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  • CLASSES

    MAOI Antidepressants

    BOXED WARNING

    Children, suicidal ideation

    The safety and effectiveness of phenelzine have not been established in pediatric patients less than 18 years of age. A boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of phenelzine may be necessary in patients with emerging suicidality or worsening depression.

    DEA CLASS

    Rx

    DESCRIPTION

    Non-selective monoamine oxidase A and B inhibitor (MAOI) antidepressant
    FDA-approved for the treatment of major depressive disorder (MDD); used off-label as a second- or third-line agent for anxiety disorders such as panic disorder and social anxiety disorder
    Primarily used for treatment-resistant cases of depression and anxiety disorders, due to dietary restrictions, adverse effect profile, and the potential for serious drug-drug interactions and drug-food interactions

    COMMON BRAND NAMES

    Nardil

    HOW SUPPLIED

    Nardil/Phenelzine/Phenelzine Sulfate Oral Tab: 15mg

    DOSAGE & INDICATIONS

    For use in treatment-resistant depression, including atypical depression.
    Oral dosage
    Adults

    Initially, 15 mg PO 3 times daily; may rapidly increase to 60 mg/day according to patient tolerance. The dosage should be individualized based on careful observation of the patient. In some cases, it may be necessary to increase dosage up to 90 mg/day to obtain a sufficient response. Onset of maximum therapeutic effect is between 2 and 6 weeks. After the maximum benefit is achieved, the dosage should be reduced slowly over several weeks to the lowest dose that maintains effectiveness, to limit cumulative MAOI effects and serious dose-related toxicity. The maintenance dose may be as low as 15 mg/day PO or 15 mg PO every other day, continued as long as required. If prescribed for extended periods, the patient should be periodically re-evaluated for drug effectiveness and safety. NOTE: In patients requiring a contraindicated drug known to interact with MAOIs, phenelzine should be discontinued for at least 2 weeks before initiating the interacting drug.

    For the treatment of panic disorder†.
    Oral dosage
    Adults

    15 mg PO once daily at bedtime initially, then titrated up to 15 mg PO 3 times daily over a 1 week period, as tolerated. According to the American Psychiatric Association (APA) treatment guidelines, monoamine oxidase inhibitors (MAOIs) appear effective for panic disorder, but because of their safety profile, they are generally reserved for patients who have failed to respond to several first-line treatments [e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), cognitive-behavioral therapy (CBT)]. NOTE: In patients requiring a contraindicated drug known to interact with MAOIs, phenelzine should be discontinued for at least 2 weeks before initiating the interacting drug. In one double-blind study assessing phenelzine with an active comparator (imipramine) and placebo in adults between the ages of 18 and 65 years with panic disorder, patients receiving phenelzine (n = 29) were initiated on 15 mg PO daily at bedtime for 3 days, followed by 15 mg PO twice daily through day 6, and 15 mg PO 3 times per day from day 7 through the end of the 12-week study period. Patients receiving phenelzine (15 mg 3 times per day) and imipramine (50 mg 3 times per day) achieved a significantly lower severity of illness, avoidance behavior, and social and work disability than patients in the placebo group by week 6; further improvements were noted by week 12. Patient and investigator rated scales were used to evaluate response to therapy, and all patients attended supportive group counseling. Specifically, the improvement over baseline scores was significantly different in both active treatment groups on all but 1 outcome variable by the 6th week of treatment (i.e., Wolpe Lang scale for imipramine and phenelzine) and on all but 1 outcome variable by the 12th week (i.e., Wolpe Lang scale for imipramine). Patients receiving phenelzine achieved significantly better scores than patients receiving imipramine on the Work and Social Disability Scale and Symptom Severity and Phobic Avoidance Scale at 12 weeks. Thirteen of the 87 initial enrollees discontinued treatment due to side effects; however, there was no differential dropout rate due to treatment assignment. 

    For the treatment of social phobia (social anxiety disorder)†.
    Oral dosage
    Adults

    Clinical trials have used 15 mg PO once daily; may increase to 60 mg/day over 2 weeks according to patient tolerance. The dosage should be individualized based on careful observation of the patient. The mean phenelzine dose is approximately 30 mg PO twice per day. In some cases, it may be necessary to increase dosage up to 90 mg/day to obtain a sufficient response. NOTE: In patients requiring a contraindicated drug known to interact with MAOIs, phenelzine should be discontinued for at least 2 weeks before initiating the interacting drug. The mean phenelzine dose is approximately 30 mg PO twice per day. According to the National Institute for Health and Care Excellence (NICE) treatment guidelines, phenelzine should be reserved for patients who are partial responders, non-responders, are intolerant to, or have declined treatment with SSRIs, SNRIs, individual cognitive behavioral therapy, or a combination of these therapies. In one controlled trial, phenelzine was compared to cognitive behavioral group therapy (CBGT) alone, CBGT plus phenelzine, or placebo for 24 weeks. In subjects randomized to phenelzine (n = 35) or CBGT plus phenelzine (n = 32), treatment was initiated at 15 mg/day PO for 3 days, then 30 mg/day for 4 days, 45 mg/day during the second week, and 60 mg/day during weeks 3 and 4. Thereafter, depending on efficacy and tolerability, the dose could be titrated up to a maximum of 90 mg/day. The mean daily dose was 65.9 mg/day in the phenelzine group and 62 mg/day in the combination group. Study results showed superiority of combined treatment over medication alone, CBGT alone, and placebo in the acute treatment of SAD. In addition, phenelzine monotherapy but not CBGT monotherapy was superior to placebo. Discontinuation rates exceeded one-third of patients assigned to phenelzine or CBGT alone; however, the rates were not significantly different across groups. Adverse events included insomnia, lightheadedness, dry mouth, weight gain, constipation, anorgasmia, and nervousness. In a separate study with a 12-week acute phase and 6-month maintenance and treatment-free phases, phenelzine was compared to CBGT, placebo, and a placebo equivalent to CBGT. Treatment with either phenelzine or CBGT resulted in a marked positive response (75% of patients) compared to the placebo groups. Phenelzine was initiated at 15 mg/day PO, increased to 30 mg/day on day 4, 45 mg/day on day 8, and 60 mg/day (30 mg twice per day) on day 15. Thereafter, depending on efficacy and tolerability, the dose could be titrated up to 90 mg/day. The mean phenelzine dose was 60 mg/day. Responders to either phenelzine or CBGT were enrolled in a 6-month maintenance phase followed by a 6-month treatment-free phase. Relapse during the maintenance phase did not differ between treatments in patients with non-generalized social phobia. However, there was a 50% relapse rate in phenelzine-treated patients with generalized social phobia versus no relapses among patients with generalized social phobia in the CBGT group. Patients treated with phenelzine showed a trend toward greater relapse during the treatment-free phase.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    90 mg/day PO.

    Geriatric

    90 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Contraindicated in patients with abnormal liver function tests, hepatic impairment, or a history of liver disease.

    Renal Impairment

    Phenelzine is contraindicated in patients with severe renal impairment. In patients with mild to moderate renal impairment, phenelzine should be used with caution due to the potential for accumulation of the drug.
     
    Intermittent hemodialysis
    It is not known whether phenelzine is removed by hemodialysis.

    ADMINISTRATION

     
    NOTE: Phenelzine can cause serious side effects; it should be reserved for patients who are refractory to other antidepressants. Potential food and drug interactions should be identified to prevent serious cardiovascular or neurological sequelae.

    Oral Administration

    Food and drug interactions with phenelzine can be serious (see Drug Interactions). Consider patient's intake of foods/beverages containing large amounts of tyramine, tryptophan, and/or caffeine.
    A Med Guide is available that provides information about the risks of antidepressant use in pediatric patients.

    STORAGE

    Nardil:
    - Store at room temperature (between 59 to 86 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Phenelzine is contraindicated in patients with known hypersensitivity to phenelzine or any of its inactive ingredients.

    Alcoholism, coadministration with other CNS depressants, ethanol ingestion, MAOI therapy

    Phenelzine is contraindicated in patients receiving other monoamine oxidase inhibitor therapy (MAOI therapy) or other drugs that possess MAOI-like activity. Do not use phenelzine with or in rapid succession to other MAOIs because severe hypertensive situations and convulsive events, fever, marked sweating, excitation, delirium, tremor, coma, and circulatory collapse may occur. Phenelzine is contraindicated when the patient is taking certain medications known to interact with MAO inhibitors; many other medications should not be used with phenelzine and drug-drug interactions should be thoroughly reviewed. Certain medications increase the risk for hypertensive emergencies, behavioral or neurological syndromes, convulsions and/or serotonin syndrome. Coadministration with other CNS depressants, including alcohol and certain narcotics, and dextromethorphan should be avoided. At least 14 days should elapse between the discontinuation of phenelzine and the start of another antidepressant, meperidine, buspirone, bupropion, or other medications that may cause serious reactions. At least 14 days should elapse between the discontinuation of phenelzine and the start of a serotonergic agent or vice-versa, with the exception of fluoxetine. Allow at least 5 weeks between discontinuation of fluoxetine and initiation of phenelzine and at least 14 days between discontinuation of phenelzine and initiation of fluoxetine or other serotonergic agents. A sufficient amount of time must be allowed for clearance of the serotonergic agent and its active metabolites. Phenelzine is also contraindicated in combination with certain foods or beverages known to interact with MAOIs; dietary restrictions apply. Phenelzine should not be used in patients with active alcoholism and ethanol ingestion should be avoided. Alcoholic beverages, such as beer (including reduced-alcohol and alcohol-free beer), wine (red and white varieties), sherry, hard liquor, or liqueurs that contain tyramine can precipitate hypertensive reactions if consumed by patients during MAOI therapy. Sudden and severe hypertensive episodes can also occur if foods containing high-pressor amines (e.g., tyramine or tryptophan) are consumed during therapy with phenelzine. Foods to avoid include: aged cheese; yeast extract; protein extract; soy sauce; fava bean or broad bean pods; smoked meats; pickled meats; chicken livers, smoked poultry; pickled poultry; smoked fish (lox, smoked salmon); pickled fish (pickled herring); fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; bananas; avocados; and any over-ripe fruit. Excessive amounts of caffeine and chocolate may also cause hypertensive reactions. Following the discontinuation of phenelzine, dietary restrictions should continue for at least 2 weeks.

    Pheochromocytoma

    Phenelzine is contraindicated in patients with pheochromocytoma, since the associated tumor secretes pressor substances (e.g., norepinephrine) whose metabolism may be inhibited by phenelzine. Impaired metabolism of norepinephrine can increase blood pressure, and potentially cause a hypertensive emergency.

    Hepatic disease, hepatitis

    Phenelzine is contraindicated in patients with a history of hepatic disease (e.g., jaundice, hepatitis) or in patients with abnormal liver function tests. Hepatic coma could occur if a MAO inhibitor is administered to patients with cirrhosis. There is a low incidence of altered hepatic function or jaundice in patients treated with phenelzine. Periodic liver function tests should be performed during phenelzine therapy; phenelzine should be discontinued at the first sign of hepatic dysfunction.

    Anuria, renal disease, renal failure, renal impairment

    Phenelzine is contraindicated in patients with severe renal impairment or renal disease (e.g., renal failure, anuria). In patients with mild to moderate renal impairment, phenelzine should be used with caution because the reduction in renal excretion can increase the cumulative effects of the MAOI.

    Seizure disorder, seizures

    Phenelzine can change the pattern of seizures and should be used with caution in patients with epilepsy or a preexisting seizure disorder. Because phenelzine lowers the convulsive threshold in some animal experiments, suitable precautions should be taken if patients with a seizure disorder are treated. Phenelzine appears to have varying effects in epileptic patients; some have a decrease in frequency of seizures, while others have more seizures.

    Driving or operating machinery

    Phenelzine may result in drowsiness or dizziness and the patient should use caution while driving or operating machinery while taking phenelzine until the effects of the drug are known. Warn patients that hypotension or faintness may occur.

    Asthma, bronchitis

    Phenelzine should be used with caution in asthma or bronchitis because of possible changes in the blockade of sympathetic neurotransmission and marked pressor effects from beta-adrenergic bronchodilators.

    Diabetes mellitus

    Phenelzine should be used with caution in diabetes mellitus; increased insulin sensitivity may occur. Requirements for insulin or oral hypoglycemics may be decreased.

    Hyperthyroidism

    Phenelzine should be used with caution in patients with hyperthyroidism because sensitivity to pressor amines may be further increased.

    Dental work, spinal anesthesia, surgery

    Patients taking phenelzine should not undergo elective surgery requiring general anesthesia. Patients should also inform their dentists of MAOI treatment prior to pursuing dental work. Also, they should not be given cocaine (can block reuptake of monoamines into the adrenergic nerve terminals) or local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine). Combined hypotensive effects can occur with phenelzine and spinal anesthesia. Phenelzine should be discontinued at least 10 days before elective surgery.

    Abrupt discontinuation, substance abuse

    Phenelzine has not been systematically studied in animals or humans for its potential for substance abuse, tolerance, or physical dependence. Drug dependency has occurred in patients using supra-therapeutic doses of phenelzine; some of these patients had a history of substance abuse. Patients should be evaluated for a prior history of drug abuse and those patients should be followed closely to identify potential signs of misuse or abuse (e.g., development of tolerance, increments of dose, drug-seeking behavior). Because a withdrawal syndrome has been observed in some patients after the discontinuation of MAOIs, abrupt discontinuation of long-term treatment is not recommended, dosage should be reduced gradually when appropriate.

    Anxiety, bipolar disorder, mania, psychosis, schizophrenia

    All effective antidepressants can transform depression into mania or hypomania in predisposed individuals. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. If a patient develops manic symptoms, phenelzine should be withheld and appropriate therapy initiated to treat the manic symptoms. Additionally, depression may be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients should be adequately screened for bipolar disorder prior to initiating an antidepressant. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Patients with depression or comorbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed for clinical worsening and suicidality, especially during the initial few months of drug therapy, or at times of dose changes. Phenelzine may aggravate coexisting symptoms in depressive patients, such as anxiety and agitation, especially at the beginning of treatment. Dosage reduction and slow dosage titration may help limit hyperstimulatory effects. Phenelzine should be used cautiously in hyperactive or agitated patients, as well as in patients with schizophrenia or psychosis because it can cause excessive stimulation. Caregivers should be advised to closely observe the patient on a daily basis and to communicate immediately with the prescriber the emergence of agitation, irritability, unusual changes in behavior, or suicidality. It should be noted that phenelzine is not approved for use in treating bipolar depression.

    Children, suicidal ideation

    The safety and effectiveness of phenelzine have not been established in pediatric patients less than 18 years of age. A boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of phenelzine may be necessary in patients with emerging suicidality or worsening depression.

    Acute myocardial infarction, angina, cardiac disease, cerebrovascular disease, head trauma, headache, heart failure, hypertension, hypertensive crisis, hypotension, increased intracranial pressure, intracranial bleeding, orthostatic hypotension, stroke

    Phenelzine is contraindicated in patients with congestive heart failure. In general, phenelzine should not be used in patients with hypertension, cardiac disease, or cerebrovascular disease (e.g., intracranial bleeding, increased intracranial pressure, recent head trauma, stroke) because of the possible adverse effects on blood pressure. Phenelzine should be avoided in patients with a history of headache because it can mask the headache associated with drug-related hypertensive reactions. Headaches during therapy may be the first symptom of a hypertensive reaction to an MAOI. Hypertensive crisis is the most serious side effect of MAOIs, and if palpitations, neck stiffness, chest pains, or headaches occur, phenelzine should be discontinued. Blood pressure should be routinely measured any time a patient receiving phenelzine complains of a headache, palpitations, diaphoresis, dizziness, neck stiffness or chest constriction, nausea, or vomiting. Phenelzine should be used with caution in elderly patients because of the increased possibility of cerebrovascular disease. MAOIs can also suppress chest pain that would otherwise serve as a warning of myocardial ischemia (e.g., angina) or acute myocardial infarction. All patients undergoing treatment with phenelzine should be closely followed for symptoms of postural or orthostatic hypotension. Hypotension has occurred in hypertensive as well as normotensive and hypotensive patients treated with phenelzine. Blood pressure usually returns to pretreatment levels rapidly when the drug is discontinued or the dosage is reduced.

    Radiographic contrast administration

    The use of metrizamide or iohexol (radiographic contrast administration) in patients receiving MAOIs can increase the risk of seizures by lowering the seizure threshold. MAOIs (such as phenelzine) should be discontinued at least 48 hours before myelography and not resumed until 24 hours after the procedure.

    Pregnancy

    The safe use of phenelzine during pregnancy has not been established. Doses of phenelzine in pregnant mice well exceeding the maximum recommended human dose have caused a significant decrease in the number of viable offspring per mouse. In addition, the growth of young dogs and rats has been retarded by doses exceeding the maximum human dose. Because pregnancy outcome data are too limited to be conclusive, phenelzine should be used during pregnancy only when the benefit to the mother clearly outweighs the potential risk to the mother or the fetus. An increased risk of malformations was found in the Collaborative Perinatal Project which monitored 21 mother-child pairs with exposure to a monoamine oxidase inhibitor (MAOI) during the first trimester of pregnancy (phenelzine pairs = 3). Limitations of this data include the small sample size, absence of malformation descriptions, and inclusion of isoniazid as an MAOI agent. Teratogenicity was not observed in two separate cases of in utero exposure to a MAOI, including phenelzine. The effects of phenelzine during labor and obstetric delivery are unknown.

    Breast-feeding

    The safe use of phenelzine during breast-feeding has not been established, and the potential benefit of the drug should be weighed against the possible hazards to the mother and nursing infant. Phenelzine can elevate serum prolactin in some patients and has caused galactorrhea in non-lactating females. Due to the lack of data, generally antidepressant alternatives to phenelzine should be considered. Due to individual variability in response to antidepressants, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. However, because a pooled analysis found that maternal use of sertraline, along with nortriptyline and paroxetine, usually produced undetectable or low drug concentrations in infant serum, these agents may be the preferred antidepressants when initiating antidepressant therapy in a breast-feeding mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Geriatric

    Reported clinical experience with phenelzine in the treatment of depression has not identified differences in response in elderly versus younger adult patients. In general, dose selection for a geriatric patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of antidepressants in residents of long-term care facilities. According to OBRA, the duration of therapy should be in accordance with pertinent literature for the condition being treated, including clinical practice guidelines. All residents being treated for depression with any antidepressant should be monitored closely for worsening of depression and/or suicidal behavior or thinking, especially during initiation of therapy and during dose changes. Antidepressants may cause dizziness, nausea, diarrhea, anxiety, nervousness, insomnia, somnolence, weight gain, anorexia, or increased appetite. Many of these effects can increase the risk for falls. MAOIs should not be administered to those with a confirmed or suspected cerebrovascular defect, confirmed cardiovascular disease or hypertension, or pheochromocytoma. MAOIs are rarely used due to their potential interactions (i.e., hypertensive crisis) with tyramine- or tryptophan-containing foods (e.g., cheese, wine) or other medications, and their profound effect on blood pressure. MAOIs should not be administered together or in rapid succession with other MAOIs, tricyclic antidepressants, bupropion, SSRIs, buspirone, sympathomimetics, meperidine, triptans, and other medications that affect serotonin or norepinephrine. Monitoring should consist of a review for continued need at least quarterly, and documentation of the rationale for continuation. When the drug is being used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the medication as outlined in the OBRA guidelines, unless a taper is clinically contraindicated.

    ADVERSE REACTIONS

    Severe

    coma / Early / 0-1.0
    lupus-like symptoms / Delayed / 0-1.0
    serotonin syndrome / Delayed / 0-1.0
    seizures / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    hypertensive crisis / Early / Incidence not known
    suicidal ideation / Delayed / Incidence not known

    Moderate

    orthostatic hypotension / Delayed / 1.0-10.0
    euphoria / Early / 1.0-10.0
    myoclonia / Delayed / 1.0-10.0
    nystagmus / Delayed / 1.0-10.0
    hyperreflexia / Delayed / 1.0-10.0
    impotence (erectile dysfunction) / Delayed / 1.0-10.0
    urinary retention / Early / 1.0-10.0
    blurred vision / Early / 1.0-10.0
    ataxia / Delayed / 0-1.0
    delirium / Early / 0-1.0
    psychosis / Early / 0-1.0
    leukopenia / Delayed / 0-1.0
    constipation / Delayed / 10.0
    elevated hepatic enzymes / Delayed / 10.0
    ejaculation dysfunction / Delayed / 10.0
    peripheral edema / Delayed / 10.0
    withdrawal / Early / 10.0
    palpitations / Early / Incidence not known
    mania / Early / Incidence not known
    jaundice / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    hypertension / Early / Incidence not known
    depression / Delayed / Incidence not known
    metabolic acidosis / Delayed / Incidence not known
    hypernatremia / Delayed / Incidence not known
    pseudoparkinsonism / Delayed / Incidence not known
    dysarthria / Delayed / Incidence not known

    Mild

    syncope / Early / 1.0-10.0
    paresthesias / Delayed / 1.0-10.0
    insomnia / Early / 1.0-10.0
    pruritus / Rapid / 1.0-10.0
    hyperhidrosis / Delayed / 1.0-10.0
    rash / Early / 1.0-10.0
    orgasm dysfunction / Delayed / 1.0-10.0
    tremor / Early / 1.0-10.0
    headache / Early / 10.0
    drowsiness / Early / 10.0
    dizziness / Early / 10.0
    xerostomia / Early / 10.0
    weight gain / Delayed / 10.0
    weakness / Early / Incidence not known
    fatigue / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    agitation / Early / Incidence not known
    appetite stimulation / Delayed / Incidence not known
    vitamin B6 deficiency / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Acetaminophen; Aspirin, ASA; Caffeine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Acetaminophen; Butalbital: (Major) The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors. This may enhance drowsiness or dizziness. Barbiturates should generally be given at a reduced dose with an MAOI.
    Acetaminophen; Butalbital; Caffeine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive. (Major) The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors. This may enhance drowsiness or dizziness. Barbiturates should generally be given at a reduced dose with an MAOI.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive. (Major) The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors. This may enhance drowsiness or dizziness. Barbiturates should generally be given at a reduced dose with an MAOI.
    Acetaminophen; Caffeine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Acetaminophen; Caffeine; Dihydrocodeine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Acetaminophen; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Acetaminophen; Dextromethorphan: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Acetaminophen; Dextromethorphan; Doxylamine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Acetaminophen; Hydrocodone: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Acetaminophen; Oxycodone: (Major) The use of oxycodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Acetaminophen; Pentazocine: (Major) The use of pentazocine is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like pentazocine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Acetaminophen; Propoxyphene: (Severe) The manufacturers of MAOIs contraindicate the use of MAOIs with some CNS-depressant drugs like propoxyphene due to additive CNS-depressant effects. If combination is necessary, use these drugs cautiously with MAOIs; warn patients to not drive or perform other hazardous activities until they know how a particular drug combination affects them.
    Acetaminophen; Tramadol: (Severe) Tramadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression.
    Alfentanil: (Major) The use of alfentanil is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI), within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Aliskiren; Amlodipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Aliskiren; Valsartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Almotriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with phenelzine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue almotriptan and phenelzine and initiate symptomatic treatment if serotonin syndrome occurs.
    Alogliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including alogliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Alogliptin; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including alogliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Alogliptin; Pioglitazone: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including alogliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Alpha-blockers: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Alpha-glucosidase Inhibitors: (Moderate) Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to certain antidiabetic agents.
    Alprazolam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Altretamine: (Moderate) Concurrent administration of altretamine and monoamine oxidase (MAO) inhibitor antidepressants may cause severe orthostatic hypotension. Four patients, all over 60 years of age, were reported to have experienced symptomatic hypotension after 4 to 7 days of concomitant therapy with altretamine and MAOIs. The mechanism of the interaction is not clear.
    Ambrisentan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives or medications with hypotensive properties such as ambrisentan. Careful monitoring of blood pressure is suggested during concurrent therapy.
    Amide local anesthetics: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Amifampridine: (Major) The concomitant use of amifampridine and drugs that lower seizure threshold may lead to an increased risk of seizures; carefully consider the risks versus benefits of combined use. Monoamine oxidase inhibitors (MAOIs) are associated with a risk for seizures in susceptible patients. Because the effect of MAOIs on the convulsive threshold may be variable, adequate precautions should be taken.
    Amiloride: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Amitriptyline: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Amitriptyline; Chlordiazepoxide: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions. (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Amlodipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Amlodipine; Atorvastatin: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Amlodipine; Benazepril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Amlodipine; Celecoxib: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Amlodipine; Olmesartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Amlodipine; Telmisartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Amlodipine; Valsartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Amobarbital: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of some barbiturates, which may increase CNS depression. Additionally, MAOIs may increase the risk of hypotension after barbiturates are used for sedation induction. When possible, MAOIs should be discontinued for at least 10 days prior to elective surgery due to potential interactions with anesthetic agents. Barbiturates should generally be given at a reduced dose with an MAOI.
    Amoxapine: (Severe) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders or within 14 days of discontinuing treatment with an MAOI. Conversely, an MAOI should not be initiated within 14 days of stopping amoxapine. Hyperpyretic crisis, severe convulsions, and deaths have occurred in patients receiving other cyclic antidepressants and MAOIs simultaneously.
    Angiotensin II receptor antagonists: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Angiotensin-converting enzyme inhibitors: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Anxiolytics; Sedatives; and Hypnotics: (Moderate) The manufacturers of MAOIs contraindicate the use of MAOIs with some CNS depressant drugs due to additive CNS depressant effects. If combination therapy is necessary, use caution; warn patients to avoid driving or performing other hazardous activities until they know how the combination affects them. A dose reduction of one or both medications may be required.
    Apraclonidine: (Severe) Apraclonidine is contraindicated for use in patients receiving monoamine oxidase inhibitors (MAOIs). Apraclonidine should not be administered to patients who have received MAOIs within the previous 14 days. Apraclonidine is a relatively selective alpha-2-adrenergic agonist that is applied topically to the eye. Although no specific drug interactions with systemic medications were identified in clinical studies of apraclonidine ophthalmic solution, the possibility of a serious interaction with MAOIs cannot be excluded.
    Armodafinil: (Major) Armodafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs). It is known that many other CNS stimulants may induce severe cardiovascular and cerebrovascular responses if administered in combination with drugs with non-selective MAO inhibitor activity. Until more is known regarding the pharmacology of armodafinil, it is prudent avoid the use of armodafinil in the presence of an MAO inhibitor. Due to the prolonged duration of action of MAOIs, a period of at least 14 days between the last dose of the MAOI and the first dose of armodafinil should elapse.
    Aspirin, ASA; Butalbital; Caffeine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive. (Major) The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors. This may enhance drowsiness or dizziness. Barbiturates should generally be given at a reduced dose with an MAOI.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive. (Major) The CNS effects of butalbital may be enhanced by monoamine oxidase (MAO) inhibitors. This may enhance drowsiness or dizziness. Barbiturates should generally be given at a reduced dose with an MAOI.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Aspirin, ASA; Caffeine; Orphenadrine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Aspirin, ASA; Carisoprodol; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Aspirin, ASA; Oxycodone: (Major) The use of oxycodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Atenolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Atenolol; Chlorthalidone: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Avoid concomitant use with monoamine oxidase inhibitors (MAOIs); Methylene Blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Methylene blue has been demonstrated to be a potent MAOI. Whenever possible, a washout period should elapse between the use of the MAOI and Methylene Blue injection. Patients treated with Methylene Blue injection should be monitored for serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use, and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome and advise them to not to take any serotonergic drugs within 72 hours after the last dose of Methylene Blue. If the IV use of Methylene Blue cannot be avoided, choose the lowest possible dose and closely observe the patient for CNS and serotonin-related effects for up to 4 hours after Methylene Blue is given.
    Atropine; Difenoxin: (Severe) The concomitant administration of diphenoxylate or difenoxin and monoamine oxidase inhibitors can cause hypertensive crisis. Avoid concurrent use.
    Atropine; Diphenoxylate: (Severe) The concomitant administration of diphenoxylate or difenoxin and monoamine oxidase inhibitors can cause hypertensive crisis. Avoid concurrent use.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of barbiturates like phenobarbital and cause additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient taking phenobarbital for epilepsy is required. Barbiturates should generally be given at a reduced dose with an MAOI.
    atypical antipsychotic: (Moderate) Due to the potential for additive sedative and cardiovascular effects (e.g., hypotension), MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Azilsartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Azilsartan; Chlorthalidone: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of barbiturates like phenobarbital and cause additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient taking phenobarbital for epilepsy is required. Barbiturates should generally be given at a reduced dose with an MAOI.
    Belladonna; Opium: (Major) Concomitant use of central nervous system depressants, such as MAOIs, can potentiate the effects of opium, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses.
    Benazepril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Bendroflumethiazide; Nadolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Benzhydrocodone; Acetaminophen: (Major) The use of benzhydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Benzodiazepines: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Avoid concomitant use with monoamine oxidase inhibitors (MAOIs); Methylene Blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Methylene blue has been demonstrated to be a potent MAOI. Whenever possible, a washout period should elapse between the use of the MAOI and Methylene Blue injection. Patients treated with Methylene Blue injection should be monitored for serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use, and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome and advise them to not to take any serotonergic drugs within 72 hours after the last dose of Methylene Blue. If the IV use of Methylene Blue cannot be avoided, choose the lowest possible dose and closely observe the patient for CNS and serotonin-related effects for up to 4 hours after Methylene Blue is given.
    Benzonatate: (Major) It may be advisable to avoid the use of benzonatate, which is structurally similar to para-amino-benzoic acid class local anesthetic agents, in patients receiving a monoamine oxidase inhibitor (MAOI). Consider alternatives to benzonatate. Patients receiving an MAOI concurrently with local anesthetics may have an increased risk of hypotension or CNS-related effects. If coadministration is medically necessary, observe the patient for additive effects such as low blood pressure, sedation, dizziness, mental confusion, or other side effects. Isolated instances of bizarre behavior, including mental confusion and visual hallucinations, have also been reported in patients taking benzonatate in combination with other prescribed drugs.
    Beta-adrenergic blockers: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Beta-agonists: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Betaxolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Bisoprolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Bosentan: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Bretylium: (Minor) Monoamine oxidase inhibitors potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
    Brimonidine: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Brimonidine; Brinzolamide: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Brimonidine; Timolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Bumetanide: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Buprenorphine: (Major) The use of buprenorphine is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like buprenorphine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Buprenorphine; Naloxone: (Major) The use of buprenorphine is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like buprenorphine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Bupropion: (Severe) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs.
    Bupropion; Naltrexone: (Severe) Monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with bupropion or within 14 days of discontinuing treatment with bupropion. Conversely, bupropion should not be initiated within 14 days of stopping an MAOI. There is an increased risk of hypertensive reactions when bupropion is used concurrently with other drugs that inhibit the reuptake of dopamine or norepinephrine or inhibit their metabolism, such as MAOIs.
    Buspirone: (Severe) Concomitant use of monoamine oxidase inhibitors (MAOIs) and buspirone is contraindicated because several cases of elevated blood pressure have been reported in patients taking MAO inhibitors who were then given buspirone; serotonin syndrome may also occur. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment. At least 14 days should elapse between the discontinuation of phenelzine and initiating buspirone, At least a 7-day interval should elapse after discontinuing tranylcypromine before initiating buspirone treatment. Monitor for serotonin-related effects during therapy transitions.
    Butabarbital: (Moderate) The CNS effects of butabarbital may be enhanced by monoamine oxidase (MAO) inhibitors. This may enhance drowsiness or dizziness. Barbiturates should generally be given at a reduced dose with an MAOI.
    Butorphanol: (Major) Avoid coadministration of butorphanol with monoamine oxidase inhibitors (MAOIs) due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Data are not available about the use of butorphanol concurrently with MAOIs. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Caffeine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Caffeine; Ergotamine: (Major) Excessive use of caffeine in any form should be avoided in patients receiving Monoamine oxidase inhibitors (MAOIs). Limit caffeine intake during MAOI use and for 1 to 2 weeks after discontinuation of any MAOI. The use of non-prescription medicines or dietary supplements containing caffeine should be avoided. Patients should try to avoid or limit the intake of all items containing caffeine such as tea, coffee, chocolate, and cola. Cardiac arrhythmias or severe hypertension may occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs if caffeine intake is excessive.
    Calcium-channel blockers: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Canagliflozin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including canagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Canagliflozin; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including canagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Candesartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Captopril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Carbamazepine: (Severe) MAOIs should not be coadministered with carbamazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of carbamazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if feasible, before administering carbamazepine. When starting MAOI therapy after discontinuing carbamazepine, it is advisable to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy; carefully monitor the patient.
    Carbetapentane; Chlorpheniramine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Guaifenesin: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Pseudoephedrine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbetapentane; Pyrilamine: (Major) Carbetapentane should be avoided in patients receiving monoamine oxidase inhibitors (MAOIs), and should generally not be used within 14 days of discontinuation of an MAOI. There are no data to specifically with carbetapentane to support an interaction. However, serious and fatal reactions, some consistent with serotonin syndrome, have been associated with dextromethorphan, another cough suppressant, during use with MAOIs. Many serious interactions may occur between MAOIs and nonprescription cough and cold products.
    Carbidopa; Levodopa: (Severe) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as phenelzine. due to increased risk of hypertensive crisis. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Carbidopa; Levodopa; Entacapone: (Severe) At least 14 days should elapse between the discontinuation of phenelzine, which is a non-selective MAO inhibitor, and the use of a COMT inhibitor to avoid potential interactions. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the 2 major enzymes involved in the metabolism of catecholamines. The combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism, which may lead to hypertensive crisis or other adverse effects. (Severe) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as phenelzine. due to increased risk of hypertensive crisis. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Carteolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Carvedilol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and phenelzine. Concurrent use may result in additive CNS depression.
    Cetirizine: (Major) Concurrent use of cetirizine or levocetirizine with a nonselective monoamine oxidase inhibitor (MAOI) should generally be avoided. Use together may increase the risk of CNS depressant and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine or levocetirizine not be used within 2 weeks of therapy with a nonselective MAOI.
    Cetirizine; Pseudoephedrine: (Major) Concurrent use of cetirizine or levocetirizine with a nonselective monoamine oxidase inhibitor (MAOI) should generally be avoided. Use together may increase the risk of CNS depressant and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine or levocetirizine not be used within 2 weeks of therapy with a nonselective MAOI.
    Chlordiazepoxide: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Chlordiazepoxide; Clidinium: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Chloroprocaine: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Chlorothiazide: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Chlorpheniramine; Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Chlorpheniramine; Dextromethorphan: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Chlorpheniramine; Hydrocodone: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Chlorpromazine: (Moderate) Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously. Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent.
    Chlorthalidone: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Chlorthalidone; Clonidine: (Severe) Monoamine oxidase inhibitors (MAOIs) may interact with antihypertensive medications. If a patient receiving an MAOI is started on clonidine, severe hypertension may occur, and this reaction may be followed by hypotension, which may be severe. Additionally, if a patient is withdrawn from clonidine, an excess of circulating catecholamines may occur. The clinician should use these agents together with caution; blood pressure should be monitored frequently. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Clevidipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Clomipramine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Clonazepam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Clonidine: (Severe) Monoamine oxidase inhibitors (MAOIs) may interact with antihypertensive medications. If a patient receiving an MAOI is started on clonidine, severe hypertension may occur, and this reaction may be followed by hypotension, which may be severe. Additionally, if a patient is withdrawn from clonidine, an excess of circulating catecholamines may occur. The clinician should use these agents together with caution; blood pressure should be monitored frequently.
    Clorazepate: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Cocaine: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Codeine; Guaifenesin: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Codeine; Phenylephrine; Promethazine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) The concurrent use of promethazine with monoamine oxidase inhibitors (MAOIs), is not recommended because of an increase in the intensity and prolongation of CNS depressant and anticholinergic effects or hypotensive actions. An increased incidence of extrapyramidal effects have been reported when some MAOIs and phenothiazines are used concomitantly and this possibility should be considered with promethazine, which has a phenothiazine-related structure. In general, sedating antihistamines such as promethazine should be avoided within 2 weeks of therapy with a MAOI if possible.
    Codeine; Promethazine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of codeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as codeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) The concurrent use of promethazine with monoamine oxidase inhibitors (MAOIs), is not recommended because of an increase in the intensity and prolongation of CNS depressant and anticholinergic effects or hypotensive actions. An increased incidence of extrapyramidal effects have been reported when some MAOIs and phenothiazines are used concomitantly and this possibility should be considered with promethazine, which has a phenothiazine-related structure. In general, sedating antihistamines such as promethazine should be avoided within 2 weeks of therapy with a MAOI if possible.
    COMT inhibitors: (Severe) At least 14 days should elapse between the discontinuation of phenelzine, which is a non-selective MAO inhibitor, and the use of a COMT inhibitor to avoid potential interactions. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the 2 major enzymes involved in the metabolism of catecholamines. The combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism, which may lead to hypertensive crisis or other adverse effects.
    Cyclobenzaprine: (Severe) Concurrent use of cyclobenzaprine and MAOIs is contraindicated. Further, use of cyclobenzaprine within 14 days of MAOI discontinuation is contraindicated. Hyperpyretic crisis, seizures and deaths have occurred in patients receiving cyclobenzaprine or structurally similar tricyclic antidepressants concomitantly with MAO inhibitor drugs. A patient taking phenelzine developed symptoms of serotonin syndrome including confusion, agitation, tremors, tachycardia, diaphoresis, hallucinations, delusions, and fever after the third oral dose of cyclobenzaprine 10 mg, which was prescribed every 8 hours. The patient remained symptomatic despite drug discontinuation. All of her symptoms progressively resolved over the next 3 days. Reinitiation of phenelzine was without consequences.
    Dapagliflozin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including dapagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Dapagliflozin; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including dapagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Dapagliflozin; Saxagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including dapagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors are added to any regimen containing antidiabetic agents, including saxagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Desflurane: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Desipramine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Desmopressin: (Moderate) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with hyponatremia and SIADH including monoamine oxidase inhibitors (MAOIs). Use combination with caution and monitor patients for signs and symptoms of hyponatremia, which may include seizures.
    Desvenlafaxine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs). MAOIs should not be used within 5 days of discontinuing treatment with duloxetine or milnacipran or within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
    Deutetrabenazine: (Severe) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of deutetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Dextromethorphan: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Dextromethorphan; Guaifenesin: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Dextromethorphan; Promethazine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites. (Major) The concurrent use of promethazine with monoamine oxidase inhibitors (MAOIs), is not recommended because of an increase in the intensity and prolongation of CNS depressant and anticholinergic effects or hypotensive actions. An increased incidence of extrapyramidal effects have been reported when some MAOIs and phenothiazines are used concomitantly and this possibility should be considered with promethazine, which has a phenothiazine-related structure. In general, sedating antihistamines such as promethazine should be avoided within 2 weeks of therapy with a MAOI if possible.
    Dextromethorphan; Quinidine: (Severe) Dextromethorphan products are contraindicated in patients taking a monoamine oxidase inhibitor (MAOI) or in patients who have taken an MAOI within the last 14 days, due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. A washout period of at least 14 days should elapse between the start of dextromethorphan after discontinuation of an MAOI. Patients should read nonprescription product labels carefully. Before initiating an MAOI after using other serotonergic agents, a sufficient amount of time must be allowed for clearance of the serotoninergic agent and its active metabolites.
    Diazepam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Diazoxide: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Severe) Dihydrocodeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of dihydrocodeine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as dihydrocodeine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Diltiazem: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Dolasetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment.
    Dorzolamide; Timolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Doxazosin: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Doxepin: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Dronabinol: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including dronabinol.
    Droperidol: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including droperidol. A dose reduction of droperidol may be needed.
    Droxidopa: (Major) Avoid concurrent use of droxidopa and phenelzine, a non-selective MAOI, as there is a potential for increased blood pressure when taken together.
    Duloxetine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs). MAOIs should not be used within 5 days of discontinuing treatment with duloxetine or milnacipran or within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
    Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with phenelzine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue eletriptan with phenelzine and initiate symptomatic treatment if serotonin syndrome occurs.
    Empagliflozin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including empagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Empagliflozin; Linagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including empagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including linagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including empagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including linagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Empagliflozin; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including empagliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Enalapril, Enalaprilat: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Enalapril; Felodipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Enflurane: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Entacapone: (Severe) At least 14 days should elapse between the discontinuation of phenelzine, which is a non-selective MAO inhibitor, and the use of a COMT inhibitor to avoid potential interactions. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the 2 major enzymes involved in the metabolism of catecholamines. The combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism, which may lead to hypertensive crisis or other adverse effects.
    Eplerenone: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with eplerenone.
    Epoprostenol: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with epoprostenol.
    Eprosartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Ertugliflozin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including ertugliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Ertugliflozin; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including ertugliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Ertugliflozin; Sitagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including ertugliflozin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including sitagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Esketamine: (Major) Closely monitor patients receiving esketamine and MAOIs for sedation and increased blood pressure, including the possibility of hypertensive crisis. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
    Eslicarbazepine: (Severe) MAOIs should not be coadministered at the same time with eslicarbazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of eslicarbazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering eslicarbazepine. When starting MAOI therapy after discontinuing eslicarbazepine, it is advised to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy. Carefully monitor the patient. Watch carefully for other effects besides effects on blood pressure, such as sedation, confusion, and increased CNS depression. If eslicarbazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients.
    Esmolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Estazolam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Ester local anesthetics: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Ethacrynic Acid: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Ethanol: (Major) Ethanol may cause additive CNS depression and some ethanol-containing products may also contain tyramine. Many manufacturers contraindicate the use of ethanol (alcohol) during traditional, non-selective MAOI therapy such as treatment with isocarboxazid, phenelzine, or tranylcypromine. Certain alchoholic beverages thatare tyramine-rich can precipitate a hypertensive reaction if consumed by patients during therapy with these MAOIs. These include some beers; wines; sherry; hard liquor; or liqueurs.
    Etomidate: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Felbamate: (Moderate) Additive CNS depression is possible if MAOIs and felbamate are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
    Felodipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Fenfluramine: (Severe) Coadministration of fenfluramine with monoamine oxidase inhibitors (MAOIs) or within 14 days after discontinuation of treatment with an MAOI is contraindicated due to the risk of serotonin syndrome.
    Fenoldopam: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Fentanyl: (Major) The use of fentanyl is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Fluphenazine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Flurazepam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Food: (Severe) Avoid foods and beverages containing a high tyramine content. Ingestion of high tyramine foods can cause a hypertensive reaction. Following discontinuation of any MAOI, dietary restrictions should continue for at least 2 weeks due to the slow recovery from the enzyme-inhibiting effects of these drugs. According to product labeling, a variety of tyramine-containing foods can precipitate severe hypertensive episodes if consumed with MAOIs: aged cheese; yeast extract; protein extract; soy sauce; fava bean or broad bean pods; smoked meats; pickled meats; smoked poultry; pickled poultry; smoked fish (lox, smoked salmon); pickled fish (pickled herring); fermented sausage (bologna, pepperoni, salami, summer sausage) or other fermented meat; liver; anchovies; sauerkraut; bananas; overripe avocados; canned figs; raisins; raspberries; any over-ripe fruit; yogurt; and sour cream. Modifications to established guidelines are available through independent sources, supported by updated analytical methods for determining tyramine content of foods, and using a safety threshold of less than 6 mg of tyramine/serving. Certain foods that are prohibited in product labeling have been found to contain little or no tyramine. Milk products including sour cream, yogurt, and processed cheese slices do not contain tyramine. The tyramine content of brewer's yeast, baker's yeast, raspberries, and avocados is low. In some analyses, avocados have been shown to contain 0 to 2.3 mg of tyramine/100 g serving. Other allowable foods according to independent sources include cottage cheese, cream cheese, freshly packaged meat or fish, beef/chicken bouillon, bananas, chocolate, peanuts, properly stored pickled or smoked fish, and soy milk. Improper storage and handling of foods, or spoilage may increase tyramine content and present a risk of hypertensive crisis. Some alcohol-containing products may also contain tyramine. Beverages that contain tyramine can precipitate a hypertensive reaction if consumed during therapy with an MAOI. These include some beers (including reduced-ethanol and ethanol-free beer); wines (red and white varieties); sherry; hard liquor; or liqueurs.
    Fosinopril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Fospropofol: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering frovatriptan with phenelzine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue frovatriptan and phenelzine and initiate symptomatic treatment if serotonin syndrome occurs.
    Furosemide: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and gabapentin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients receiving gabapentin for epilepsy is required.
    Gallium Ga 68 Dotatate: (Moderate) Exaggerated hypotensive effects may result when MAOIs are used in combination with other antihypertensive drugs, including diuretics; patients should be observed for symptoms of orthostatic hypotension
    General anesthetics: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Ginseng, Panax ginseng: (Severe) There have been two reports in the literature describing a possible, but not definitive, interaction between ginseng and phenelzine; it is not clear if other MAOIs would interact, but caution is warranted. In one case, headache and tremulousness were reported in a 64-year old when ginseng was added to phenelzine. A second patient suffered from irritability, headache, and vague visual hallucinations during combined use of ginseng and phenelzine. Some of these effects have been reported with the use of phenelzine alone.
    Glipizide; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Glyburide; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Granisetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as the monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment.
    Green Tea: (Major) It may be advisable to avoid the combination of green tea and monoamine oxidase inhibitors, and wait for at least 14 days after the discontinuation of MAOIs before consuming green tea. Monoamine oxidase inhibitors prevent the metabolism of catecholamines, which may be additive with inhibition of the catechol-o-methyltransferase (COMT) enzyme by green tea. Also, some green tea products contain caffeine; caffeine interacts with MAOIs. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Excessive caffeine must be avoided while taking MAOIs and for two weeks after discontinuing their use.
    Guaifenesin; Hydrocodone: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Guanabenz: (Severe) Guanabenz withdrawal can result in an increase in serum catecholamine levels. Thus, drugs that alter the metabolism or uptake of catecholamines, such as guanabenz, should not be initiated for at least 2 weeks after discontinuation of monoamine oxidase inhibitors (MAOIs).
    Guanfacine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. In addition, when beginning treatment with antihypertensives that initially increase the release of catecholamine stores, such as guanfacine, hypertensive crisis may occur. Abrupt cessation of therapy with central alpha-2 adrenergic agonists like guanfacine may be associated with increases (from depressed on-therapy levels) in plasma and urinary catecholamines, symptoms of nervousness and anxiety and, less commonly, increases in blood pressure to levels significantly greater than those prior to therapy, which may affect MAO inhibiting therapy.
    Halothane: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Homatropine; Hydrocodone: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Hydantoins: (Moderate) Additive CNS depression is possible if MAOIs and hydantoins (e.g., ethotoin, fosphenytoin, phenytoin) are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy taking a hydantoin anticonvulsant is required.
    Hydralazine: (Major) Additive hypotensive effects may be seen when phenelzine, a MAOI, is combined with hydralazine, a potent vasodilator. In addition, hydralazine may cause pronounced tachycardia when combined with MAOIs. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and an antihypertensive agent.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Major) Additive hypotensive effects may be seen when phenelzine, a MAOI, is combined with hydralazine, a potent vasodilator. In addition, hydralazine may cause pronounced tachycardia when combined with MAOIs. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and an antihypertensive agent. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Major) Additive hypotensive effects may be seen when phenelzine, a MAOI, is combined with hydralazine, a potent vasodilator. In addition, hydralazine may cause pronounced tachycardia when combined with MAOIs. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and an antihypertensive agent.
    Hydrochlorothiazide, HCTZ: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Severe) The manufacturer of methyldopa contraindicates its use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations. A paradoxical pressor effect has been noted with methyldopa use. Data describing this interaction are limited. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Hydrocodone: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Hydrocodone; Ibuprofen: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Hydrocodone; Phenylephrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Hydrocodone; Pseudoephedrine: (Major) The use of hydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the past 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Hydromorphone: (Major) The use of hydromorphone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Severe) Avoid concomitant use with monoamine oxidase inhibitors (MAOIs); Methylene Blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Methylene blue has been demonstrated to be a potent MAOI. Whenever possible, a washout period should elapse between the use of the MAOI and Methylene Blue injection. Patients treated with Methylene Blue injection should be monitored for serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use, and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome and advise them to not to take any serotonergic drugs within 72 hours after the last dose of Methylene Blue. If the IV use of Methylene Blue cannot be avoided, choose the lowest possible dose and closely observe the patient for CNS and serotonin-related effects for up to 4 hours after Methylene Blue is given.
    Ibuprofen; Oxycodone: (Major) The use of oxycodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Iloprost: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with iloprost.
    Imipramine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Incretin Mimetics: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Indapamide: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives. Monitor blood pressure during concurrent therapy of MAOIs with diuretics such as indapamide.
    Insulins: (Moderate) Monitor patients receiving monoamine oxidase inhibitors (MAOIs) concomitantly with insulin for changes in glycemic control. Animal data indicate that MAOIs may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulins.
    Iobenguane I 131: (Major) Discontinue monoamine oxidase inhibitors for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart monoamine oxidase inhibitors until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as monoamine oxidase inhibitors, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Iohexol: (Major) Use of medications that lower the seizure threshold, such as monoamine oxidase inhibitors, should be carefully evaluated when considering intrathecal radiopaque contrast agents. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
    Iopamidol: (Major) Use of medications that lower the seizure threshold, such as monoamine oxidase inhibitors, should be carefully evaluated when considering intrathecal radiopaque contrast agents. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
    Iopromide: (Major) Use of medications that lower the seizure threshold, such as monoamine oxidase inhibitors, should be carefully evaluated when considering intrathecal radiopaque contrast agents. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
    Ioversol: (Major) Use of medications that lower the seizure threshold, such as monoamine oxidase inhibitors, should be carefully evaluated when considering intrathecal radiopaque contrast agents. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
    Irbesartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Isoflurane: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Isoniazid, INH: (Major) In theory, concurrent use of isoniazid, INH with non-selective monoamine oxidase inhibitors (MAOIs), such as phenelzine, increase the risk of a hypertensive crisis. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with non-selective monoamine oxidase inhibitors (MAOIs), such as phenelzine, increase the risk of a hypertensive crisis. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity.
    Isoniazid, INH; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with non-selective monoamine oxidase inhibitors (MAOIs), such as phenelzine, increase the risk of a hypertensive crisis. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity.
    Isosulfan Blue: (Major) Use of medications that lower the seizure threshold, such as monoamine oxidase inhibitors, should be carefully evaluated when considering intrathecal radiopaque contrast agents. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
    Isradipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Ketamine: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Labetalol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Lamotrigine: (Moderate) Additive CNS depression is possible if MAOIs and lamotrigine are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
    Lasmiditan: (Major) Avoid coadministration of lasmiditan and phenelzine due to the risk of serotonin syndrome. Additionally, additive CNS depression may occur. If concomitant use is unavoidable, use the lowest appropriate medication dosages, and monitor for excessive sedation, somnolence, and serotonin syndrome. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and monoamine oxidase inhibitors (MAOIs). Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Levetiracetam: (Moderate) Additive CNS depression is possible if MAOIs and levetiracetam are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
    Levobetaxolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Levobunolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Levocetirizine: (Major) Concurrent use of cetirizine or levocetirizine with a nonselective monoamine oxidase inhibitor (MAOI) should generally be avoided. Use together may increase the risk of CNS depressant and anticholinergic side effects. The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine or levocetirizine not be used within 2 weeks of therapy with a nonselective MAOI.
    Levodopa: (Severe) Levodopa is contraindicated for concurrent use with non-selective MAOIs, such as phenelzine. due to increased risk of hypertensive crisis. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Levomethadyl: (Major) The use of levomethadyl is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression and increased hypotensive responses. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Levomilnacipran: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs). MAOIs should not be used within 5 days of discontinuing treatment with duloxetine or milnacipran or within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
    Levorphanol: (Major) The use of levorphanol is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Linagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including linagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Linagliptin; Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including linagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Lisinopril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Lithium: (Moderate) There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and nonselective monoamine oxidase inhibitors (MAOIs). If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, lithium and other serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Loop diuretics: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Lorazepam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Lorcaserin: (Major) Avoid concurrent use of monoamine oxidase inhibitors (MAOIs) and lorcaserin if possible; use with extreme caution and only if medically necessary. MAOIs are not recommended to be taken with serotonergic medications due to the risk for serotonin syndrome. Lorcaserin affects serotonergic neurotransmitter systems. Patients receiving this combination should be monitored for the emergence of serotonin syndrome.
    Losartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Loxapine: (Moderate) Due to the potential for additive CNS and cardiovascular effects such as hypotension, sedation, and anticholinergic effects, MAOIs and antipsychotics should be used together cautiously; some experts recommend initiating low doses of the antipsychotic and careful dosage titration.
    Magnesium Salts: (Minor) Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with antidepressants.
    Mannitol: (Moderate) Exaggerated hypotensive effects may result when MAOIs are used in combination with other antihypertensive drugs, including diuretics; patients should be observed for symptoms of orthostatic hypotension
    Maprotiline: (Severe) Concurrent use of phenelzine, a non-selective monoamine oxidase inhibitor (MAOI), and maprotiline, a selective norepinephrine reuptake inhibitor, is contraindicated by the manufacturer of maprotiline. The noradrenergic effects of both maprotiline and phenelzine may result in hypertensive crisis. A minimum of 14 days should elapse after discontinuation of phenelzine before treatment with maprotiline is initiated. After stopping treatment with maprotiline, a time period of 4 to 5 half-lives of maprotiline and any active metabolites should elapse before starting treatment with phenelzine. The product labeling for phenelzine states that use with maprotiline should be avoided if possible; if the decision is made to administer phenelzine with maprotiline or within less than 10 days after discontinuation of maprotiline, the patient should be cautioned regarding the possibility of an interaction.
    Meglitinides: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Meperidine: (Severe) The use of meperidine is contraindicated in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. The combination is also contraindicated due to serious effects that have been reported following a single dose of meperidine in patients receiving MAOI therapy including excitation, seizures, delirium, hyperpyrexia, circulatory collapse, coma, and death. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Meperidine; Promethazine: (Severe) The use of meperidine is contraindicated in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. The combination is also contraindicated due to serious effects that have been reported following a single dose of meperidine in patients receiving MAOI therapy including excitation, seizures, delirium, hyperpyrexia, circulatory collapse, coma, and death. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) The concurrent use of promethazine with monoamine oxidase inhibitors (MAOIs), is not recommended because of an increase in the intensity and prolongation of CNS depressant and anticholinergic effects or hypotensive actions. An increased incidence of extrapyramidal effects have been reported when some MAOIs and phenothiazines are used concomitantly and this possibility should be considered with promethazine, which has a phenothiazine-related structure. In general, sedating antihistamines such as promethazine should be avoided within 2 weeks of therapy with a MAOI if possible.
    Mephobarbital: (Major) The CNS effects of mephobarbital may be enhanced and prolonged by monoamine oxidase (MAO) inhibitors. This may enhance drowsiness or dizziness. Barbiturates should generally be given at a reduced dose with an MAOI.
    Mesoridazine: (Moderate) Concurrent use of MAOIs and phenothiazines, such as mesoridazine, may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Metformin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Metformin; Pioglitazone: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Metformin; Repaglinide: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Metformin; Rosiglitazone: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Metformin; Saxagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors are added to any regimen containing antidiabetic agents, including saxagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Metformin; Sitagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including metformin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including sitagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Methadone: (Major) The use of methadone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Methazolamide: (Moderate) Exaggerated hypotensive effects may result when MAOIs are used in combination with other antihypertensive drugs, including diuretics. Patients should be observed for symptoms of orthostatic hypotension. Dose adjustments of the antihypertensive may be required.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Severe) Avoid concomitant use with monoamine oxidase inhibitors (MAOIs); Methylene Blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Methylene blue has been demonstrated to be a potent MAOI. Whenever possible, a washout period should elapse between the use of the MAOI and Methylene Blue injection. Patients treated with Methylene Blue injection should be monitored for serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use, and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome and advise them to not to take any serotonergic drugs within 72 hours after the last dose of Methylene Blue. If the IV use of Methylene Blue cannot be avoided, choose the lowest possible dose and closely observe the patient for CNS and serotonin-related effects for up to 4 hours after Methylene Blue is given.
    Methohexital: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of some barbiturates, which may increase CNS depression. Additionally, MAOIs may increase the risk of hypotension after barbiturates are used for sedation induction. When possible, MAOIs should be discontinued for at least 10 days prior to elective surgery due to potential interactions with anesthetic agents.
    Methyclothiazide: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Methyldopa: (Severe) The manufacturer of methyldopa contraindicates its use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations. A paradoxical pressor effect has been noted with methyldopa use. Data describing this interaction are limited.
    Methylene Blue: (Severe) Avoid concomitant use with monoamine oxidase inhibitors (MAOIs); Methylene Blue injection may cause serious or fatal serotonergic syndrome when used in combination with serotonergic drugs. Methylene blue has been demonstrated to be a potent MAOI. Whenever possible, a washout period should elapse between the use of the MAOI and Methylene Blue injection. Patients treated with Methylene Blue injection should be monitored for serotonin syndrome. If symptoms of serotonin syndrome occur, discontinue use, and initiate supportive treatment. Inform patients of the increased risk of serotonin syndrome and advise them to not to take any serotonergic drugs within 72 hours after the last dose of Methylene Blue. If the IV use of Methylene Blue cannot be avoided, choose the lowest possible dose and closely observe the patient for CNS and serotonin-related effects for up to 4 hours after Methylene Blue is given.
    Metoclopramide: (Moderate) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs.
    Metolazone: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Metoprolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Midazolam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Milnacipran: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs). MAOIs should not be used within 5 days of discontinuing treatment with duloxetine or milnacipran or within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
    Minoxidil: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Mirabegron: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
    Mirtazapine: (Severe) Use of mirtazapine concurrently with the monoamine oxidase inhibitors (MAOIs) is contraindicated. If combined, there is a possibility of developing serious reactions such as serotonin syndrome. At least 2 weeks should elapse between stopping one agent and beginning the other. Monitor for serotonin-related side effects during therapy transitions.
    Mivacurium: (Moderate) Plasma cholinesterase activity may be diminished by chronic administration of phenelzine; consider the possibility of prolonged neuromuscular block after administration of mivacurium in patients with reduced plasma cholinesterase activity. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Modafinil: (Major) Modafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs). It is known that many other CNS stimulants may induce severe cardiovascular and cerebrovascular responses if administered in combination with drugs with non-selective MAO inhibitor activity. Until more is known regarding the pharmacology of modafinil, it is prudent avoid the use of modafinil in the presence of an MAO inhibitor. Due to the prolonged duration of action of MAOIs, a period of at least 14 days between the last dose of the MAOI and the first dose of modafinil should elapse.
    Moexipril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Morphine: (Severe) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Morphine; Naltrexone: (Severe) Morphine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. Concomitant use of morphine with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as morphine. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Nabilone: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including nabilone.
    Nadolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Nalbuphine: (Major) The use of nalbuphine is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like nalbuphine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Naproxen; Sumatriptan: (Severe) Concurrent administration of sumatriptan and selective monoamine oxidase A inhibitors (e.g., moclobemide) or non-selective monoamine oxidase inhibitors (MAOIs) or use of sumatriptan within 2 weeks of discontinuation of an MAOI is contraindicated. Sumatriptan appears to be metabolized by monoamine oxidase, predominantly MAO-type A; therefore, plasma concentrations of sumatriptan may be increased by concurrent use of MAO-A inhibitors or non-selective inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid). Because oral sumatriptan usually undergoes first-pass metabolism, the increase of AUC after coadministration of a non-selective MAOI is greater than the interaction with subcutaneous sumatriptan combined with an MAO-A selective inhibitor. The effects of a selective MAO-A inhibitor on the AUC after intranasal sumatriptan use would be expected to be greater than the effect after SC sumatriptan but smaller than the effect after oral sumatriptan. In a study of healthy female volunteers (n = 14), pretreatment with moclobemide decreased the clearance of subcutaneous sumatriptan resulting in a 2-fold increase in sumatriptan AUC and a 40% increase in elimination half-life. In a similar study of oral sumatriptan, pretreatment with an MAO-A inhibitor followed by 25-mg PO of sumatriptan resulted in an approximately 7-fold increase in sumatriptan AUC.
    Naratriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering naratriptan with phenelzine. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue naratriptan and phenelzine and initiate symptomatic treatment if serotonin syndrome occurs.
    Nateglinide: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Nebivolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Nebivolol; Valsartan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Nefazodone: (Severe) Nefazodone is considered contraindicated for concurrent use with MAOIs. Because nefazodone inhibits the reuptake of serotonin and, to a lesser extent, norepinephrine, combination with a MAOI could possibly produce confusion, delirium, coma, seizures, hyperthermia, or other, less severe, symptoms. Although severe reactions have been seen when drugs with a pharmacological profile similar to nefazodone were used with MAOI therapy, no controlled trials have been done with nefazodone. At least 2 weeks should elapse between the discontinuation of MAOI therapy and the start of nefazodone therapy, or at least 1 week should elapse between the discontinuation of nefazodone and the initiation of a MAOI.
    Netupitant, Fosnetupitant; Palonosetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment.
    Nicardipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Nifedipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Nimodipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Nisoldipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Nitroglycerin: (Moderate) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as monoamine oxidase inhibitors (MAOIs). Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with MAOIs.
    Nitroprusside: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with vasodilators.
    Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold, such as monoamine oxidase inhibitors, should be carefully evaluated when considering intrathecal radiopaque contrast agents. While the contributory role of such medications has not been established, some physicians discontinue these drugs at least 48 hours before and for at least 24 hours after intrathecal use.
    Nortriptyline: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Olmesartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Ondansetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering ondansetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue ondansetron and concurrent serotonergic agents and initiate appropriate medical treatment.
    Oxazepam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Oxcarbazepine: (Severe) MAOIs should not be coadministered at the same time with oxcarbazepine, a dibenzazepine-related drug. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. At least 7 days should elapse between discontinuation of oxcarbazepine and initiation of an MAOI. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering oxcarbazepine. When starting MAOI therapy after discontinuing oxcarbazepine, it is advised to begin the MAOI at one-half the normal starting dosage for at least the first week of therapy; carefully monitor the patient.
    Oxycodone: (Major) The use of oxycodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Oxymetazoline: (Major) Oxymetazoline should generally not be used in patients taking non-selective monoamine oxidase inhibitors (MAOIs). The combination of an MAOI and a sympathomimetic drug, including decongestants given via topical, nasal, or ophthalmic routes, may rarely result in high blood pressure or in more serious cases, hypertensive crisis. Avoid use during and up to 2 weeks following discontinuation of the MAOI. Consider alternative treatments for the patient's condition.
    Oxymorphone: (Major) The use of oxymorphone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Ozanimod: (Severe) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with MAO inhibitors. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
    Palonosetron: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment.
    Penbutolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Pentazocine: (Major) The use of pentazocine is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like pentazocine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Pentazocine; Naloxone: (Major) The use of pentazocine is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like pentazocine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Pentobarbital: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of some barbiturates, which may increase CNS depression. Additionally, MAOIs may increase the risk of hypotension after barbiturates are used for sedation induction. When possible, MAOIs should be discontinued for at least 10 days prior to elective surgery due to potential interactions with anesthetic agents. Barbiturates should generally be given at a reduced dose with an MAOI.
    Perampanel: (Moderate) Use of perampanel with CNS depressants, including monoamine oxidase inhibitors (MAOIs), may increase CNS depression. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient taking perampanel for epilepsy is required.
    Perindopril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Perindopril; Amlodipine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Perphenazine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Perphenazine; Amitriptyline: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions. (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Phenobarbital: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of barbiturates like phenobarbital and cause additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient taking phenobarbital for epilepsy is required. Barbiturates should generally be given at a reduced dose with an MAOI.
    Phenoxybenzamine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Phentolamine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Phenylephrine; Promethazine: (Major) The concurrent use of promethazine with monoamine oxidase inhibitors (MAOIs), is not recommended because of an increase in the intensity and prolongation of CNS depressant and anticholinergic effects or hypotensive actions. An increased incidence of extrapyramidal effects have been reported when some MAOIs and phenothiazines are used concomitantly and this possibility should be considered with promethazine, which has a phenothiazine-related structure. In general, sedating antihistamines such as promethazine should be avoided within 2 weeks of therapy with a MAOI if possible.
    Pindolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Potassium-sparing diuretics: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Pramlintide: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including pramlintide. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Prazosin: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of monoamine oxidase inhibitors (MAOIs) and pregabalin. Concurrent use may result in additive CNS depression. MAOIs can cause a variable change in seizure patterns; therefore, careful monitoring of patients receiving pregabalin for a seizure disorder is required.
    Primidone: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of barbiturates like primidone and cause additive CNS depression. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient taking primidone for epilepsy is required. Barbiturates should generally be given at a reduced dose with an MAOI.
    Procaine: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Procarbazine: (Severe) Procarbazine is a weak monoamine oxidase inhibitor. Avoid concomitant administration with other monoamine oxidase inhibitors because of the possibility of severe hyperpyretic or hypertensive crises, convulsions, or death. In general, at least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Prochlorperazine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Promethazine: (Major) The concurrent use of promethazine with monoamine oxidase inhibitors (MAOIs), is not recommended because of an increase in the intensity and prolongation of CNS depressant and anticholinergic effects or hypotensive actions. An increased incidence of extrapyramidal effects have been reported when some MAOIs and phenothiazines are used concomitantly and this possibility should be considered with promethazine, which has a phenothiazine-related structure. In general, sedating antihistamines such as promethazine should be avoided within 2 weeks of therapy with a MAOI if possible.
    Propofol: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Propoxyphene: (Severe) The manufacturers of MAOIs contraindicate the use of MAOIs with some CNS-depressant drugs like propoxyphene due to additive CNS-depressant effects. If combination is necessary, use these drugs cautiously with MAOIs; warn patients to not drive or perform other hazardous activities until they know how a particular drug combination affects them.
    Propranolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Protriptyline: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Quazepam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Quinapril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Ramelteon: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including ramelteon.
    Ramipril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Rasagiline: (Severe) Rasagiline should not be used concurrently with or in rapid succession to other monoamine oxidase inhibitors (MAOIs). The combination or rapid succession of MAOI treatment could result in severe CNS or cardiovascular reactions, including hypertensive crises, hyperpyrexia, CNS excitation, delirium, tremor, seizures, coma, circulatory collapse or death. At least 14 days should elapse between the discontinuation of rasagiline and the initiation of another MAOI or the discontinuation of another MAOI and the initiation of rasagiline.
    Remifentanil: (Major) The use of remifentanil is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Repaglinide: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Reserpine: (Severe) The concomitant use of reserpine and monoamine oxidase inhibitors (MAOIs) is contraindicated. Acutely, reserpine can increase the risk of hypertensive crisis by causing an initial release of catecholamines from bound stores. During chronic administration, additive CNS depressant effects and hypotension are possible.
    Rizatriptan: (Severe) Rizatriptan is contraindicated for use with a monoamine oxidase A inhibitor (MAO-A inhibitor) or nonselective MAOI (e.g., phenelzine) or within 2 weeks of discontinuing such a MAOI, due to the risk for serotonin syndrome and increased rizatriptan exposure. Rizatriptan is principally metabolized by monoamine oxidase A (MAO-A). During a drug interaction study with meclobemide (a selective MAO-A inhibitor), the mean increase in rizatriptan Cmax was 41%, and the mean increases in the AUC of rizatriptan and its metabolite were 119% and 400%, respectively.
    Sacubitril; Valsartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Safinamide: (Severe) Concurrent use of safinamide with other monoamine oxidase inhibitors (MAOIs) or use of other MAOIs within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Serotonin syndrome has also been reported during coadministration of MAOIs, presumably due to additive effects on central serotonin levels.
    Saxagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors are added to any regimen containing antidiabetic agents, including saxagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas.
    Secobarbital: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of some barbiturates, which may increase CNS depression. Additionally, MAOIs may increase the risk of hypotension after barbiturates are used for sedation induction prior to surgeries or procedures. Barbiturates should generally be given at a reduced dose with an MAOI.
    Sedating H1-blockers: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Consider alternative therapy to these antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many nonprescription products for coughs, colds, allergy, hay fever, or insomnia contain sedating antihistamines. Patients receiving an MAOI should be counseled that it is essential to consult their health care provider or pharmacist prior to the use of any nonprescription products. Advise against driving or engaging in other activities requiring mental alertness until patients know how this combination affects them.
    Selective norepinephrine reuptake inhibitors: (Severe) The use of selective norepinephrine reuptake inhibitors with monoamine oxidase inhibitors (MAOIs) is contraindicated. At least 2 weeks should elapse between the discontinuation of a drug with MAO inhibiting activity and the start of selective norepinephrine reuptake inhibitors, or vice-versa. Selective norepinephrine reuptake inhibitors potentiate certain catecholamines by inhibiting neuronal reuptake. Reactions with MAOIs may include confusion, seizures, and severe hypertension as well as less severe symptoms.
    Selective serotonin reuptake inhibitors: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with selective serotonin reuptake inhibitors (SSRIs). MAOIs should not be used within 5 weeks of discontinuing treatment with fluoxetine or within 14 days of discontinuing treatment with other SSRIs. Conversely, SSRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
    Selegiline: (Severe) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
    Serotonin norepinephrine reuptake inhibitors: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs). MAOIs should not be used within 5 days of discontinuing treatment with duloxetine or milnacipran or within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
    Sevoflurane: (Severe) Patients taking monoamine oxidase inhibitors (MAOIs) should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS depression and cardiovascular reactions. Additive hypotensive effects are possible with the combined use of MAOIs and spinal anesthetics. MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Sibutramine: (Severe) Coadministration of monoamine oxidase inhibitors (MAOIs) and sibutramine is contraindicated due to the potential for serotonin syndrome. Sibutramine is a serotonin reuptake inhibitor. There should be at least a 2-week interval between discontinuation of MAOI therapy and initiation of sibutramine therapy. Similarly, there should be at least a 2-week interval after stopping sibutramine therapy and the start of MAOI therapy.
    Sildenafil: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with sildenafil. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with sildenafil.
    Simvastatin; Sitagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including sitagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Sitagliptin: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including sitagliptin. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Sodium Oxybate: (Major) Avoid use within 2 weeks of each other. Data for an interaction with sodium oxybate and MAOIs are lacking, but use of other CNS depressants may potentiate the CNS-depressant effects of sodium oxybate.
    Solriamfetol: (Severe) The concurrent use of noradrenergic drugs, such as solriamfetol, and monoamine oxidase inhibitors (MAOIs) or use of solriamfetol within 14 days of MAOI therapy is contraindicated due to the increased risk for hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.
    Spironolactone: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    St. John's Wort, Hypericum perforatum: (Severe) St. John's wort, Hypericum perforatum should not be used concurrently with monoamine oxidase inhibitors (MAOIs) because of the possibility of serotonin syndrome. Since serotonin is deaminated by monoamine oxidase type A, administration of non-selective MAOIs concurrently with St. John's wort could potentially lead to an excess of central serotonin. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Succinimides: (Moderate) Additive CNS depression is possible if MAOIs and succinimides are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
    Succinylcholine: (Moderate) Plasma cholinesterase activity may be diminished by chronic administration of phenelzine; consider the possibility of prolonged neuromuscular block after administration of succinylcholine in patients with reduced plasma cholinesterase activity. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Sufentanil: (Major) The use of sufentanil is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Sulfonylureas: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents, including sulfonylureas. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to the oral sulfonylureas.
    Sumatriptan: (Severe) Concurrent administration of sumatriptan and selective monoamine oxidase A inhibitors (e.g., moclobemide) or non-selective monoamine oxidase inhibitors (MAOIs) or use of sumatriptan within 2 weeks of discontinuation of an MAOI is contraindicated. Sumatriptan appears to be metabolized by monoamine oxidase, predominantly MAO-type A; therefore, plasma concentrations of sumatriptan may be increased by concurrent use of MAO-A inhibitors or non-selective inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid). Because oral sumatriptan usually undergoes first-pass metabolism, the increase of AUC after coadministration of a non-selective MAOI is greater than the interaction with subcutaneous sumatriptan combined with an MAO-A selective inhibitor. The effects of a selective MAO-A inhibitor on the AUC after intranasal sumatriptan use would be expected to be greater than the effect after SC sumatriptan but smaller than the effect after oral sumatriptan. In a study of healthy female volunteers (n = 14), pretreatment with moclobemide decreased the clearance of subcutaneous sumatriptan resulting in a 2-fold increase in sumatriptan AUC and a 40% increase in elimination half-life. In a similar study of oral sumatriptan, pretreatment with an MAO-A inhibitor followed by 25-mg PO of sumatriptan resulted in an approximately 7-fold increase in sumatriptan AUC.
    Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and monoamine oxidase inhibitors (MAOIs). Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants.
    Sympathomimetics: (Severe) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use.
    Tapentadol: (Severe) Tapentadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Concomitant use may result in serious adverse effects including serotonin syndrome and respiratory depression. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tapentadol.
    Tedizolid: (Major) This combination should be avoided if possible. Although interactions with monamine oxidase inhibitors (MAOIs) were not evaluated in clinical trials, caution is warranted with the concurrent use of tedizolid and MAOIs due to the potential risk of severe hypertensive crisis and possibly serotonin syndrome. Consider if another antibiotic would be appropriate for the patient. Tedizolid is an oxazolidinone-class antibacterial that is also a weak reversible, non-selective inhibitor of MAO. Serotonin syndrome has been reported when another oxazolidinone-class antibacterial has been administered with certain serotonergic agents.
    Telmisartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Temazepam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Terazosin: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy with antihypertensives such as alpha-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Tetrabenazine: (Severe) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy within the past 14 days. The major metabolites of tetrabenazine (alpha-dihydrotetrabenazine [HTBZ] and beta-HTBZ) are reversible inhibitors of vesicular monoamine transporter 2 (VMAT2). Inhibition of VMAT2 results in decreased uptake of monoamines into synaptic vesicles and depletion of monoamine stores.
    Tetracaine: (Major) Combined hypotensive effects are possible with use of monoamine oxidase inhibitors (MAOIs) and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Tetrahydrozoline: (Major) In general, tetrahydrozoline should not be combined with monoamine oxidase inhibitors (MAOIs). The combination of an MAOI and a sympathomimetic drug, including those given via nasal or ophthalmic routes, may result in hypertensive crisis. Avoid use during and up to 2 weeks following discontinuation of the MAOI. Consider alternative treatments for the patient's condition.
    Thiazide diuretics: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Thiazolidinediones: (Moderate) Serum glucose should be monitored closely when monoamine oxidase inhibitors (MAOIs) are added to any regimen containing antidiabetic agents. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents.
    Thiopental: (Major) Monoamine oxidase inhibitors (MAOIs) may prolong the effect of some barbiturates, which may increase CNS depression. Additionally, MAOIs may increase the risk of hypotension after barbiturates are used for sedation induction. When possible, MAOIs should be discontinued for at least 10 days prior to elective surgery due to potential interactions with anesthetic agents. Barbiturates should generally be given at a reduced dose with an MAOI.
    Thioridazine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Thiothixene: (Moderate) Concurrent use of monoamine oxidase inhibitors (MAOIs) and thiothixene may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and thiothixene should be used together cautiously.
    Tiagabine: (Moderate) Additive CNS depression is possible if monoamine oxidase inhibitors (MAOIs) and tiagabine are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
    Timolol: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with beta-blockers. Limited data suggest that bradycardia is worsened when MAOIs are administered to patients receiving beta-blockers. Although the sinus bradycardia observed was not severe, until more data are available, clinicians should use MAOIs cautiously in patients receiving beta-blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Tolcapone: (Severe) At least 14 days should elapse between the discontinuation of phenelzine, which is a non-selective MAO inhibitor, and the use of a COMT inhibitor to avoid potential interactions. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the 2 major enzymes involved in the metabolism of catecholamines. The combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism, which may lead to hypertensive crisis or other adverse effects.
    Torsemide: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Tramadol: (Severe) Tramadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression.
    Trandolapril: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Trandolapril; Verapamil: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with angiotensin-converting enzyme inhibitors (ACE inhibitors). Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider. (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Trazodone: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with trazodone or within 14 days of discontinuing treatment with trazodone. Conversely, trazodone should not be initiated within 14 days of stopping an MAOI.
    Treprostinil: (Moderate) Additive hypotensive effects may be seen when MAOIs are combined with antihypertensives or medications with hypotensive properties. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with treprostinil.
    Triamterene: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with diuretics. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Triazolam: (Moderate) The CNS depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. In addition, MAOIs can cause a variable change in seizure patterns, so careful monitoring of patients with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Tricyclic antidepressants: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Trifluoperazine: (Moderate) Concurrent use of MAOIs and phenothiazines may prolong or intensify the hypotensive, anticholinergic, or sedative effects of either agent. Due to the potential for additive CNS and cardiovascular effects, MAOIs and phenothiazines should be used together cautiously.
    Trimipramine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with tricyclic antidepressants (TCAs) or within 14 days of discontinuing treatment with a TCA. Conversely, TCAs should not be initiated within 14 days of stopping an MAOI. Monitor for serotonin-related side effects during therapy transitions.
    Valbenazine: (Major) Avoid the use of valbenazine with monoamine oxidase inhibitors (MAOIs). Concomitant use of valbenazine with MAOIs may increase the concentration of monoamine neurotransmitters in synapses, potentially leading to an increased risk of adverse reactions such as serotonin syndrome, or an attenuated treatment effect of valbenazine.
    Valerian, Valeriana officinalis: (Major) Any substances that act on the CNS may theoretically interact with valerian, Valeriana officinalis. The valerian derivative, dihydrovaltrate, binds at barbiturate binding sites; valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain; the non-volatile monoterpenes (valepotriates) have sedative activity. Patients taking MAOIs should discuss the use of herbal supplements with their health care professional prior to consuming valerian; combinations should be approached with caution in the absence of clinical data.
    Valproic Acid, Divalproex Sodium: (Moderate) Additive CNS depression is possible if MAOIs and valproic acid (or valproate, divalproex sodium) are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.
    Valsartan: (Moderate) Additive hypotensive effects may be seen when phenelzine is combined with angiotensin II receptor antagonists. Careful monitoring of blood pressure is suggested during concurrent therapy of phenelzine with angiotensin II receptor antagonists. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider during concurrent use of phenelzine and angiotensin II receptor antagonists.
    Venlafaxine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with serotonin norepinephrine reuptake inhibitors (SNRIs). MAOIs should not be used within 5 days of discontinuing treatment with duloxetine or milnacipran or within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Monitor the patient for serotonin-related effects during therapy transitions.
    Verapamil: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Careful monitoring of blood pressure is suggested during concurrent therapy of MAOIs with calcium-channel blockers. Patients should be instructed to rise slowly from a sitting position, and to report syncope or changes in blood pressure or heart rate to their health care provider.
    Vilazodone: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders, such as phenelzine, are contraindicated for use with vilazodone or within 14 days of discontinuing treatment with vilazodone. Conversely, vilazodone should not be initiated within 14 days of stopping an MAOI.
    Vortioxetine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with vortioxetine or within 21 days of discontinuing treatment with vortioxetine. Conversely, vortioxetine should not be initiated within 14 days of stopping an MAOI. Monitor patients for serotonin-related side effects during therapy transitions.
    Yohimbine: (Severe) Monoamine oxidase inhibitors (MAOIs) should not be used concurrently with or in rapid succession drugs that possess MAO-inhibiting activity, such as yohimbine. It would be prudent to avoid yohimbine during MAOI therapy and for 2 weeks after the discontinuation of a MAOI. Consider other alternatives to yohimbine. Use together could result in severe CNS or cardiovascular reactions, including hypertensive crisis or other serious side effects. At high doses, yohimbine may nonselectively inhibit monoamine oxidase (MAO) and also, at normal doses, activates the sympathetic nervous system via selective central alpha 2-adrenoceptor antagonism.
    Zolmitriptan: (Severe) The administration of zolmitriptan to patients currently receiving a monoamine oxidase-A inhibitor (e.g., moclobemide) or within 2 weeks of discontinuing an MAO-A inhibitor is contraindicated. Zolmitriptan and its metabolite are metabolized by monoamine oxidase A (MAO-A); therefore, plasma concentrations of zolmitriptan may be increased by concurrent use of selective MAO-A inhibitors or non-selective MAO-A and MAO-B inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid). Following one week of administration of moclobemide 150 mg PO twice daily, there was an increase of about 25% in both Cmax and AUC for zolmitriptan and a 3-fold increase in the Cmax and AUC of the active N-desmethyl metabolite of zolmitriptan.
    Zonisamide: (Moderate) Additive CNS depression is possible if MAOIs and zonisamide are coadministered. MAOIs can also cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required.

    PREGNANCY AND LACTATION

    Pregnancy

    The safe use of phenelzine during pregnancy has not been established. Doses of phenelzine in pregnant mice well exceeding the maximum recommended human dose have caused a significant decrease in the number of viable offspring per mouse. In addition, the growth of young dogs and rats has been retarded by doses exceeding the maximum human dose. Because pregnancy outcome data are too limited to be conclusive, phenelzine should be used during pregnancy only when the benefit to the mother clearly outweighs the potential risk to the mother or the fetus. An increased risk of malformations was found in the Collaborative Perinatal Project which monitored 21 mother-child pairs with exposure to a monoamine oxidase inhibitor (MAOI) during the first trimester of pregnancy (phenelzine pairs = 3). Limitations of this data include the small sample size, absence of malformation descriptions, and inclusion of isoniazid as an MAOI agent. Teratogenicity was not observed in two separate cases of in utero exposure to a MAOI, including phenelzine. The effects of phenelzine during labor and obstetric delivery are unknown.

    The safe use of phenelzine during breast-feeding has not been established, and the potential benefit of the drug should be weighed against the possible hazards to the mother and nursing infant. Phenelzine can elevate serum prolactin in some patients and has caused galactorrhea in non-lactating females. Due to the lack of data, generally antidepressant alternatives to phenelzine should be considered. Due to individual variability in response to antidepressants, it may be prudent to continue the existing regimen if ongoing treatment is deemed necessary during breast-feeding. However, because a pooled analysis found that maternal use of sertraline, along with nortriptyline and paroxetine, usually produced undetectable or low drug concentrations in infant serum, these agents may be the preferred antidepressants when initiating antidepressant therapy in a breast-feeding mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Phenelzine inhibits monoamine oxidase by binding to it irreversibly, similar to other traditional MAOIs such as tranylcypromine, isocarboxazid, and pargyline. Like other irreversible inhibitors, the MAO enzyme activity cannot be restored until the body replaces the enzyme through new enzyme synthesis, which takes a period of time after drug discontinuation, usually requiring up to 2 weeks. Depression is believed to result from dysregulation of CNS neurotransmitter systems. Antidepressant activity arises from the increased availability of monoamines, resulting from the inhibition of the enzyme monoamine oxidase (MAO). Reduction of MAO activity causes an increased concentration of neurotransmitters, such as epinephrine, norepinephrine, and dopamine, at various storage sites in the central nervous system and sympathetic nervous system.
     
    Phenelzine is a nonselective MAOI and desensitizes alpha- and beta-adrenergic and serotonin receptors. The delay of up to 4 weeks in therapeutic response to MAOI drugs may be accounted for by alterations in receptor characteristics rather than by increased neurotransmitter concentration. Inhibition of MAO in the GI tract and liver can cause systemic absorption of large amounts of tyramine, such as from ingestion of foods high in tyramine content. Consequently, severe hypertension may occur from a massive displacement of norepinephrine by tyramine from adrenergic storage sites. The exact mechanism by which MAOIs produce hypotension is unknown, but it has been proposed to be the result of actions at alpha- or beta-adrenergic receptors by false neurotransmitters which also aid in causing hypertensive crisis. It has been suggested that slow accumulation of these false neurotransmitters from MAO inhibition (e.g., octopamine produced from tyramine) occurs in neurons. It is also thought that octopamine may displace norepinephrine at these sites, simultaneously releasing octopamine, and causing a blockade of sympathetic neurotransmission. This is in contrast to the large release of norepinephrine which occurs from more rapid absorption of tyramine from the GI tract, causing a hypertensive crisis. MAOIs also interfere with the hepatic metabolism of many drugs.

    PHARMACOKINETICS

    Phenelzine is administered orally. There is insufficient evidence on distribution, and dosage is adjusted to suit patient response. The drug is rapidly metabolized in the liver and may produce active metabolites. Excretion is mainly as metabolites in the urine. The half-life is fairly short and is unrelated to the length of enzyme inhibition, which is prolonged.

    Oral Route

    Phenelzine is completely absorbed from the GI tract. Peak plasma concentrations are achieved between 2—4 hours. Onset of antidepressant action can take anywhere from 7 days to 8 weeks.