chlordiazepoxide/amitriptyline (Rx)

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

Contraindicated (17)

• 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.

• fezolinetant

  amitriptyline will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• 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 (157)

• 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.

• adagrasib

  adagrasib, amitriptyline. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

• 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

  artemether and amitriptyline 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.
  
  benzhydrocodone/acetaminophen and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

  buprenorphine subdermal implant and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine transdermal and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and amitriptyline both increase QTc interval. 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.

• buspirone

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

• calcium/magnesium/potassium/sodium oxybates

  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.

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

• 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.

• encorafenib

  encorafenib and amitriptyline both increase QTc interval. 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.
  
  granisetron and amitriptyline both increase QTc interval. 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.

• levoketoconazole

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

• 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.

• mirtazapine

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

• mobocertinib

  mobocertinib will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently

• 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.

• olopatadine intranasal

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

• 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.

• selinexor

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

• 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.

• serdexmethylphenidate/dexmethylphenidate

  amitriptyline, serdexmethylphenidate/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.

• 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.
  
  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 (491)

• 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. .

• acrivastine

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

• aclidinium

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

• acrivastine

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

• albuterol

  albuterol and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  chlordiazepoxide increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.
  
  alfuzosin and amitriptyline 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.

• amisulpride

  amitriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.
  
  amisulpride and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amisulpride and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.
  
  amisulpride and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• amitriptyline

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

• amobarbital

  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amobarbital, amitriptyline. Other (see comment). Use Caution/Monitor. 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.

• amobarbital

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

• amoxapine

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

• aprepitant

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

• arformoterol

  arformoterol and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  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.
  
  aripiprazole and amitriptyline both increase QTc interval. 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.

• asenapine

  asenapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  asenapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  asenapine transdermal and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and amitriptyline both increase sedation. Use Caution/Monitor.
  
  asenapine transdermal and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• atazanavir

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

• atomoxetine

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

• avapritinib

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

• atorvastatin

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

• avapritinib

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

• azelastine

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

• azithromycin

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

• baclofen

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

• baclofen

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

• bedaquiline

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

• belladonna alkaloids

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

• belladonna and opium

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

• belzutifan

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

• benperidol

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

• benperidol

  chlordiazepoxide and benperidol 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.
  
  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.

• bosentan

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

• bethanechol

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

• brexanolone

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

• brexpiprazole

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

• brimonidine

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

• brivaracetam

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

• ceritinib

  ceritinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ceritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• 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.
  
  clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• cobicistat

  cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.
  
  cobicistat will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response

• cocaine topical

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

• codeine

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

• 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.

• daridorexant

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

• 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.

• degarelix

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

• desflurane

  desflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  desflurane and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  desflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.

• 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.
  
  deutetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• 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.

• dextroamphetamine transdermal

  amitriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response.

• dextromoramide

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

• dextromoramide

  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.

• difelikefalin

  difelikefalin and amitriptyline both increase sedation. Use Caution/Monitor.
  
  difelikefalin and chlordiazepoxide both increase sedation. 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.
  
  donepezil and amitriptyline both increase QTc interval. Use Caution/Monitor.

• 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 and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  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.
  
  eliglustat and amitriptyline both increase QTc interval. Use Caution/Monitor.

• 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.

• entrectinib

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

• ephedrine

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

• eribulin

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

• 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.

• fingolimod

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

• 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.

• fosaprepitant

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

• fosphenytoin

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

• foscarnet

  amitriptyline and foscarnet both increase QTc interval. 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.

• ganaxolone

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

• ganaxolone

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

• gemifloxacin

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

• gilteritinib

  gilteritinib and amitriptyline both increase QTc interval. 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.
  
  chlordiazepoxide and haloperidol both increase sedation. Use Caution/Monitor.

• henbane

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

• hydromorphone

  chlordiazepoxide and hydromorphone both increase sedation. 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

  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.
  
  hydroxyzine and amitriptyline both increase QTc interval. 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.

• isoflurane

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

• 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 and amitriptyline both increase QTc interval. 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.

• levoketoconazole

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

• levoketoconazole

  levoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• levorphanol

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

• levothyroxine

  levothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• lisdexamfetamine

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

• liothyronine

  liothyronine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liotrix

  liotrix increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• 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).

• lithium

  amitriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  lithium and amitriptyline both increase QTc interval. Use Caution/Monitor.

• lofepramine

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

• mavacamten

  amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• 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.

• methylphenidate transdermal

  methylphenidate transdermal will increase the level or effect of amitriptyline by decreasing elimination. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

• 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.
  
  olanzapine and amitriptyline both increase QTc interval. 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.

• 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.

• sertraline

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

• sevoflurane

  sevoflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  sevoflurane and amitriptyline both increase QTc interval. 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.
  
  solifenacin and amitriptyline both increase QTc interval. 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.

• tetrabenazine

  tetrabenazine and amitriptyline both increase QTc interval. 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.

• thyroid desiccated

  thyroid desiccated increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• 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.

• tiotropium

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

• 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.

• valbenazine

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

• 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.

• voclosporin

  voclosporin, amitriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• 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.

• warfarin

  amitriptyline increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• 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 (125)

• acarbose

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

• acetazolamide

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

• anastrozole

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

• 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.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of chlordiazepoxide 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 (DSC)

  hydroxyprogesterone caproate (DSC), 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.

• larotrectinib

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

• levofloxacin

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

• levoketoconazole

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

• 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.

• 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.

• serdexmethylphenidate/dexmethylphenidate

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

• 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.

• 5-HTP

  Monitor Closely (1)amitriptyline and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

• abametapir

  Serious - Use Alternative (1)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.

• abiraterone

  Monitor Closely (2)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

  Monitor Closely (1)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. .

• acarbose

  Minor (1)amitriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• aclidinium

  Monitor Closely (1)aclidinium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• acrivastine

  Monitor Closely (2)acrivastine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  acrivastine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• adagrasib

  Serious - Use Alternative (1)adagrasib, amitriptyline. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

• albuterol

  Monitor Closely (3)albuterol and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  chlordiazepoxide increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• alfentanil

  Monitor Closely (2)alfentanil and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and alfentanil both increase sedation. Use Caution/Monitor.

• alfuzosin

  Monitor Closely (2)amitriptyline and alfuzosin both increase QTc interval. Use Caution/Monitor.
  
  alfuzosin and amitriptyline both increase QTc interval. Use Caution/Monitor.

• almotriptan

  Monitor Closely (1)almotriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• alprazolam

  Monitor Closely (2)alprazolam and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  alprazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (1)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

  Monitor Closely (1)amiodarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  Monitor Closely (4)amitriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.
  
  amisulpride and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amisulpride and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.
  
  amisulpride and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• amitriptyline

  Monitor Closely (1)chlordiazepoxide and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  Monitor Closely (6)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. Use Caution/Monitor.
  
  amobarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amobarbital, amitriptyline. Other (see comment). Use Caution/Monitor. 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.

• amoxapine

  Monitor Closely (3)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.Serious - Use Alternative (2)amitriptyline and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anticholinergic/sedative combos

  Monitor Closely (1)anticholinergic/sedative combos and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• apalutamide

  Serious - Use Alternative (1)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.

• apomorphine

  Monitor Closely (3)chlordiazepoxide and apomorphine both increase sedation. Use Caution/Monitor.
  
  apomorphine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and apomorphine both increase sedation. Use Caution/Monitor.

• aprepitant

  Monitor Closely (1)aprepitant will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  Monitor Closely (3)chlordiazepoxide increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• aripiprazole

  Monitor Closely (3)aripiprazole and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and aripiprazole both increase sedation. Use Caution/Monitor.
  
  aripiprazole and amitriptyline both increase QTc interval. Use Caution/Monitor.

• armodafinil

  Monitor Closely (3)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.Minor (1)armodafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• arsenic trioxide

  Serious - Use Alternative (1)amitriptyline and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  Serious - Use Alternative (1)artemether and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Serious - Use Alternative (1)amitriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)artemether/lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• asenapine

  Monitor Closely (3)asenapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  asenapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  Monitor Closely (3)asenapine transdermal and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and amitriptyline both increase sedation. Use Caution/Monitor.
  
  asenapine transdermal and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• atazanavir

  Monitor Closely (3)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.

• atomoxetine

  Monitor Closely (1)atomoxetine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• atorvastatin

  Monitor Closely (1)atorvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• atracurium

  Monitor Closely (1)atracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine

  Monitor Closely (1)atropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.Minor (1)amitriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

• atropine IV/IM

  Monitor Closely (1)atropine IV/IM and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)amitriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

• avapritinib

  Monitor Closely (2)avapritinib and amitriptyline both increase sedation. Use Caution/Monitor.
  
  avapritinib and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• azelastine

  Monitor Closely (2)azelastine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  azelastine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• azithromycin

  Monitor Closely (1)amitriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.

• baclofen

  Monitor Closely (2)baclofen and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and baclofen both increase sedation. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

  Minor (1)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.

• bedaquiline

  Monitor Closely (1)amitriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• belladonna alkaloids

  Monitor Closely (1)belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• belladonna and opium

  Monitor Closely (3)chlordiazepoxide and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna and opium and amitriptyline both increase sedation. Use Caution/Monitor.
  
  belladonna and opium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• benperidol

  Monitor Closely (2)chlordiazepoxide and benperidol both increase sedation. Use Caution/Monitor.
  
  benperidol and amitriptyline both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)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.Serious - Use Alternative (3)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.
  
  benzhydrocodone/acetaminophen and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzphetamine

  Monitor Closely (2)chlordiazepoxide increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• benztropine

  Monitor Closely (1)benztropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. Additive anticholinergic adverse effects may be seen with concurrent use.

• bethanechol

  Monitor Closely (1)bethanechol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• bortezomib

  Minor (1)bortezomib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brexanolone

  Monitor Closely (1)brexanolone, chlordiazepoxide. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (2)brexpiprazole and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brexpiprazole and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (2)brimonidine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brimonidine and chlordiazepoxide both increase sedation. Use Caution/Monitor.Minor (2)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.

• brivaracetam

  Monitor Closely (2)brivaracetam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brivaracetam and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• brompheniramine

  Monitor Closely (2)brompheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brompheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• budesonide

  Minor (1)budesonide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• buprenorphine

  Monitor Closely (2)buprenorphine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and buprenorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine buccal

  Monitor Closely (2)chlordiazepoxide and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  Monitor Closely (2)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.Serious - Use Alternative (3)buprenorphine subdermal implant and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Serious - Use Alternative (3)buprenorphine transdermal and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine transdermal and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (2)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.Serious - Use Alternative (1)buprenorphine, long-acting injection and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• bupropion

  Monitor Closely (2)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.

• buspirone

  Serious - Use Alternative (1)amitriptyline and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

• butabarbital

  Monitor Closely (4)butabarbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  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.Minor (1)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

  Monitor Closely (4)butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• butorphanol

  Monitor Closely (2)chlordiazepoxide and butorphanol both increase sedation. Use Caution/Monitor.
  
  butorphanol and amitriptyline both increase sedation. Use Caution/Monitor.

• caffeine

  Monitor Closely (2)amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlordiazepoxide increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (2)chlordiazepoxide, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  amitriptyline, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• carbachol

  Monitor Closely (1)carbachol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• carbamazepine

  Monitor Closely (2)carbamazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  carbamazepine will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine decreases levels of amitriptyline by increasing metabolism. Minor/Significance Unknown.

• carbinoxamine

  Monitor Closely (2)carbinoxamine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  carbinoxamine and amitriptyline both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (2)carisoprodol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and carisoprodol both increase sedation. Use Caution/Monitor.

• cenobamate

  Monitor Closely (2)cenobamate, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate, chlordiazepoxide. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  Monitor Closely (2)ceritinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ceritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• cevimeline

  Monitor Closely (1)cevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• chloral hydrate

  Monitor Closely (2)chlordiazepoxide and chloral hydrate both increase sedation. Use Caution/Monitor.
  
  chloral hydrate and amitriptyline both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide and amitriptyline both increase sedation. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)chloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

• chlorpheniramine

  Monitor Closely (2)chlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (2)chlordiazepoxide and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)chlorpromazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amitriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• chlorpropamide

  Minor (1)amitriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (2)chlordiazepoxide and chlorzoxazone both increase sedation. Use Caution/Monitor.
  
  chlorzoxazone and amitriptyline both increase sedation. Use Caution/Monitor.

• cimetidine

  Monitor Closely (2)cimetidine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  cimetidine increases levels of chlordiazepoxide by decreasing metabolism. Use Caution/Monitor.

• cinnarizine

  Monitor Closely (2)cinnarizine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  cinnarizine and amitriptyline both increase sedation. Use Caution/Monitor.

• ciprofloxacin

  Minor (1)ciprofloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• cisatracurium

  Monitor Closely (1)cisatracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• citalopram

  Serious - Use Alternative (2)citalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Citalopram may increase TCA levels. Increased risk of serotonin syndrome or neuroleptic malignant syndrome. Potential risk for QT prolongation. ECG monitoring is recommended.
  
  citalopram and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  Monitor Closely (2)clarithromycin will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  clarithromycin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)clarithromycin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  amitriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clemastine

  Monitor Closely (2)clemastine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  clemastine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (3)amitriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  chlordiazepoxide, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  clobazam will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

• clomipramine

  Monitor Closely (3)amitriptyline and clomipramine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and clomipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

• clonazepam

  Monitor Closely (2)chlordiazepoxide and clonazepam both increase sedation. Use Caution/Monitor.
  
  clonazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• clonidine

  Monitor Closely (1)clonidine, chlordiazepoxide. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration enhances CNS depressant effects.Serious - Use Alternative (1)amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• clorazepate

  Monitor Closely (2)chlordiazepoxide and clorazepate both increase sedation. Use Caution/Monitor.
  
  clorazepate and amitriptyline both increase sedation. Use Caution/Monitor.

• clotrimazole

  Monitor Closely (1)clotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)clotrimazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• clozapine

  Monitor Closely (3)chlordiazepoxide and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• cobicistat

  Monitor Closely (3)cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.
  
  cobicistat will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response

• cocaine topical

  Monitor Closely (1)amitriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.

• codeine

  Monitor Closely (2)chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
  
  codeine and amitriptyline both increase sedation. Use Caution/Monitor.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)conivaptan will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• conjugated estrogens

  Minor (1)conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• conjugated estrogens, vaginal

  Minor (1)conjugated estrogens, vaginal, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• cortisone

  Minor (1)cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• crizotinib

  Monitor Closely (1)crizotinib and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclizine

  Monitor Closely (3)cyclizine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  cyclizine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  cyclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (2)chlordiazepoxide and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  cyclobenzaprine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Monitor Closely (2)cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  cyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

  Monitor Closely (2)cyproheptadine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  cyproheptadine and amitriptyline both increase sedation. Use Caution/Monitor.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dacomitinib

  Serious - Use Alternative (2)dacomitinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
  
  dacomitinib will increase the level or effect of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dantrolene

  Monitor Closely (2)chlordiazepoxide and dantrolene both increase sedation. Use Caution/Monitor.
  
  dantrolene and amitriptyline both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (2)chlordiazepoxide and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  amitriptyline and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  Monitor Closely (2)darifenacin and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  darifenacin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  Monitor Closely (2)darunavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or trazodone may require dose titration of antidepressant to desired effect (eg, using the lowest feasible initial or maintenance dose). Monitor for antidepressant response.
  
  darunavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Potential for increased toxicity. Use alternatives if available. Consider lowering benzodiazepine dose.

• dasatinib

  Monitor Closely (1)amitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dasatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• debrisoquine

  Monitor Closely (1)amitriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.

• degarelix

  Monitor Closely (1)degarelix and amitriptyline both increase QTc interval. Use Caution/Monitor.

• desflurane

  Monitor Closely (3)desflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  desflurane and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  desflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)desflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• desipramine

  Monitor Closely (3)amitriptyline and desipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  chlordiazepoxide and desipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and desipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and desipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• desvenlafaxine

  Serious - Use Alternative (1)amitriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• deutetrabenazine

  Monitor Closely (3)amitriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• dexamethasone

  Minor (1)dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dexchlorpheniramine

  Monitor Closely (2)dexchlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (3)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.Serious - Use Alternative (1)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.

• dexmedetomidine

  Monitor Closely (2)dexmedetomidine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and dexmedetomidine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (2)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.Serious - Use Alternative (1)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.Minor (1)dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• dextroamphetamine

  Monitor Closely (4)amitriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  amitriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.Serious - Use Alternative (1)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.

• dextroamphetamine transdermal

  Monitor Closely (1)amitriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response.

• dextromethorphan

  Serious - Use Alternative (1)amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• dextromoramide

  Monitor Closely (2)chlordiazepoxide and dextromoramide both increase sedation. Use Caution/Monitor.
  
  dextromoramide and amitriptyline both increase sedation. Use Caution/Monitor.

• DHEA, herbal

  Minor (1)DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diamorphine

  Monitor Closely (2)chlordiazepoxide and diamorphine both increase sedation. Use Caution/Monitor.
  
  diamorphine and amitriptyline both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (2)diazepam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and diazepam both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (2)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

  Monitor Closely (1)dicyclomine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• diethylpropion

  Monitor Closely (2)chlordiazepoxide increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• difelikefalin

  Monitor Closely (2)difelikefalin and amitriptyline both increase sedation. Use Caution/Monitor.
  
  difelikefalin and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (2)difenoxin hcl and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and difenoxin hcl both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (1)amitriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• dihydroergotamine intranasal

  Monitor Closely (1)amitriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

• diltiazem

  Monitor Closely (1)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

  Monitor Closely (2)dimenhydrinate and amitriptyline both increase sedation. Use Caution/Monitor.
  
  dimenhydrinate and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (3)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

  Monitor Closely (2)chlordiazepoxide and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl and amitriptyline both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (2)chlordiazepoxide and dipipanone both increase sedation. Use Caution/Monitor.
  
  dipipanone and amitriptyline both increase sedation. Use Caution/Monitor.

• disopyramide

  Contraindicated (1)amitriptyline and disopyramide both increase QTc interval. Contraindicated.

• disulfiram

  Minor (1)disulfiram increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• dobutamine

  Monitor Closely (2)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.Serious - Use Alternative (1)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

  Monitor Closely (1)dofetilide increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Monitor Closely (1)amitriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dolasetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• donepezil

  Monitor Closely (2)donepezil and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  donepezil increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• dopamine

  Monitor Closely (2)chlordiazepoxide increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (2)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.Serious - Use Alternative (1)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

  Monitor Closely (3)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.Serious - Use Alternative (2)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

  Monitor Closely (3)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.Serious - Use Alternative (2)amitriptyline and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and doxepin both increase QTc interval. Avoid or Use Alternate Drug.

• doxylamine

  Monitor Closely (2)doxylamine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and doxylamine both increase sedation. Use Caution/Monitor.

• dronedarone

  Contraindicated (2)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.Serious - Use Alternative (2)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

  Monitor Closely (2)chlordiazepoxide and droperidol both increase sedation. Use Caution/Monitor.
  
  droperidol and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• duloxetine

  Serious - Use Alternative (1)duloxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• duvelisib

  Monitor Closely (1)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

  Monitor Closely (1)echothiophate iodide increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• efavirenz

  Monitor Closely (4)efavirenz and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  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

  Monitor Closely (2)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

  Monitor Closely (1)eletriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• eliglustat

  Monitor Closely (4)eliglustat and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  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.
  
  eliglustat increases levels of chlordiazepoxide by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (2)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

  Monitor Closely (1)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.Serious - Use Alternative (1)encorafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  Monitor Closely (1)entrectinib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• enzalutamide

  Serious - Use Alternative (1)enzalutamide will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• ephedrine

  Monitor Closely (3)amitriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.
  
  amitriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlordiazepoxide increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (3)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.Serious - Use Alternative (2)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 inhaled

  Monitor Closely (1)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

  Monitor Closely (3)amitriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.
  
  chlordiazepoxide increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)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.

• ergotamine

  Monitor Closely (1)amitriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• eribulin

  Monitor Closely (1)eribulin and amitriptyline both increase QTc interval. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (3)amitriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
  
  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.

• erythromycin ethylsuccinate

  Serious - Use Alternative (3)amitriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
  
  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.

• erythromycin lactobionate

  Serious - Use Alternative (3)amitriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
  
  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.

• erythromycin stearate

  Serious - Use Alternative (3)amitriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
  
  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.

• escitalopram

  Serious - Use Alternative (2)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.

• esketamine intranasal

  Monitor Closely (2)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

  Monitor Closely (1)eslicarbazepine acetate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esomeprazole

  Monitor Closely (1)esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)esomeprazole will increase the level or effect of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• estazolam

  Monitor Closely (2)estazolam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and estazolam both increase sedation. Use Caution/Monitor.

• estradiol

  Minor (1)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

  Minor (1)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

  Minor (1)estrogens esterified, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.

• estropipate

  Minor (1)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

  Monitor Closely (2)amitriptyline and ethanol both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and ethanol both increase sedation. Use Caution/Monitor.Minor (1)ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills.

• ethinylestradiol

  Minor (1)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

  Monitor Closely (2)etomidate and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  etomidate and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)etomidate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• etravirine

  Monitor Closely (2)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.Minor (1)etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

  Minor (2)amitriptyline and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  chlordiazepoxide and eucalyptus both increase sedation. Minor/Significance Unknown.

• ezogabine

  Monitor Closely (1)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

  Monitor Closely (2)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.
  
  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.

• felbamate

  Monitor Closely (1)felbamate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• felodipine

  Monitor Closely (1)felodipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• fenfluramine

  Monitor Closely (4)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.Serious - Use Alternative (1)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.

• fesoterodine

  Monitor Closely (1)fesoterodine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• fexinidazole

  Serious - Use Alternative (2)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.

• fezolinetant

  Contraindicated (1)amitriptyline will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• fingolimod

  Monitor Closely (1)fingolimod and amitriptyline both increase QTc interval. Use Caution/Monitor.

• flavoxate

  Monitor Closely (1)flavoxate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• flecainide

  Monitor Closely (1)amitriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

• fleroxacin

  Minor (1)fleroxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• flibanserin

  Monitor Closely (1)chlordiazepoxide and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluconazole

  Monitor Closely (2)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.Minor (1)fluconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)amitriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fludrocortisone

  Minor (1)fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)amitriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)fluoxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.

• fluphenazine

  Monitor Closely (2)fluphenazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and fluphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fluphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• flurazepam

  Monitor Closely (2)chlordiazepoxide and flurazepam both increase sedation. Use Caution/Monitor.
  
  flurazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (1)fluvoxamine and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluvoxamine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (2)chlordiazepoxide increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)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.
  
  amitriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug.

• fosamprenavir

  Monitor Closely (2)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.Serious - Use Alternative (1)fosamprenavir increases levels of amitriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• foscarnet

  Monitor Closely (1)amitriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

• fosphenytoin

  Monitor Closely (3)fosphenytoin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  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

  Monitor Closely (1)amitriptyline and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  Monitor Closely (1)frovatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• gabapentin

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)galantamine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• ganaxolone

  Monitor Closely (2)amitriptyline and ganaxolone both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (1)gemifloxacin and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)gemifloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• gilteritinib

  Monitor Closely (1)gilteritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)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.

• glecaprevir/pibrentasvir

  Monitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• glimepiride

  Minor (1)amitriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• glipizide

  Minor (1)amitriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.

• glyburide

  Minor (1)amitriptyline increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

• glycopyrrolate

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (1)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.

• granisetron

  Serious - Use Alternative (2)granisetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
  
  granisetron and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• green tea

  Minor (1)green tea decreases effects of chlordiazepoxide by pharmacodynamic antagonism. Minor/Significance Unknown. Caffeine component of green tea may decrease sedative effects of benzodiazepines.

• griseofulvin

  Minor (1)griseofulvin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• guanfacine

  Serious - Use Alternative (1)amitriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• haloperidol

  Monitor Closely (2)haloperidol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and haloperidol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

• henbane

  Monitor Closely (1)henbane and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• homatropine

  Monitor Closely (1)homatropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• huperzine A

  Monitor Closely (1)huperzine A increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocodone

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• hydrocortisone

  Minor (1)hydrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydromorphone

  Monitor Closely (2)chlordiazepoxide and hydromorphone both increase sedation. Use Caution/Monitor.
  
  hydromorphone and amitriptyline both increase sedation. Use Caution/Monitor.

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)hydroxychloroquine sulfate and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyprogesterone caproate (DSC)

  Minor (1)hydroxyprogesterone caproate (DSC), amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• hydroxyzine

  Monitor Closely (3)hydroxyzine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• hyoscyamine

  Monitor Closely (1)hyoscyamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hyoscyamine spray

  Monitor Closely (1)hyoscyamine spray and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ibutilide

  Contraindicated (1)amitriptyline and ibutilide both increase QTc interval. Contraindicated.

• idelalisib

  Serious - Use Alternative (1)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

• iloperidone

  Monitor Closely (4)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.
  
  chlordiazepoxide and iloperidone both increase sedation. Use Caution/Monitor.
  
  amitriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and amitriptyline both increase sedation. Use Caution/Monitor.

• imipramine

  Monitor Closely (3)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.Serious - Use Alternative (2)amitriptyline and imipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• indacaterol, inhaled

  Monitor Closely (1)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.

• indapamide

  Contraindicated (1)amitriptyline and indapamide both increase QTc interval. Contraindicated.

• indinavir

  Monitor Closely (2)indinavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  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.

• insulin aspart

  Minor (1)amitriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin detemir

  Minor (1)amitriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glargine

  Minor (1)amitriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glulisine

  Minor (1)amitriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin lispro

  Minor (1)amitriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin NPH

  Minor (1)amitriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin regular human

  Minor (1)amitriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.

• iobenguane I 123

  Contraindicated (1)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.

• iobenguane I 131

  Serious - Use Alternative (1)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.

• ipratropium

  Monitor Closely (1)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.

• isocarboxazid

  Contraindicated (1)isocarboxazid and amitriptyline both increase serotonin levels. Contraindicated.

• isoflurane

  Monitor Closely (1)isoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.

• isoniazid

  Monitor Closely (2)amitriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  isoniazid will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isoproterenol

  Monitor Closely (2)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.Serious - Use Alternative (1)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.Minor (1)isoproterenol, amitriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

• istradefylline

  Monitor Closely (2)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

  Monitor Closely (3)itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  itraconazole and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  itraconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ivacaftor

  Monitor Closely (1)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.

• ivosidenib

  Serious - Use Alternative (2)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.

• ketamine

  Monitor Closely (2)ketamine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  ketamine and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)ketamine, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• ketoconazole

  Monitor Closely (3)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.Minor (1)ketoconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

  Monitor Closely (2)chlordiazepoxide and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  amitriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-tryptophan

  Monitor Closely (1)amitriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

• lapatinib

  Monitor Closely (1)amitriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• larotrectinib

  Minor (1)larotrectinib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lasmiditan

  Monitor Closely (3)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.
  
  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.Serious - Use Alternative (1)lasmiditan increases effects of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• lefamulin

  Serious - Use Alternative (1)lefamulin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• lemborexant

  Monitor Closely (2)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

  Monitor Closely (2)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

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• levofloxacin

  Monitor Closely (1)amitriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)levofloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• levoketoconazole

  Monitor Closely (3)levoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)levoketoconazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)amitriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• levomilnacipran

  Serious - Use Alternative (1)levomilnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• levorphanol

  Monitor Closely (2)levorphanol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and levorphanol both increase sedation. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)levothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• linezolid

  Serious - Use Alternative (1)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.

• liothyronine

  Monitor Closely (1)liothyronine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liotrix

  Monitor Closely (1)liotrix increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• lisdexamfetamine

  Monitor Closely (3)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.Serious - Use Alternative (1)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.

• lithium

  Monitor Closely (2)lithium and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)lithium, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

• lofepramine

  Monitor Closely (3)amitriptyline and lofepramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  chlordiazepoxide and lofepramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.

• lofexidine

  Monitor Closely (3)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.

• lonafarnib

  Serious - Use Alternative (1)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.

• lopinavir

  Monitor Closely (1)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

  Monitor Closely (2)chlordiazepoxide and loprazolam both increase sedation. Use Caution/Monitor.
  
  loprazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• loratadine

  Monitor Closely (1)loratadine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lorazepam

  Monitor Closely (2)chlordiazepoxide and lorazepam both increase sedation. Use Caution/Monitor.
  
  lorazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (1)lorcaserin will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• lormetazepam

  Monitor Closely (2)chlordiazepoxide and lormetazepam both increase sedation. Use Caution/Monitor.
  
  lormetazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (2)chlordiazepoxide and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine and amitriptyline both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (2)chlordiazepoxide and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  loxapine inhaled and amitriptyline both increase sedation. Use Caution/Monitor.

• lsd

  Monitor Closely (1)amitriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

• lumefantrine

  Serious - Use Alternative (1)amitriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lurasidone

  Monitor Closely (3)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, 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.
  
  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.

• macimorelin

  Serious - Use Alternative (1)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

  Monitor Closely (3)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.Serious - Use Alternative (2)amitriptyline and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.

• maraviroc

  Monitor Closely (1)maraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• marijuana

  Monitor Closely (2)amitriptyline and marijuana both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mavacamten

  Monitor Closely (1)amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• meclizine

  Monitor Closely (1)meclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• mefloquine

  Serious - Use Alternative (1)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.

• melatonin

  Monitor Closely (2)amitriptyline and melatonin both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (2)chlordiazepoxide and meperidine both increase sedation. Use Caution/Monitor.
  
  meperidine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

• meprobamate

  Monitor Closely (2)amitriptyline and meprobamate both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and meprobamate both increase sedation. Use Caution/Monitor.

• mestranol

  Minor (1)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.

• metaproterenol

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• metaxalone

  Monitor Closely (2)chlordiazepoxide and metaxalone both increase sedation. Use Caution/Monitor.
  
  metaxalone and amitriptyline both increase sedation. Use Caution/Monitor.

• metformin

  Minor (1)amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• methadone

  Monitor Closely (3)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

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• methocarbamol

  Monitor Closely (2)chlordiazepoxide and methocarbamol both increase sedation. Use Caution/Monitor.
  
  methocarbamol and amitriptyline both increase sedation. Use Caution/Monitor.

• methscopolamine

  Monitor Closely (1)methscopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methylene blue

  Serious - Use Alternative (1)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

  Monitor Closely (2)chlordiazepoxide increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• methylphenidate

  Monitor Closely (1)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.

• methylphenidate transdermal

  Monitor Closely (1)methylphenidate transdermal will increase the level or effect of amitriptyline by decreasing elimination. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

• methylprednisolone

  Minor (1)methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (2)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.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metyrapone

  Minor (2)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

  Minor (2)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.

• midazolam

  Monitor Closely (2)midazolam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and midazolam both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)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

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• mifepristone

  Monitor Closely (1)mifepristone, amitriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• miglitol

  Minor (1)amitriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.

• milnacipran

  Serious - Use Alternative (1)milnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• mipomersen

  Monitor Closely (1)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

  Monitor Closely (1)mirabegron will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (3)chlordiazepoxide and mirtazapine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  amitriptyline and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• mitotane

  Monitor Closely (1)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.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently

• modafinil

  Monitor Closely (3)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

  Monitor Closely (3)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

  Monitor Closely (2)chlordiazepoxide and motherwort both increase sedation. Use Caution/Monitor.
  
  amitriptyline and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  Minor (1)moxifloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)amitriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• moxonidine

  Monitor Closely (2)chlordiazepoxide and moxonidine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (2)chlordiazepoxide and nabilone both increase sedation. Use Caution/Monitor.
  
  amitriptyline and nabilone both increase sedation. Use Caution/Monitor.

• nafcillin

  Monitor Closely (1)nafcillin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (2)chlordiazepoxide and nalbuphine both increase sedation. Use Caution/Monitor.
  
  nalbuphine and amitriptyline both increase sedation. Use Caution/Monitor.

• naratriptan

  Monitor Closely (1)naratriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• nateglinide

  Minor (1)amitriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• nefazodone

  Monitor Closely (2)nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  nefazodone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)nefazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  nefazodone will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• nefopam

  Monitor Closely (1)nefopam, amitriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.

• nelfinavir

  Monitor Closely (2)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

  Monitor Closely (1)neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• netupitant/palonosetron

  Serious - Use Alternative (1)netupitant/palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• nevirapine

  Minor (1)nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nicardipine

  Monitor Closely (1)nicardipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  Serious - Use Alternative (1)amitriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (3)amitriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlordiazepoxide 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.Serious - Use Alternative (1)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

  Monitor Closely (3)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.Serious - Use Alternative (2)amitriptyline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide

  Serious - Use Alternative (1)amitriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  Serious - Use Alternative (1)amitriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Monitor Closely (1)amitriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)ofloxacin increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• olanzapine

  Monitor Closely (3)chlordiazepoxide and olanzapine both increase sedation. Use Caution/Monitor.
  
  olanzapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  olanzapine and amitriptyline both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (3)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

  Monitor Closely (1)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

• olopatadine intranasal

  Serious - Use Alternative (2)chlordiazepoxide and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  amitriptyline and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• omeprazole

  Minor (1)omeprazole increases levels of chlordiazepoxide by decreasing metabolism. Minor/Significance Unknown.

• onabotulinumtoxinA

  Monitor Closely (1)onabotulinumtoxinA and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• ondansetron

  Serious - Use Alternative (2)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.

• opium tincture

  Monitor Closely (2)chlordiazepoxide and opium tincture both increase sedation. Use Caution/Monitor.
  
  opium tincture and amitriptyline both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (3)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

  Monitor Closely (1)osilodrostat and amitriptyline both increase QTc interval. Use Caution/Monitor.

• osimertinib

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)chlordiazepoxide and oxazepam both increase sedation. Use Caution/Monitor.
  
  oxazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Minor (2)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.

• oxybutynin

  Monitor Closely (1)oxybutynin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin topical

  Monitor Closely (1)oxybutynin topical and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin transdermal

  Monitor Closely (1)oxybutynin transdermal and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxycodone

  Monitor Closely (2)oxycodone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and oxycodone both increase sedation. Use Caution/Monitor.

• oxymetazoline intranasal

  Monitor Closely (1)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

  Monitor Closely (2)oxymorphone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and oxymorphone both increase sedation. Use Caution/Monitor.

• ozanimod

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• paliperidone

  Monitor Closely (3)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.

• palonosetron

  Serious - Use Alternative (1)palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• panax ginseng

  Minor (1)panax ginseng increases effects of amitriptyline by pharmacodynamic synergism. Minor/Significance Unknown.

• pancuronium

  Monitor Closely (1)pancuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• papaveretum

  Monitor Closely (2)chlordiazepoxide and papaveretum both increase sedation. Use Caution/Monitor.
  
  papaveretum and amitriptyline both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (2)amitriptyline and papaverine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Minor (1)parecoxib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• paroxetine

  Monitor Closely (1)amitriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)paroxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• pasireotide

  Monitor Closely (1)amitriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  Monitor Closely (1)amitriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.

• peginterferon alfa 2b

  Monitor Closely (1)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.

• pentamidine

  Contraindicated (1)amitriptyline and pentamidine both increase QTc interval. Contraindicated.

• pentazocine

  Monitor Closely (3)chlordiazepoxide and pentazocine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  pentazocine and amitriptyline both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (4)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.Minor (1)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.

• perampanel

  Monitor Closely (1)perampanel and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• perphenazine

  Monitor Closely (2)perphenazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• phendimetrazine

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• phenelzine

  Contraindicated (1)phenelzine and amitriptyline both increase serotonin levels. Contraindicated.

• phenobarbital

  Monitor Closely (6)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.Minor (1)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.

• phentermine

  Monitor Closely (2)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.Serious - Use Alternative (1)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

  Monitor Closely (2)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.Serious - Use Alternative (1)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 ophthalmic

  Monitor Closely (1)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.

• phenylephrine PO

  Monitor Closely (1)amitriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Serious - Use Alternative (1)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.

• phenytoin

  Monitor Closely (3)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

  Monitor Closely (2)amitriptyline and pholcodine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and pholcodine both increase sedation. Use Caution/Monitor.

• physostigmine

  Monitor Closely (1)physostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pilocarpine

  Monitor Closely (1)pilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pimozide

  Contraindicated (1)amitriptyline and pimozide both increase QTc interval. Contraindicated.Monitor Closely (2)chlordiazepoxide and pimozide both increase sedation. Use Caution/Monitor.
  
  pimozide and amitriptyline both increase sedation. Use Caution/Monitor.

• pioglitazone

  Minor (1)amitriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (2)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.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• pleurisy root

  Minor (1)pleurisy root decreases effects of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• ponatinib

  Monitor Closely (1)ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• posaconazole

  Monitor Closely (2)posaconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (2)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.

• pralidoxime

  Monitor Closely (1)pralidoxime and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• prednisone

  Minor (1)prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pregabalin

  Monitor Closely (2)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

  Monitor Closely (5)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.Minor (1)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.

• procainamide

  Contraindicated (1)amitriptyline and procainamide both increase QTc interval. Contraindicated.

• procarbazine

  Contraindicated (1)procarbazine and amitriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

• prochlorperazine

  Monitor Closely (3)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.Minor (2)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

  Minor (1)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

  Serious - Use Alternative (1)promazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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

  Monitor Closely (3)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.Minor (2)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.

• propantheline

  Monitor Closely (1)propantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• propofol

  Monitor Closely (2)propofol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  propofol and chlordiazepoxide both increase sedation. Use Caution/Monitor.Minor (1)propofol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• propylhexedrine

  Monitor Closely (2)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.Serious - Use Alternative (1)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

  Monitor Closely (3)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.Serious - Use Alternative (2)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

  Serious - Use Alternative (1)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.

• pyridostigmine

  Monitor Closely (1)pyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• quazepam

  Monitor Closely (2)chlordiazepoxide and quazepam both increase sedation. Use Caution/Monitor.
  
  quazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• quercetin

  Monitor Closely (1)quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quetiapine

  Monitor Closely (3)chlordiazepoxide and quetiapine both increase sedation. Use Caution/Monitor.
  
  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.
  
  quetiapine and amitriptyline both increase sedation. Use Caution/Monitor.

• quinidine

  Contraindicated (1)quinidine and amitriptyline both increase QTc interval. Contraindicated.Serious - Use Alternative (1)quinidine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinine

  Monitor Closely (1)amitriptyline and quinine both increase QTc interval. Use Caution/Monitor.

• quinupristin/dalfopristin

  Minor (1)quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

  Monitor Closely (2)chlordiazepoxide and ramelteon both increase sedation. Use Caution/Monitor.
  
  amitriptyline and ramelteon both increase sedation. Use Caution/Monitor.

• ranolazine

  Monitor Closely (1)amitriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)ranolazine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• rapacuronium

  Monitor Closely (1)rapacuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• rasagiline

  Serious - Use Alternative (1)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.

• remifentanil

  Monitor Closely (1)amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

• remimazolam

  Monitor Closely (2)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.

• repaglinide

  Minor (1)amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)ribociclib increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.

• rifabutin

  Monitor Closely (3)rifabutin will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  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.Minor (1)rifabutin decreases levels of chlordiazepoxide by increasing metabolism. Minor/Significance Unknown.

• rifampin

  Monitor Closely (4)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.Minor (1)rifampin decreases levels of chlordiazepoxide by increasing metabolism. Minor/Significance Unknown.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rilpivirine

  Monitor Closely (1)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

  Monitor Closely (3)chlordiazepoxide and risperidone both increase sedation. Use Caution/Monitor.
  
  amitriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  risperidone and amitriptyline both increase sedation. Use Caution/Monitor.

• ritonavir

  Monitor Closely (3)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

  Monitor Closely (1)rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• rizatriptan

  Monitor Closely (1)rizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• rocuronium

  Monitor Closely (1)rocuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• rolapitant

  Monitor Closely (2)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.
  
  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

  Monitor Closely (1)amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

• rosiglitazone

  Minor (1)amitriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• rucaparib

  Monitor Closely (1)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.

• rufinamide

  Minor (1)rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• safinamide

  Contraindicated (1)amitriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

• sage

  Minor (2)chlordiazepoxide and sage both increase sedation. Minor/Significance Unknown.
  
  amitriptyline and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• SAMe

  Monitor Closely (1)amitriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

• saquinavir

  Monitor Closely (1)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

  Monitor Closely (1)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.

• saxagliptin

  Minor (1)amitriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• scopolamine

  Monitor Closely (1)scopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

  Monitor Closely (2)chlordiazepoxide and scullcap both increase sedation. Use Caution/Monitor.
  
  amitriptyline and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (4)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.Minor (1)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.

• selegiline

  Contraindicated (1)selegiline and amitriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicated

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• selinexor

  Serious - Use Alternative (2)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.

• selpercatinib

  Monitor Closely (1)selpercatinib increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

• serdexmethylphenidate/dexmethylphenidate

  Serious - Use Alternative (1)amitriptyline, serdexmethylphenidate/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.Minor (1)serdexmethylphenidate/dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• sertraline

  Monitor Closely (1)sertraline and amitriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)sertraline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• sevoflurane

  Monitor Closely (3)sevoflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  sevoflurane and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  sevoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)sevoflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• shepherd's purse

  Monitor Closely (2)amitriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and shepherd's purse both increase sedation. Use Caution/Monitor.

• simvastatin

  Monitor Closely (1)simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sirolimus

  Monitor Closely (1)sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sitagliptin

  Minor (1)amitriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• sodium oxybate

  Serious - Use Alternative (2)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.
  
  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.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (2)solifenacin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  solifenacin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sorafenib

  Monitor Closely (1)sorafenib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• sotalol

  Contraindicated (1)amitriptyline and sotalol both increase QTc interval. Contraindicated.

• St John's Wort

  Monitor Closely (2)St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)amitriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (3)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.
  
  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

  Monitor Closely (1)succinylcholine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• sufentanil

  Monitor Closely (2)chlordiazepoxide and sufentanil both increase sedation. Use Caution/Monitor.
  
  sufentanil and amitriptyline both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• sulfamethoxazole

  Monitor Closely (1)amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• sumatriptan

  Monitor Closely (1)sumatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• sumatriptan intranasal

  Monitor Closely (1)sumatriptan intranasal and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• suvorexant

  Monitor Closely (2)suvorexant and chlordiazepoxide both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary
  
  suvorexant and amitriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tacrolimus

  Monitor Closely (1)tacrolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tapentadol

  Monitor Closely (3)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

  Monitor Closely (1)tazemetostat will decrease the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor Closely (1)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.

• tedizolid

  Serious - Use Alternative (1)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.

• teduglutide

  Monitor Closely (1)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.

• telavancin

  Monitor Closely (1)amitriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

  Monitor Closely (2)chlordiazepoxide and temazepam both increase sedation. Use Caution/Monitor.
  
  temazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• terbinafine

  Monitor Closely (2)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

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tetrabenazine

  Monitor Closely (1)tetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• thioridazine

  Monitor Closely (2)chlordiazepoxide and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)thioridazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• thiothixene

  Monitor Closely (2)chlordiazepoxide and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene and amitriptyline both increase sedation. Use Caution/Monitor.

• thyroid desiccated

  Monitor Closely (1)thyroid desiccated increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• tiotropium

  Monitor Closely (1)tiotropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tipranavir

  Monitor Closely (1)tipranavir increases levels of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Use alternatives if available. Consider lowering benzodiazepine dose.

• tolazamide

  Minor (1)amitriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolbutamide

  Minor (1)amitriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolterodine

  Monitor Closely (1)tolterodine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tolvaptan

  Monitor Closely (1)tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• topiramate

  Monitor Closely (3)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.

• toremifene

  Serious - Use Alternative (1)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.

• tramadol

  Monitor Closely (3)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.

• tranylcypromine

  Contraindicated (1)tranylcypromine and amitriptyline both increase serotonin levels. Contraindicated.

• trazodone

  Monitor Closely (4)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.Serious - Use Alternative (2)amitriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
  
  trazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• triazolam

  Monitor Closely (2)chlordiazepoxide and triazolam both increase sedation. Use Caution/Monitor.
  
  triazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (2)chlordiazepoxide and triclofos both increase sedation. Use Caution/Monitor.
  
  triclofos and amitriptyline both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (2)chlordiazepoxide and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trifluoperazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• trihexyphenidyl

  Monitor Closely (1)trihexyphenidyl and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimethoprim

  Monitor Closely (1)amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimipramine

  Monitor Closely (3)chlordiazepoxide and trimipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• triprolidine

  Monitor Closely (2)triprolidine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  triprolidine and chlordiazepoxide both increase sedation. Use Caution/Monitor.

• tropisetron

  Monitor Closely (1)amitriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

• trospium chloride

  Monitor Closely (1)trospium chloride and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tucatinib

  Monitor Closely (1)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.Serious - Use Alternative (1)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

  Serious - Use Alternative (2)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

• valbenazine

  Monitor Closely (1)valbenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• valerian

  Monitor Closely (1)valerian and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)valerian and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug.

• vandetanib

  Serious - Use Alternative (1)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.

• vasopressin

  Minor (1)amitriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

• vecuronium

  Monitor Closely (1)vecuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• vemurafenib

  Serious - Use Alternative (1)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

  Monitor Closely (1)amitriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)venlafaxine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• verapamil

  Monitor Closely (1)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. Minor (2)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.

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (2)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

  Serious - Use Alternative (1)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. .

• vildagliptin

  Minor (1)amitriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• vinpocetine

  Minor (1)chlordiazepoxide increases effects of vinpocetine by unspecified interaction mechanism. Minor/Significance Unknown. Desirable interaction enhanced memory improvement (based on preliminary trial).

• voclosporin

  Monitor Closely (1)voclosporin, amitriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

  Monitor Closely (3)voriconazole will increase the level or effect of chlordiazepoxide by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  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.Minor (2)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.

• vortioxetine

  Serious - Use Alternative (1)amitriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

• voxelotor

  Serious - Use Alternative (1)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.

• warfarin

  Monitor Closely (1)amitriptyline increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• xylometazoline

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• yohimbe

  Serious - Use Alternative (1)yohimbe, amitriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.

• yohimbine

  Monitor Closely (2)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.Serious - Use Alternative (1)amitriptyline, yohimbine. 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.

• zafirlukast

  Minor (1)zafirlukast will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ziconotide

  Monitor Closely (2)amitriptyline and ziconotide both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (2)chlordiazepoxide and ziprasidone both increase sedation. Use Caution/Monitor.
  
  ziprasidone and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zolmitriptan

  Monitor Closely (1)zolmitriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• zolpidem

  Minor (2)zolpidem, chlordiazepoxide. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.
  
  zolpidem, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

• zotepine

  Monitor Closely (1)chlordiazepoxide and zotepine both increase sedation. Use Caution/Monitor.