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Isocarboxazid: Drug information

Isocarboxazid: Drug information
(For additional information see "Isocarboxazid: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Suicidality and antidepressant drugs:

Antidepressants increased the risk, compared with placebo, of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of isocarboxazid 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 associated with increases in the risk of suicide. Closely monitor and observe 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 their health care provider. Isocarboxazid is not approved for use in pediatric patients.

Pooled analyses of short-term (4- to 16-weeks), placebo-controlled trials of 9 antidepressant drugs (selective serotonin reuptake inhibitors [SSRIs] and others) in children and adolescents with MDD, obsessive-compulsive disorder (OCD), or other psychiatric disorders (a total of 24 trials involving more than 4,400 patients) have revealed a greater risk of adverse reactions representing suicidal thinking or behavior (suicidality) during the first few months of treatment in those receiving antidepressants. The average risk of such reactions in patients receiving antidepressants was 4%, twice the placebo risk of 2%. No suicides occurred in these trials.

Brand Names: US
  • Marplan
Pharmacologic Category
  • Antidepressant, Monoamine Oxidase Inhibitor
Dosing: Adult
Major depressive disorder

Major depressive disorder (unipolar) (alternative agent): Oral: Initial: 10 mg twice daily; may increase daily dose based on response and tolerability in increments of 10 mg every 2 to 4 days up to 40 mg/day by the end of the first week (divided into 2 to 4 doses per day). After first week, may increase by up to 20 mg/week to a maximum of 60 mg/day. May take 3 to 6 weeks to see effects. If no response obtained within 6 weeks, additional titration is unlikely to be beneficial. Note: Use caution with doses >40 mg/day; experience is limited.

Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower taper (eg, over 4 weeks) include history of antidepressant withdrawal symptoms or high doses of antidepressants (APA 2010; Hirsch 2020). 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 (Haddad 2001; Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching to or from isocarboxazid, 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 isocarboxazid.

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

Allow at least 7 to 14 days to elapse between discontinuing isocarboxazid 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

Use is contraindicated in severe impairment. Use with caution in mild-to-moderate impairment to avoid accumulation.

Dosing: Hepatic Impairment: Adult

Use is contraindicated in patients with a history of liver disease or abnormal liver function tests.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

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

>10%: Nervous system: Dizziness (29%), headache (15%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (4%), palpitations (2%), syncope (2%)

Dermatologic: Diaphoresis (2%)

Gastrointestinal: Constipation (7%), diarrhea (2%), nausea (6%), xerostomia (9%)

Genitourinary: Erectile dysfunction (2%), urinary frequency (2%), urinary hesitancy (1%)

Nervous system: Anxiety (2%), chills (2%), drowsiness (4%), feeling of heaviness (2%), forgetfulness (2%), hyperactive behavior (2%), lethargy (2%), myoclonus (2%), paresthesia (2%), sedated state (2%), sleep disturbance (5%), tremor (4%)

Frequency not defined:

Cardiovascular: Hypotension

Hepatic: Abnormal liver function, jaundice

Nervous system: Decreased seizure threshold, suicidal ideation, suicidal tendencies

Postmarketing:

Dermatologic: Skin photosensitivity, spider telangiectasia

Endocrine & metabolic: SIADH

Gastrointestinal: Melanoglossia

Genitourinary: Dysuria, sexual disorder, urinary incontinence, urinary retention

Hematologic & oncologic: Hematologic abnormality

Nervous system: Akathisia, ataxia, coma, euphoria, hallucination, neuritis

Contraindications

Hypersensitivity to isocarboxazid or any component of the formulation; cardiovascular disease (including hypertension); cerebrovascular defect (suspected or confirmed); history of headache; history of hepatic disease or abnormal liver function tests; pheochromocytoma; severe renal impairment

Concurrent use of antihistamines, antihypertensives, bupropion, buspirone, caffeine (excessive use), CNS depressants (including ethanol and opioids), dextromethorphan, diuretics, general anesthesia used during elective surgery (discontinue isocarboxazid ≥10 days prior to elective surgery), local vasoconstrictors, meperidine, MAO inhibitors or dibenzazepine derivatives (eg, amitriptyline, clomipramine, desipramine, imipramine, nortriptyline, protriptyline, doxepin, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, trimipramine), SSRIs or SNRIs, spinal anesthesia (hypotension may be exaggerated), sympathomimetics (including amphetamines, cocaine, phenylephrine, pseudoephedrine) or related compounds (methyldopa, reserpine, levodopa, tryptophan), or foods high in tyramine content

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 MAO inhibitor discontinuation and bupropion initiation.

Buspirone: At least 10 days should elapse between isocarboxazid discontinuation and buspirone initiation.

MAO inhibitors or dibenzazepine derivatives: At least 1 week should elapse between the use of another MAO inhibitor or dibenzazepine derivative and isocarboxazid use.

Meperidine: At least 2-3 weeks should elapse between MAO inhibitor discontinuation and meperidine use.

SSRIs or SNRIs: At least 2 weeks should elapse between the discontinuation of sertraline or paroxetine and the initiation of isocarboxazid. At least 5 weeks should elapse between the discontinuation of fluoxetine and the initiation of isocarboxazid. At least 5 days to 1 week should elapse between discontinuation of a SNRI (timeframe dependent on specific SNRI) and the initiation of isocarboxazid. At least 2 weeks should elapse between the discontinuation of isocarboxazid and the initiation of SSRIs or SNRIs.

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 to 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 health care provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Isocarboxazid is FDA approved for the treatment of depression in children ≥16 years of age.

- The possibility of a suicide attempt is inherent in patients with 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:

• Hypertensive crisis: Cases of hypertensive crisis (sometimes fatal) have occurred; symptoms include severe headache, nausea/vomiting, neck stiffness/soreness, photophobia, and sweating. Monitor blood pressure closely in all patients. May occur with foods/supplements high in tyramine, tryptophan, phenylalanine, or tyrosine content; treatment with phentolamine is recommended for hypertensive crisis.

• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect 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).

Disease-related concerns:

• Angina: Monoamine oxidase inhibitors (MAOIs) may mask anginal pain.

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

• Substance use disorder: Use with caution in patients with a history of substance use disorder; potential for drug dependency exists, especially in patients using excessive doses.

• Hepatic impairment: Use is contraindicated in patients with a history of liver disease or abnormal LFTs. Decreased hepatic function may result in decreased clearance and increased half-life and plasma concentrations. Consider switching to a different antidepressant class due to side effect profile, risk of worsening hepatotoxicity and apparent pharmacokinetic changes in chronic liver disease (Mullish 2014).

• 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. Isocarboxazid is not FDA approved for the treatment of bipolar depression.

• Renal impairment: Use with caution in patients with renal impairment; contraindicated in patients with severe impairment.

• Seizure disorder: Use with caution in patients at risk of 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:

• Anxiety and agitation: May aggravate coexisting symptoms in depression, such as anxiety and agitation.

• Surgical patients: According to the manufacturer isocarboxazid use within 10 days prior 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:

• 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, 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).

• Electroconvulsive therapy: May increase the risks associated with electroconvulsive therapy; consider discontinuing, when possible, prior to ECT treatment.

• Myelography: Discontinue at least 48 hours prior to myelography; do not resume for at least 24 hours postprocedure.

Dosage Forms: US

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

Tablet, Oral:

Marplan: 10 mg [scored]

Generic Equivalent Available: US

No

Pricing: US

Tablets (Marplan Oral)

10 mg (per each): $5.68

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.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/011961s045lbl.pdf#page=16, must be dispensed with this medication.

Use: Labeled Indications

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

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Agents with Blood Glucose Lowering Effects: Monoamine Oxidase Inhibitors may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Alosetron: May enhance the serotonergic effect 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 therapy

Alpha-/Beta-Agonists (Indirect-Acting): Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 combination

Alpha1-Agonists: Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 combination

Altretamine: May enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Antidepressant). Risk C: Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect 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): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

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

Amphetamines: Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 combination

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect 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 therapy

Apraclonidine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Apraclonidine. Monoamine Oxidase Inhibitors may increase the serum concentration of Apraclonidine. Risk X: Avoid combination

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

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

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

Atomoxetine: Monoamine Oxidase Inhibitors may enhance the neurotoxic (central) effect of Atomoxetine. Risk X: Avoid combination

Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Atropine (Ophthalmic). Risk X: Avoid combination

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Benzhydrocodone: May enhance the serotonergic effect 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 enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

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

Bezafibrate: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Risk X: Avoid combination

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

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: Isocarboxazid may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

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

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

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

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Buprenorphine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

BuPROPion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of BuPROPion. Risk X: Avoid combination

BusPIRone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Butorphanol: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CarBAMazepine: May enhance the adverse/toxic effect 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 combination

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

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

Cerebrolysin: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

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

Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

Clemastine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Clemastine. Risk C: Monitor therapy

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

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

Cocaine (Topical): May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

Codeine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Codeine. Risk X: Avoid combination

COMT Inhibitors: May enhance the adverse/toxic effect 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 enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Cyproheptadine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Cyproheptadine. Cyproheptadine may diminish the serotonergic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Dapoxetine: May enhance the serotonergic effect 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 combination

Deutetrabenazine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Deutetrabenazine. Risk X: Avoid combination

Dexmethylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Dexmethylphenidate. Risk X: Avoid combination

Dextromethorphan: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid combination

Diamorphine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Diamorphine. Risk X: Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Diethylpropion: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Diethylpropion. Risk X: Avoid combination

Dihydrocodeine: May enhance the adverse/toxic effect 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 enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Domperidone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Domperidone. Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Domperidone. Domperidone may diminish the therapeutic effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

DOPamine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect 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 enhance the hypertensive effect of Doxapram. Risk C: Monitor therapy

Doxylamine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Doxylamine. Risk X: Avoid combination

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

Droxidopa: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Droxidopa. Risk X: Avoid combination

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

EPINEPHrine (Nasal): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Nasal). Risk C: Monitor therapy

EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Oral Inhalation). Risk X: Avoid combination

Epinephrine (Racemic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Epinephrine (Racemic). Risk C: Monitor therapy

EPINEPHrine (Systemic): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of EPINEPHrine (Systemic). Risk C: Monitor therapy

Ergot Derivatives: May enhance the serotonergic effect 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 therapy

Esketamine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk C: Monitor therapy

Fenfluramine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

FentaNYL: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

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

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

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Gepirone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Guanethidine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

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

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

HYDROcodone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROcodone. HYDROcodone may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. 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 enhance the adverse/toxic effect 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 enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

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

Indoramin: Monoamine Oxidase Inhibitors may enhance the hypotensive effect of Indoramin. Risk X: Avoid combination

Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may diminish the therapeutic effect 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 combination

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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 enhance the adverse/toxic effect 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

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Isometheptene: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Isometheptene. Risk X: Avoid combination

Isoproterenol: Monoamine Oxidase Inhibitors may enhance the therapeutic effect of Isoproterenol. Risk C: Monitor therapy

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Lasmiditan: May enhance the serotonergic effect 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 therapy

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

Levomethadone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Levonordefrin: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Levonordefrin. Risk X: Avoid combination

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Linezolid: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Lithium: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect 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

Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect 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 therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

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

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

Maprotiline: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Meperidine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Meptazinol: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Meptazinol. Risk X: Avoid combination

Mequitazine: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Mequitazine. Risk X: Avoid combination

Metaraminol: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Metaraminol. Risk C: Monitor therapy

Metaxalone: May enhance the serotonergic effect 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 therapy

Methadone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

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

Methyldopa: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Methyldopa. Risk X: Avoid combination

Methylene Blue: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination

Methylphenidate: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Methylphenidate. Risk X: Avoid combination

Metoclopramide: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Mianserin: Monoamine Oxidase Inhibitors may enhance the neurotoxic effect of Mianserin. Risk X: Avoid combination

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Mivacurium: Monoamine Oxidase Inhibitors may increase the serum concentration of Mivacurium. Risk C: Monitor therapy

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

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Monoamine Oxidase Inhibitors (Antidepressant): May enhance the hypertensive effect of other Monoamine Oxidase Inhibitors (Antidepressant). Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of other Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

Monoamine Oxidase Inhibitors (Type B): Monoamine Oxidase Inhibitors (Antidepressant) may enhance the hypertensive effect of Monoamine Oxidase Inhibitors (Type B). Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination

Morphine (Systemic): Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Morphine (Systemic). Risk X: Avoid combination

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nalbuphine: Monoamine Oxidase Inhibitors may enhance the CNS depressant effect of Nalbuphine. Nalbuphine may enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Nalbuphine may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. 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 enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination

Nefopam: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Nefopam. Risk X: Avoid combination

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Norepinephrine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Norepinephrine. Risk C: Monitor therapy

Normethadone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Normethadone. Risk X: Avoid combination

Obinutuzumab: May enhance the hypotensive effect 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 enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Ondansetron: May enhance the serotonergic effect 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 therapy

Opicapone: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy

Opioid Agonists: May enhance the serotonergic effect 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 therapy

Opium: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Opium. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect 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 therapy

OxyCODONE: May enhance the serotonergic effect 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 enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Ozanimod: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

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

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

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

Pheniramine: May enhance the anticholinergic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Pholcodine: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

Pizotifen: Monoamine Oxidase Inhibitors may enhance the anticholinergic effect of Pizotifen. Risk X: Avoid combination

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

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination

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

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

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

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

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Ramosetron: May enhance the serotonergic effect 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 therapy

Reboxetine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reboxetine. Risk X: Avoid combination

Remifentanil: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Remifentanil may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. 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 enhance the adverse/toxic effect 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

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

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

Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Antidepressant). This could result in serotonin syndrome. Risk X: Avoid combination

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

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

Serotonin/Norepinephrine Reuptake Inhibitors: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

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

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

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect 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 therapy

Solriamfetol: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Solriamfetol. Risk X: Avoid combination

St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the 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 therapy

SUFentanil: May enhance the adverse/toxic effect 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 combination

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

Syrian Rue: May enhance the serotonergic effect 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 therapy

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

Tetrabenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Tetrahydrozoline (Nasal): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Tetrahydrozoline (Nasal). Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

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

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

Tianeptine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

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

Tricyclic Antidepressants: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination

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

Tryptophan: Monoamine Oxidase Inhibitors (Antidepressant) may enhance the serotonergic effect of Tryptophan. This could result in serotonin syndrome. Risk X: Avoid combination

Tyrosine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Valbenazine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Viloxazine: May enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination

Ziprasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Ziprasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy

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

Food Interactions

Concurrent ingestion of foods rich in tyramine, dopamine, tyrosine, phenylalanine, tryptophan, or caffeine may cause sudden and severe high blood pressure (hypertensive crisis or serotonin syndrome). Management: Avoid tyramine-containing foods (aged or matured cheese, air-dried or cured meats including sausages and salamis; fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce, and other soybean condiments). Food's freshness is also an important concern; improperly stored or spoiled food can create an environment in which tyramine concentrations may increase (Walker 1996). Avoid foods containing dopamine, tyrosine, phenylalanine, tryptophan, or caffeine.

Pregnancy Considerations

Animal reproduction studies have not been conducted.

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 isocarboxazid is present in breast milk. The manufacturer recommends using in women who are nursing only if clearly needed.

Dietary Considerations

Avoid tyramine-containing foods/beverages. Some examples include aged or matured cheese, air-dried or cured meats (including sausages and salamis), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce and other soybean condiments. Food's freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase (Walker 1996).

Monitoring Parameters

Renal function (baseline, periodic); liver function (baseline, periodic); blood pressure, heart rate; mood, suicidal ideation (especially at the beginning of therapy or when doses are increased or decreased)

Mechanism of Action

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

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: 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).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (BE) Belgium: Marplan;
  • (CL) Chile: Marplan;
  • (DK) Denmark: Marplan;
  • (GB) United Kingdom: Marplan;
  • (IE) Ireland: Marplan;
  • (TR) Turkey: Marplan;
  • (UY) Uruguay: Marplan
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  2. Bauer M, Severus E, Köhler S, Whybrow PC, Angst J, Möller HJ; WFSBP Task Force on Treatment Guidelines for Unipolar Depressive Disorders. World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for biological treatment of unipolar depressive disorders. Part 2: maintenance treatment of major depressive disorder-update 2015. World J Biol Psychiatry. 2015;16(2):76-95. doi:10.3109/15622975.2014.1001786 [PubMed 25677972]
  3. Grunze H, Vieta E, Goodwin GM, et al; Members of the WFSBP Task Force on Bipolar Affective Disorders working on this topic. The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of bipolar disorders: Acute and long-term treatment of mixed states in bipolar disorder. World J Biol Psychiatry. 2018;19(1):2-58. doi:10.1080/15622975.2017.1384850 [PubMed 29098925]
  4. Haddad PM. Antidepressant discontinuation syndromes. Drug Saf. 2001;24(3):183-197. doi:10.2165/00002018-200124030-00003 [PubMed 11347722]
  5. Hirsch M, Birnbaum RJ. Discontinuing antidepressant medications in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 18, 2020.
  6. Huyse FJ, Touw DJ, van Schijndel RS, et al, “Psychotropic Drugs and the Perioperative Period: A Proposal for a Guideline in Elective Surgery,” Psychosomatics, 2006, 47(1):8-22. [PubMed 16384803]
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  8. Marplan tablets (isocarboxazid) [prescribing information]. Parsippany, NJ; Validus Pharmaceuticals LLC; November 2020.
  9. Mullish BH, Kabir MS, Thursz MR, Dhar A. Review article: depression and the use of antidepressants in patients with chronic liver disease or liver transplantation. Aliment Pharmacol Ther. 2014;40(8):880-892. doi:10.1111/apt.12925 [PubMed 25175904]
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  13. Shelton RC. Steps following attainment of remission: discontinuation of antidepressant therapy. Prim Care Companion J Clin Psychiatry. 2001;3(4):168-174. [PubMed 15014601]
  14. Szegedi A, Jansen WT, van Willigenburg AP, van der Meulen E, Stassen HH, Thase ME. Early improvement in the first 2 weeks as a predictor of treatment outcome in patients with major depressive disorder: a meta-analysis including 6562 patients. J Clin Psychiatry. 2009;70(3):344-353. doi:10.4088/jcp.07m03780 [PubMed 19254516]
  15. Walker SE, Shulman KI, Tailor S, Gardner D. Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. J Clin Psychopharmacol. 1996;16(5):383-388. [PubMed 8889911]
  16. Yatham LN, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder. Bipolar Disord. 2018;20(2):97-170. doi: 10.1111/bdi.12609. [PubMed 29536616]
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