (2)carbamazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. carbamazepine will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine decreases levels of amitriptyline by increasing metabolism. Minor/Significance Unknown.carbinoxamineMonitor Closely (2)carbinoxamine and chlordiazepoxide both increase sedation. Use Caution/Monitor. carbinoxamine and amitriptyline both increase sedation. Use Caution/Monitor.carisoprodolMonitor Closely (2)carisoprodol and amitriptyline both increase sedation. Use Caution/Monitor. chlordiazepoxide and carisoprodol both increase sedation. Use Caution/Monitor.cenobamateMonitor Closely (2)cenobamate, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. cenobamate, chlordiazepoxide. Either increases effects of the other by sedation. Use Caution/Monitor.ceritinibMonitor Closely (2)ceritinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. ceritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.cevimelineMonitor Closely (1)cevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.chloral hydrateMonitor Closely (2)chlordiazepoxide and chloral hydrate both increase sedation. Use Caution/Monitor. chloral hydrate and amitriptyline both increase sedation. Use Caution/Monitor.chlordiazepoxideMonitor Closely (1)chlordiazepoxide and amitriptyline both increase sedation. Use Caution/Monitor.chloroquineMonitor Closely (1)chloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.chlorpheniramineMonitor Closely (2)chlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor. chlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.chlorpromazineMonitor Closely (2)chlordiazepoxide and chlorpromazine both increase sedation. Use Caution/Monitor. chlorpromazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)chlorpromazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amitriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. amitriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.chlorpropamideMinor (1)amitriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.chlorzoxazoneMonitor Closely (2)chlordiazepoxide and chlorzoxazone both increase sedation. Use Caution/Monitor. chlorzoxazone and amitriptyline both increase sedation. Use Caution/Monitor.cimetidineMonitor Closely (2)cimetidine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. cimetidine increases levels of chlordiazepoxide by decreasing metabolism. Use Caution/Monitor.cinnarizineMonitor Closely (2)cinnarizine and chlordiazepoxide both increase sedation. Use Caution/Monitor. cinnarizine and amitriptyline both increase sedation. Use Caution/Monitor.ciprofloxacinMinor (1)ciprofloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.cisatracuriumMonitor Closely (1)cisatracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.citalopramSerious - Use Alternative (2)citalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Citalopram may increase TCA levels. Increased risk of serotonin syndrome or neuroleptic malignant syndrome. Potential risk for QT prolongation. ECG monitoring is recommended. citalopram and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.clarithromycinMonitor Closely (2)clarithromycin will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. clarithromycin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)clarithromycin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. amitriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.clemastineMonitor Closely (2)clemastine and amitriptyline both increase sedation. Use Caution/Monitor. clemastine and chlordiazepoxide both increase sedation. Use Caution/Monitor.clobazamMonitor Closely (3)amitriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression). 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). clobazam will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly. clomipramineMonitor Closely (3)amitriptyline and clomipramine both increase sedation. Use Caution/Monitor. chlordiazepoxide and clomipramine both increase sedation. Use Caution/Monitor. amitriptyline and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug. amitriptyline and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.clonazepamMonitor Closely (2)chlordiazepoxide and clonazepam both increase sedation. Use Caution/Monitor. clonazepam and amitriptyline both increase sedation. Use Caution/Monitor.clonidineMonitor Closely (1)clonidine, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.Serious - Use Alternative (1)amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.clorazepateMonitor Closely (2)chlordiazepoxide and clorazepate both increase sedation. Use Caution/Monitor. clorazepate and amitriptyline both increase sedation. Use Caution/Monitor.clotrimazoleMonitor Closely (1)clotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)clotrimazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.clozapineMonitor Closely (3)chlordiazepoxide and clozapine both increase sedation. Use Caution/Monitor. clozapine and amitriptyline both increase sedation. Use Caution/Monitor. clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.cobicistatMonitor Closely (3)cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat. cobicistat will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant responsecocaine topicalMonitor Closely (1)amitriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeineMonitor Closely (2)chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor. codeine and amitriptyline both increase sedation. Use Caution/Monitor.conivaptanMonitor Closely (1)conivaptan will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)conivaptan will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.conjugated estrogensMinor (1)conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.conjugated estrogens, vaginalMinor (1)conjugated estrogens, vaginal, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.cortisoneMinor (1)cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.crizotinibMonitor Closely (1)crizotinib and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.crofelemerMonitor Closely (1)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.cyclizineMonitor Closely (3)cyclizine and amitriptyline both increase sedation. Use Caution/Monitor. cyclizine and chlordiazepoxide both increase sedation. Use Caution/Monitor. cyclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.cyclobenzaprineMonitor Closely (2)chlordiazepoxide and cyclobenzaprine both increase sedation. Use Caution/Monitor. cyclobenzaprine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.cyclophosphamideMinor (1)cyclophosphamide will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyclosporineMonitor Closely (2)cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. cyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cyproheptadineMonitor Closely (2)cyproheptadine and chlordiazepoxide both increase sedation. Use Caution/Monitor. cyproheptadine and amitriptyline both increase sedation. Use Caution/Monitor.dabrafenibMonitor Closely (1)dabrafenib will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.dacomitinibSerious - Use Alternative (2)dacomitinib will increase the level or effect of amitriptyline 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. 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. dantroleneMonitor Closely (2)chlordiazepoxide and dantrolene both increase sedation. Use Caution/Monitor. dantrolene and amitriptyline both increase sedation. Use Caution/Monitor.daridorexantMonitor Closely (2)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. amitriptyline 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. darifenacinMonitor Closely (2)darifenacin and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. darifenacin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.darunavirMonitor Closely (2)darunavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or trazodone may require dose titration of antidepressant to desired effect (eg, using the lowest feasible initial or maintenance dose). Monitor for antidepressant response. 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.dasatinibMonitor Closely (1)amitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dasatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.debrisoquineMonitor Closely (1)amitriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.degarelixMonitor Closely (1)degarelix and amitriptyline both increase QTc interval. Use Caution/Monitor.desfluraneMonitor Closely (3)desflurane and amitriptyline both increase sedation. Use Caution/Monitor. desflurane and chlordiazepoxide both increase sedation. Use Caution/Monitor. desflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)desflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.desipramineMonitor Closely (3)amitriptyline and desipramine both decrease cholinergic effects/transmission. Use Caution/Monitor. chlordiazepoxide and desipramine both increase sedation. Use Caution/Monitor. amitriptyline and desipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and desipramine both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.desvenlafaxineSerious - Use Alternative (1)amitriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.deutetrabenazineMonitor Closely (3)amitriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor. chlordiazepoxide and deutetrabenazine both increase sedation. Use Caution/Monitor. deutetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).dexamethasoneMinor (1)dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.dexchlorpheniramineMonitor Closely (2)dexchlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor. dexchlorpheniramine and chlordiazepoxide both increase sedation.