both increase serotonin levels. Avoid or Use Alternate Drug.lofexidineMonitor Closely (2)protriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor. protriptyline and lofexidine both increase sedation. Use Caution/Monitor.loprazolamMonitor Closely (1)loprazolam and protriptyline both increase sedation. Use Caution/Monitor.lorazepamMonitor Closely (1)lorazepam and protriptyline both increase sedation. Use Caution/Monitor.lorcaserinMonitor Closely (1)lorcaserin will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.lormetazepamMonitor Closely (1)lormetazepam and protriptyline both increase sedation. Use Caution/Monitor.loxapineMonitor Closely (1)loxapine and protriptyline both increase sedation. Use Caution/Monitor.loxapine inhaledMonitor Closely (1)loxapine inhaled and protriptyline both increase sedation. Use Caution/Monitor.lsdMonitor Closely (1)protriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.lumefantrineSerious - Use Alternative (1)protriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.lurasidoneMonitor Closely (1)lurasidone, protriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .macimorelinSerious - Use Alternative (1)macimorelin and protriptyline 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.maprotilineMonitor Closely (2)maprotiline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. maprotiline and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)maprotiline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. maprotiline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.marijuanaMonitor Closely (1)protriptyline and marijuana both increase sedation. Use Caution/Monitor.meclizineMonitor Closely (1)meclizine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.mefloquineSerious - Use Alternative (1)mefloquine increases toxicity of protriptyline by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.melatoninMonitor Closely (1)protriptyline and melatonin both increase sedation. Use Caution/Monitor.meperidineMonitor Closely (1)meperidine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.meprobamateMonitor Closely (1)protriptyline and meprobamate both increase sedation. Use Caution/Monitor.mestranolMinor (1)mestranol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.metaproterenolMonitor Closely (1)protriptyline increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.metaxaloneMonitor Closely (1)metaxalone and protriptyline both increase sedation. Use Caution/Monitor.metforminMinor (1)protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.methadoneMonitor Closely (2)protriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely. methadone and protriptyline both increase sedation. Use Caution/Monitor.methamphetamineMonitor Closely (1)protriptyline increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.methocarbamolMonitor Closely (1)methocarbamol and protriptyline both increase sedation. Use Caution/Monitor.methscopolamineMonitor Closely (1)methscopolamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.methylene blueSerious - Use Alternative (1)methylene blue and protriptyline 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.methylenedioxymethamphetamineMonitor Closely (1)protriptyline increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.methylphenidateMonitor Closely (1)protriptyline, 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 transdermalMonitor Closely (1)methylphenidate transdermal will increase the level or effect of protriptyline 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. metoclopramide intranasalSerious - Use Alternative (1)protriptyline, 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.midazolamMonitor Closely (1)midazolam and protriptyline both increase sedation. Use Caution/Monitor.midodrineMonitor Closely (1)protriptyline increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.mifepristoneMonitor Closely (1)mifepristone, protriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.miglitolMinor (1)protriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.milnacipranSerious - Use Alternative (1)milnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.mirabegronMonitor Closely (1)mirabegron will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.mirtazapineMonitor Closely (2)protriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely. protriptyline and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.mobocertinibSerious - Use Alternative (1)mobocertinib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.modafinilMonitor Closely (1)protriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.morphineMonitor Closely (2)protriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. morphine and protriptyline both increase sedation. Use Caution/Monitor.motherwortMonitor Closely (1)protriptyline and motherwort both increase sedation. Use Caution/Monitor.moxifloxacinSerious - Use Alternative (1)protriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.moxonidineMonitor Closely (1)protriptyline and moxonidine both increase sedation. Use Caution/Monitor.nabiloneMonitor Closely (1)protriptyline and nabilone both increase sedation. Use Caution/Monitor.nalbuphineMonitor Closely (1)nalbuphine and protriptyline both increase sedation. Use Caution/Monitor.naratriptanMonitor Closely (1)naratriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.nateglinideMinor (1)protriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.nefazodoneSerious - Use Alternative (1)nefazodone and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.nefopamMonitor Closely (1)nefopam, protriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.neostigmineMonitor Closely (1)neostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.netupitant/palonosetronSerious - Use Alternative (1)netupitant/palonosetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.nilotinibSerious - Use Alternative (1)protriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.norepinephrineMonitor Closely (2)protriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor. protriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.nortriptylineMonitor Closely (2)nortriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. nortriptyline and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)nortriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. nortriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.octreotideSerious - Use Alternative (1)protriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.octreotide (Antidote)Serious - Use Alternative (1)protriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.ofloxacinMonitor Closely (1)protriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.olanzapineMonitor Closely (2)olanzapine and protriptyline both increase sedation. Use Caution/Monitor. olanzapine and protriptyline both increase QTc interval. Use Caution/Monitor.oliceridineMonitor Closely (2)protriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. protriptyline 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.olodaterol inhaledMonitor Closely (1)protriptyline 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 arrhythmiasolopatadine intranasalSerious - Use Alternative (1)protriptyline 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. onabotulinumtoxinAMonitor Closely (1)onabotulinumtoxinA and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.ondansetronSerious - Use Alternative (2)protriptyline 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, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.opium tinctureMonitor Closely (1)opium tincture and protriptyline both increase sedation. Use Caution/Monitor.orphenadrineMonitor Closely (2)protriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor. orphenadrine and protriptyline both increase sedation. Use Caution/Monitor.osimertinibMonitor Closely (1)osimertinib and protriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.oxazepamMonitor Closely (1)oxazepam and protriptyline both increase sedation. Use Caution/Monitor.oxybutyninMonitor Closely (1)oxybutynin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.oxybutynin topicalMonitor Closely (1)oxybutynin topical and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.oxybutynin transdermalMonitor Closely (1)oxybutynin transdermal and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.oxycodoneMonitor Closely (1)oxycodone and protriptyline both increase sedation. Use Caution/Monitor.oxymetazoline intranasalMonitor Closely (1)protriptyline 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.oxymorphoneMonitor Closely (1)oxymorphone and protriptyline both increase sedation. Use Caution/Monitor.ozanimodMonitor Closely (1)ozanimod and protriptyline 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 protriptyline 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.paliperidoneMonitor Closely (2)protriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely. paliperidone and protriptyline both increase sedation. Use Caution/Monitor.palonosetronSerious - Use Alternative (1)palonosetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.panax ginsengMinor (1)panax ginseng increases effects of protriptyline by pharmacodynamic synergism. Minor/Significance Unknown.pancuroniumMonitor Closely (1)pancuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.papaveretumMonitor Closely (1)papaveretum and protriptyline both increase sedation. Use Caution/Monitor.papaverineMonitor Closely (1)protriptyline and papaverine both increase sedation. Use Caution/Monitor.paroxetineMonitor Closely (1)protriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)paroxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.pasireotideMonitor Closely (1)protriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.pazopanibMonitor Closely (1)protriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.peginterferon alfa 2bMonitor Closely (1)peginterferon alfa 2b, protriptyline. 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.pentamidineContraindicated (1)protriptyline and pentamidine both increase QTc interval. Contraindicated.pentazocineMonitor Closely (2)protriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely. pentazocine and protriptyline both increase sedation. Use Caution/Monitor.pentobarbitalMonitor Closely (1)pentobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)pentobarbital, protriptyline. 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.perphenazineMonitor Closely (1)perphenazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)protriptyline, perphenazine. Either increases levels of the