Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).phendimetrazineContraindicated (1)phenelzine increases effects of phendimetrazine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.phenobarbitalMinor (1)phenelzine increases levels of phenobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.phentermineContraindicated (1)phenelzine increases effects of phentermine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.phenylephrineContraindicated (1)phenelzine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.phenylephrine ophthalmicMonitor Closely (1)phenelzine increases effects of phenylephrine ophthalmic by pharmacodynamic synergism. Use Caution/Monitor. Some systemic absorption of ophthalmic phenylephrine; reduce dose within 21 days of MAO inhibitors.phenylephrine POContraindicated (1)phenelzine increases effects of phenylephrine PO by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.pimavanserinMonitor Closely (1)phenelzine, pimavanserin. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).pimozideMonitor Closely (1)phenelzine, pimozide. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).pirbuterolSerious - Use Alternative (1)phenelzine increases effects of pirbuterol by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.pleurisy rootMinor (1)pleurisy root decreases effects of phenelzine by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.pregabalinMonitor Closely (1)pregabalin, phenelzine. 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.primidoneMinor (1)phenelzine increases levels of primidone by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.procarbazineContraindicated (1)phenelzine and procarbazine both increase serotonin levels. Contraindicated. At least 2 weeks should elapse between discontinuation of one MAOI and initiation of therapy with the other.promethazineMonitor Closely (1)phenelzine increases effects of promethazine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .propofolSerious - Use Alternative (1)phenelzine increases levels of propofol by pharmacodynamic synergism. Avoid or Use Alternate Drug.propylhexedrineContraindicated (1)phenelzine increases effects of propylhexedrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.protriptylineContraindicated (1)phenelzine and protriptyline both increase serotonin levels. Contraindicated.pseudoephedrineContraindicated (1)phenelzine increases effects of pseudoephedrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.quetiapineMonitor Closely (1)phenelzine, quetiapine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).rasagilineContraindicated (1)rasagiline and phenelzine both increase serotonin levels. Contraindicated. Increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of rasagiline and initiation of another MAOI or discontinuation of another MAOI and initiation of rasagiline.remifentanilMonitor Closely (1)remifentanil increases toxicity of phenelzine by serotonin levels. Modify Therapy/Monitor Closely. Increases risk of serotonin syndrome.remimazolamMonitor Closely (1)remimazolam, phenelzine. 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.risperidoneMonitor Closely (1)phenelzine, risperidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).rizatriptanSerious - Use Alternative (2)rizatriptan and phenelzine both increase serotonin levels. Avoid or Use Alternate Drug. phenelzine increases levels of rizatriptan by decreasing metabolism. Contraindicated.safinamideContraindicated (1)phenelzine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration increases risk of nonselective MAO inhibition, that may lead to hypertensive crisis. At least 14 days should elapse between discontinuating safinamide and initiating MAOIs.salmeterolSerious - Use Alternative (1)phenelzine increases effects of salmeterol by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.SAMeSerious - Use Alternative (1)phenelzine and SAMe both increase serotonin levels. Avoid or Use Alternate Drug.secobarbitalMinor (1)phenelzine increases levels of secobarbital by decreasing metabolism. Minor/Significance Unknown. Theoretical interaction.selegilineContraindicated (1)selegiline and phenelzine both increase serotonin levels. Contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of another MAOI.selegiline transdermalContraindicated (1)selegiline transdermal and phenelzine both increase serotonin levels. Contraindicated.serdexmethylphenidate/dexmethylphenidateContraindicated (1)phenelzine increases effects of serdexmethylphenidate/dexmethylphenidate by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.sertralineContraindicated (1)phenelzine and sertraline both increase serotonin levels. Contraindicated.sevofluraneSerious - Use Alternative (1)phenelzine increases levels of sevoflurane by pharmacodynamic synergism. Avoid or Use Alternate Drug.solriamfetolContraindicated (1)phenelzine will increase the level or effect of solriamfetol by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Contraindicated. Do no use solriamfetol during and/or within 14 days of discontinuing MAOI treatment. MAOIs irreversibly inhibit the enzyme monamine oxidase, an enzyme involved in the degradation of various monoamines, including dopamine and norepinephrine. Solriamfetol increases synaptic dopamine and norepinephrine.St John's WortContraindicated (1)phenelzine and St John's Wort both increase serotonin levels. Contraindicated.succinylcholineMinor (1)phenelzine increases levels of succinylcholine by decreasing metabolism. Minor/Significance Unknown.sufentanilSerious - Use Alternative (1)phenelzine increases toxicity of sufentanil by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.sufentanil SLSerious - Use Alternative (1)phenelzine increases toxicity of sufentanil SL by serotonin levels. Avoid or Use Alternate Drug. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (eg, respiratory depression, coma). Opioids are not recommended for patients taking MAOIs or within 14 days of stopping MAOIs. If urgent opioid treatment needed, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.sulfadiazineMinor (1)phenelzine increases levels of sulfadiazine by unspecified interaction mechanism. Minor/Significance Unknown.sulfamethoxazoleMinor (1)phenelzine increases levels of sulfamethoxazole by unspecified interaction mechanism. Minor/Significance Unknown.sulfisoxazoleMinor (1)phenelzine increases levels of sulfisoxazole by unspecified interaction mechanism. Minor/Significance Unknown.sumatriptanSerious - Use Alternative (2)sumatriptan and phenelzine both increase serotonin levels. Avoid or Use Alternate Drug. phenelzine increases levels of sumatriptan by decreasing metabolism. Contraindicated.sumatriptan intranasalSerious - Use Alternative (2)sumatriptan intranasal and phenelzine both increase serotonin levels. Avoid or Use Alternate Drug. phenelzine increases levels of sumatriptan intranasal by decreasing metabolism. Contraindicated.tapentadolMonitor Closely (1)phenelzine and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)phenelzine increases toxicity of tapentadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.tedizolidSerious - Use Alternative (1)tedizolid, phenelzine. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Interaction with MAOIs were not studied in clinical trials; drugs within the same class(eg linezolid) are contraindicated with MAOIs.terbutalineSerious - Use Alternative (1)phenelzine increases effects of terbutaline by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.tetrabenazineContraindicated (1)tetrabenazine, phenelzine. Other (see comment). Contraindicated. Comment: Risk of acute hypertensive episode; separate by 14 d. Mechanism: MAOI causes accumulation of NE in neuron and tetrabenazine stimulates NE release.thiothixeneMonitor Closely (1)phenelzine, thiothixene. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).tolazamideMonitor Closely (1)phenelzine increases effects of tolazamide by unknown mechanism. Use Caution/Monitor.tolbutamideMonitor Closely (1)phenelzine increases effects of tolbutamide by unknown mechanism. Use Caution/Monitor.tolcaponeContraindicated (1)tolcapone, phenelzine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Both nonselective MAO inhibitors and tolcapone inhibit catecholamine metabolism, leading to increased levels of catecholamines. Potential for dangerously high HR or BP.tramadolSerious - Use Alternative (2)phenelzine and tramadol both increase serotonin levels. Avoid or Use Alternate Drug. phenelzine increases toxicity of tramadol by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.tranylcypromineContraindicated (1)phenelzine and tranylcypromine both increase serotonin levels. Contraindicated.trazodoneContraindicated (1)phenelzine and trazodone both increase serotonin levels. Contraindicated.trifluoperazineMonitor Closely (1)phenelzine, trifluoperazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).trimipramineContraindicated (1)phenelzine and trimipramine both increase serotonin levels. Contraindicated.tyramineContraindicated (1)phenelzine increases effects of tyramine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode. Tyramine containing foods include cheese, red wine, caviar, herring, canned figs, fermented meats, fava beans, yeast extracts, miso, avocado.umeclidinium bromide/vilanterol inhaledSerious - Use Alternative (1)phenelzine 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 potentiatedvalbenazineSerious - Use Alternative (1)phenelzine, valbenazine. Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of valbenazine with MAOIs may increase monoamine neurotransmitter concentration in synapses, potentially increasing risk of serotonin syndrome or attenuating valbenazine effect.valerianMonitor Closely (1)valerian and phenelzine both increase sedation. Use Caution/Monitor.venlafaxineContraindicated (1)phenelzine and venlafaxine both increase serotonin levels. Contraindicated.vilanterol/fluticasone furoate inhaledSerious - Use Alternative (1)phenelzine 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 potentiatedvilazodoneContraindicated (1)phenelzine, vilazodone. Either increases toxicity of the other by serotonin levels. Contraindicated. Coadministration with MAO-A inhibitors are contraindicated. Do not prescribe vilazodone within 14 days of discontinuing or starting an MAO inhibitor.vortioxetineContraindicated (1)phenelzine increases toxicity of vortioxetine by serotonin levels. Contraindicated.xylometazolineContraindicated (1)phenelzine increases effects of xylometazoline by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.yohimbeMonitor Closely (1)yohimbe increases effects of phenelzine by pharmacodynamic synergism. Use Caution/Monitor.yohimbineContraindicated (1)phenelzine increases effects of yohimbine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.ziprasidoneMonitor Closely (1)phenelzine, ziprasidone. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).zolmitriptanSerious - Use Alternative (2)zolmitriptan and phenelzine both increase serotonin levels. Avoid or Use Alternate Drug. phenelzine increases levels of zolmitriptan by decreasing metabolism. Contraindicated. Frequency Not Defined Common Orthostatic hypotension Asthenia Dizziness Headache Drowsiness Fatigue Hyperreflexia Sleep disturbance Somnolence Weakness Tremor Constipation Dry mouth Weight gain Less Common Confusion Decreased memory Paresthesia Anorexia Nausea Vomiting Impotence Increased LFT's Nystagmus Urinary frequency or retention Uncommon Edema Anxiety Irritation Hypomania Hypermetabolic syndrome (hyperpyrexia, tachycardia, tachypnea, increased CPK, acidosis) Arthralgia SIADH Rare Hypertensive crisis Ataxia Seizure Worsening depression Suicide Edema of glottis Leukopenia Hepatic necrosis, jaundice Drug-induced lupus erythematosus Visual disturbance Black Box Warnings In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years In children and young adults, risks must be weighed against the benefits of taking antidepressants Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments The patient’s family should communicate any abrupt changes in behavior to the healthcare provider Worsening behavior and suicidal tendencies that