chlordiazepoxide/amitriptyline (Rx)

Brand and Other Names:Limbitrol, Limbitrol DS
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Dosing & Uses

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Dosage Forms & Strengths

chlordiazepoxide/amitriptyline

tablet: Schedule IV

  • 5mg/12.5mg
  • 10mg/25mg

Depression with Anxiety

1 tablet (5-10 mg chlordiazepoxide/12.5-25 mg amitriptyline) PO three/four times daily; may increase to 6 tablets if necessary; 2 tablets reported to be effective in some patients

Safety and efficacy not established

Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)

Consider alternatives; if must use, initiate with lower initial dose; long-acting active metabolites

1 tablet (5 mg/12.5 mg) PO three times daily

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Interactions

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            Contraindicated (16)

            • disopyramide

              amitriptyline and disopyramide both increase QTc interval. Contraindicated.

            • dronedarone

              dronedarone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              dronedarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

            • ibutilide

              amitriptyline and ibutilide both increase QTc interval. Contraindicated.

            • indapamide

              amitriptyline and indapamide both increase QTc interval. Contraindicated.

            • iobenguane I 123

              amitriptyline decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.

            • isocarboxazid

              isocarboxazid and amitriptyline both increase serotonin levels. Contraindicated.

            • pentamidine

              amitriptyline and pentamidine both increase QTc interval. Contraindicated.

            • phenelzine

              phenelzine and amitriptyline both increase serotonin levels. Contraindicated.

            • pimozide

              amitriptyline and pimozide both increase QTc interval. Contraindicated.

            • procainamide

              amitriptyline and procainamide both increase QTc interval. Contraindicated.

            • procarbazine

              procarbazine and amitriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

            • quinidine

              quinidine and amitriptyline both increase QTc interval. Contraindicated.

            • safinamide

              amitriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • selegiline

              selegiline and amitriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicated

            • sotalol

              amitriptyline and sotalol both increase QTc interval. Contraindicated.

            • tranylcypromine

              tranylcypromine and amitriptyline both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (143)

            • 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.

            • albuterol

              amitriptyline, albuterol. 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.

            • amiodarone

              amitriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

            • amoxapine

              amitriptyline and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • arformoterol

              amitriptyline, arformoterol. 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.

            • arsenic trioxide

              amitriptyline and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              amitriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • benzphetamine

              amitriptyline, 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.

            • buspirone

              amitriptyline and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

              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.

            • chlorpromazine

              chlorpromazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • cobicistat

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

            • citalopram

              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.

            • clarithromycin

              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.

            • clomipramine

              amitriptyline and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • clonidine

              amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

            • conivaptan

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

            • cyclobenzaprine

              amitriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dacomitinib

              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.

            • dasatinib

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

            • enzalutamide

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

            • desipramine

              amitriptyline and desipramine both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • desvenlafaxine

              amitriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dexfenfluramine

              amitriptyline, dexfenfluramine. 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.

            • dexmethylphenidate

              amitriptyline, dexmethylphenidate. 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.

            • dextroamphetamine

              amitriptyline, dextroamphetamine. 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.

            • dextromethorphan

              amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • diethylpropion

              amitriptyline, diethylpropion. 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.

            • dobutamine

              amitriptyline, dobutamine. 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.

            • dofetilide

              amitriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

            • dolasetron

              dolasetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • dopamine

              amitriptyline, dopamine. 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.

            • dopexamine

              amitriptyline, dopexamine. 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.

            • dosulepin

              amitriptyline and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.

            • doxepin

              amitriptyline and doxepin both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.

            • dronedarone

              amitriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.

              dronedarone and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • droperidol

              amitriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • duloxetine

              duloxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • ephedrine

              amitriptyline, ephedrine. 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.

            • epinephrine

              epinephrine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline, epinephrine. 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.

            • epinephrine racemic

              epinephrine racemic and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline, epinephrine racemic. 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.

            • erythromycin base

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

              erythromycin base will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              amitriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

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

              erythromycin ethylsuccinate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              amitriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

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

              erythromycin lactobionate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              amitriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

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

              erythromycin stearate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

              amitriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

              escitalopram increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.

            • fenfluramine

              amitriptyline, fenfluramine. 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.

            • fexinidazole

              fexinidazole and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

              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.

            • fluconazole

              amitriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • fluoxetine

              fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.

              fluoxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluphenazine

              fluphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • formoterol

              amitriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline, formoterol. 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.

            • fosamprenavir

              fosamprenavir increases levels of amitriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

            • givosiran

              givosiran will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

            • granisetron

              granisetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • guanfacine

              amitriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

            • haloperidol

              amitriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • 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

            • imipramine

              amitriptyline and imipramine both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • iobenguane I 131

              amitriptyline will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

            • isoproterenol

              amitriptyline, isoproterenol. 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.

            • 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.

              ivosidenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

            • ketoconazole

              amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • 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.

            • lasmiditan

              lasmiditan increases effects of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • lefamulin

              lefamulin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • levalbuterol

              amitriptyline, levalbuterol. 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.

            • levomilnacipran

              levomilnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • linezolid

              linezolid and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

            • lisdexamfetamine

              amitriptyline, lisdexamfetamine. 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.

            • lofepramine

              amitriptyline and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • lorcaserin

              amitriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • lumefantrine

              amitriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • macimorelin

              macimorelin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

            • maprotiline

              amitriptyline and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.

            • mefloquine

              mefloquine increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

            • meperidine

              amitriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

            • metaproterenol

              amitriptyline, metaproterenol. 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.

            • methamphetamine

              amitriptyline, methamphetamine. 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.

            • methylene blue

              methylene blue and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • methylenedioxymethamphetamine

              amitriptyline, methylenedioxymethamphetamine. 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.

            • 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.

              amitriptyline, 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.

            • midodrine

              amitriptyline, midodrine. 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.

            • nefazodone

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

            • milnacipran

              milnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • moxifloxacin

              amitriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • nefazodone

              nefazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • netupitant/palonosetron

              netupitant/palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • nilotinib

              amitriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • norepinephrine

              amitriptyline, norepinephrine. 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.

            • nortriptyline

              amitriptyline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • octreotide

              amitriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

            • octreotide (Antidote)

              amitriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

            • ondansetron

              amitriptyline and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.

              ondansetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • ozanimod

              ozanimod increases toxicity of amitriptyline by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • palonosetron

              palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • perphenazine

              perphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • phendimetrazine

              amitriptyline, phendimetrazine. 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.

            • phentermine

              amitriptyline, phentermine. 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.

            • phenylephrine

              amitriptyline, phenylephrine. 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.

            • phenylephrine PO

              amitriptyline, phenylephrine PO. 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.

            • pirbuterol

              amitriptyline, pirbuterol. 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.

            • pitolisant

              amitriptyline decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.

            • promazine

              promazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • propylhexedrine

              amitriptyline, propylhexedrine. 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.

            • protriptyline

              amitriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • pseudoephedrine

              amitriptyline increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • quinidine

              quinidine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • ranolazine

              ranolazine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • rasagiline

              rasagiline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Severe CNS toxicity associated with hyperpyrexia has been reported with the combined treatment of an antidepressant and rasagiline. Avoid combination within 14 days of MAOI use.

            • ribociclib

              ribociclib increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.

            • salmeterol

              amitriptyline, salmeterol. 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.

            • selegiline transdermal

              selegiline transdermal and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, amitriptyline. 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.

              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.

            • sertraline

              sertraline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • sodium oxybate

              amitriptyline, 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.

            • St John's Wort

              amitriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • tedizolid

              tedizolid, amitriptyline. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

            • terbutaline

              amitriptyline, terbutaline. 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.

            • thioridazine

              thioridazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • toremifene

              amitriptyline and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.

            • trazodone

              amitriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

              trazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • trifluoperazine

              trifluoperazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • trimipramine

              amitriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • 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.

            • umeclidinium bromide/vilanterol inhaled

              amitriptyline increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

              amitriptyline and umeclidinium bromide/vilanterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated

            • valerian

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

            • vandetanib

              amitriptyline, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.

            • vemurafenib

              vemurafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.

            • venlafaxine

              venlafaxine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • vilanterol/fluticasone furoate inhaled

              amitriptyline and vilanterol/fluticasone furoate inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated

              amitriptyline increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • vilazodone

              amitriptyline, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            • vortioxetine

              amitriptyline, vortioxetine. Either increases effects of the other by serotonin levels. 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.

            • xylometazoline

              amitriptyline, xylometazoline. 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.

            Monitor Closely (455)

            • 5-HTP

              amitriptyline and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

            • abiraterone

              abiraterone increases levels of amitriptyline 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.

              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.

            • abobotulinumtoxinA

              abobotulinumtoxinA increases effects of amitriptyline by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects. .

            • albuterol

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

            • aclidinium

              aclidinium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • albuterol

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

            • alfentanil

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

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

            • alfuzosin

              amitriptyline and alfuzosin both increase QTc interval. Use Caution/Monitor.

            • alprazolam

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

            • almotriptan

              almotriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • alprazolam

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

            • amifampridine

              amitriptyline increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

            • amiodarone

              amiodarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • amitriptyline

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

            • amobarbital

              amobarbital and amitriptyline 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.

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

              amobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • amoxapine

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

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

              amitriptyline and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • anticholinergic/sedative combos

              anticholinergic/sedative combos and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • apomorphine

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

            • apomorphine

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

            • aprepitant

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

            • arformoterol

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

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

            • aripiprazole

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

              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.

              armodafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • atazanavir

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

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

              atazanavir increases levels of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor.

            • atorvastatin

              atorvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • azelastine

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

            • atracurium

              atracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • atropine

              atropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • atropine IV/IM

              atropine IV/IM and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • azelastine

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

            • azithromycin

              amitriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.

            • baclofen

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

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

            • bedaquiline

              amitriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

            • belladonna and opium

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

            • belladonna alkaloids

              belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • belladonna and opium

              belladonna and opium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • benperidol

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

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

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that 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.

            • benzphetamine

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

            • benzphetamine

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

            • benztropine

              benztropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. Additive anticholinergic adverse effects may be seen with concurrent use.

            • bethanechol

              bethanechol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • 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 amitriptyline both increase sedation. Use Caution/Monitor.

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

            • buprenorphine

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

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

            • buprenorphine buccal

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

              buprenorphine buccal and amitriptyline 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.

              amitriptyline, 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.

            • 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.

              amitriptyline, 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.

            • bupropion

              amitriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              bupropion will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • butabarbital

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

            • butabarbital

              butabarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

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

            • butalbital

              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.

            • butorphanol

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

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

            • caffeine

              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.

            • carbachol

              carbachol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • carbamazepine

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

            • carbamazepine

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

            • carbinoxamine

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

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

            • carisoprodol

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

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

            • cenobamate

              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.

            • cevimeline

              cevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • chloral hydrate

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

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chloroquine

              chloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

            • chlorpheniramine

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

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

            • chlorpromazine

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

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

            • chlorzoxazone

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

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

            • cimetidine

              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.

            • cinnarizine

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

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

            • cisatracurium

              cisatracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • clarithromycin

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

            • clarithromycin

              clarithromycin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clemastine

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

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

            • clobazam

              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.

            • clomipramine

              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.

            • clonazepam

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

              clonazepam and amitriptyline 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

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

            • clorazepate

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

            • clotrimazole

              clotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clozapine

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

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

            • cobicistat

              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 response

              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.

            • codeine

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

            • cocaine

              amitriptyline and cocaine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • codeine

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

            • conivaptan

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

            • crizotinib

              crizotinib and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • 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 amitriptyline both increase sedation. Use Caution/Monitor.

              cyclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • cyclobenzaprine

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

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

            • cyclosporine

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

              cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cyproheptadine

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

            • cyproheptadine

              cyproheptadine and amitriptyline 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.

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

            • darifenacin

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

              darifenacin and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • 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.

            • darunavir

              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.

            • dasatinib

              amitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.

            • debrisoquine

              amitriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.

            • desflurane

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

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

            • desipramine

              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.

            • deutetrabenazine

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

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

            • dexchlorpheniramine

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

              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.

              amitriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

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

            • dexmedetomidine

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

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

            • dexmethylphenidate

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

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

            • dextroamphetamine

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

              amitriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.

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

              amitriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.

            • dextromoramide

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

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

            • diamorphine

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

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

            • diazepam

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

              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.

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

            • dicyclomine

              dicyclomine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • diethylpropion

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

            • diethylpropion

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

            • difenoxin hcl

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

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

            • dihydroergotamine

              amitriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dimenhydrinate

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

            • dihydroergotamine intranasal

              amitriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

            • diltiazem

              diltiazem will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with amitriptyline may alter blood pressure control.

            • dimenhydrinate

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

            • diphenhydramine

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

              diphenhydramine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

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

            • diphenoxylate hcl

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

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

            • dipipanone

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

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

            • dobutamine

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

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

            • dofetilide

              dofetilide increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

            • dopamine

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

            • dolasetron

              amitriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.

            • donepezil

              donepezil increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • dopamine

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

            • dopexamine

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

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

            • dosulepin

              amitriptyline and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

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

            • doxepin

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

              amitriptyline and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • doxylamine

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

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

            • droperidol

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

              droperidol and amitriptyline 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

            • echothiophate iodide

              echothiophate iodide increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • efavirenz

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

              efavirenz will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              efavirenz will decrease the level or effect of amitriptyline 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.

              elagolix will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • eletriptan

              eletriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • eliglustat

              eliglustat increases levels of amitriptyline 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.

              eliglustat increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

              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

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

              amitriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.

            • ephedrine

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

            • epinephrine

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

              amitriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.

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

            • epinephrine inhaled

              amitriptyline and epinephrine inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Tricyclic antidepressants may potentiate epinephrine effect on cardiovascular system.

            • epinephrine racemic

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

            • epinephrine racemic

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

              amitriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.

            • ergotamine

              amitriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • esketamine intranasal

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

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

            • eslicarbazepine acetate

              eslicarbazepine acetate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • estazolam

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

            • esomeprazole

              esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • estazolam

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

            • ethanol

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

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

            • etomidate

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

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

            • etravirine

              etravirine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • ezogabine

              ezogabine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.

            • 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.

            • fedratinib

              fedratinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

            • felbamate

              felbamate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • felodipine

              felodipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fenfluramine

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

              amitriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

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

              fenfluramine, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

            • fesoterodine

              fesoterodine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • flibanserin

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

            • flavoxate

              flavoxate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • flecainide

              amitriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

            • fluconazole

              fluconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

            • fluoxetine

              amitriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.

            • fluphenazine

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

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

            • flurazepam

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

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

            • fluvoxamine

              fluvoxamine and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely.

            • formoterol

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

            • formoterol

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

            • fosamprenavir

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

              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.

            • foscarnet

              amitriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

            • fosphenytoin

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

            • fosphenytoin

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

              fosphenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fostemsavir

              amitriptyline and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

            • frovatriptan

              frovatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • gabapentin

              gabapentin, amitriptyline. 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, 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.

              gabapentin enacarbil, amitriptyline. 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.

            • galantamine

              galantamine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • haloperidol

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

            • glecaprevir/pibrentasvir

              glecaprevir/pibrentasvir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • glycopyrrolate

              glycopyrrolate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

              amitriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.

            • glycopyrrolate inhaled

              glycopyrrolate inhaled and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

              amitriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

            • glycopyrronium tosylate topical

              glycopyrronium tosylate topical, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

            • grapefruit

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

            • haloperidol

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

            • henbane

              henbane and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • homatropine

              homatropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • huperzine A

              huperzine A increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydrocodone

              hydrocodone, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that 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.

            • hydromorphone

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

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

            • hydroxyzine

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

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

            • hyoscyamine

              hyoscyamine and amitriptyline both decrease cholinergic effects/transmission. 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.

            • hyoscyamine spray

              hyoscyamine spray and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • iloperidone

              amitriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • imipramine

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

              amitriptyline and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • indacaterol, inhaled

              indacaterol, inhaled, amitriptyline. QTc interval. Use Caution/Monitor. Indacaterol should be administered with extreme caution to patients treated with TCAs. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

            • 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.

            • indinavir

              indinavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ipratropium

              ipratropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

            • isoniazid

              isoniazid will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              amitriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

            • isoproterenol

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

              amitriptyline 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.

              istradefylline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • itraconazole

              itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

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

            • ivacaftor

              ivacaftor increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ketamine

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

            • ketamine

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

            • ketoconazole

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

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

              ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ketotifen, ophthalmic

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

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

            • L-tryptophan

              amitriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • lapatinib

              amitriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.

            • lasmiditan

              lasmiditan, amitriptyline. 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.

              amitriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

            • lemborexant

              lemborexant, amitriptyline. 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.

              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.

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

            • levalbuterol

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

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

            • levofloxacin

              amitriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

            • levorphanol

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

            • levorphanol

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

            • lisdexamfetamine

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

              amitriptyline, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).

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

            • lithium

              amitriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lofepramine

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

            • lofepramine

              amitriptyline and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • lofexidine

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

              amitriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.

              amitriptyline 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

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

            • loprazolam

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

            • loratadine

              loratadine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lorazepam

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

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

            • lorcaserin

              lorcaserin will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. 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.

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

            • loxapine

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

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

            • loxapine inhaled

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

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

            • lsd

              amitriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • lurasidone

              lurasidone increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

              lurasidone, amitriptyline. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

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

              amitriptyline and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • maraviroc

              maraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

            • marijuana

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

            • marijuana

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

            • meclizine

              meclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • melatonin

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

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

            • meperidine

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

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

            • meprobamate

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

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

            • metaproterenol

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

              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.

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

            • methadone

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

              amitriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • methamphetamine

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

              amitriptyline 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.

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

            • methscopolamine

              methscopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • methylenedioxymethamphetamine

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

            • methylenedioxymethamphetamine

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

            • methylphenidate

              amitriptyline, methylphenidate. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • midazolam

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

              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.

              midazolam intranasal, amitriptyline. 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.

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

            • mifepristone

              mifepristone, amitriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

            • mirtazapine

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

            • mipomersen

              mipomersen, amitriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mirabegron

              mirabegron will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mirtazapine

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

              amitriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

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

              modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • morphine

              amitriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

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

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

            • motherwort

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

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

            • moxonidine

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

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

            • nabilone

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

              amitriptyline 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

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

            • nalbuphine

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

            • naratriptan

              naratriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nefazodone

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

              nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nefopam

              nefopam, amitriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.

            • 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.

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

            • neostigmine

              neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • norepinephrine

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

            • nicardipine

              nicardipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nifedipine

              nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • norepinephrine

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

              amitriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.

            • nortriptyline

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

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

              amitriptyline and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • ofloxacin

              amitriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

            • olanzapine

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

            • olanzapine

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

            • oliceridine

              amitriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

              amitriptyline increases toxicity of oliceridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

              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.

            • olodaterol inhaled

              amitriptyline and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. TCAs prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

            • opium tincture

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

            • onabotulinumtoxinA

              onabotulinumtoxinA and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

            • opium tincture

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

            • orphenadrine

              amitriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

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

            • osilodrostat

              osilodrostat and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • oxazepam

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

            • osimertinib

              osimertinib and amitriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • oxaliplatin

              oxaliplatin will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

            • oxazepam

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

            • oxybutynin

              oxybutynin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin topical

              oxybutynin topical and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin transdermal

              oxybutynin transdermal and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxycodone

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

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

            • oxymetazoline intranasal

              amitriptyline increases effects of oxymetazoline intranasal by pharmacodynamic synergism. Use Caution/Monitor. TCAs inhibit norepinephrine uptake in adrenergic neurons, thereby increasing synaptic norepinephrine levels. Coadministration with alpha1 agonists may cause increased adrenergic receptor stimulation. When oxymetazoline is combined with intranasal tetracaine for dental anesthesia, avoid or use alternant anesthetic in patients taking TCAs.

            • oxymorphone

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

            • oxymorphone

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

            • ozanimod

              ozanimod and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paliperidone

              amitriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

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

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

            • pancuronium

              pancuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • papaveretum

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

            • papaveretum

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

            • papaverine

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

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

            • paroxetine

              amitriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.

            • pentazocine

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

            • pasireotide

              amitriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • pazopanib

              amitriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b, amitriptyline. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pentazocine

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

              amitriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • pentobarbital

              pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

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

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

            • perampanel

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

            • perphenazine

              perphenazine and amitriptyline 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.

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

            • phenobarbital

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

              phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

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

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

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

            • phentermine

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

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

            • phenylephrine

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

              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. .

            • phenylephrine PO

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

            • phenylephrine ophthalmic

              amitriptyline, phenylephrine ophthalmic. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • phenytoin

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

              phenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

              phenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

            • pholcodine

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

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

            • physostigmine

              physostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • pimozide

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

            • pilocarpine

              pilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • pilocarpine ophthalmic

              pilocarpine ophthalmic increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • pimozide

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

            • pirbuterol

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

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

            • ponatinib

              ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • posaconazole

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

            • posaconazole

              amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • pralidoxime

              pralidoxime and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • pregabalin

              pregabalin, amitriptyline. 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.

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

              primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

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

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

            • prochlorperazine

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

              prochlorperazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

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

            • promethazine

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

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

              promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • propantheline

              propantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • propofol

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

            • propofol

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

            • propylhexedrine

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

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

            • protriptyline

              amitriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

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

            • pyridostigmine

              pyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • quazepam

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

            • quazepam

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

            • quercetin

              quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • quetiapine

              quetiapine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

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

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

            • quinine

              amitriptyline and quinine both increase QTc interval. Use Caution/Monitor.

            • ramelteon

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

            • ramelteon

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

            • ranolazine

              amitriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

            • rapacuronium

              rapacuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • remifentanil

              amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

            • 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.

              remimazolam, amitriptyline. 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 amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              rifabutin decreases levels of amitriptyline by increasing 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 amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

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

              rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rifapentine

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

            • risperidone

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

            • rilpivirine

              rilpivirine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • risperidone

              amitriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.

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

            • ritonavir

              ritonavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              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.

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

            • rivastigmine

              rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • 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.

            • rizatriptan

              rizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • rocuronium

              rocuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • rolapitant

              rolapitant will increase the level or effect of amitriptyline 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.

            • romidepsin

              amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

            • 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.

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

            • SAMe

              amitriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • 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.

            • sarecycline

              sarecycline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • scopolamine

              scopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • scullcap

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

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

            • secobarbital

              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

              secobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

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

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

            • selpercatinib

              selpercatinib increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

            • sevoflurane

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

            • sevoflurane

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

            • shepherd's purse

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

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

            • simvastatin

              simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. 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.

            • sirolimus

              sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              amitriptyline, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

            • solifenacin

              solifenacin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • sorafenib

              sorafenib and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • St John's Wort

              St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • stiripentol

              stiripentol, amitriptyline. 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.

            • succinylcholine

              succinylcholine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • sufentanil

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

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

            • sufentanil SL

              sufentanil SL, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that 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.

            • suvorexant

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

            • sulfamethoxazole

              amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • sumatriptan

              sumatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • suvorexant

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

            • tacrolimus

              tacrolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tapentadol

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

              amitriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

              tapentadol and amitriptyline 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.

            • telavancin

              amitriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

            • 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.

              temazepam and amitriptyline 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.

              terbinafine will increase the level or effect of amitriptyline 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.

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

            • teriflunomide

              teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • thioridazine

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

            • thioridazine

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

            • thiothixene

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

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

            • tiotropium

              tiotropium and amitriptyline both decrease cholinergic effects/transmission. 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.

            • tolterodine

              tolterodine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • tolvaptan

              tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • topiramate

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

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

              topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels.

            • tramadol

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

              amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

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

            • trazodone

              amitriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

              trazodone will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

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

            • triazolam

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

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

            • triclofos

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

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

            • trifluoperazine

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

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

            • trihexyphenidyl

              trihexyphenidyl and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

            • trimipramine

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

            • trimethoprim

              amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

            • trimipramine

              amitriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

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

            • triprolidine

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

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

            • tropisetron

              amitriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

            • voriconazole

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

            • trospium chloride

              trospium chloride and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • tucatinib

              tucatinib will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • valerian

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

            • vecuronium

              vecuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • venlafaxine

              amitriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.

            • verapamil

              verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive.

            • voriconazole

              voriconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              amitriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • xylometazoline

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

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

            • yohimbine

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

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

            • ziconotide

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

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

            • ziprasidone

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

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

            • zolmitriptan

              zolmitriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • zotepine

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

            Minor (121)

            • acarbose

              amitriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

            • amobarbital

              amobarbital, 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.

            • armodafinil

              armodafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • atropine

              amitriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • atropine IV/IM

              amitriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

            • bazedoxifene/conjugated estrogens

              bazedoxifene/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.

            • bortezomib

              bortezomib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • bosentan

              bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • brimonidine

              amitriptyline decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.

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

            • budesonide

              budesonide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ciprofloxacin

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

            • butabarbital

              butabarbital, 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.

            • butalbital

              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.

            • carbamazepine

              carbamazepine decreases levels of amitriptyline by increasing metabolism. Minor/Significance Unknown.

            • chlorpromazine

              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.

            • chlorpropamide

              amitriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • clotrimazole

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

            • conjugated estrogens

              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, vaginal

              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.

            • cortisone

              cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • desflurane

              desflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • dexamethasone

              dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dexmethylphenidate

              dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • disulfiram

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

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • esomeprazole

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

            • estradiol

              estradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • estrogens conjugated synthetic

              estrogens conjugated synthetic, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • estrogens esterified

              estrogens esterified, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.

            • estropipate

              estropipate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • ethanol

              ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills.

            • ethinylestradiol

              ethinylestradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • etomidate

              etomidate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • etravirine

              etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eucalyptus

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

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

            • felodipine

              felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. 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.

            • fludrocortisone

              fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fluphenazine

              amitriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • gemifloxacin

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

            • glimepiride

              amitriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

            • glipizide

              amitriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.

            • glyburide

              amitriptyline increases effects of glyburide by pharmacodynamic synergism. 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.

            • griseofulvin

              griseofulvin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • hydroxyprogesterone caproate

              hydroxyprogesterone caproate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • insulin aspart

              amitriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin detemir

              amitriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin glargine

              amitriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin glulisine

              amitriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin lispro

              amitriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin NPH

              amitriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin regular human

              amitriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.

            • isoniazid

              isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • isoproterenol

              isoproterenol, amitriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

            • itraconazole

              itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ketamine

              ketamine, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • ketoconazole

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

            • lapatinib

              lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • levofloxacin

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

            • lithium

              lithium, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

            • lumefantrine

              lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • mestranol

              mestranol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • metformin

              amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metronidazole

              metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metyrapone

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

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

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

            • miglitol

              amitriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.

            • moxifloxacin

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

            • modafinil

              modafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nateglinide

              amitriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • nevirapine

              nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

              nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nilotinib

              nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 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.

            • oxcarbazepine

              oxcarbazepine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              oxcarbazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • panax ginseng

              panax ginseng increases effects of amitriptyline by pharmacodynamic synergism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital, 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.

            • perphenazine

              amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • phenobarbital

              phenobarbital, 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.

            • pioglitazone

              amitriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

            • pleurisy root

              pleurisy root decreases effects of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

            • posaconazole

              posaconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

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

            • prednisone

              prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • rifabutin

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

            • primidone

              primidone, 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.

            • prochlorperazine

              amitriptyline, prochlorperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, prochlorperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • progesterone micronized

              progesterone micronized, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • promazine

              amitriptyline, promazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, promazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • promethazine

              amitriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • propofol

              propofol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • repaglinide

              amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • rifampin

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

            • rosiglitazone

              amitriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

            • rufinamide

              rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

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

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

            • saxagliptin

              amitriptyline increases effects of saxagliptin by pharmacodynamic synergism. 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).

            • secobarbital

              secobarbital, 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.

            • sevoflurane

              sevoflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • sitagliptin

              amitriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

            • thioridazine

              amitriptyline, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • tolazamide

              amitriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • tolbutamide

              amitriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • trifluoperazine

              amitriptyline, trifluoperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, trifluoperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • vasopressin

              amitriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

            • verapamil

              verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

            • vildagliptin

              amitriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

            • voriconazole

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

              voriconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zafirlukast

              zafirlukast will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • zolpidem

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

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            Adverse Effects

            Frequency Not Defined

            Drowsiness

            Dry mouth

            Constipation

            Blurred vision

            Dizziness

            Bloating

            Vivid dreams

            Impotence

            Tremor

            Confusion

            Nasal congestion

            Edema

            Syncope

            Ataxia

            EEG abnormalities

            Menstrual irregularities

            Blood dyscrasias (agranulocytosis)

            Hepatic dysfunction (jaundice)

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            Warnings

            Black Box Warnings

            Children and Antidepressants

            • In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (age <24 yr) taking antidepressants for major depressive disorders and other psychiatric illnesses
            • This increase was not seen in patients aged >24 yr; slight decrease in suicidal thinking was seen in adults >65 yr; risks must be weighed in children and young adults against the benefits of taking antidepressants
            • Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; monitor during the initial 1-2 months of therapy and dosage adjustments
            • Patient’s family should communicate to the healthcare provider any abrupt changes in behavior
            • Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy
            • Not approved for pediatric patients

            Antipsychotics & Dementia

            • Patients with dementia-related psychosis that are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials; deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature
            • Not approved for treatment of dementia-related psychosis

            Central nervous system (CNS) depressants

            • 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
            • Assess each patient’s risk prior to prescribing and monitor regularly for the development of these behaviors or conditions
            • 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
            • 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

            Severe cardiovascular disorders

            Angle clossure glaucoma

            Within 14 days of MAOIs

            Any drugs or conditions that prolong QT interval

            Acute recovery post-MI

            Cautions

            Caution in BPH, urinary/GI retention, increased IOP, thyroid dysfunction, open-angle glaucoma, seizure disorders, brain tumor, respiratory impairment, respiratory disease,

            Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (aged 18-24 yr)

            Write prescription for smallest effective dose

            Risk of anticholinergic side-effects

            May cause orthostatic hypotension

            Paradoxical reactions including hyperactive or aggressive behavior reported

            Both agents may cause sedation and impair ability to perform tasks requiring mental alertness

            SIADH and hyponatremia reported with therapy

            Some patients may experience a large increase in amitriptyline concentration in presence of topiramate; any adjustments in amitriptyline dose should be made according to patient's clinical response and not on basis of plasma level

            Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases risk of drug-related mortality compared to use of opioids alone; if a decision is made to prescribe the drug concomitantly with opioids, prescribe the 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 the drug is used with opioids

            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

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            Pregnancy & Lactation

            Pregnancy Category: D

            Lactation: Excretion in milk unknown; not recommended

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

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

            Amitriptyline: Antidepressant; neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; elicits anticholinergic effects

            Absorption

            Bioavailability: Slow and erratic following IM admin (chlordiazepoxide)

            Peak serum time: 4 hr (amitriptyline)

            Peak serum time: 0.5-2 hr

            Onset of action: 1-5 min (IV, chlordiazepoxide)

            Onset of action: 6 weeks

            Duration: 15-60 min (IV, chlordiazepoxide)

            Vd: 3.3 L/kg (chlordiazepoxide)

            Metabolism

            Chlordiazepoxide: demoxepam, desmethylchlordiazepoxide, desmethyldiazepam, oxazepam

            Amiptriptyline: hepatic metabolism via CYP2C19, CYP3A4; nortriptyline is an active metabolite

            Elimination

            Half-Life

            • Chlordiazepoxide: 6.6-28 hr
            • Amitriptyline: 9-27 hr

            Excretion

            • Chlordiazepoxide: Predominately urine
            • Amitriptyline: Urine (25-50%), small amounts in bile
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            Images

            No images available for this drug.
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            Patient Handout

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

            FormularyPatient Discounts

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