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  • CLASSES

    MAOI Antidepressants

    BOXED WARNING

    Children, suicidal ideation

    The safety and effectiveness of phenelzine have not been established in children or adolescents. In October 2004, the FDA directed manufacturers of all antidepressants to include a boxed warning detailing the risk of suicide in pediatric patients. A causal role has been established for antidepressants in inducing suicidality in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Pooled analysis of short-term clinical trials during early phase treatment with SSRIs and other antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavior. The clinical need for an antidepressant in children or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose changes. It is unknown if the suicidality risk in children and young adults extends to longer-term therapy (i.e., beyond several months). The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary psychiatric disorder. All patients with a history of suicidal ideation or behaviors and those with suicidal ideation prior to treatment are considered at an increased risk for suicidal ideation or attempts, and should be closely monitored during treatment with phenelzine. In patients who exhibit changes in symptoms, worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. All antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

    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 children or adolescents. In October 2004, the FDA directed manufacturers of all antidepressants to include a boxed warning detailing the risk of suicide in pediatric patients. A causal role has been established for antidepressants in inducing suicidality in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n = 4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Pooled analysis of short-term clinical trials during early phase treatment with SSRIs and other antidepressants in young adults (18 to 24 years) also showed an increased risk of suicidal thinking and behavior. The clinical need for an antidepressant in children or young adults for any use must be weighed against the risk of increased suicidality; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose changes. It is unknown if the suicidality risk in children and young adults extends to longer-term therapy (i.e., beyond several months). The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary psychiatric disorder. All patients with a history of suicidal ideation or behaviors and those with suicidal ideation prior to treatment are considered at an increased risk for suicidal ideation or attempts, and should be closely monitored during treatment with phenelzine. In patients who exhibit changes in symptoms, worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. All antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

    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
    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 (unspecified) / 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

    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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    Acetaminophen; Butalbital: (Major) Additive CNS depression may occur if butalbital is used concomitantly with monoamine oxidase inhibitors.
    Acetaminophen; Butalbital; Caffeine: (Major) Additive CNS depression may occur if butalbital is used concomitantly with monoamine oxidase inhibitors. (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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. 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. (Major) Additive CNS depression may occur if butalbital is used concomitantly with monoamine oxidase inhibitors. (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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. 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. (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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    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. 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.
    Acetaminophen; Dextromethorphan: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Acetaminophen; Dextromethorphan; Doxylamine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Acetaminophen; Hydrocodone: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Acetaminophen; Oxycodone: (Major) Concomitant use of oxycodone with other CNS depressants, such as MAOIs, can lead to additive respiratory or CNS depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Advise patients against driving or performing other tasks requiring alertness until they know how the combination affects them.
    Acetaminophen; Pentazocine: (Major) Patients receiving concurrent pentazocine and MAOIs are at increased risk for developing serotonin syndrome; pentazocine should be used cautiously, if at all, in these patients.
    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. Concomitant use of tramadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome or seizures. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tramadol.
    Alfentanil: (Major) Alfentanil belongs to the phenylpiperidine group of opioids. Meperidine, also a phenylpiperidine agent, has been reported to produce a life-threatening serotonin syndrome when coadministered with monoamine oxidase inhibitors. In addition to the potential for serotonin syndrome, opioids also potentiate the respiratory and CNS depression and hypotension caused by MAOIs. Severe and unpredictable potentiation of MAOIs has been reported rarely with alfentanil. Appropriate monitoring and immediate availability of vasodilators and beta blockers for the treatment of hypertension is recommended if alfentanil is used within 14 days of MAOI administration. Advise patients against driving or performing other hazardous activities after receiving alfentanil.
    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: (Severe) Whenever possible, do not give serotonin-receptor agonists like almotriptan concurrently with non-selective monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine, isocarboxazid) or within 2 weeks of discontinuation of MAOI therapy. If use together is unavoidable, co-use should be approached with caution and the patient monitored for signs of serotonergic excess and triptan-related side effects. Inhibitors of MAO type A may potentiate the clinical effects of almotriptan by reducing the metabolism of almotriptan and also by decreasing the metabolism of serotonin. Although unlikely to occur with 5HT1 agonists when given alone, combining medications that potentiate serotonin neurotransmission could result in serotonin syndrome. Almotriptan is metabolized by one minor and two major pathways: Monoamine oxidase (MAO)-mediated oxidative deamination (approximately 27% of the dose), and CYP450-mediated oxidation (approximately 12% of the dose) are the two major routes of metabolism. The representative selective MAO-A inhibitor moclobemide decreases almotriptan clearance by 27% and increases Cmax roughly 6%; however, dosage adjustments of almotriptan are not necessary. It is not known whether selective monoamine oxidase B inhibitors (e.g., selegiline) interact with almotriptan at clinically relevant dosages; at higher selegiline doses (> 20 mg) the selectivity of selegiline may be lost.
    Alogliptin: (Moderate) Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. Animal data indicate that tranylcypromine stimulates insulin secretion. It has also been proposed that MAOIs may interfere with the adrenergic response to hypoglycemia but it is uncertain how significant this action may be. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Alogliptin; Metformin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. Animal data indicate that tranylcypromine stimulates insulin secretion. It has also been proposed that MAOIs may interfere with the adrenergic response to hypoglycemia but it is uncertain how significant this action may be. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Alogliptin; Pioglitazone: (Moderate) Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and other antidiabetic agents. Animal data indicate that tranylcypromine stimulates insulin secretion. It has also been proposed that MAOIs may interfere with the adrenergic response to hypoglycemia but it is uncertain how significant this action may be. Serum glucose should be monitored closely when MAOIs are added to any regimen containing 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) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Alprazolam: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Altretamine: (Severe) Avoid concomitant use of antidepressant MAOIs during altretamine therapy whenever possible. Concurrent administration of altretamine and antidepressants of the monoamine oxidase (MAO) inhibitor class 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 MAO inhibitors (MAOIs). The mechanism of the interaction is not clear. While clinical reports of this interaction do not exist for selegiline transdermal, orthostatic hypotension has been reported as an uncommon but potentially significant adverse event in the elderly utilizing selegiline transdermal. The cautious use of altretamine and selegiline transdermal in this at-risk population should be observed to avoid pharmacodynamic interactions.
    Ambrisentan: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives or medications with hypotensive properties suah as ambrisentan. Careful monitoring of blood pressure is suggested during concurrent therapy.
    Amide local anesthetics: (Severe) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to etidocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Administration of a phenothiazine or a butyrophenone may reduce or reverse the pressor effect of epinephrine. Phenelzine, tranylcypromine, and transdermal selegiline are contraindicated for use for at least 10 days prior to elective surgery.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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; 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) MAOIs may prolong the effect of some barbiturates. Additionally, patients receiving MAOIs may have an increased risk of hypotension after administration of barbiturates used for sedation induction.
    Amoxapine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with heterocyclic antidepressants (e.g., trazodone, mirtazapine, amoxapine, maptrotiline) or within 14 days of discontinuing treatment with a heterocyclic antidepressant. Conversely, heterocyclic antidepressants should not be initiated within 14 days of stopping an MAOI. The manufacturer of rasagiline does not contraindicate the combination but recommends avoiding use of antidepressants with rasagiline or within 14 days of discontinuing rasagiline. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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 MAOIs. Apraclonidine should not be administered to patients who have received MAOIs within the previous 14 days.
    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) Additive CNS depression may occur if butalbital is used concomitantly with monoamine oxidase inhibitors. (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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. 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. (Major) Additive CNS depression may occur if butalbital is used concomitantly with monoamine oxidase inhibitors. (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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. 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. (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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. 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.
    Aspirin, ASA; Oxycodone: (Major) Concomitant use of oxycodone with other CNS depressants, such as MAOIs, can lead to additive respiratory or CNS depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Advise patients against driving or performing other tasks requiring alertness until they know how the combination affects them.
    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) Concurrent use of methylene blue and MAOIs (e.g., tranylcypromine, isocarboxazid, phenelzine, and including selective MAOIs such as selegiline, rasagiline) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and traditional MAOIs similarly increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with MAO-inhibiting agents or linezolid are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If emergent treatment with methylene blue is required in a patient receiving an MAOI, the MAOI should be stopped immediately and the patient should be monitored for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, the MAOI should be stopped at least 2 weeks prior to methylene blue treatment. Because rasagiline is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction with serotonin-enhancing medications may be less likely to occur than with other traditional MAO inhibitors.
    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) can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. MAOIs may prolong the effect of phenobarbital and cause additive CNS depression.
    atypical antipsychotic: (Moderate) Due to the potential for additive CNS and cardiovascular effects, 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) can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. MAOIs may prolong the effect of phenobarbital and cause additive CNS depression.
    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.
    Benzodiazepines: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Severe) Concurrent use of methylene blue and MAOIs (e.g., tranylcypromine, isocarboxazid, phenelzine, and including selective MAOIs such as selegiline, rasagiline) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and traditional MAOIs similarly increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with MAO-inhibiting agents or linezolid are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If emergent treatment with methylene blue is required in a patient receiving an MAOI, the MAOI should be stopped immediately and the patient should be monitored for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, the MAOI should be stopped at least 2 weeks prior to methylene blue treatment. Because rasagiline is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction with serotonin-enhancing medications may be less likely to occur than with other traditional MAO inhibitors.
    Benzonatate: (Major) These drugs should be prescribed with caution. It may be advisable to avoid the use of benzonatate, which is structurally similar to local anesthetic agents, in patients receiving a monoamine oxidase inhibitor (MAOI). Consider alternatives to benzonatate. Patients receiving a MAOI concurrently with local anesthetics may have an increased risk of hypotension or CNS-related effects. If co-use is medically necessary, observe the patient for additive effects such as low blood pressure, sedation, dizziness, mental confusion, or other side effects.
    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 co-use, 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. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline concurrently. 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.
    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 MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    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) Concurrent use of opioids with other drugs that modulate serotonergic function, such as monoamine oxidase inhibitors (MAOIs), has resulted in serotonin syndrome in some cases. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If combination treatment is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected. In addition, both MAOIs and buprenorphine have CNS depressant effects which may be additive during combination therapy. Patients should be advised to avoid driving or other tasks requiring mental alertness until the effects of the combination are known.
    Buprenorphine; Naloxone: (Major) Concurrent use of opioids with other drugs that modulate serotonergic function, such as monoamine oxidase inhibitors (MAOIs), has resulted in serotonin syndrome in some cases. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If combination treatment is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected. In addition, both MAOIs and buprenorphine have CNS depressant effects which may be additive during combination therapy. Patients should be advised to avoid driving or other tasks requiring mental alertness until the effects of the combination are known.
    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 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 HCL. A 10-day interval after discontinuing isocarboxazid is recommended before initiating buspirone treatment.
    Butabarbital: (Major) Monoamine oxidase inhibitors may prolong the effect of some barbiturates. Barbiturates should be used cautiously in patients receiving MAOIs.
    Butorphanol: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including butorphanol.
    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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet. (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.Selegiline can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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. Ordinarily, selegiline may be an exception, it can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Attention to the dose dependent nature of selegiline's selectivity is critical if it is to be used without elaborate restrictions being placed on diet.
    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) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Canagliflozin; Metformin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing 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 at the same time 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 the clinical situation permits, before administering carbamazepine. When starting MAOI therapy after discontinuing carbamazepine, 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 carbamazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients. Carbamazepine has also been shown to significantly elevate the levels of the MAOI selegiline, which may further increase the risk of a hypertensive crisis.
    Carbetapentane; Chlorpheniramine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Guaifenesin: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Phenylephrine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Pseudoephedrine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Pyrilamine: (Major) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    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) 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. (Major) Patients should not receive a COMT inhibitor in combination with non-selective MAOIs such as phenelzine. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines and the combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of phenelzine and the use of a COMT inhibitor to avoid potential interactions.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    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.
    Cetirizine: (Major) The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within two weeks of therapy with a MAOI.
    Cetirizine; Pseudoephedrine: (Major) The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within two weeks of therapy with a 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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Chloroprocaine: (Severe) Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to chloroprocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine, tranylcypromine, and transdermal selegiline 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. 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.
    Chlorpheniramine; Dextromethorphan: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    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. 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.
    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. 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.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Chlorpheniramine; Hydrocodone: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Chlorpromazine: (Major) 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.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Clonazepam: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Codeine: (Severe) Codeine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. 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.
    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. 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.
    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. 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. (Severe) The concurrent use of MAOIs with sedating H1-blockers is not recommended because of an increase in the intensity and prolongation of CNS-depressant and anticholinergic effects. Most manufacturers recommend that H1-antagonists not be used within two weeks of therapy with a MAOI.
    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. 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. (Severe) The concurrent use of MAOIs with sedating H1-blockers is not recommended because of an increase in the intensity and prolongation of CNS-depressant and anticholinergic effects. Most manufacturers recommend that H1-antagonists not be used within two weeks of therapy with a MAOI.
    COMT inhibitors: (Major) Patients should not receive a COMT inhibitor in combination with non-selective MAOIs such as phenelzine. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines and the combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of phenelzine and the use of a COMT inhibitor to avoid potential interactions.
    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) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Dapagliflozin; Metformin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Dapagliflozin; Saxagliptin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Desflurane: (Moderate) Use of monoamine oxidase inhibitors (MAOIs) with inhaled anesthetics, such as desflurane, may increase the risk of hemodynamic instability during surgery. Caution is advised if these drugs are administered together.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with SIADH including MAOIs. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
    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 within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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 should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Dextromethorphan: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Dextromethorphan; Guaifenesin: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Dextromethorphan; Promethazine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan. (Severe) The concurrent use of MAOIs with sedating H1-blockers is not recommended because of an increase in the intensity and prolongation of CNS-depressant and anticholinergic effects. Most manufacturers recommend that H1-antagonists not be used within two weeks of therapy with a MAOI.
    Dextromethorphan; Quinidine: (Severe) Dextromethorphan should be used cautiously, if at all, in patients receiving MAOIs; dextromethorphan is usually contraindicated in patients receiving traditional non-selective inhibitors of MAO (e.g., isocarboxazid, tranylcypromine, phenelzine). Dextromethorphan can block neuronal uptake of serotonin and may produce excessive concentrations of serotonin in the CNS if combined with monoamine oxidase inhibitors (MAOIs), with the potential for severe reactions. The interaction may cause symptoms similar to those seen with meperidine and MAOIs. A single case report is noted of an acute, fatal drug reaction immediately following the ingestion of a cough mixture containing dextromethorphan in a patient who had been taking phenelzine; the 26-year old female felt nauseated and dizzy, then collapsed. Her temperature rose to 42 degrees C and 4 hours later she died of a cardiac arrest. Similar cases of interactions between phenelzine or isocarboxazid and dextromethorphan have been reported in the medical literature. There has also been a report of an interaction in which drowsiness and bizarre behavior appeared following the ingestion of a dextromethorphan lozenge with phenelzine. Patients should avoid the use of dextromethorphan-containing medications during MAOI use and for 2 weeks following MAOI discontinuation. Selective inhibitors of MAO-B (e.g., selegiline) also contain warnings regarding avoiding use of dextromethorphan concurrently when possible; the manufacturer of selegiline transdermal specifically contraindicates the combined use with dextromethorphan.
    Diazepam: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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. 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.
    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) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Dolasetron: (Major) 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. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Dronabinol, THC: (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. Following administration of droperidol, lower doses of the other CNS depressant should be used.
    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 within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Eletriptan: (Severe) Unlike many other serotonin recepetor agonists, eletriptan is not a substrate for monoamine oxidase (MAO) enzymes; therefore, the metabolism of eletriptan is not affected by monoamine oxidase inhibitors (MAOIs). However, combining medications that potentiate serotonin neurotransmission could result in serotonin syndrome and whenever possible, it is recommended that co-use be avoided. Non-selective MAOIs such as phenelzine, isocarboxazid, tranylcypromine decrease serotonin metabolism. Serotonin syndrome consists of symptoms such as mental status changes (e.g., agitation, confusion, hallucinations), diaphoresis, hyperreflexia, hypertension, diarrhea, fever, tremor, and, in some instances, respiratory failure. If it is required that eletriptan be given to patients receiving another serotonergic drug, appropriate observation of the patient is recommended. It should be noted that selegiline, a selective MAO-B inhibitor, may interact with eletriptan at higher doses (> 20 mg) since the MAO-B selectivity of the drug diminishes at higher doses.
    Empagliflozin: (Moderate) Selected monoamine oxidase inhibitors (MAOIs) have potentiated hypoglycemia in animal models; there are conflicting data regarding hypoglycemic reactions in humans. These effects do not appear to be due to MAO activity, but rather, a change in gluconeogenesis or insulin sensitivity related to a hydrazine chemical structure. It is not clear if all MAOIs affect blood glucose control or potentiate antidiabetic medications. When initiating MAOIs in a patient receiving antidiabetic agents, the patient should monitor their blood glucose and report any changes in blood sugar control.
    Empagliflozin; Linagliptin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents, such as linagliptin. (Moderate) Selected monoamine oxidase inhibitors (MAOIs) have potentiated hypoglycemia in animal models; there are conflicting data regarding hypoglycemic reactions in humans. These effects do not appear to be due to MAO activity, but rather, a change in gluconeogenesis or insulin sensitivity related to a hydrazine chemical structure. It is not clear if all MAOIs affect blood glucose control or potentiate antidiabetic medications. When initiating MAOIs in a patient receiving antidiabetic agents, the patient should monitor their blood glucose and report any changes in blood sugar control.
    Empagliflozin; Metformin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Selected monoamine oxidase inhibitors (MAOIs) have potentiated hypoglycemia in animal models; there are conflicting data regarding hypoglycemic reactions in humans. These effects do not appear to be due to MAO activity, but rather, a change in gluconeogenesis or insulin sensitivity related to a hydrazine chemical structure. It is not clear if all MAOIs affect blood glucose control or potentiate antidiabetic medications. When initiating MAOIs in a patient receiving antidiabetic agents, the patient should monitor their blood glucose and report any changes in blood sugar control.
    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 MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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: (Major) Patients should not receive a COMT inhibitor in combination with non-selective MAOIs such as phenelzine. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines and the combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of phenelzine and the use of a COMT inhibitor to avoid potential interactions.
    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 vasodilators.
    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 vasodilators.
    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.
    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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Ester local anesthetics: (Severe) Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to chloroprocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine, tranylcypromine, and transdermal selegiline 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 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. Selegeline can only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages containing high concentrations of pressor amines such as tyramine. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing products have been reported in patients receiving the normal daily doses of selegiline.
    Etomidate: (Severe) Patients taking MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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) MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.
    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.
    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 14 days. Concomitant use of fentanyl with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. Serotonin syndrome and death occurred in1 patient previously stable on the MAOI tranylcypromine following an uneventful CABG surgery in which fentanyl was administered. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as fentanyl.
    Fluphenazine: (Major) 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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Food: (Severe) Food interactions with MAOIs can be serious. Beverages containing caffeine or ethanol may also be hazardous. Excessive caffeine consumption can produce severe hypertensive crises or dangerous cardiac arrhythmias if administered to patients taking an MAOI. Preparations containing caffeine should be used sparingly such as tea, coffee, chocolate, cola, guarana, or 'stay awake' products. Some non-prescription medicines also contain caffeine and should not be taken without health care professional advice. 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 < 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. 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. Selegeline may be an exception. However, rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients receiving the normal daily doses of selegiline. Selegiline can ordinarily only be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day). At doses of 20 mg/day, selegiline can interact with foods and beverages containing high concentrations of pressor amines such as tyramine. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg per day. Transdermal selegiline has specific dietary guidelines for each strength of patch. Tyramine-rich foods and beverages should be avoided beginning on the first day of selegiline transdermal 9 mg/24 hour or 12 mg/24 hour treatment. Avoidance should be continued for 2 weeks after a dose reduction to selegiline transdermal 6 mg/24 hours or following the discontinuation of selegiline transdermal 9 mg/24 hours or 12 mg/24 hours. At the 6 mg/24 hour transdermal dose, selegiline is selective for MAO type B and food/beverage/dietary supplement restrictions are not required. At transdermal doses of 9 or 12 mg/24 hour, the interaction of selegiline transdermal with foods and beverages containing high concentrations of pressor amines such as tyramine cannot be ruled out.
    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 MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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: (Severe) The manufacturers of some serotonin agonists contraindicate the administration of their drugs to patients receiving non-selective monoamine oxidase inhibitors (MAOIs) or within 2 weeks of discontinuation of such MAO inhibitors. Although unlikely to occur with 5HT1 agonists when given alone, combining medications that potentiate serotonin neurotransmission could result in serotonin syndrome. The monoamine oxidase (MAO) type A enzyme metabolizes serotonin. Non-selective traditional MAOIs (e.g., phenelzine, tranylcypromine, isocarboxazid) increase the plasma concentrations of these drugs and some of their active metabolites, thus increasing levels of serotonin. Serious CNS reactions, such as 'serotonin syndrome' (presenting as agitation, restlessness, aggressive behavior, insomnia, poor concentration, headache, paresthesia, incoordination, worsening of obsessive thoughts or compulsive behavior, nausea, abdominal cramps, diarrhea, palpitations, or chills) are possible.
    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) Monoamine oxidase inhibitors (MAOIs) can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.
    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 MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Glyburide; Metformin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Granisetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as phenelzine. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Green Tea: (Severe) Green tea catechins inhibit Catechol O methyltransferase, COMT in animals. Monoamine oxidase, MAO and COMT are the two major enzymes involved in the metabolism of catecholamines. It may be prudent to avoid the combination of green tea and monoamine oxidase inhibitors. As is recommended with other COMT inhibitors, 14 days should lapse between the discontinuation of nonselective MAOIs and the use of green tea. In addition, some, but not all, 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. Caffeine use should be minimized or avoided during and for 12 weeks after discontinuation of any MAOI. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, serious reactions with green tea are expected to be less likely to occur than with non-selective MAOIs such as phenelzine or tranylcypromine.
    Guaifenesin; Hydrocodone: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    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 monoamine oxidase inhibitors (MAOIs) should be used cautiously in patients who are undergoing guanabenz withdrawal.
    Guanfacine: (Severe) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) are combined with antihypertensives. Certain antihypertensive-MAOI combinations warrant particular caution. 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. A similar reaction with MAOIs may be anticipated with concurrent administration of guanfacine since both guanfacine and clonidine are centrally-acting alpha-2 adrenergic agonists. Concurrent administration of guanfacine and MAOIs should be avoided if possible.
    Guarana: (Severe) Caffeine, an active constituent of guarana, interacts with MAOIs (including drugs with MAOI activity such as furazolidone, isoniazid, INH, linezolid, procarbazine, and high doses of yohimbine). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Guarana should be avoided during and for 1 to 2 weeks after discontinuation of any MAOI. Rasagiline is a selective MAO-B inhibitor at manufacturer recommended doses; therefore, serious reactions with guarana are expected to be less likely to occur with rasagiline.
    Halothane: (Severe) Patients taking MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hydantoins: (Moderate) MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.
    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. Data describing this interaction are limited. In addition, other reports describe safe use of these agents in combination. (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) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hydrocodone; Ibuprofen: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hydrocodone; Phenylephrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hydrocodone; Pseudoephedrine: (Major) Hydrocodone is not recommended for use in patients who have received MAOIs within 14 days. Certain products are contraindicated due to the risk: benefit ratio (e.g., hydrocodone-containing cough syrups). Consider if an alternative to the hydrocodone-containing product is available and appropriate. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. Also, potentiation of the effects of the MAOI have been reported, which may increase the risk for adverse events. If combination therapy is necessary, advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hydromorphone: (Major) Concomitant use of hydromorphone with monoamine oxidase inhibitors (MAOIs) can potentiate the effects of hydromorphone and may lead to additive respiratory or CNS depression. If concurrent use of hydromorphone and a MAOI is required, carefully monitor the patient for hypotension, excessive sedation, respiratory depression, and CNS depression. The manufacturer of hydromorphone extended-release tablets (Palladone) recommends discontinuation of the MAOI for at least 14 days before starting Palladone. Advise patients against driving or performing other hazardous activities until they know how the combination affects them.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Severe) Concurrent use of methylene blue and MAOIs (e.g., tranylcypromine, isocarboxazid, phenelzine, and including selective MAOIs such as selegiline, rasagiline) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and traditional MAOIs similarly increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with MAO-inhibiting agents or linezolid are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If emergent treatment with methylene blue is required in a patient receiving an MAOI, the MAOI should be stopped immediately and the patient should be monitored for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, the MAOI should be stopped at least 2 weeks prior to methylene blue treatment. Because rasagiline is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction with serotonin-enhancing medications may be less likely to occur than with other traditional MAO inhibitors.
    Ibuprofen; Oxycodone: (Major) Concomitant use of oxycodone with other CNS depressants, such as MAOIs, can lead to additive respiratory or CNS depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Advise patients against driving or performing other tasks requiring alertness until they know how the combination affects them.
    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 vasodilators.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Incretin Mimetics: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing 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.
    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 insulin and oral sulfonylureas.
    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 MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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.
    Kava Kava, Piper methysticum: (Major) Avoid the concomitant use of psycho-active herbs, such as kava kava, with MAOIs whenever possible. The German Commission E and other groups warn that any substances that act on the CNS, including MAOIs, may interact with the phytomedicinal kava kava, Piper methysticum. These interactions are probably pharmacodynamic in nature, or result from additive mechanisms of action.
    Ketamine: (Severe) Patients taking MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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) MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.
    Levetiracetam: (Moderate) MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.
    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) The anticholinergic activity of MAOIs is minimal; however, anticholinergic effects sometimes occur. Most manufacturers recommend that cetirizine/levocetirizine not be used within two weeks of therapy with a 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) Concomitant use of central nervous system depressants, such as MAOIs, can potentiate the effects of levomethadyl, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses.
    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 within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Levorphanol: (Major) Levorphanol is specifically not recommended for use with monoamine oxidase inhibitors (MAOIs) due to possible additive CNS depressant effects.
    Linagliptin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents, such as linagliptin.
    Linagliptin; Metformin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAOIs) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents, such as linagliptin.
    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: (Major) There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and monoamine oxidase inhibitors. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, 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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required when benzodiazepines are used in the treatment of epilepsy.
    Lorcaserin: (Major) Avoid use together if possible. The 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, 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) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with heterocyclic antidepressants (e.g., trazodone, mirtazapine, amoxapine, maptrotiline) or within 14 days of discontinuing treatment with a heterocyclic antidepressant. Conversely, heterocyclic antidepressants should not be initiated within 14 days of stopping an MAOI. The manufacturer of rasagiline does not contraindicate the combination but recommends avoiding use of antidepressants with rasagiline or within 14 days of discontinuing rasagiline. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Meglitinides: (Moderate) Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to antidiabetic agents. It has also been proposed that MAOIs may interfere with the adrenergic response to hypoglycemia but it is uncertain how significant this action may be. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Meperidine: (Severe) Meperidine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Severe reactions including coma, severe respiratory depression, cyanosis, and hypotension have occurred; some reactions have been fatal. The mechanism of these reactions is unclear; however, it may be related to a preexisting hyperphenylalaninemia. Concomitant use of meperidine with other serotonergic drugs such as MAOIs may result in serotonin syndrome with excitation; sweating; rigidity; hypertension; severe respiratory depression; coma; and circulatory collapse, possibly resulting in death. Intravenous hydrocortisone or prednisolone has been used to treat severe reactions, with the addition of intravenous chlorpromazine in cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of opiate antagonists in the treatment of these reactions is unknown.
    Meperidine; Promethazine: (Severe) Meperidine use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Severe reactions including coma, severe respiratory depression, cyanosis, and hypotension have occurred; some reactions have been fatal. The mechanism of these reactions is unclear; however, it may be related to a preexisting hyperphenylalaninemia. Concomitant use of meperidine with other serotonergic drugs such as MAOIs may result in serotonin syndrome with excitation; sweating; rigidity; hypertension; severe respiratory depression; coma; and circulatory collapse, possibly resulting in death. Intravenous hydrocortisone or prednisolone has been used to treat severe reactions, with the addition of intravenous chlorpromazine in cases exhibiting hypertension and hyperpyrexia. The usefulness and safety of opiate antagonists in the treatment of these reactions is unknown. (Severe) The concurrent use of MAOIs with sedating H1-blockers is not recommended because of an increase in the intensity and prolongation of CNS-depressant and anticholinergic effects. Most manufacturers recommend that H1-antagonists not be used within two weeks of therapy with a MAOI.
    Mephobarbital: (Major) MAOIs may prolong the effect of mephobarbital and cause additive CNS depression. MAOIs can also cause a change in seizure patterns, so an adjustment in the dose of any anticonvulsant may be necessary.
    Mesoridazine: (Major) 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.
    Metformin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Metformin; Pioglitazone: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Metformin; Repaglinide: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to antidiabetic agents. It has also been proposed that MAOIs may interfere with the adrenergic response to hypoglycemia but it is uncertain how significant this action may be. Serum glucose should be monitored closely when MAOIs are added to any regimen containing antidiabetic agents.
    Metformin; Rosiglitazone: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Metformin; Saxagliptin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Metformin; Sitagliptin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents. Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost. (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Methadone: (Major) Due to the severity of the interaction of meperidine (a related opioid) with monoamine oxidase inhibitors (MAOIs), a sensitivity test for methadone should be performed in patients taking phenelzine by administering repeated small incremental doses of methadone over several hours while carefully monitoring the patient's condition and vital signs. Concomitant use of methadone with a MAOI can lead to additive respiratory depression. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant. Respiratory depression, hypotension, and profound sedation or coma may result.
    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; hypotension usually responds to phenelzine dosage reduction or to discontinuation, if needed.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Severe) Concurrent use of methylene blue and MAOIs (e.g., tranylcypromine, isocarboxazid, phenelzine, and including selective MAOIs such as selegiline, rasagiline) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and traditional MAOIs similarly increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with MAO-inhibiting agents or linezolid are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If emergent treatment with methylene blue is required in a patient receiving an MAOI, the MAOI should be stopped immediately and the patient should be monitored for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, the MAOI should be stopped at least 2 weeks prior to methylene blue treatment. Because rasagiline is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction with serotonin-enhancing medications may be less likely to occur than with other traditional MAO inhibitors.
    Methohexital: (Severe) Patients receiving monoamine oxidase inhibitors (MAOIs) may have an increased risk of hypotension after administration of general anesthetics, although specific studies are not available. Combined hypotensive effects are also possible with the combined use of MAOIs and spinal anesthetics. In general, MAOIs should be discontinued for at least 10 days prior to elective surgery.
    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. Data describing this interaction are limited. In addition, other reports describe safe use of these agents in combination.
    Methylene Blue: (Severe) Concurrent use of methylene blue and MAOIs (e.g., tranylcypromine, isocarboxazid, phenelzine, and including selective MAOIs such as selegiline, rasagiline) should generally be avoided due to the potential for serotonin syndrome. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and traditional MAOIs similarly increase central serotonin effects. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with MAO-inhibiting agents or linezolid are at a comparable risk or if methylene blue administered by other routes (e.g., orally, local injection) or in doses less than 1 mg/kg IV can produce a similar outcome. Published interaction reports between intravenously administered methylene blue and serotonergic psychiatric agents have documented symptoms including lethargy, confusion, delirium, agitation, aggression, obtundation, myoclonus, expressive aphasia, hypertonia, pyrexia, elevated blood pressure, seizures, and/or coma. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death. If emergent treatment with methylene blue is required in a patient receiving an MAOI, the MAOI should be stopped immediately and the patient should be monitored for symptoms of CNS toxicity for two weeks or until 24 hours after the last dose of methylene blue, whichever comes first. During non-emergent use of methylene blue, the MAOI should be stopped at least 2 weeks prior to methylene blue treatment. Because rasagiline is a selective monoamine oxidase-B (MAO-B) inhibitor at manufacturer recommended doses, an interaction with serotonin-enhancing medications may be less likely to occur than with other traditional MAO inhibitors.
    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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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 within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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: (Major) While the manufacturer does not discuss the use of mirabegron in patients on MAOI therapy, it may be best to use this combination cautiously. Mirabegron is a selective beta-3 adrenergic agonist that may elevate blood pressure slightly at clinically used doses, and it is possible that this sympathomimetic activity could raise the risk of hypertensive crisis in patients receiving monoamine oxidase inhibitors (MAOIs), similar to other adrenergic medications. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (i.e., at mirabegron doses of 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 one agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
    Mirtazapine: (Severe) Due to the risk of serotonin syndrome, monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders are contraindicated for use with heterocyclic antidepressants (e.g., trazodone, mirtazapine, amoxapine, maptrotiline) or within 14 days of discontinuing treatment with a heterocyclic antidepressant. Conversely, heterocyclic antidepressants should not be initiated within 14 days of stopping an MAOI. The manufacturer of rasagiline does not contraindicate the combination but recommends avoiding use of antidepressants with rasagiline or within 14 days of discontinuing rasagiline. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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. 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.
    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. 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.
    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: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including nalbuphine. Use nalbuphine cautiously with MAOIs; warn patients to not drive or perform other hazardous activities until they know how a particular drug combination affects them. In some cases, the dosages of the CNS depressants may need reduced.
    Naproxen; Sumatriptan: (Severe) Concurrent administration of sumatriptan and an MAO-A inhibitor or use of sumatriptan within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated. Sumatriptan appears to be metabolized by monoamine oxidase (MAO), predominantly MAO-type A; therefore, plasma concentrations of sumatriptan may be increased by concurrent use of selective MAO-A inhibitors (e.g., meclobemide) or non-selective MAO-A and MAO-B inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid). Because oral sumatriptan usually undergoes first-pass metabolism, the increase of AUC after coadministration of an MAO-A inhibitor is greater than the interaction with subcutaneous sumatriptan combined with an MAO-A inhibitor. The effects of an MAOI on the AUC after intranasal sumatriptan use would be expected to be greater than the effect after sumatriptan SC but smaller than the effect after sumatriptan PO. In a study of healthy female volunteers (n=14), pretreatment with an MAO-A inhibitor (moclobemide) decreased the clearance of subcutaneous sumatriptan resulting in a 2-fold increase in sumatriptan AUC and a 40% increase in elimination half-life. The interaction was not evident with an MAO-B inhibitor (e.g., selegiline). 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: (Severe) Use of naratriptan and non-selective monoamine oxidase inhibitors (e.g., phenelzine) should be avoided if possible. Because the monoamine oxidase (MAO) type A enzyme metabolizes serotonin, inhibition of MAO-A increases central serotonin levels, which could be additive with the serotonin-enhancing effects of naratriptan. Although unlikely to occur with 5HT1 agonists when given alone, combining medications that potentiate serotonin neurotransmission could result in serotonin syndrome. Serotonin syndrome consists of symptoms such as mental status changes (e.g., agitation, confusion, hallucinations), diaphoresis, hyperreflexia, hypertension, diarrhea, fever, tremor, and, in some instances, respiratory failure. Do not give naratriptan within 2 weeks of discontinuation of MAOI therapy.
    Nateglinide: (Moderate) Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to antidiabetic agents. It has also been proposed that MAOIs may interfere with the adrenergic response to hypoglycemia but it is uncertain how significant this action may be. Serum glucose should be monitored closely when MAOIs are added to any regimen containing 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; Palonosetron: (Major) 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. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    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: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with antidepressants.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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: (Major) 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. If serotonin syndrome is suspected, discontinue ondansetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Oxazepam: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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. Watch carefully for other effects besides effects on blood pressure, such as sedation, confusion, and increased CNS depression. If oxcarbazepine is used for the treatment of epilepsy, be aware that MAOI effects can include lowering of seizure threshold in some patients.
    Oxycodone: (Major) Concomitant use of oxycodone with other CNS depressants, such as MAOIs, can lead to additive respiratory or CNS depression, hypotension, profound sedation, or coma. Prior to concurrent use of oxycodone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Initiate oxycodone at one-third to one-half the usual dosage in patients that are concurrently receiving another CNS depressant. Also consider using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression. Advise patients against driving or performing other tasks requiring alertness until they know how the combination affects them.
    Oxymetazoline: (Major) Oxymetazoline should not be used in patients taking non-selective monoamine oxidase inhibitors (MAOIs); also avoid use in patients taking selegiline. 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.
    Oxymorphone: (Major) Some manufacturers of oxymorphone recommend against use within 14 days of treatment with a monoamine oxidase inhibitor (MAOI) because severe and unpredictable potentiation by MAO inhibitors has been reported with opiates. During concurrent use of other CNS depressants, additive respiratory or CNS depressant effects, hypotension, profound sedation, coma, or death may occur. If concurrent use is necessary, assess the level of tolerance to CNS depression that has developed, the duration of use, the patient's overall response to treatment, and the patient's use of alcohol or illicit drugs. Initiate oxymorphone at one-third to one-half the usual dosage in patients concurrently receiving another CNS depressant and slowly titrate the dose based on efficacy and tolerability. Consider a lower dose of the CNS depressant. Advise patients against driving or performing other activities requiring mental alertness until they know how the combination affects them.
    Palonosetron: (Major) 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. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    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) Patients receiving concurrent pentazocine and MAOIs are at increased risk for developing serotonin syndrome; pentazocine should be used cautiously, if at all, in these patients.
    Pentazocine; Naloxone: (Major) Patients receiving concurrent pentazocine and MAOIs are at increased risk for developing serotonin syndrome; pentazocine should be used cautiously, if at all, in these patients.
    Pentobarbital: (Major) Monoamine oxidase inhibitors (MAOIs) can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. MAOIs may prolong the effect of pentobarbital and cause additive CNS depression.
    Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as MAOIs.
    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: (Major) 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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. (Major) 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) can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. MAOIs may prolong the effect of phenobarbital and cause additive CNS depression.
    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: (Severe) The concurrent use of MAOIs with sedating H1-blockers is not recommended because of an increase in the intensity and prolongation of CNS-depressant and anticholinergic effects. Most manufacturers recommend that H1-antagonists not be used within two weeks of therapy with a MAOI.
    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) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    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.
    Primidone: (Major) Monoamine oxidase inhibitors (MAOIs) can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. MAOIs may prolong the effect of barbiturates like primidone and cause additive CNS depression.
    Procaine: (Severe) Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to chloroprocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine, tranylcypromine, and transdermal selegiline 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: (Major) 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: (Severe) The concurrent use of MAOIs with sedating H1-blockers is not recommended because of an increase in the intensity and prolongation of CNS-depressant and anticholinergic effects. Most manufacturers recommend that H1-antagonists not be used within two weeks of therapy with a MAOI.
    Propofol: (Severe) Patients taking MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Quazepam: (Moderate) The CNS-depressant effects of MAOIs can be potentiated with concomitant administration of other drugs known to cause CNS depression including benzodiazepines. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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) (e.g., isocarboxazid, pargyline, phenelzine, tranylcypromine, selegiline, or transdermal selegiline). The combination or rapid succession of MAOI treatment could result in severe CNS or cardiovascular reactions, including hypertensive crises, hyperpyrexia, CNS excitation, delirium, tremor, convulsions, 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) Remifentanil use is not recommended in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Concomitant use of remifentanil 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 remifentanil. If urgent use is necessary, use test doses of remifentanil with frequent titration of small doses and close monitoring. If serotonin syndrome is suspected, discontinue remifentanil and/or the MAOI.
    Repaglinide: (Moderate) Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to antidiabetic agents. It has also been proposed that MAOIs may interfere with the adrenergic response to hypoglycemia but it is uncertain how significant this action may be. Serum glucose should be monitored closely when MAOIs are added to any regimen containing 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) The administration of rizatriptan to patients currently receiving a monoamine oxidase A inhibitor or within 2 weeks of discontinuing a monoamine oxidase A inhibitor is contraindicated. Rizatriptan is principally metabolized by monoamine oxidase A (MAO-A); therefore, plasma concentrations of rizatriptan may be increased by concurrent use of selective MAO-A inhibitors (e.g., meclobemide) or non-selective MAO-A and MAO-B inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid) and rizatriptan. During a drug interaction study with meclobemide, 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. According to the manufacturer, no interaction is expected between rizatriptan and selective MAO-B inhibitors. However, it should be noted that selegiline, a selective MAO-B inhibitor, may interact with rizatriptan at higher doses (> 20 mg) since the MAO-B selectivity of the drug diminishes at higher doses.
    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.
    S-adenosyl-L-methionine, SAM-e: (Major) Pharmacologic studies suggest that S-adenosyl-L-methionine, SAM-e may have additive pharmacodynamic effects with traditional antidepressant therapies such as the tricyclic antidepressants or MAOIs, but the pharmacology is poorly understood. Pharmacology studies indicate that SAM-e augments dopaminergic and serotonergic systems, and may have a weak inhibitory effect on MAO-B within the CNS. The routine addition of SAM-e to other conventional antidepressant medications, especially MAOIs, should be approached with caution until the mechanism of action of SAM-e with regard to neurotransmitter function or receptor activity is clarified. This dietary supplement is probably best avoided in combination with prescription antidepressants unless closely monitored by a health care professional.
    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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Saxagliptin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Secobarbital: (Major) MAOIs may prolong the effect of primidone and cause additive CNS depression.
    Sedating H1-blockers: (Major) Concurrent use of monoamine oxidase inhibitors (MAOIs) and sedating H1-blockers (sedating antihistamines) may result in additive sedation, anticholinergic effects, or hypotensive reactions. Consider alternative therapy to antihistamines where possible. If alternative combinations are not available, these medications may be used together with close monitoring. Many non-prescription 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 healthcare provider or pharmacist prior to the use of any non-prescription products. Patients should also be advised against driving or engaging in other activities requiring mental alertness until they know how this combination affects them.
    Selective norepinephrine reuptake inhibitors: (Severe) The use of selective norepinephrine reuptake inhibitors with monoamine oxidase inhibitors 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. Since some of these catecholamines are deaminated by monoamine oxidase, the administration of drugs that inhibit this enzyme concurrently with an atomoxetine can lead to serious reactions, such as those seen with other reuptake inhibitors. These reactions 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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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 within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Sevoflurane: (Severe) Patients taking MAOIs should not undergo elective surgery, including dental procedures, that require the use of general anesthetics due to the potential for CNS and cardiovascular reactions. Combined 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) The concomitant use of sibutramine with MAOIs is contraindicated. Sibutramine is a serotonin reuptake inhibitor. Since serotonin is deaminated by monoamine oxidase-A, concurrent administration of sibutramine with drugs that inhibit this enzyme such as MAOIs can lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. 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) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Sitagliptin: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Sodium Oxybate: (Severe) Sympathomimetics and psychostimulants are contraindicated in patients receiving MAOIs. When administeringan MAOI in close proximity to a sympathomimetic or psychostimulant, at least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other. MAOIs can increase the amount of norepinephrine in neuronal storage sites. Administration of an indirect-acting sympathomimetic (e.g., those that cause release of norepinephrine) to patients receiving a MAOI may invoke a severe hypertensive reaction. Data describing an interaction between some psychostimulants (e.g., modafinil or sodium oxybate) and MAOIs are less readily available, but, in general, all psychostimulants should be avoided in patients receiving a MAOI.
    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 MAOIs or drugs that possess MAOI-like activity because of the possibility of severe hyperpyretic or hypertensive crises, convulsions, or death. Since serotonin is deaminated by monoamine oxidase type A, administration of non-selective MAOIs concurrently with St. John's wort could potentially lead to a serious reaction known as 'serotonin syndrome'. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Succinimides: (Moderate) MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.
    Succinylcholine: (Major) Limited data suggest that the neuromuscular blocking effect of succinylcholine may be enhanced by drugs that reduce plasma pseudocholinesterase, such as monoamine oxidase inhibitors (MAOIs). These drugs should be used together with caution.
    Sufentanil: (Major) Concomitant use of sufentanil with other central nervous system (CNS) depressants, such as monoamine oxidase inhibitors (MAOIs), can potentiate sufentanil-induced CNS or respiratory depression and cardiovascular effects and the duration of these effects. Dose reduction of sufentanil and/or the concurrent CNS depressant is recommended. Advise patients against driving or performing other hazardous activities after receiving sufentanil.
    Sulfonylureas: (Moderate) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Sumatriptan: (Severe) Concurrent administration of sumatriptan and an MAO-A inhibitor or use of sumatriptan within 2 weeks of discontinuation of MAO-A inhibitor therapy is contraindicated. Sumatriptan appears to be metabolized by monoamine oxidase (MAO), predominantly MAO-type A; therefore, plasma concentrations of sumatriptan may be increased by concurrent use of selective MAO-A inhibitors (e.g., meclobemide) or non-selective MAO-A and MAO-B inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid). Because oral sumatriptan usually undergoes first-pass metabolism, the increase of AUC after coadministration of an MAO-A inhibitor is greater than the interaction with subcutaneous sumatriptan combined with an MAO-A inhibitor. The effects of an MAOI on the AUC after intranasal sumatriptan use would be expected to be greater than the effect after sumatriptan SC but smaller than the effect after sumatriptan PO. In a study of healthy female volunteers (n=14), pretreatment with an MAO-A inhibitor (moclobemide) decreased the clearance of subcutaneous sumatriptan resulting in a 2-fold increase in sumatriptan AUC and a 40% increase in elimination half-life. The interaction was not evident with an MAO-B inhibitor (e.g., selegiline). 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.
    Sympathomimetics: (Severe) In general, all types of sympathomimetics and psychostimulants 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 even 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 of tapentadol 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 tapentadol.
    Tedizolid: (Major) 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, particularly with non-selective MAOIs (e.g., phenelzine, tranylcypromine, isocarboxazid). However, caution is also warranted with selective agents, such as selegiline and rasagiline. Although rasagiline differs from other MAOIs because it is MAO-B selective at recommended doses, it may be advisable to avoid co-administration with tedizolid until specific information becomes available about the safety of this combination. Tedizolid is an antibiotic that is also a weak reversible, non-selective MAO inhibitor, similar to linezolid, which is structurally related. Serotonin syndrome has been reported when linezolid has been administerd with certain serotonergic agents. In theory, serotonin syndome could occur with the concomitant use of MAOIs; however, the FDA states that it is unclear if concomitant use of linezolid and agents with lesser degrees of serotonergic activity would pose a comparable risk. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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: (Severe) Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. Use of epinephrine added to chloroprocaine with monoamine oxidase inhibitors (MAOIs) or drugs with MAOI activity (e.g., furazolidone, linezolid, or procarbazine) is not recommended. When local anesthetics containing sympathomimetic vasoconstrictors are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs and agents with MAOI activity can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine, tranylcypromine, and transdermal selegiline are contraindicated for use for at least 10 days prior to elective surgery.
    Tetrahydrozoline: (Severe) 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.
    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) Animal data indicate that monoamine oxidase inhibitors (MAO inhibitors) may stimulate insulin secretion. Inhibitors of MAO type A have been shown to prolong the hypoglycemic response to insulin and oral sulfonylureas. Serum glucose should be monitored closely when MAOI-type medications, including the selective MAO-B inhibitor selegiline, are added to any regimen containing antidiabetic agents.Although at low doses selegiline is selective for MAO type B, in doses above 30 to 40 mg/day, this selectivity is lost.
    Thiopental: (Severe) Patients receiving MAOIs may have an increased risk of hypotension after administration of general anesthetics. In general, MAOIs should be discontinued for at least 10 days prior to elective surgery.
    Thioridazine: (Major) 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: (Major) 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) MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.
    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: (Major) Patients should not receive a COMT inhibitor in combination with non-selective MAOIs such as phenelzine. Monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines and the combination of a COMT inhibitor and phenelzine may result in inhibition of the majority of pathways responsible for normal catecholamine metabolism. Typically, at least 14-days should elapse between the discontinuation of phenelzine and the use of a COMT inhibitor to avoid potential interactions.
    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. Concomitant use of tramadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome or seizures. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tramadol.
    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 heterocyclic antidepressants (e.g., trazodone, mirtazapine, amoxapine, maptrotiline) or within 14 days of discontinuing treatment with a heterocyclic antidepressant. Conversely, heterocyclic antidepressants should not be initiated within 14 days of stopping an MAOI. The manufacturer of rasagiline does not contraindicate the combination but recommends avoiding use of antidepressants with rasagiline or within 14 days of discontinuing rasagiline. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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 vasodilators.
    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. MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient 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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Trifluoperazine: (Major) 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. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Trospium: (Moderate) MAOIs exhibit secondary anticholinergic actions. Additive anticholinergic effects may be seen when MAOIs are used concomitantly with antimuscarinics such as trospium. Additive CNS effects are also possible when antimuscarinic drugs are combined with MAOIs.
    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) Concomitant use of CNS depressants with valproic acid can cause additive CNS depression. MAOIs, used concomitantly with valproic acid, can increase CNS depression and also can lower the seizure threshold,
    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 within 7 days of discontinuing treatment with other SNRIs. Conversely, SNRIs should not be initiated within 14 days of stopping an MAOI. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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 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. The manufacturer of rasagiline does not contraindicate the combination but recommends avoiding use of antidepressants with rasagiline or within 14 days of discontinuing rasagiline. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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. The manufacturer of rasagiline does not contraindicate the combination but recommends avoiding use of antidepressants with rasagiline or within 14 days of discontinuing rasagiline. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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. The combination or rapid succession of MAOI treatment could result in severe CNS or cardiovascular reactions, including hypertensive crises. 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. It is best to avoid use of yohimbine with non-selective monoamine oxidase inhibitors (MAOIs), such as phenelzine, isocarboxazid, tranylcypromine, and even drugs with selective MAOI activity, such as selegiline and selegiline, transdermal, or rasagiline. The activity of yohimbine might result in increased blood pressure or other serious side effects. It would be prudent to avoid yohimbine during MAOI therapy and for 2 weeks after the discontinuation of a MAOI.
    Zolmitriptan: (Severe) The administration of zolmitriptan to patients currently receiving a monoamine oxidase A inhibitor or within 2 weeks of discontinuing a monoamine oxidase A inhibitor is contraindicated. Zolmitriptan is metabolized by monoamine oxidase A (MAO-A); therefore, plasma concentrations of zolmitriptan may be increased by concurrent use of selective MAO-A inhibitors (e.g., meclobemide) or non-selective MAO-A and MAO-B inhibitors (e.g., phenelzine, tranylcypromine, isocarboxazid). Following one week of administration of the MAO-A inhibitor 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. Selegiline, a selective MAO-B inhibitor, at a dose of 10 mg/day for 1 week, had no effect on the pharmacokinetics of zolmitriptan and its metabolite. However, it should be noted that selegiline may interact with zolmitriptan at higher doses (> 20 mg) since the MAO-B selectivity of the drug diminishes at higher doses. It is not known whether other selective MAOIs interact with zolmitriptan.
    Zonisamide: (Moderate) MAOIs can cause a variable change in seizure patterns, so careful monitoring of the patient with epilepsy is required. Also, additive CNS depression is possible if MAOIs and anticonvulsants are coadministered.

    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.