affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.Serious - Use Alternative (1)benzhydrocodone/acetaminophen and imipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebenzphetamineMonitor Closely (1)imipramine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)imipramine, benzphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.benztropineMonitor Closely (1)benztropine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. bethanecholMonitor Closely (1)bethanechol increases and imipramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.bortezomibMonitor Closely (1)bortezomib will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.bosentanMinor (1)bosentan will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.brexpiprazoleMonitor Closely (2)brexpiprazole and imipramine both increase sedation. Use Caution/Monitor. imipramine will increase the level or effect of brexpiprazole by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Administer a quarter of brexpiprazole dose if coadministered with a moderate CYP2D6 inhibitor PLUS a strong/moderate CYP3A4 inhibitor.brimonidineMonitor Closely (1)brimonidine and imipramine both increase sedation. Use Caution/Monitor.Minor (1)imipramine decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.brivaracetamMonitor Closely (1)brivaracetam and imipramine both increase sedation. Use Caution/Monitor.brompheniramineMonitor Closely (1)brompheniramine and imipramine both increase sedation. Use Caution/Monitor.budesonideMinor (1)budesonide will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.buprenorphineMonitor Closely (1)buprenorphine and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine and imipramine both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine buccalMonitor Closely (1)buprenorphine buccal and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal and imipramine both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine subdermal implantMonitor Closely (1)imipramine, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.Serious - Use Alternative (2)buprenorphine subdermal implant and imipramine both increase QTc interval. Avoid or Use Alternate Drug. buprenorphine subdermal implant and imipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebuprenorphine transdermalSerious - Use Alternative (2)buprenorphine transdermal and imipramine both increase QTc interval. Avoid or Use Alternate Drug. buprenorphine transdermal and imipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebuprenorphine, long-acting injectionMonitor Closely (1)imipramine, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.Serious - Use Alternative (2)buprenorphine, long-acting injection and imipramine both increase QTc interval. Avoid or Use Alternate Drug. buprenorphine, long-acting injection and imipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebupropionMonitor Closely (2)bupropion will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. imipramine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.buspironeSerious - Use Alternative (1)imipramine and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.butabarbitalMonitor Closely (4)butabarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. butabarbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. butabarbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. butabarbital and imipramine both increase sedation. Use Caution/Monitor.Minor (1)butabarbital, imipramine. 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.butalbitalMonitor Closely (4)butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. butalbital will decrease the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. butalbital will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. butalbital and imipramine both increase sedation. Use Caution/Monitor.Minor (1)butalbital, imipramine. 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 (1)butorphanol and imipramine both increase sedation. Use Caution/Monitor.caffeineMonitor Closely (1)imipramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.calcium/magnesium/potassium/sodium oxybatesSerious - Use Alternative (1)imipramine, 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.cannabidiolMonitor Closely (1)cannabidiol will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider reducing the dose of sensitive CYP2C19 substrates, as clinically appropriate, when coadministered with cannabidiol. captoprilMinor (1)imipramine, captopril. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. May increase risk of hypotension.carbacholMonitor Closely (1)carbachol increases and imipramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.carbamazepineMonitor Closely (2)carbamazepine will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. carbamazepine will decrease the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine decreases levels of imipramine by increasing metabolism. Minor/Significance Unknown.carbinoxamineMonitor Closely (1)carbinoxamine and imipramine both increase sedation. Use Caution/Monitor.carisoprodolMonitor Closely (1)carisoprodol and imipramine both increase sedation. Use Caution/Monitor.celecoxibMonitor Closely (1)celecoxib will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.cenobamateMonitor Closely (1)cenobamate will increase the level or effect of imipramine by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Consider a dose reduction of CYP2C19 substrates, as clinically appropriate, when used concomitantly with cenobamate. cevimelineMonitor Closely (1)cevimeline increases and imipramine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.chloral hydrateMonitor Closely (1)chloral hydrate and imipramine both increase sedation. Use Caution/Monitor.chlordiazepoxideMonitor Closely (1)chlordiazepoxide and imipramine both increase sedation. Use Caution/Monitor.chloroquineMonitor Closely (1)chloroquine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.chlorpheniramineMonitor Closely (1)chlorpheniramine and imipramine both increase sedation. Use Caution/Monitor.chlorpromazineMonitor Closely (1)chlorpromazine and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)chlorpromazine and imipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)imipramine, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. imipramine, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.chlorpropamideMinor (1)imipramine increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.chlorzoxazoneMonitor Closely (1)chlorzoxazone and imipramine both increase sedation. Use Caution/Monitor.cholestyramineMonitor Closely (1)cholestyramine decreases levels of imipramine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.cigarette smokingMonitor Closely (1)cigarette smoking will decrease the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.cimetidineMonitor Closely (3)cimetidine will increase the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor. cimetidine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. cimetidine will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cinnarizineMonitor Closely (1)cinnarizine and imipramine both increase sedation. Use Caution/Monitor.ciprofloxacinSerious - Use Alternative (1)ciprofloxacin will increase the level or effect of imipramine by affecting hepatic enzyme CYP1A2 metabolism. Avoid or Use Alternate Drug. Concurrent use of drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias. It is important to monitor therapy carefully.cisatracuriumMonitor Closely (1)cisatracurium and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.citalopramSerious - Use Alternative (1)citalopram and imipramine 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.clarithromycinSerious - Use Alternative (2)imipramine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug. clarithromycin will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.clemastineMonitor Closely (1)clemastine and imipramine both increase sedation. Use Caution/Monitor.clobazamMonitor Closely (2)clobazam will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly. imipramine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).clomipramineMonitor Closely (2)clomipramine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor. clomipramine and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)clomipramine and imipramine both increase QTc interval. Avoid or Use Alternate Drug. clomipramine and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.clonazepamMonitor Closely (1)clonazepam and imipramine both increase sedation. Use Caution/Monitor.clonidineSerious - Use Alternative (1)imipramine decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.clorazepateMonitor Closely (1)clorazepate and imipramine both increase sedation. Use Caution/Monitor.clozapineMonitor Closely (1)clozapine and imipramine both increase sedation. Use Caution/Monitor.cobicistatMonitor Closely (1)cobicistat will increase the level or effect of imipramine 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. cocaine topicalMonitor Closely (1)imipramine and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeineMonitor Closely (2)codeine and imipramine both increase sedation. Use Caution/Monitor. imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.colestipolMinor (1)colestipol decreases levels of imipramine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.conivaptanMonitor Closely (1)conivaptan will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.conjugated estrogensMinor (1)conjugated estrogens, imipramine. 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, imipramine. 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 imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.cyclizineMonitor Closely (2)cyclizine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor. cyclizine and imipramine both increase sedation. Use Caution/Monitor.cyclobenzaprineMonitor Closely (2)cyclobenzaprine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor. cyclobenzaprine and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)imipramine and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.cyclosporineMonitor Closely (1)cyclosporine will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.cyproheptadineMonitor Closely (1)cyproheptadine and imipramine both increase sedation. Use Caution/Monitor.dacomitinibSerious - Use Alternative (1)dacomitinib will increase the level or effect of imipramine 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 (1)dantrolene and imipramine both increase sedation. Use Caution/Monitor.daridorexantMonitor Closely (1)imipramine 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 (3)darifenacin will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. darifenacin will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. darifenacin and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.darunavirMonitor Closely (1)darunavir will increase the level or effect of imipramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or