Phenelzine: Drug information

For additional information see "Phenelzine: Patient drug information"

For abbreviations, symbols, and age group definitions show table

ALERT: US Boxed Warning

Suicidality and antidepressant drugs:

Antidepressants increased the risk compared with placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of phenelzine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Closely observe and appropriately monitor patients of all ages who are started on antidepressant therapy for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider. Phenelzine is not approved for use in pediatric patients.

Brand Names: US

Nardil

Brand Names: Canada

Nardil

Pharmacologic Category

Antidepressant, Monoamine Oxidase Inhibitor

Dosing: Adult

Major depressive disorder

Major depressive disorder (unipolar): Oral: Initial: 15 mg once to 3 times daily; increase dose based on response and tolerability in increments of 15 mg at intervals ≥2 to 4 days (some experts titrate at intervals of every 2 to 3 weeks) up to 60 mg/day in 3 divided doses. Some patients may require up to 90 mg/day for optimal response (Ref).

Social anxiety disorder

Social anxiety disorder (off-label use) (alternative agent): Oral: Initial: 15 mg once daily for 3 days, then 30 mg once daily for 4 days. At the beginning of the second week, increase to 45 mg once daily, and at the beginning of the third week, increase to 60 mg/day. Doses as high as 90 mg/day have been studied. Doses ≥60 mg/day should be divided into 2 equal daily doses (Ref).

Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). For brief treatment (eg, 2 or 3 weeks) may taper over 1 to 2 weeks; <2 weeks treatment generally does not warrant tapering (Ref). Reasons for a slower taper (eg, over 4 weeks) include history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). More severe symptoms have been associated with monoamine oxidase inhibitors (MAOIs); more conservative tapers may be necessary. If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).

Switching antidepressants:

Switching to or from phenelzine, another MAOI, or an alternative antidepressant:

Allow 14 days to elapse between discontinuing an alternative antidepressant without long half-life metabolites (eg, tricyclic antidepressants, paroxetine, fluvoxamine, venlafaxine) or MAOI and initiation of phenelzine.

Allow 5 weeks to elapse between discontinuing fluoxetine (with long half-life metabolites) and initiation of phenelzine.

Allow 14 days to elapse between discontinuing phenelzine and initiation of an alternative antidepressant or MAOI.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Mild to moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling.

Severe impairment: Use is contraindicated.

Dosing: Liver Impairment: Adult

Use is contraindicated.

Dosing: Older Adult

Major depressive disorder (unipolar): Oral: Select dose with caution, generally initiating at the lower end of the dosing range; some clinicians recommend an initial dose of 7.5 mg/day, increasing the daily dose in increments of 7.5 mg every 4 to 8 days as tolerated to a usual therapeutic dose of 22.5 to 60 mg/day (Ref).

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Altered blood pressure, edema, hypertensive crisis, orthostatic hypotension

Dermatologic: Diaphoresis, pruritus, skin rash

Endocrine & metabolic: Hypernatremia, metabolic syndrome (hypermetabolic), weight gain

Gastrointestinal: Constipation, gastrointestinal distress, glottis edema, xerostomia

Genitourinary: Sexual disorder (including anorgasmia, ejaculatory disorder, impotence), urinary retention

Hepatic: Increased serum transaminases, jaundice

Nervous system: Acute anxiety, agitation, asthenia, ataxia, dizziness, drowsiness, euphoria, fatigue, headache, hyperreflexia, jitteriness, mania (including hypomania), paresthesia, schizophrenia (precipitation of), shock-like coma, sleep disturbance (including hypersomnia, insomnia), speech disturbance (palilalia), suicidal ideation, suicidal tendencies, tremor, twitching

Ophthalmic: Blurred vision, glaucoma, nystagmus disorder

Miscellaneous: Fever

Postmarketing:

Endocrine & metabolic: Pyridoxine deficiency (Demers 1984), SIADH (Giese 1989)

Genitourinary: Priapism (Yeragani 1987)

Hematologic & oncologic: Leukopenia (Tipermas 1984), sarcoma (angiosarcoma of liver) (Daneshmend 1979)

Hepatic: Hepatic injury (Bonkovsky 1986), hepatic necrosis

Nervous system: Delirium (White 1987), delusion (Aizenberg 1991), myoclonus (White 1987), parkinsonism (Gillman 1986), peripheral neuropathy (Goodheart 1991), psychosis (Sheehy 1978), seizure (Bhugra 1986), withdrawal syndrome (with abrupt discontinuation) (Palladino 1983)

Neuromuscular & skeletal: Lupus-like syndrome (Swartz 1978)

Contraindications

Hypersensitivity to phenelzine or any component of the formulation; congestive heart failure; pheochromocytoma; abnormal liver function tests or history of hepatic disease; renal disease or severe renal impairment

Concurrent use of bupropion, buspirone, caffeine (excessive use), CNS depressants (eg, alcohol), cocaine or local anesthesia containing sympathomimetic vasoconstrictors, dextromethorphan, elective surgery requiring general anesthesia (discontinue phenelzine ≥10 days prior to elective surgery), guanethidine, meperidine, MAO inhibitors or dibenzazepine derivatives (eg, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline, doxepin, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, perphenazine, trimipramine), ophthalmic agents (eg, apraclonidine), SSRIs or SNRIs, spinal anesthesia, sympathomimetics (including amphetamines, methylphenidate, dopamine, norepinephrine) or related compounds (levodopa, methyldopa, phenylalanine, tryptophan, tyrosine), or foods high in tyramine content (or within 2 weeks of stopping treatment).

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Bupropion: At least 14 days should elapse between phenelzine discontinuation and bupropion initiation.

Buspirone: At least 14 days (10 days in the Canadian labeling) should elapse between phenelzine discontinuation and buspirone initiation.

SSRIs or SNRIs: At least 2 weeks should elapse between the discontinuation of SNRIs and SSRIs and the initiation of phenelzine. At least 5 weeks should elapse between the discontinuation of fluoxetine and the initiation of phenelzine. At least 2 weeks (10 days in the Canadian labeling) should elapse between the discontinuation of phenelzine and the initiation of SNRIs and SSRIs.

At least 2 weeks should elapse between the discontinuation of phenelzine and the initiation of the following agents: Serotoninergic agents (including SNRIs, SSRIs, fluoxetine, and tricyclics), bupropion, buspirone, and other antidepressants.

General anesthesia, spinal anesthesia (hypotension may be exaggerated). Use caution with local anesthetics containing sympathomimetic agents. Phenelzine should be discontinued at least 10 days prior to elective surgery.

Foods high in tyramine or dopamine content; foods and/or supplements containing tyrosine, phenylalanine, tryptophan, or caffeine

Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with reserpine

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years. Closely monitor patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increases or decreases); the patient’s family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Phenelzine is not FDA approved for the treatment of depression in children ≤18 years of age.

• The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

• Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Hypertensive crisis: Cases of hypertensive crisis (sometimes fatal) have occurred; symptoms include occipital headache which may radiate frontally, palpitations, nausea/vomiting, neck stiffness/soreness, photophobia, and sweating. Tachycardia and bradycardia may be present, and associated constricting chest pain and dilated pupils may occur. Monitor blood pressure closely in all patients; discontinue treatment immediately upon occurrence of palpitations or frequent headaches. May occur with foods/supplements high in tyramine, tryptophan, dopamine, phenylalanine, or tyrosine content. Treatment with phentolamine is recommended for hypertensive crisis.

• Hypotension: May cause postural hypotension and may result in syncope; use with caution in patients at risk of this effect, patients with preexisting hypertension or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Increase dosage more gradually in patients showing a tendency toward hypotension.

• Intracranial bleeding: Intracranial bleeding has been reported in association with the increase in blood pressure.

Disease-related concerns:

• Diabetes: Use with caution in patients with diabetes mellitus; sensitization to the effects of insulin may occur, monitor blood glucose closely.

• Glaucoma: Use with caution in patients with angle-closure glaucoma

• Mania/hypomania: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer should also be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Phenelzine is not FDA approved for the treatment of bipolar depression.

• Seizure disorder: Use with caution in patients at risk for seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold.

• Thyroid dysfunction: Use with caution in patients with hyperthyroidism.

Special populations:

• Older adult: The monoamine oxidase inhibitors (MAOIs) are effective and generally well-tolerated by older patients. It is the potential interactions with tyramine or tryptophan-containing foods and other drugs, and their effects on BP, that have limited their use (Volz 1998).

• Surgical patients: According to the manufacturer, phenelzine use within 10 days prior to elective surgery is contraindicated. The decision to continue or withhold MAOIs must be done in collaboration with the patient's psychiatrist. Currently, an MAO-safe anesthetic technique which excludes the use of meperidine and indirect-acting adrenergic agonists is recommended for patients requiring continued MAOI therapy (Huyse 2006).

Other warnings/precautions:

• Appropriate use: Phenelzine is not generally considered a first-line agent for the treatment of depression; phenelzine is typically used in patients who have failed to respond to other treatments. There is less conclusive evidence of the usefulness of phenelzine in severely depressed patients with endogenous features.

• Discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms with MAOIs commonly include aggressiveness, agitation, delirium, confusion, depression associated with cognitive impairment, disorientation, hypomania, insomnia, irritability, mania, myoclonic jerks, seizures, and thought disorganization (eg, paranoid delusions and hallucinations). Greater risks for developing a discontinuation syndrome have been associated with high doses, longer durations of treatment, and abrupt discontinuation (APA 2010; Haddad 2001; Lejoyeux 1997).

• Myelography: Discontinue at least 48 hours prior to myelography; do not resume therapy until at least 24 hours after procedure.

• Pyridoxine deficiency: Pyridoxine deficiency has occurred; symptoms include numbness and edema of hands; may respond to supplementation (Stewart 1984).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Nardil: 15 mg

Generic: 15 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Nardil Oral)

15 mg (per each): $3.09

Tablets (Phenelzine Sulfate Oral)

15 mg (per each): $0.84

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Nardil: 15 mg [contains edetate (edta) disodium]

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/ucm100211.pdf, must be dispensed with this medication.

Use: Labeled Indications

Major depressive disorder (unipolar): Treatment of unipolar major depressive disorder in adults.

Use: Off-Label: Adult

Social anxiety disorder

Medication Safety Issues

Sound-alike/look-alike issues:

Phenelzine may be confused with phenytoin

Nardil may be confused with Norinyl

Metabolism/Transport Effects

Inhibits Monoamine Oxidase;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents with Blood Glucose Lowering Effects: Monoamine Oxidase Inhibitors may increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor

Alcohol (Ethyl): May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Alosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Alpha-/Beta-Agonists (Indirect-Acting): Monoamine Oxidase Inhibitors may increase hypertensive effects of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid

Alpha1-Agonists: Monoamine Oxidase Inhibitors may increase hypertensive effects of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid

Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor

Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification

Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor

Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Amphetamines: Monoamine Oxidase Inhibitors may increase hypertensive effects of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Risk X: Avoid

Antiemetics (5HT3 Antagonists): May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor

Antipsychotic Agents: Serotonergic Agents (High Risk) may increase adverse/toxic effects of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor

Apraclonidine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Apraclonidine. Monoamine Oxidase Inhibitors may increase serum concentration of Apraclonidine. Risk X: Avoid

Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor

ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Atomoxetine: Monoamine Oxidase Inhibitors may increase neurotoxic (central) effects of Atomoxetine. Risk X: Avoid

Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may increase hypertensive effects of Atropine (Ophthalmic). Risk X: Avoid

Avocado: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor

Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Benzhydrocodone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of benzhydrocodone is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and frequent titration of small benzhydrocodone. Risk D: Consider Therapy Modification

Beta2-Agonists: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor

Betahistine: Monoamine Oxidase Inhibitors may increase serum concentration of Betahistine. Risk C: Monitor

Bezafibrate: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Bezafibrate. Risk X: Avoid

Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor

Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Bornaprine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor

Brexanolone: Phenelzine may increase CNS depressant effects of Brexanolone. Risk C: Monitor

Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Brimonidine (Ophthalmic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor

Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Brimonidine (Topical): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Topical). Risk C: Monitor

Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid

Buprenorphine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

BuPROPion: Monoamine Oxidase Inhibitors may increase hypertensive effects of BuPROPion. Risk X: Avoid

BusPIRone: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

Butorphanol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

CarBAMazepine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Do not use carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Risk X: Avoid

Carbinoxamine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Carbinoxamine. Specifically, the anticholinergic effects of carbinoxamine may be enhanced and prolonged. Risk X: Avoid

Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Cerebrolysin: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor

Chlorphenesin Carbamate: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor

ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Clemastine: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Clemastine. Risk C: Monitor

Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Cocaine (Topical): Phenelzine may increase vasoconstricting effects of Cocaine (Topical). Risk X: Avoid

Codeine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Codeine. Risk X: Avoid

COMT Inhibitors: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Avoid coadministration of COMT inhibitors and nonselective monoamine oxidase inhibitors (MAOIs) (eg, isocarboxazid, phenelzine, tranylcypromine, linezolid, methylene blue) whenever possible. Risk D: Consider Therapy Modification

Cyclobenzaprine: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

Cyproheptadine: May decrease serotonergic effects of Monoamine Oxidase Inhibitors. Monoamine Oxidase Inhibitors may increase anticholinergic effects of Cyproheptadine. Risk X: Avoid

Dapoxetine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid

Deutetrabenazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Deutetrabenazine. Risk X: Avoid

Dexmethylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Dexmethylphenidate. Risk X: Avoid

Dextromethorphan: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid

Diamorphine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Diamorphine. Risk X: Avoid

Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Diethylpropion: Monoamine Oxidase Inhibitors may increase hypertensive effects of Diethylpropion. Risk X: Avoid

Difenoxin: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor

Dihydrocodeine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Consider avoiding use of dihydrocodeine while the patient is taking monoamine oxidase inhibitors (MAOIs) and for 2 weeks after MAOI discontinuation. Risk D: Consider Therapy Modification

Diphenoxylate: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Domperidone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Domperidone. Monoamine Oxidase Inhibitors may decrease therapeutic effects of Domperidone. Domperidone may decrease therapeutic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor

DOPamine: Monoamine Oxidase Inhibitors may increase hypertensive effects of DOPamine. Management: Initiate dopamine at no greater than one-tenth (1/10) of the usual dose in patients who are taking (or have taken within the last 2 to 3 weeks) monoamine oxidase inhibitors. Monitor for an exaggerated hypertensive response to dopamine. Risk D: Consider Therapy Modification

Doxapram: Monoamine Oxidase Inhibitors may increase hypertensive effects of Doxapram. Risk C: Monitor

Doxylamine: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Doxylamine. Risk X: Avoid

DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Droxidopa: Monoamine Oxidase Inhibitors may increase hypertensive effects of Droxidopa. Risk X: Avoid

EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may increase hypertensive effects of EPINEPHrine (Oral Inhalation). Risk X: Avoid

Epinephrine (Racemic): Monoamine Oxidase Inhibitors (Antidepressant) may increase adverse/toxic effects of Epinephrine (Racemic). Risk X: Avoid

EPINEPHrine (Systemic): Monoamine Oxidase Inhibitors may increase hypertensive effects of EPINEPHrine (Systemic). Risk C: Monitor

Ergot Derivatives: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Esketamine (Nasal): May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor

Fenfluramine: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

FentaNYL: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Gepirone: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

Guanethidine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

HYDROcodone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROcodone. Management: Consider alternatives to this combination when possible. If coadministration is required, use test doses, titrate small doses frequently, and monitor patients closely for evidence of serotonergic and opioid toxicities. Risk D: Consider Therapy Modification

HYDROmorphone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROmorphone. Management: Coadministration of hydromorphone and monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) is not recommended. If required, use test doses, titrate small doses frequently, and monitor for CNS and respitatory depression. Risk D: Consider Therapy Modification

Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor

Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Indoramin: Monoamine Oxidase Inhibitors may increase hypotensive effects of Indoramin. Risk X: Avoid

Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid

Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification

Isoproterenol: Monoamine Oxidase Inhibitors may increase therapeutic effects of Isoproterenol. Risk C: Monitor

Lasmiditan: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Levodopa-Foslevodopa: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Of particular concern is the development of hypertensive reactions when levodopa is used with nonselective MAOI. Risk X: Avoid

Levomethadone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Levonordefrin: Monoamine Oxidase Inhibitors may increase hypertensive effects of Levonordefrin. Management: Avoid the use of levonordefrin during or within 2 weeks of treatment with a monoamine oxidase inhibitor whenever possible. If levonordefrin cannot be avoided during this period, monitor closely for enhanced or prolonged increases in blood pressure. Risk D: Consider Therapy Modification

Linezolid: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

Lithium: Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Lithium. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes). Risk D: Consider Therapy Modification

Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Maprotiline: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Meperidine: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

Meptazinol: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Meptazinol. Risk X: Avoid

Mequitazine: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Mequitazine. Risk X: Avoid

Metaraminol: Monoamine Oxidase Inhibitors may increase hypertensive effects of Metaraminol. Risk C: Monitor

Metaxalone: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor

Methadone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

Methotrimeprazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methotrimeprazine. Specifically, monoamine oxidase inhibitors may enhance dopamine blockade, possible increasing the risk for neuroleptic malignant syndrome. Methotrimeprazine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

Methyldopa: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methyldopa. Risk X: Avoid

Methylene Blue: Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid

Methylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Methylphenidate. Risk X: Avoid

Metoclopramide: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Mianserin: Monoamine Oxidase Inhibitors may increase neurotoxic effects of Mianserin. Risk X: Avoid

Mivacurium: Phenelzine may increase serum concentration of Mivacurium. Risk C: Monitor

Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Monoamine Oxidase Inhibitors (Antidepressant): May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Monoamine Oxidase Inhibitors (Antidepressant) may increase hypertensive effects of Monoamine Oxidase Inhibitors (Antidepressant). Risk X: Avoid

Monoamine Oxidase Inhibitors (Type B): Monoamine Oxidase Inhibitors (Antidepressant) may increase hypertensive effects of Monoamine Oxidase Inhibitors (Type B). Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid

Morphine (Systemic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Morphine (Systemic). Risk X: Avoid

Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nalbuphine: Monoamine Oxidase Inhibitors may increase CNS depressant effects of Nalbuphine. Nalbuphine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Nalbuphine may increase hypertensive effects of Monoamine Oxidase Inhibitors. Management: Use of nalbuphine is not recommended in patients taking MAOIs, or within 14 days of stopping MAOI therapy. If urgent nalbuphine use is needed, use test doses and frequent titration while monitoring blood pressure, CNS depression, and serotonergic toxicity Risk D: Consider Therapy Modification

Nefazodone: Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid

Nefopam: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Nefopam. Risk X: Avoid

Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor

Norepinephrine: Monoamine Oxidase Inhibitors may increase hypertensive effects of Norepinephrine. Risk C: Monitor

Normethadone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Normethadone. Risk X: Avoid

Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification

OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Ondansetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Opicapone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Opioid Agonists: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Opipramol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

Opium: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Opium. Risk X: Avoid

Oxitriptan: Serotonergic Agents (High Risk) may increase serotonergic effects of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

OxyCODONE: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome. Risk D: Consider Therapy Modification

OxyMORphone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Ozanimod: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pheniramine: May increase anticholinergic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Pholcodine: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor

Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid

Pizotifen: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Pizotifen. Risk X: Avoid

Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor

Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Psilocybin: Antidepressants may decrease therapeutic effects of Psilocybin. Risk C: Monitor

QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Ramosetron: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Reboxetine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Reboxetine. Risk X: Avoid

Remifentanil: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and titrate small doses of remifentanil frequently. Risk D: Consider Therapy Modification

Reserpine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Monitor closely for paradoxical effects of reserpine (eg, excitation, hypertension). Risk D: Consider Therapy Modification

RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor

Selective Serotonin Reuptake Inhibitor: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

Serotonergic Non-Opioid CNS Depressants: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid

Serotonin 5-HT1D Receptor Agonists (Triptans): May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase serum concentration of Serotonin 5-HT1D Receptor Agonists (Triptans). Risk X: Avoid

Serotonin/Norepinephrine Reuptake Inhibitor: Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid

Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor

Sevoflurane: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Sevoflurane. Specifically, the risk of hemodynamic instability may be increased. Risk C: Monitor

Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor

Solriamfetol: Monoamine Oxidase Inhibitors may increase hypertensive effects of Solriamfetol. Risk X: Avoid

St John's Wort: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Succinylcholine: Phenelzine may increase neuromuscular-blocking effects of Succinylcholine. Management: Consider a lower initial succinylcholine dose in patients taking phenelzine, or those who have taken phenelzine within the previous 2 weeks. Monitor for increased succinylcholine effects (eg, prolonged apnea) in patients who recently received phenelzine. Risk D: Consider Therapy Modification

SUFentanil: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. Risk X: Avoid

Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor

Syrian Rue: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

Tapentadol: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid

Tetrabenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor

Tianeptine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Tilidine: May increase serotonergic effects of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor

TraMADol: Monoamine Oxidase Inhibitors (Antidepressant) may increase adverse/toxic effects of TraMADol. Specifically, the risk for serotonin syndrome/serotonin toxicity and seizures may be increased.. Risk X: Avoid

Tricyclic Antidepressants: Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid

Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor

Tryptophan: Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Tryptophan. This could result in serotonin syndrome. Risk X: Avoid

Tyrosine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Valbenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Viloxazine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid

Ziprasidone: Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Ziprasidone. This could result in serotonin syndrome. Risk X: Avoid

Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor

Food Interactions

Concurrent ingestion of foods and beverages rich in tyramine, dopamine, tyrosine, phenylalanine, tryptophan, or caffeine may cause sudden and severe high blood pressure (hypertensive crisis). Management: Avoid high protein food that has undergone protein breakdown by aging, fermentation, pickling, smoking, or bacterial contamination, meat extract, cheeses (especially aged varieties), yogurt, pickled herring, liver, yeast extract (including brewer’s yeast in large quantities), dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna), fava or broad bean pods, sauerkraut, and excessive amount or caffeine and/or chocolate. Avoid beverages containing tyramine (eg, beer, wine). Food’s freshness is also an important concern; avoid any spoiled or improperly refrigerated, handled, or stored protein rich foods (eg, meat, fish and dairy products [including foods that have undergone smoking to improve flavor]). Continue to avoid these foods and beverages for 2 weeks after discontinuing phenelzine.

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Information related to the use of phenelzine in pregnancy is limited (Frayne 2014; Gracious 1997; Pavy 1995).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Breastfeeding Considerations

It is not known if phenelzine is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.

Dietary Considerations

Avoid tyramine-containing foods/beverages during therapy and for 2 weeks after discontinuing phenelzine. Examples include cheeses (especially aged varieties); yogurt; high protein food that has undergone protein breakdown by aging, fermentation, pickling, smoking, or bacterial contamination; meat extract; pickled herring; liver; yeast extract; dry sausage (Genoa salami, hard salami, pepperoni, Lebanon bologna); fava or broad bean pods; beer, wine; sauerkraut; excessive amount or caffeine and/or chocolate. Avoid any spoiled or improperly refrigerated, handled, or stored protein rich foods (eg, meat, fish and dairy products [including foods that have undergone smoking to improve flavor]).

Monitoring Parameters

Blood glucose; renal and hepatic function; blood pressure, heart rate; mental status; worsening of depression, suicidality, or unusual changes in behavior (especially at the beginning of therapy or when doses are increased or decreased)

Mechanism of Action

Thought to act by increasing endogenous concentrations of norepinephrine, dopamine, and serotonin through inhibition of the enzyme (monoamine oxidase) responsible for the breakdown of these neurotransmitters (Wimbiscus 2010).

Pharmacokinetics (Adult Data Unless Noted)

Onset of action:

Anxiety disorders (social anxiety disorder): Initial effects may be observed within 2 weeks of treatment, with continued improvements through 4 to 6 weeks (WFSBP [Bandelow 2023]).

Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009).

Duration: May continue to have a therapeutic effect and interactions 2 weeks after discontinuing therapy (Feinberg 1981)

Absorption: Well absorbed

Metabolism: Oxidized via monoamine oxidase (primary pathway) and acetylation (minor pathway)

Time to peak: 43 minutes

Half-life elimination: 11.6 hours

Excretion: Urine (73% as metabolites)

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Nardil;
(AU) Australia: Nardil | Phenelzine sulfate usp;
(FR) France: Nardil;
(IE) Ireland: Nardil;
(IL) Israel: Nardelzine;
(IT) Italy: Margyl;
(NL) Netherlands: Nardil;
(NO) Norway: Phenelzine sulfate greenstone | Phenelzine sulfate lupin;
(NZ) New Zealand: Nardil;
(PL) Poland: Nardil;
(PR) Puerto Rico: Nardil

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Zyvox (liezolid) [prescribing information]. New York, New York: Pharmacia & Upjohn Co; July 2015.

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Phenelzine: Drug information