feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat. cocaine topicalMonitor Closely (1)protriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeineMonitor Closely (1)codeine and protriptyline both increase sedation. Use Caution/Monitor.conjugated estrogensMinor (1)conjugated estrogens, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.conjugated estrogens, vaginalMinor (1)conjugated estrogens, vaginal, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.crizotinibMonitor Closely (1)crizotinib and protriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.cyclizineMonitor Closely (2)cyclizine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. cyclizine and protriptyline both increase sedation. Use Caution/Monitor.cyclobenzaprineMonitor Closely (2)cyclobenzaprine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. cyclobenzaprine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.cyproheptadineMonitor Closely (1)cyproheptadine and protriptyline both increase sedation. Use Caution/Monitor.dacomitinibSerious - Use Alternative (1)dacomitinib will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities. dantroleneMonitor Closely (1)dantrolene and protriptyline both increase sedation. Use Caution/Monitor.daridorexantMonitor Closely (1)protriptyline and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. darifenacinMonitor Closely (1)darifenacin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.dasatinibMonitor Closely (1)protriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.debrisoquineMonitor Closely (1)protriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.degarelixMonitor Closely (1)degarelix and protriptyline both increase QTc interval. Use Caution/Monitor.desfluraneMonitor Closely (2)desflurane and protriptyline both increase QTc interval. Use Caution/Monitor. desflurane and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)desflurane, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.desipramineMonitor Closely (2)desipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. desipramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)desipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. desipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.desvenlafaxineSerious - Use Alternative (1)protriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.deutetrabenazineMonitor Closely (2)protriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor. deutetrabenazine and protriptyline 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).dexchlorpheniramineMonitor Closely (1)dexchlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.dexfenfluramineMonitor Closely (2)protriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely. protriptyline increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.dexmedetomidineMonitor Closely (1)dexmedetomidine and protriptyline both increase sedation. Use Caution/Monitor.dexmethylphenidateMonitor Closely (1)protriptyline increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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 protriptyline by decreasing metabolism. Minor/Significance Unknown.dextroamphetamineMonitor Closely (3)protriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor. protriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely. protriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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 transdermalMonitor Closely (1)protriptyline 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.dextromethorphanSerious - Use Alternative (1)protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.dextromoramideMonitor Closely (1)dextromoramide and protriptyline both increase sedation. Use Caution/Monitor.diamorphineMonitor Closely (1)diamorphine and protriptyline both increase sedation. Use Caution/Monitor.diazepamMonitor Closely (1)diazepam and protriptyline both increase sedation. Use Caution/Monitor.diazepam intranasalMonitor Closely (1)diazepam intranasal, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.dicyclomineMonitor Closely (1)dicyclomine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.diethylpropionMonitor Closely (1)protriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.difelikefalinMonitor Closely (1)difelikefalin and protriptyline both increase sedation. Use Caution/Monitor.difenoxin hclMonitor Closely (1)difenoxin hcl and protriptyline both increase sedation. Use Caution/Monitor.dihydroergotamineMonitor Closely (1)protriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.dihydroergotamine intranasalMonitor Closely (1)protriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.dimenhydrinateMonitor Closely (1)dimenhydrinate and protriptyline both increase sedation. Use Caution/Monitor.diphenhydramineMonitor Closely (2)diphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor.diphenoxylate hclMonitor Closely (1)diphenoxylate hcl and protriptyline both increase sedation. Use Caution/Monitor.dipipanoneMonitor Closely (1)dipipanone and protriptyline both increase sedation. Use Caution/Monitor.disopyramideContraindicated (1)protriptyline and disopyramide both increase QTc interval. Contraindicated.dobutamineMonitor Closely (1)protriptyline increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.dofetilideMonitor Closely (1)dofetilide increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.dolasetronMonitor Closely (1)protriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dolasetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.donepezilMonitor Closely (2)donepezil increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor. donepezil and protriptyline both increase QTc interval. Use Caution/Monitor.dopamineMonitor Closely (1)protriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.dopexamineMonitor Closely (1)protriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.doxepinMonitor Closely (2)doxepin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. doxepin and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)doxepin and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. doxepin and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.doxylamineMonitor Closely (1)doxylamine and protriptyline both increase sedation. Use Caution/Monitor.dronedaroneSerious - Use Alternative (1)protriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.droperidolMonitor Closely (1)droperidol and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.duloxetineSerious - Use Alternative (1)duloxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.echothiophate iodideMonitor Closely (1)echothiophate iodide increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.efavirenzMonitor Closely (1)efavirenz and protriptyline both increase QTc interval. Use Caution/Monitor.eletriptanMonitor Closely (1)eletriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.eliglustatMonitor Closely (2)eliglustat and protriptyline both increase QTc interval. Use Caution/Monitor. eliglustat increases levels of protriptyline 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 DFMonitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of protriptyline 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.encorafenibSerious - Use Alternative (1)encorafenib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.entrectinibMonitor Closely (1)entrectinib and protriptyline both increase QTc interval. Use Caution/Monitor.ephedrineMonitor Closely (2)protriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor. protriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.epinephrineMonitor Closely (2)protriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor. protriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)epinephrine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. protriptyline, 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 inhaledMonitor Closely (1)protriptyline 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 racemicMonitor Closely (2)protriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor. protriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)epinephrine racemic and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. protriptyline, 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.ergotamineMonitor Closely (1)protriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.eribulinMonitor Closely (1)eribulin and protriptyline both increase QTc interval. Use Caution/Monitor.erythromycin baseSerious - Use Alternative (1)protriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.erythromycin ethylsuccinateSerious - Use Alternative (1)protriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.erythromycin lactobionateSerious - Use Alternative (1)protriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.erythromycin stearateSerious - Use Alternative (1)protriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.escitalopramMonitor Closely (1)escitalopram increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)escitalopram and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.esketamine intranasalMonitor Closely (1)esketamine intranasal, protriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.estazolamMonitor Closely (1)estazolam and protriptyline both increase sedation. Use Caution/Monitor.estradiolMinor (1)estradiol, protriptyline. 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 syntheticMinor (1)estrogens conjugated synthetic, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.estrogens esterifiedMinor (1)estrogens esterified, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.estropipateMinor (1)estropipate, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.ethanolMonitor Closely (1)protriptyline and ethanol both increase sedation. Use Caution/Monitor.ethinylestradiolMinor (1)ethinylestradiol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.etomidateMonitor Closely (1)etomidate and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)etomidate, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.eucalyptusMinor (1)protriptyline and eucalyptus both increase sedation. Minor/Significance Unknown.ezogabineMonitor Closely (1)ezogabine, protriptyline. Either increases toxicity of the other by QTc interval.