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  • CLASSES

    Anti-Parkinson Agents, MAO type B Inhibitors
    MAOI Antidepressants

    BOXED WARNING

    Children, suicidal ideation

    Safety and efficacy of oral selegiline have not been established in pediatric patients less than 18 years of age. Transdermal selegiline, an antidepressant, is contraindicated in children less than 12 years due to the risk of hypertensive crisis. Children younger than 12 years of age appear to have greater drug exposure compared to adolescents and adults with transdermal use, and children may not be able to reliably adhere to the required dietary restrictions. A flexible-dose controlled trial of transdermal selegiline failed to demonstrate efficacy in children adolescents 12 years and older over placebo, although the overall safety profile was similar to adults. A boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of selegiline may be necessary in patients with emerging suicidality or worsening depression.

    DEA CLASS

    Rx

    DESCRIPTION

    Selective type-B monoamine oxidase inhibitor (MAOI) available orally and as a transdermal patch
    Oral formulations used as an adjunct treatment in Parkinson's disease; transdermal patch approved for major depressive disorder in adults
    Tyramine reactions, such as hypertensive crisis, are unlikely but possible at therapeutic dosing; follow tyramine restrictions as recommended
    Close monitoring is required in pediatrics and young adults receiving antidepressant therapy due to an increased risk of suicidality during the initial stages of treatment; transdermal selegiline is contraindicated in children less than 12 years due to an increased risk of hypertensive crisis

    COMMON BRAND NAMES

    Carbex, Eldepryl, EMSAM, Zelapar

    HOW SUPPLIED

    Carbex/Selegiline/Selegiline Hydrochloride Oral Tab: 5mg
    Eldepryl/Selegiline/Selegiline Hydrochloride Oral Cap: 5mg
    EMSAM Topical Film ER: 6mg, 9mg, 12mg, 24h
    Zelapar Oral Tab Orally Dis: 1.25mg

    DOSAGE & INDICATIONS

    For the treatment of Parkinson's disease or parkinsonism in combination with levodopa or levodopa/carbidopa.
    Oral dosage (tablets and capsules, e.g., Eldepryl)
    Adults

    5 mg PO twice daily, administered with breakfast and lunch.

    Oral dosage (orally disintegrating tablets, e.g., Zelapar ODT)
    Adults

    1.25 mg PO once daily in the morning, before breakfast and without liquid. Give for at least 6 weeks. After 6 weeks if needed for efficacy and tolerated, the dose may be increased to 2.5 mg PO once daily in the morning, before breakfast and without liquid. ODT doses more than 2.5 mg daily have not been shown to confer additional benefit, and safe use of more than 2.5 mg/day without dietary tyramine restrictions has not been established. Dose reductions of levodopa may be needed if dopaminergic side effects, including dyskinesia and hallucinations emerge. In clinical trials with selegiline ODT, the mean reduction of 'off' time was 13.1% for selegiline ODT and 5.1% for placebo. Selegeline ODT-treated patients had an average of 2.2 hours per day less "off" time compared to baseline. Placebo-treated patients had 0.6 hours/day less "off" time compared to baseline. These differences were statistically significant.

    For the treatment of major depression.
    Transdermal dosage
    Adults

    The initial and target dose is 6 mg in 24 hours applied transdermally once daily. If clinically indicated, dose increases should occur in increments of 3 mg/24 hours at intervals of no less than 2 weeks. Effective dose range: 6 to 12 mg/24 hours. Max: 12 mg/24 hours. It is not known if the higher doses are more effective than the lowest dose. Inform patients to avoid tyramine-containing foods/beverages/dietary supplements beginning on the first day of selegiline 9 mg/24 hours or 12 mg/24 hours patch. Continue to avoid tyramine for 2 weeks after a dose reduction to selegiline 6 mg/24 hours or following the discontinuation of selegiline 9 mg/24 hours or 12 mg/24 hours.

    MAXIMUM DOSAGE

    Adults

    10 mg/day PO (oral tablets or capsules); 2.5 mg/day PO (orally-disintegrating tablet); Emsam 12 mg/24 hour transdermally.

    Geriatric

    10 mg/day PO (oral tablets or capsules); 2.5 mg/day PO (orally-disintegrating tablet); Emsam 12 mg/24 hour transdermally.

    Adolescents

    Safety and efficacy have not been established.

    Children

    12 years: Safety and efficacy have not been established.
    Less than 12 years: Transdermal patch is contraindicated.

    Infants

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Mild to Moderate hepatic impairment (Child-Pugh score 5 to 9): A dose reduction of selegiline orally disintegrating tablets (from 2.5 mg/day to 1.25 mg/day) may be required depending on clinical response. No adjustment of transdermal selegiline is needed. Specific guidelines for dosage adjustments for oral selegiline tablets and capsules are not available.
    Severe hepatic impairment (Child-Pugh score greater than 9): Selegiline orally disintegrating tablets are not recommended. Transdermal selegiline has not been studied. Specific guidelines for oral selegiline tablets or capsules in severe hepatic impairment are not available.

    Renal Impairment

    No dose adjustment of selegiline orally disintegrating tablets is required in patients with mild to moderate renal impairment (CrCl 30 to 89 mL/minute). Selegiline orally disintegrating tablets are not recommended in patients with severe renal impairment or end-stage renal disease (CrCl less than 30 mL/minute). No dosage adjustment of transdermal selegiline is needed in patients with mild, moderate, or severe renal impairment; transdermal selegiline has not been studied in patients with end-stage renal disease. Specific guidelines for dosage adjustment of oral selegiline tablets or caspules are not available.

    ADMINISTRATION

    Oral Administration

    Specific manufacturer recommendations for dietary tyramine intake must be followed to minimize the risk of a hypertensive crisis.

    Oral Solid Formulations

    Oral tablet or capsule (e.g., Eldepryl)
    Administer twice daily with breakfast and lunch.
    Do not administer doses greater than 10 mg/day because of the risk of hypertensive crisis.
     
    Orally-disintegrating tablets (e.g., Zelapar)
    Do not push selegiline ODT through the foil backing; peel back the backing of 1 or 2 blisters (as prescribed) with dry hands, and gently remove the tablet(s).
    Immediately place the tablet(s) on top of the patient's tongue where it will disintegrate in seconds. Do not swallow the ODT tablet.
    The patient should avoid ingesting food or liquids for 5 minutes before and after taking selegiline ODT.
    Do not administer doses greater than 2.5 mg/day because of the risk of hypertensive crisis.

    Topical Administration
    Transdermal Patch Formulations

    Dietary tyramine intake restrictions must be followed to minimize the risk of a hypertensive crisis when using the 9 mg/24 hour or 12 mg/24 hour transdermal patch strengths. Patients should continue to avoid tyramine-rich foods or beverages for 2 weeks after a dose reduction to the 6 mg/24 dose or following discontinuation of the 9 mg/24 hour or 12 mg/24 hour patch.
     
    Transdermal Patch Administration (Emsam)
    Before application, wash the area with soap and warm water, and dry thoroughly.
    Choose an application site of dry, intact skin on the upper chest or back, upper thigh, or the outer surface of the upper arm. The patch should be applied to an area of skin that is not hairy, oily, irritated, broken, scarred, or calloused.
    The patch should be applied immediately after removal from the pouch. Do not store the patch outside of the sealed pouch.
    Remove the transdermal patch from the pouch by tearing at the notches on the pouch. Do not use scissors.
    Do not cut or trim the patch.
    To apply the patch, remove half of the release liner and discard it. Press the sticky side of the transdermal system firmly against the cleaned skin site. Remove the second half of the release liner and press the remaining sticky side firmly against the skin. Ensure that the transdermal system is flat against the skin and is sticking securely. Be sure the edges are stuck to the skin surface.
    After application, hands should be washed with soap and water.
    Advise patients to wear only 1 patch at a time.
    Usual activities, including exercise, bathing, and swimming can be maintained while wearing the patch. Avoid exposing the application site to external sources of direct heat, such as heating pads or electric blankets, heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight.
    If the patch falls off, apply a new patch to a new site and resume the previous dose schedule. In dermal adhesion studies, roughly 6% to 7% of patches applied to the upper torso became detached during a 10-day period.
    Change patch once daily (every 24 hours). Remove the old patch before applying a new one.
    Rotate patch sites between the upper arm, upper chest, upper thigh, and upper back. New patches can be applied to sites near the previous site, but not to the same site.
    Disposal: Once a patch is removed, a used patch should be folded to stick to itself and discarded in a waste receptacle out of the reach of children and pets.

    STORAGE

    Carbex:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Eldepryl:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    EMSAM:
    - Do not store outside of the sealed pouch
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Zelapar:
    - Product should be used within 3 months after opening
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in original container

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Selegiline is contraindicated in patients with a hypersensitivity to selegiline or any inactive ingredients of the formulations.

    MAOI therapy

    Selegiline is an irreversible, selective monoamine oxidase (MAO) type B inhibitor. Therefore, selegiline is contraindicated in patients receiving any other MAOI therapy due to the risk for hypertensive crisis.. selegiline transdermal system is contraindicated with selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), St. John's wort, the tricyclic antidepressants (TCAs), cyclobenzaprine, the opiate analgesics meperidine, tramadol, and other opiate agonists, and the antitussive agent dextromethorphan because of a risk of serotonin syndrome or bizarre behaviors when selegiline is used with these agents. Other drugs (e.g., carbamazepine) are contraindicated due to a risk of serious high blood pressure, including crisis. After stopping treatment with drugs contraindicated with selegiline, a time period equal to 4 to 5 half-lives (approximately 1 week) of the drug or any active metabolite should elapse before starting therapy with selegiline. At least 2 weeks should elapse after stopping selegiline before starting therapy with any drug that is contraindicated with selegiline.

    Alcoholism, ethanol ingestion, hypertension, hypertensive crisis

    The monoamine oxidase (MAO) enzyme system is important in the catabolism of dietary amines (e.g., tyramine), and selegiline acts as an irreversible MAO inhibitor. MAO exists as 2 isoenzymes, referred to as MAO-A and MAO-B. Selegiline shows greater affinity for MAO-B; however, as selegiline concentrations increase, this selectivity is lost with resulting dose-related inhibition of MAO-A. Intestinal MAO is predominantly type A, while in the brain both isoenzymes exist. Significant inhibition of intestinal MAO-A activity can impose a cardiovascular safety risk. MAOIs have been associated with hypertensive crisis caused by the ingestion of foods, beverages, or nutritional supplements with a high concentration of tyramine. Clinical data do not support the need for tyramine dietary modification at the selegiline transdermal dose of 6 mg/24 hour; however, unrestricted dietary tyramine data in clinical trials evaluating the 9 mg/24 hour or 12 mg/24 hour patch are limited and tyramine restrictions should be followed with these higher doses. Study results of selegiline orally disintegrating tablets (ODT) showed that an increase in tyramine sensitivity for blood pressure responses appears to begin at a dose of 5 mg/day; however, hypertensive crisis has also been reported with selegiline ODT use that was not above the recommended dosing. Patients receiving selegiline ODT should be advised to avoid certain foods containing a very large amount of tyramine (e.g., aged cheese) because of the potential for large increases in blood pressure. Oral selegiline tablets and capsules can ordinarily be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day); however, hypertensive reactions at recommended doses associated with dietary influences have been reported. Advise patients of dietary tyramine-restriction recommendations. Selegiline should not be used in patients with alcoholism. Tyramine-rich foods and beverages 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; any over-ripe fruit; and tap beer and beers that have not been pasteurized. The manufacturer of transdermal selegiline recommends avoiding ethanol ingestion and specifically recommends avoiding tyramine-rich alcoholic beverages such as all varieties of tap beer and beers that have not been pasteurized during use of the 9 mg/24 hour or 12 mg/24 hour patch and for 2 weeks after discontinuation or dose reduction to 6 mg/24 hour due to the risk for hypertensive crisis. Patients receiving any formulation of selegiline should be monitored for new onset hypertension or exacerbation of pre-existing hypertension. Hypertensive crisis, which can be fatal, may manifest as occipital headache which may radiate frontally, palpitation, neck stiffness or soreness, nausea, vomiting, sweating with possible fever and cold, clammy skin, dilated pupils, photophobia, tachycardia or bradycardia with possible constricting chest pain, or intracranial bleeding. A complete drug, food, and dietary supplement history should be obtained in all patients prior to prescribing selegiline. Patients should be instructed on the signs and symptoms of severe hypertension and advised to seek immediate medical attention if these signs or symptoms are present. If a hypertensive crisis occurs, selegiline should be discontinued immediately and the appropriate medical treatment should be initiated to lower blood pressure (e.g., phentolamine, labetalol, nitroprusside) and treat associated symptoms. Patients must be closely monitored until the symptoms have stabilized.

    Pheochromocytoma

    Transdermal selegiline is contraindicated in patients with pheochromocytoma. The associated tumor secretes pressor substances (e.g., norepinephrine) and the metabolism of these pressor substances may be reduced by MAOIs and potentially cause a hypertensive crisis. Oral forms of selegiline should generally also be avoided in these patients, due to similar reasons.

    Children, suicidal ideation

    Safety and efficacy of oral selegiline have not been established in pediatric patients less than 18 years of age. Transdermal selegiline, an antidepressant, is contraindicated in children less than 12 years due to the risk of hypertensive crisis. Children younger than 12 years of age appear to have greater drug exposure compared to adolescents and adults with transdermal use, and children may not be able to reliably adhere to the required dietary restrictions. A flexible-dose controlled trial of transdermal selegiline failed to demonstrate efficacy in children adolescents 12 years and older over placebo, although the overall safety profile was similar to adults. A boxed warning in the product label describes the risk of suicidality and suicidal ideation in children, adolescent, and young adult patients receiving antidepressants. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of selegiline may be necessary in patients with emerging suicidality or worsening depression.

    Bipolar disorder, mania

    Patients should be adequately screened for a personal or family history of bipolar disorder, mania, or hypomania prior to initiating an antidepressant, such as the selegiline transdermal patch. Treatment of a depressive episode with antidepressants, such as transdermal selegiline, has been associated with the precipitation of mania or hypomania in patients with bipolar disorder. Screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. Depression may also be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients with depression or comorbid depression in the setting of other psychiatric illness being treated with an antidepressant should be observed for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes. 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 emergence of suicidality. If a patient develops manic symptoms, transdermal selegiline should be withheld, and appropriate therapy initiated to treat the manic symptoms.

    Behavioral changes, psychosis, schizophrenia

    Postmarketing reports indicate that patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during oral selegiline treatment or after starting or increasing the dose. Other drugs prescribed to improve the symptoms of Parkinson’s disease can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of 1 or more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium. Patients with a major psychotic disorder, such as schizophrenia, should generally not be treated with selegiline because the dopamine-enhancing properties of selegiline may cause or exacerbate hallucinations and psychosis. In addition, certain medications used to treat psychosis, such as dopamine antagonists, may exacerbate the symptoms of Parkinson's disease and may decrease the effectiveness of selegiline. Behavioral changes have also been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Families and caregivers of patients being treated with selegiline, for both psychiatric and nonpsychiatric indications, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers.

    Impulse control symptoms

    Some patients receiving medications for Parkinson's disease that increase dopaminergic tone have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in Parkinson's patients receiving selegiline. Likewise, patients should be instructed to report such changes while receiving selegiline. Dose reduction or discontinuation should be considered in those who experience these effects.

    Hypotension, orthostatic hypotension

    Patients should be advised that they may develop symptomatic or asymptomatic hypotension while taking oral selegiline, particularly during treatment initiation. Caution patients against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially during treatment initiation. The incidence of orthostatic hypotension was higher in elderly adult patients than younger adult patients (3% vs. 0%). Orthostatic hypotension has also occurred with other oral dose forms. During clinical trial evaluation of transdermal selegiline, orthostatic hypotension occurred more frequently with the use of transdermal selegiline than placebo (10% vs. 7%). Patients with a pre-existing tendency towards changes in postural blood pressure should be observed closely for changes in blood pressure throughout treatment, and dose increases should be made carefully.

    Hepatic disease

    Caution is advisable in patients with hepatic disease; selegiline undergoes hepatic metabolism to active metabolites. Dosages of selegiline orally disintegrating tablets (ODT) in patients with mild to moderate hepatic impairment (Child-Pugh 5 to 9) are adjusted to clinical response. Selegiline ODT is not recommended in patients with severe hepatic impairment. No adjustment of transdermal selegiline is required in patients with mild or moderate liver impairment (Child-Pugh 5 to 9); transdermal selegiline has not been studied in patients with severe liver impairment (Child-Pugh score 10 to 15). Use oral selegiline tablets or capsules with caution in hepatically impaired patients; no specific recommendations are available.

    Renal failure, renal impairment

    Caution is advisable in patients with renal impairment; specific manufacturer recommendations should be followed. No dosage adjustment of transdermal selegiline is needed in patients with mild, moderate, or severe renal impairment; however, there are no data in patients with end-stage renal disease (ESRD). No dose adjustment of selegiline orally disintegrating tablets (ODT) is required in patients with mild to moderate renal impairment with a creatinine clearance (CrCl) 30 to 89 mL/minute). Selegiline ODT is not recommended in patients with severe renal impairment or end-stage renal disease (CrCl less than 30 mL/minute). No specific guidance is available for oral selegiline tablets or capsules in patients with renal impairment or renal failure.

    Melanoma

    Epidemiological studies have shown that patients with Parkinson's disease (PD) have a 2- to 6-fold higher risk of developing melanoma than the general population. It is recommended that a qualified practitioner (e.g., dermatologist) monitor for skin cancer on a regular basis during PD treatment with oral selegiline capsules and tablets. Advise patients to regularly monitor for skin changes and to promptly report these changes to their provider. The orally disintegrating tablets and transdermal selegiline products do not list this precaution in their product labels, since this observation appears to be more related to factors other than selegiline use.

    Coadministration with other CNS depressants, driving or operating machinery, narcolepsy, sleep apnea, sudden sleep onset

    Although selegliline has not been shown to increase the impairment of mental and motor skills caused by alcohol, the concomitant use of selegiline transdermal patch and alcohol in depressed patients is not recommended. Coadministration with other CNS depressants may also increase the risk for psychomotor impairment. All patients taking selegiline (oral and transdermal) should be cautioned about driving or operating machinery until they know how the drug affects them. There have been reports of patients with Parkinson's disease who have experienced sudden sleep onset while performing activities of daily living, including driving. In some cases, excessive drowsiness has resulted in auto accidents or other harmful events in the course of daily living. Symptoms of excessive drowsiness may not be preceded by warning signs such as somnolence. Excessive drowsiness has, in some cases, occurred as late as 1 year after the initiation of treatment. Before initiating treatment with selegiline for Parkinson's disease, advise patients about the potential for drowsiness and specifically assess conditions that may increase this risk, such as the presence of sleep disorders (e.g., narcolepsy, sleep apnea) or coadministration with other CNS depressants. Assessment for somnolence is suggested throughout therapy. Selegiline should generally be discontinued in those who have experienced a sudden episode of sleep while engaged in activities of daily living. If selegiline is continued in these patients, activities requiring mental alertness should be avoided. It is not known if a reduction in dosage will subsequently reduce or eliminate excessive somnolence or sudden episodes of sleep.

    Abrupt discontinuation

    Although not reported with selegiline during clinical trials for Parkinson's disease, a symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy. Avoid abrupt discontinuation of therapy when possible.

    Pregnancy

    Because there are no adequate and well-controlled studies of selegiline use in pregnant women, oral selegiline should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The available data on transdermal selegiline in pregnant women are not sufficient to provide information on the risk of drug-associated adverse outcomes during pregnancy. When treating a pregnant woman for depression with transdermal selegiline, the potential risks of taking a monoamine oxidase inhibitor (MAOI), particularly the risk of hypertensive crisis during pregnancy, should be weighed against the established benefits of treating depression with an antidepressant. Selegiline has a low molecular weight and would be expected to cross the placenta. A case report of oral selegiline used in a pregnant woman who continued the drug throughout gestation noted no teratogenic defects or developmental delays in a healthy male infant over a 10-year period. However, animal studies suggest the potential for neurological changes. Decreases in fetal weight, delayed ossification, and embryo-fetal post-implantation lethality have been noted during the period of organogenesis in animal studies at doses up to 60 times the maximum recommended human dose (MRHD). Slight increases in visceral malformations have been seen during the period of embryo-fetal development in animal studies at doses up to 64 times the MRHD. An increase in stillborn pups and post-implantation loss has been seen in rat studies. Throughout lactation and post-weaning periods, decreases in pup weight, retarded pup physical development, and retarded pup neurobehavioral and sexual development were seen at all doses up to 60 times the MRHD. These findings suggest persistent effects on the offspring of treated dams. A no-effect dose was not established for developmental toxicity. It is not known how these animal findings relate to effects in pregnant women. Selegiline has no established use in labor and delivery. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to selegiline; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1-866-961-2388.

    Breast-feeding

    It is unknown if selegiline is excreted into human breast milk, effects the breast-fed infant, or effects milk production. Selegiline has a low molecular weight (188 for the free base) and would be expected to cross into human breast milk. During treatment with the oral capsule or tablet formulations of selegiline, a decision should be made whether to discontinue the drug or discontinue breast-feeding, taking into account the importance of the drug to the mother. Consideration should be given to discontinuing the use of all but absolutely essential drug treatments in nursing women. Because of the potential for serious adverse effects in a breast-fed infant, including hypertensive crisis, the manufacturer for the orally disintegrating tablets recommends against breast-feeding during treatment and for 7 days after the final dose. The manufacturer for transdermal selegiline recommends against breast-feeding during treatment with transdermal selegiline and for 5 days after the final dose. A case report describes maternal use of oral selegiline 10 mg/day, levodopa 400 mg, and benserazide 100 mg daily throughout pregnancy and for 3 days while breast-feeding; the child was followed for 10 years and no developmental abnormalities were found. Although rasagiline may be considered as an alternative therapy to selegiline for the adjunct treatment of Parkinson's disease in breast-feeding women, safety data are lacking. In addition, both rasagiline and selegiline can inhibit prolactin secretion, and thus, interference with proper lactation is possible. Psychotropic medications affect neurotransmitter function in the developing central nervous system, and therefore, the accurate prediction of long-term adverse effects may not be possible. Alternatives to selegiline for the treatment of depression may be considered. 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 preferable to other antidepressants when initiating antidepressant therapy in a breast-feeding mother.

    Geriatric

    Geriatric patients should be advised that they may develop symptomatic or asymptomatic hypotension while taking selegiline, particularly during treatment initiation. Caution patients against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially during treatment initiation. The elderly population with Parkinson's disease, already at risk for falls, may be at greater risk with the use of selegiline; therefore, caution is warranted. During clinical trials of selegiline orally disintegrating tablets (ODT), the incidence of orthostatic hypotension was higher in geriatric patients than younger patients (3% vs. 0%). There were no overall differences in effectiveness between geriatric and younger adult patients who participated in clinical studies with transdermal selegiline; however, patients 50 years and older receiving transdermal selegiline appeared to be at higher risk for rash than younger adult patients receiving placebo (4.4% vs. 3.4%). The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, antiparkinson medications may cause significant confusion, restlessness, delirium, dyskinesia, nausea, dizziness, hallucinations, and agitation. In addition, there is an increased risk of postural hypotension and falls, particularly during concurrent use of antihypertensive medications. During use of transdermal selegiline as an antidepressant, the OBRA guidelines state that 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. Monoamine oxidase inhibitors (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.

    Phenylketonuria

    Caution is advised when administering selegiline orally disintegrating tablets to patients with phenylketonuria (PKU). Each selegiline orally disintegrating tablet contains 1.25 mg of phenylalanine (a component of aspartame), which can be harmful to patients with PKU. Before prescribing the orally disintegrating tablets to patients with PKU, consider the combined daily amount of phenylalanine from all sources.

    Ambient temperature increase, heating pad, sunlight (UV) exposure

    The effect of direct heat applied to the selegiline transdermal patch on the bioavailability of selegiline has not been studied. However, in theory, heat may result in an increase in the amount of selegiline absorbed from the patch and produce elevated serum levels of selegiline. Patients should be advised to avoid exposing the patch application site to external sources of direct heat, such as a heating pad or electric blanket, or any external ambient temperature increase from heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight (UV) exposure.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / Incidence not known
    akinesia / Delayed / Incidence not known
    tardive dyskinesia / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    cholecystitis / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    cardiac arrest / Early / Incidence not known
    bradycardia / Rapid / Incidence not known
    atrial flutter / Early / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    AV block / Early / Incidence not known
    atrial fibrillation / Early / Incidence not known
    heart failure / Delayed / Incidence not known
    hypertensive crisis / Early / Incidence not known
    prostatic hypertrophy / Delayed / Incidence not known
    epididymitis / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    ocular hemorrhage / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    retinal detachment / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known
    pneumothorax / Early / Incidence not known
    bronchospasm / Rapid / Incidence not known
    pleural effusion / Delayed / Incidence not known
    cyanosis / Early / Incidence not known
    hyperkalemia / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known

    Moderate

    orthostatic hypotension / Delayed / 0-21.0
    confusion / Early / 6.1-6.1
    hallucinations / Early / 4.0-6.1
    dyskinesia / Delayed / 6.0-6.0
    stomatitis / Delayed / 5.0-5.0
    constipation / Delayed / 4.0-4.0
    ataxia / Delayed / 3.0-3.0
    hypertension / Early / 3.0-3.0
    erythema / Early / 0-3.0
    dyspnea / Early / 3.0-3.0
    dysphagia / Delayed / 2.0-2.0
    chest pain (unspecified) / Early / 2.0-2.0
    oral ulceration / Delayed / 2.0-2.0
    depression / Delayed / 0-2.0
    hypokalemia / Delayed / 2.0-2.0
    mania / Early / 0-1.0
    psychosis / Early / Incidence not known
    encephalopathy / Delayed / Incidence not known
    hypertonia / Delayed / Incidence not known
    involuntary movements / Delayed / Incidence not known
    subdural hematoma / Early / Incidence not known
    hypotonia / Delayed / Incidence not known
    myoclonia / Delayed / Incidence not known
    neuropathic pain / Delayed / Incidence not known
    aphasia / Delayed / Incidence not known
    migraine / Early / Incidence not known
    amnesia / Delayed / Incidence not known
    dystonic reaction / Delayed / Incidence not known
    memory impairment / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    teeth grinding (bruxism) / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    cholelithiasis / Delayed / Incidence not known
    gastritis / Delayed / Incidence not known
    colitis / Delayed / Incidence not known
    angina / Early / Incidence not known
    hypotension / Rapid / Incidence not known
    peripheral edema / Delayed / Incidence not known
    peripheral vasodilation / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    supraventricular tachycardia (SVT) / Early / Incidence not known
    urinary retention / Early / Incidence not known
    ejaculation dysfunction / Delayed / Incidence not known
    impotence (erectile dysfunction) / Delayed / Incidence not known
    cystitis / Delayed / Incidence not known
    nephrolithiasis / Delayed / Incidence not known
    urinary incontinence / Early / Incidence not known
    glossitis / Early / Incidence not known
    impulse control symptoms / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    amblyopia / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    cataracts / Delayed / Incidence not known
    blepharospasm / Early / Incidence not known
    edema / Delayed / Incidence not known
    atopic dermatitis / Delayed / Incidence not known
    hematoma / Early / Incidence not known
    skin ulcer / Delayed / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    bone pain / Delayed / Incidence not known
    flank pain / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known
    gout / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    diabetes mellitus / Delayed / Incidence not known
    fluid retention / Delayed / Incidence not known
    hyperphosphatemia / Delayed / Incidence not known
    hypercholesterolemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    hyponatremia / Delayed / Incidence not known
    dehydration / Delayed / Incidence not known
    hyperlipidemia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known

    Mild

    nausea / Early / 11.0-20.4
    headache / Early / 4.1-18.0
    dizziness / Early / 11.0-14.3
    insomnia / Early / 7.0-12.0
    diarrhea / Early / 2.0-9.0
    abdominal pain / Early / 8.2-8.2
    xerostomia / Early / 4.0-8.0
    rhinitis / Early / 7.0-7.0
    dyspepsia / Early / 4.0-5.0
    back pain / Delayed / 5.0-5.0
    pharyngitis / Delayed / 3.0-4.0
    rash / Early / 4.0-4.0
    drowsiness / Early / 3.0-3.0
    tremor / Early / 3.0-3.0
    vomiting / Early / 3.0-3.0
    muscle cramps / Delayed / 3.0-3.0
    flatulence / Early / 2.0-2.0
    ecchymosis / Delayed / 2.0-2.0
    irritability / Delayed / Incidence not known
    hyporeflexia / Delayed / Incidence not known
    agitation / Early / Incidence not known
    emotional lability / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    lethargy / Early / Incidence not known
    malaise / Early / Incidence not known
    fatigue / Early / Incidence not known
    hyperkinesis / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    hypersalivation / Early / Incidence not known
    nightmares / Early / Incidence not known
    weakness / Early / Incidence not known
    paranoia / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    restlessness / Early / Incidence not known
    weight loss / Delayed / Incidence not known
    gingivitis / Delayed / Incidence not known
    pyrosis (heartburn) / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    syncope / Early / Incidence not known
    increased urinary frequency / Early / Incidence not known
    orgasm dysfunction / Delayed / Incidence not known
    urinary urgency / Early / Incidence not known
    nocturia / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    pruritus / Rapid / Incidence not known
    skin irritation / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    diplopia / Early / Incidence not known
    tinnitus / Delayed / Incidence not known
    xerophthalmia / Early / Incidence not known
    epistaxis / Delayed / Incidence not known
    sinusitis / Delayed / Incidence not known
    fever / Early / Incidence not known
    infection / Delayed / Incidence not known
    hiccups / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    alopecia / Delayed / Incidence not known
    pallor / Early / Incidence not known
    photosensitivity / Delayed / Incidence not known
    skin discoloration / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    seborrhea / Delayed / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    arthropathy / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    chills / Rapid / Incidence not known
    myalgia / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    hypovitaminosis / Delayed / Incidence not known
    leukocytosis / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Acetaminophen; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Acetaminophen; Caffeine; Dihydrocodeine: (Major) Avoid use if possible. Dihydrocodeine is closely related to codeine and is usually considered contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with dihydrocodeine. After stopping treatment with dihydrocodeine, a time period equal to 4 to 5 half-lives of the drug or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Acetaminophen; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Acetaminophen; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
    Acetaminophen; Dextromethorphan; Doxylamine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and doxylamine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Contraindicated) The product label for isometheptene contraindicates use with monoamine oxidase inhibitors (MAOIs), including transdermal selegiline, due to the risk of hypertensive crisis. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Isometheptene should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Acetaminophen; Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Guaifenesin; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Acetaminophen; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Acetaminophen; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pyrilamine. Concurrent use may result in additive CNS depression.
    Acetaminophen; Pentazocine: (Contraindicated) Coadministration of pentazocine and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with pentazocine. After stopping treatment with pentazocine, a time period equal to 4 to 5 half-lives of pentazocine or any active metabolite should elapse before starting therapy with selegiline.
    Acetaminophen; Propoxyphene: (Contraindicated) Coadministration of propoxyphene and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with propoxyphene. After stopping treatment with propoxyphene, a time period equal to 4 to 5 half-lives of propoxyphene or any active metabolite should elapse before starting therapy with selegiline.
    Acetaminophen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Acrivastine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid coadministration of selegiline with acrivastine due to the risk of additive CNS depression.
    Alfentanil: (Moderate) Monitor patients for hypertension and serotonin syndrome and ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed, if alfentanil is administered to patients who have received selegiline within 14 days. Selegiline interactions with alfentanil may also manifest as opioid toxicity. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Almotriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering almotriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with almotriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue almotriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
    Alprazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Amitriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Amobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Amoxapine: (Contraindicated) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with amoxapine. After stopping treatment with amoxapine, a time period equal to 4 to 5 half-lives of amoxapine or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and cyclic antidepressants simultaneously.
    Amphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use.
    Amphetamine; Dextroamphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use.
    Amphetamines: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use.
    Anxiolytics; Sedatives; and Hypnotics: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
    Apalutamide: (Moderate) Use caution if selegiline and apalutamide are used concomitantly. Although apalutamide is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Aripiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Armodafinil: (Moderate) Use caution during concomitant use of selegiline and armodafinil. Armodafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs); however, it is known that many other CNS stimulants may induce severe cardiovascular reactions, such as hypertensive crisis, if administered in combination with drugs with non-selective MAO inhibitor activity.
    Articaine; Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Asenapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Aspirin, ASA; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Major) Avoid use if possible. Dihydrocodeine is closely related to codeine and is usually considered contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with dihydrocodeine. After stopping treatment with dihydrocodeine, a time period equal to 4 to 5 half-lives of the drug or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Aspirin, ASA; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Atomoxetine: (Contraindicated) Selective norepinephrine reuptake inhibitors are contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a selective norepinephrine reuptake inhibitor. After stopping treatment with the reuptake inhibitor, a time period equal to 4 to 5 half-lives of the reuptake inhibitor or any active metabolite should elapse before starting therapy with selegiline.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient 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, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. 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). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
    Atropine; Difenoxin: (Major) Avoid concomitant use of selegiline and diphenoxylate or difenoxin due to the theoretical risk of hypertensive crisis. The chemical structure of difenoxin and diphenoxylate are similar to opioids that are known to precipitate these events when used with MAO inhibitors.
    atypical antipsychotic: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Azelastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and azelastine. Concurrent use may result in additive CNS depression.
    Azelastine; Fluticasone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and azelastine. Concurrent use may result in additive CNS depression.
    Barbiturates: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with selegiline may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of opium with selegiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Benzhydrocodone; Acetaminophen: (Major) The use of benzhydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Benzodiazepines: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient 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, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. 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). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
    Benzphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use.
    Bretylium: (Minor) Selegiline, a monoamine oxidase type B inhibitor, might potentiate the effects of the early release of catecholamines from nerve endings produced by bretylium, such as transient hypertension and increased frequency of arrhythmias. Bretylium causes an early release of norepinephrine from the adrenergic nerve terminals.
    Brexpiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    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) 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: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Carbetapentane; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and brompheniramine. Concurrent use may result in additive CNS depression.
    Buprenorphine: (Major) Avoid concomitant use of buprenorphine in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like buprenorphine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Buprenorphine; Naloxone: (Major) Avoid concomitant use of buprenorphine in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid like buprenorphine is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Bupropion: (Contraindicated) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline.
    Bupropion; Naltrexone: (Contraindicated) The manufacturer of bupropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with bupropion. After stopping treatment with bupropion, a time period equal to 4 to 5 half-lives of bupropion or any active metabolite should elapse before starting therapy with selegiline.
    Buspirone: (Contraindicated) Concomitant use of transdermal selegiline with buspirone or within 14 days after discontinuation of treatment with either agent is contraindicated due to the risk of serotonin syndrome. For selegiline oral formulations, monitor blood pressure for hypertension during concomitant use of buspirone. If a hypertensive crisis occurs, selegiline should be discontinued immediately and therapy to lower blood pressure should be instituted immediately.
    Butabarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Butalbital; Acetaminophen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Butorphanol: (Major) Avoid coadministration of butorphanol with selegiline due to the risk for serotonin syndrome and additive CNS depression. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor for CNS depression and the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Caffeine; Sodium Benzoate: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Calcium, Magnesium, Potassium, Sodium Oxybates: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and sodium oxybate. Concurrent use may result in additive CNS depression.
    Carbamazepine: (Contraindicated) Carbamazepine is contraindicated for use with selegiline, an inhibitor of monoamine oxidase type B, because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with carbamazepine. After stopping treatment with carbamazepine, a time period equal to 4 to 5 half-lives of carbamazepine or any active metabolite should elapse before starting therapy with selegiline. When used with selegiline transdermal, carbamazepine has been shown to significantly elevate selegiline levels, which may increase the risk of a hypertensive crisis.
    Carbetapentane; Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Carbetapentane; Guaifenesin; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Carbetapentane; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Carbetapentane; Phenylephrine; Pyrilamine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pyrilamine. Concurrent use may result in additive CNS depression.
    Carbetapentane; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Carbetapentane; Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pyrilamine. Concurrent use may result in additive CNS depression.
    Carbidopa; Levodopa: (Moderate) Concurrent therapy with levodopa and selective monoamine oxidase inhibitors type B, such as selegiline, may be associated with additive orthostatic hypotension. Although these agents are commonly used together for the treatment of Parkinson's disease, patients receiving this combination should be monitored for orthostatic hypotension. Dosage adjustments should be made as needed.
    Carbidopa; Levodopa; Entacapone: (Moderate) Concurrent therapy with levodopa and selective monoamine oxidase inhibitors type B, such as selegiline, may be associated with additive orthostatic hypotension. Although these agents are commonly used together for the treatment of Parkinson's disease, patients receiving this combination should be monitored for orthostatic hypotension. Dosage adjustments should be made as needed.
    Carbinoxamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and carbinoxamine. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and carbinoxamine. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and carbinoxamine. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and carbinoxamine. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and carbinoxamine. Concurrent use may result in additive CNS depression.
    Carbinoxamine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and carbinoxamine. Concurrent use may result in additive CNS depression.
    Cariprazine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and selegiline. Concurrent use may result in additive CNS depression.
    Cetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and cetirizine or levocetirizine. Concurrent use may result in additive CNS depression.
    Cetirizine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and cetirizine or levocetirizine. Concurrent use may result in additive CNS depression.
    Chlophedianol; Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexbrompheniramine. Concurrent use may result in additive CNS depression.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexchlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlophedianol; Guaifenesin; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Chloral Hydrate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
    Chlorcyclizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorcyclizine. Concurrent use may result in additive CNS depression.
    Chlordiazepoxide: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Chlordiazepoxide; Amitriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Chlordiazepoxide; Clidinium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Chlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid use if possible. Dihydrocodeine is closely related to codeine and is usually considered contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with dihydrocodeine. After stopping treatment with dihydrocodeine, a time period equal to 4 to 5 half-lives of the drug or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid use if possible. Dihydrocodeine is closely related to codeine and is usually considered contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with dihydrocodeine. After stopping treatment with dihydrocodeine, a time period equal to 4 to 5 half-lives of the drug or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and chlorpheniramine. Concurrent use may result in additive CNS depression.
    Chlorpromazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Citalopram: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Clemastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and clemastine. Concurrent use may result in additive CNS depression.
    Clomipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Clonazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Clorazepate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Clozapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Codeine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Codeine; Guaifenesin: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Codeine; Phenylephrine; Promethazine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Codeine; Promethazine: (Contraindicated) Codeine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with codeine. After stopping treatment with codeine, a time period equal to 4 to 5 half-lives of codeine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Cyclobenzaprine: (Contraindicated) Cyclobenzaprine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with cyclobenzaprine. After stopping treatment with cyclobenzaprine, a time period equal to 4 to 5 half-lives of cyclobenzaprine or any active metabolite should elapse before starting therapy with selegiline.
    Cyproheptadine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and cyproheptadine. Concurrent use may result in additive CNS depression.
    Desflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Desipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Desloratadine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Desogestrel; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Desvenlafaxine: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Deutetrabenazine: (Contraindicated) Deutetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy, such as selegiline, 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.
    Dexbrompheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexbrompheniramine. Concurrent use may result in additive CNS depression.
    Dexbrompheniramine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexbrompheniramine. Concurrent use may result in additive CNS depression.
    Dexchlorpheniramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexchlorpheniramine. Concurrent use may result in additive CNS depression.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dexchlorpheniramine. Concurrent use may result in additive CNS depression.
    Dextroamphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use.
    Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Dextromethorphan; Guaifenesin: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Dextromethorphan; Quinidine: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan.
    Diazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Diethylpropion: (Contraindicated) The product label for diethylpropion contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Diethylpropion should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid use if possible. Dihydrocodeine is closely related to codeine and is usually considered contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with dihydrocodeine. After stopping treatment with dihydrocodeine, a time period equal to 4 to 5 half-lives of the drug or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Dimenhydrinate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dimenhydrinate. Concurrent use may result in additive CNS depression.
    Diphenhydramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Ibuprofen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Naproxen: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Diphenhydramine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and diphenhydramine. Concurrent use may result in additive CNS depression.
    Diphenoxylate; Atropine: (Major) Avoid concomitant use of selegiline and diphenoxylate or difenoxin due to the theoretical risk of hypertensive crisis. The chemical structure of difenoxin and diphenoxylate are similar to opioids that are known to precipitate these events when used with MAO inhibitors.
    Dobutamine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as dobutamine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Dolasetron: (Moderate) Concomitant use of selegiline and serotonin receptor antagonists may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Dopamine: (Major) Patients who have been treated with monoamine oxidase inhibitors (MAOIs), such as selegiline, within two to three weeks prior to the administration of dopamine should receive initial doses of dopamine no greater than one-tenth of the usual dose. Because dopamine is metabolized by monoamine oxidase, inhibition of this enzyme by MAOIs prolongs and potentiates the effect of dopamine.
    Doxapram: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as doxapram. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Doxepin: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Doxylamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and doxylamine. Concurrent use may result in additive CNS depression.
    Doxylamine; Pyridoxine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and doxylamine. Concurrent use may result in additive CNS depression.
    Dronabinol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and dronabinol. Concurrent use may result in additive CNS depression.
    Droperidol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and droperidol. Concurrent use may result in additive CNS depression.
    Drospirenone; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Duloxetine: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Eletriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering eletriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with eletriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue eletriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
    Enflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Enzalutamide: (Moderate) Use caution if selegiline and enzalutamide are used concomitantly. Although enzalutamide is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Ephedrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as ephedrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Ephedrine; Guaifenesin: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as ephedrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Ergotamine; Caffeine: (Moderate) Although psychostimulants are contraindicated for use with other monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with selegiline because of the selective monoamine oxidase-B (MAO-B) inhibition of selegiline at manufacturer recommended doses. However, cardiac arrhythmias or severe hypertension is possible if doses are exceeded or caffeine intake is excessive.
    Escitalopram: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Esketamine: (Moderate) Closely monitor patients receiving esketamine and selegiline for sedation and increased blood pressure, including the possibility of hypertensive crisis.
    Eslicarbazepine: (Contraindicated) Eslicarbazepine is a prodrug of carbamazepine, which is contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with eslicarbazepine. After stopping treatment with eslicarbazepine, a time period equal to 4 to 5 half-lives of the active moiety carbamazepine should elapse before starting therapy with selegiline.
    Estazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Eszopiclone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
    Ethanol: (Major) Advise patients to avoid the use of alcohol or alcohol-containing products with selegiline. Use may cause additive CNS depression and some alcohol-containing products may also contain tyramine. Certain alcoholic beverages that are tyramine-rich can precipitate a hypertensive reaction if consumed by patients during therapy with selegiline. These include some beers; wines; sherry; hard liquor; or liqueurs.
    Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Ethinyl Estradiol; Norelgestromin: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Ethinyl Estradiol; Norgestrel: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Etomidate: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Etonogestrel; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Fenfluramine: (Contraindicated) Fenfluramine is contraindicated for use with monoamine oxidase inhibitorsr (MAOIs), such as selegiline, due to the risk of serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with fenfluramine. After stopping treatment with fenfluramine, a time period equal to 4 to 5 half-lives of fenfluramine or any active metabolite should elapse before starting therapy with selegiline.
    Fentanyl: (Major) The use of fentanyl is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within the previous 14 days or are currently taking an MAOI due to a risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small opioid doses to treat pain while closely monitoring blood pressure and signs and symptoms of serotonin syndrome and CNS and respiratory depression.
    Fexofenadine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Fluoxetine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Fluphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Flurazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Fluvoxamine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Fosphenytoin: (Moderate) Use caution if selegiline and fosphenytoin are used concomitantly. Although fosphenytoin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Fospropofol: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Frovatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering frovatriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with frovatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue frovatriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
    Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and gabapentin. Concurrent use may result in additive CNS depression.
    General anesthetics: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Granisetron: (Moderate) Concomitant use of selegiline and serotonin receptor antagonists may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Guaifenesin; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Guaifenesin; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Guaifenesin; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Guanabenz: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) such as selegiline are combined with antihypertensives. In addition, when beginning treatment with antihypertensives that initially increase the release of catecholamine stores, such as guanabenz, hypertensive crisis may occur. Because selegiline is a selective MAO-B inhibitor at manufacturer recommended doses, serious reactions with agents affecting catecholamine release are less likely than with non-selective MAOIs.
    Guanfacine: (Moderate) Additive hypotensive effects may be seen when monoamine oxidase inhibitors (MAOIs) such as selegiline are combined with antihypertensives. In addition, when beginning treatment with antihypertensives that initially increase the release of catecholamine stores, such as guanfacine, hypertensive crisis may occur. Because selegiline is a selective MAO-B inhibitor at manufacturer recommended doses, serious reactions with agents affecting catecholamine release are less likely than with non-selective MAOIs. Abrupt cessation of therapy with central alpha-2 adrenergic agonists like guanfacine may be associated with increases (from depressed on-therapy levels) in plasma and urinary catecholamines, symptoms of nervousness and anxiety and, less commonly, increases in blood pressure to levels significantly greater than those prior to therapy, which may affect MAO inhibiting therapy.
    Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, selegiline and haloperidol may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Halothane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Homatropine; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Contraindicated) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
    Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Avoid concomitant use of hydrocodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydromorphone: (Major) Avoid concomitant use of hydromorphone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Hydroxyzine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and hydroxyzine. Concurrent use may result in additive CNS depression.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient 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, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. 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). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
    Ibuprofen; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Ibuprofen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Iloperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Imipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Iobenguane I 131: (Major) Discontinue monoamine oxidase inhibitors for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart monoamine oxidase inhibitors until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as monoamine oxidase inhibitors, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Isocarboxazid: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
    Isoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Isoniazid, INH: (Major) Concurrent use of selegiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and selegiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although selegiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of selegiline decreases with increasing dosages.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concurrent use of selegiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and selegiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although selegiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of selegiline decreases with increasing dosages. (Moderate) Use caution if selegiline and rifampin are used concomitantly. Although rifampin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Isoniazid, INH; Rifampin: (Major) Concurrent use of selegiline and isoniazid may increase the risk of a hypertensive crisis. Isoniazid has monoamine oxidase inhibiting activity and selegiline is a monoamine oxidase inhibitor (MAOI) type B. Monoamine oxidase type A is the primary enzyme in the gastrointestinal tract, and is responsible for the breakdown of dietary amines such as tyramine. When monoamine oxidase is inhibited by an MAOI, tyramine is absorbed systemically and may result in a hypertensive crisis. Although selegiline is a selective monoamine oxidase inhibitor type B, there is a risk of hypertension during ingestion of substances high in tyramine or during concurrent use of other drugs with MAOI activity such as isoniazid, since the MAOI-B selectivity of selegiline decreases with increasing dosages. (Moderate) Use caution if selegiline and rifampin are used concomitantly. Although rifampin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Isoproterenol: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as isoproterenol. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Ketamine: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Lasmiditan: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and selegiline. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and selegiline. Dosage adjustments of lemborexant and selegiline may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
    Levocetirizine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and cetirizine or levocetirizine. Concurrent use may result in additive CNS depression.
    Levodopa: (Moderate) Concurrent therapy with levodopa and selective monoamine oxidase inhibitors type B, such as selegiline, may be associated with additive orthostatic hypotension. Although these agents are commonly used together for the treatment of Parkinson's disease, patients receiving this combination should be monitored for orthostatic hypotension. Dosage adjustments should be made as needed.
    Levomilnacipran: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Levorphanol: (Moderate) Concomitant use of opioid agonists with selegiline may cause excessive sedation, somnolence, and serotonin syndrome. Limit the use of levorphanol with selegiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Linezolid: (Contraindicated) Concurrent use of linezolid with selegiline, a monoamine oxidase inhibitor type B (MAO-B inhibitor), or use of linezolid within 2 weeks of taking selegiline is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including MAOIs, which can potentiate central serotonin levels.
    Lisdexamfetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use.
    Lithium: (Moderate) Concomitant use of selegiline and lithium may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Loratadine; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Lorazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Lorcaserin: (Moderate) Concomitant use of selegiline and lorcaserin may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Loxapine: (Moderate) Due to opposing effects on central dopaminergic activity, loxapine and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible; consider an atypical antipsychotic as an alternative to loxapine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Lumateperone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Lurasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Maprotiline: (Contraindicated) Concurrent use of selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), and maprotiline, a selective norepinephrine reuptake inhibitor, is contraindicated due to the potential for severe or life-threatening reactions such as hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with maprotiline. After stopping treatment with maprotiline, a time period equal to 4 to 5 half-lives of maprotiline or any active metabolite should elapse before starting therapy with selegiline.
    Meperidine: (Contraindicated) Coadministration of meperidine and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with meperidine. After stopping treatment with meperidine, a time period equal to 4 to 5 half-lives of meperidine or any active metabolite should elapse before starting therapy with selegiline. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received MAO inhibiting agents within the past 14 days, and may increase the risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Meperidine; Promethazine: (Contraindicated) Coadministration of meperidine and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with meperidine. After stopping treatment with meperidine, a time period equal to 4 to 5 half-lives of meperidine or any active metabolite should elapse before starting therapy with selegiline. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received MAO inhibiting agents within the past 14 days, and may increase the risk for serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Mephobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Meprobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
    Mesoridazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Mestranol; Norethindrone: (Moderate) Selegiline concentrations may be increased by the co-administration of oral contraceptives containing estrogens and progestins. Dose reductions in selegiline may be necessary in patients on hormonal combined contraceptive agents.
    Methadone: (Contraindicated) Coadministration of methadone and selegiline is contraindicated due to a risk for serotonin syndrome and opioid toxicity, including respiratory depression. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with methadone. After stopping treatment with methadone, a time period equal to 4 to 5 half-lives of methadone or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of an alternate opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Methamphetamine: (Contraindicated) The product labels for amphetamines contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis or serotonin syndrome. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Amphetamines should not be used concurrently with MAOIs or within 14 days before or after their use.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient 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, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. 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). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
    Methohexital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Methyldopa: (Contraindicated) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
    Methylene Blue: (Major) Concurrent use of intravenous (IV) methylene blue and MAOIs such as selegiline should generally be avoided due to the potential for serotonin syndrome. If emergent treatment with methylene blue is required in a patient receiving an MAOI, it is advisable to discontinue the MAOI and monitor the patient 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, it is advisable to discontinue the MAOI at least 2 weeks prior to methylene blue treatment, but also taking into consideration the half-life of selegiline. Because selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, an interaction may be less likely to occur than with other traditional MAOIs. 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). Cases of serotonin syndrome have been reported, primarily following administration of IV methylene blue (1 to 8 mg/kg) as a visualizing agent in patients receiving serotonergic agents.
    Methylphenidate Derivatives: (Contraindicated) The product labels for methylphenidate and its derivatives contraindicate use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Methylphenidate derivatives should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Metoclopramide: (Major) Close monitoring is advisable if combination therapy is necessary. Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. The risk of extrapyramidal effects may be increased during concurrent use of metoclopramide and selegiline, and the therapeutic benefits of selegiline in treating Parkinson's disease may be diminished during use of a central dopamine antagonist such as metoclopramide. In addition, because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs.
    Midazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Midodrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as midodrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Milnacipran: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Mirtazapine: (Contraindicated) Mirtazapine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with mirtazapine. After stopping treatment with mirtazapine, a time period equal to 4 to 5 half-lives of mirtazapine or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
    Mitotane: (Moderate) Use caution if selegiline and mitotane are used concomitantly. Although mitotane is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Modafinil: (Moderate) Use caution during concomitant use of selegiline and modafinil. Modafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs); however, it is known that many other CNS stimulants may induce severe cardiovascular reactions, such as hypertensive crisis, if administered in combination with drugs with non-selective MAO inhibitor activity.
    Molindone: (Major) Due to opposing effects on central dopaminergic activity, selegiline and molindone may interfere with the effectiveness of each other. If possible, avoid concurrent use and consider an atypical antipsychotic as an alternative to molindone. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Monoamine oxidase inhibitors: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
    Morphine: (Contraindicated) Morphine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If possible, wait 14 days between discontinuation of selegiline and initiation of treatment with morphine. After stopping treatment with morphine, a time period equal to 4 to 5 half-lives of morphine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Morphine; Naltrexone: (Contraindicated) Morphine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If possible, wait 14 days between discontinuation of selegiline and initiation of treatment with morphine. After stopping treatment with morphine, a time period equal to 4 to 5 half-lives of morphine or any active metabolite should elapse before starting therapy with selegiline. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of alternate opioids to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Nabilone: (Major) Avoid coadministration of selegiline with nabilone due to the risk of additive CNS depression.
    Nalbuphine: (Major) Avoid concomitant use of nalbuphine in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Naproxen; Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Naratriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering naratriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with naratriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue naratriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
    Nefazodone: (Contraindicated) Nefazodone is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with nefazodone. After stopping treatment with nefazodone, a time period equal to 4 to 5 half-lives of nefazodone or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and sertonoergic antidepressants simultaneously.
    Norepinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as norepinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Norethindrone; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Norgestimate; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Nortriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Olanzapine; Fluoxetine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions. (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Olanzapine; Samidorphan: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Oliceridine: (Moderate) Concomitant use of oliceridine with selegiline may cause excessive sedation and somnolence. Limit the use of oliceridine with selegiline to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
    Ondansetron: (Moderate) Concomitant use of selegiline and serotonin receptor antagonists may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Oxazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Oxcarbazepine: (Contraindicated) Oxcarbazepine is the keto-analogue of carbamazepine, which is contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with oxcarbazepine. After stopping treatment with oxcarbazepine, a time period equal to 4 to 5 half-lives of oxcarbazepine or any active metabolite should elapse before starting therapy with selegiline.
    Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Oxymetazoline: (Moderate) Use these drugs together with caution. Monitor blood pressure for hypertension during concomitant use of selegiline and oxymetazoline. Although oxymetazoline is used by nasal or ophthalmic routes, the use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued immediately and therapy to lower blood pressure should be instituted immediately.
    Oxymorphone: (Major) Avoid concomitant use of oxymorphone in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity.
    Ozanimod: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like selegiline, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with selegiline. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors selegiline has not been studied; however, there may be an increased risk of hypertensive crisis.
    Paliperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Palonosetron: (Moderate) Concomitant use of selegiline and serotonin receptor antagonists may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Paroxetine: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Pentazocine: (Contraindicated) Coadministration of pentazocine and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with pentazocine. After stopping treatment with pentazocine, a time period equal to 4 to 5 half-lives of pentazocine or any active metabolite should elapse before starting therapy with selegiline.
    Pentazocine; Naloxone: (Contraindicated) Coadministration of pentazocine and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with pentazocine. After stopping treatment with pentazocine, a time period equal to 4 to 5 half-lives of pentazocine or any active metabolite should elapse before starting therapy with selegiline.
    Pentobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Perampanel: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and perampanel. Concurrent use may result in additive CNS depression.
    Perphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Perphenazine; Amitriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Phendimetrazine: (Contraindicated) The product label for phendimetrazine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phendimetrazine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Phenelzine: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
    Phenobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Phenothiazines: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Phentermine: (Contraindicated) The product label for phentermine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phentermine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Phentermine; Topiramate: (Contraindicated) The product label for phentermine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phentermine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Phenytoin: (Moderate) Use caution if selegiline and phenytoin are used concomitantly. Although phenytoin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pregabalin. Concurrent use may result in additive CNS depression.
    Prilocaine; Epinephrine: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately.
    Primidone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Procarbazine: (Major) Avoid use of these drugs together if possible. Concurrent use of selegiline and procarbazine may increase the risk of hypertensive crisis or serotonin syndrome. Procarbazine is an antineoplastic agent which exhibits weak monoamine oxidase (MAO) inhibitor activity and selegiline is a selective monoamine oxidase inhibitor (MAOI) type B. Although selegiline is a selective MAO-B inhibitor, there is a risk of hypertension or serotonin syndrome during concurrent use of other drugs with MAO inhibiting activity such as procarbazine, since the selectivity of selegiline decreases with increasing dosages. Monitoring of blood pressure is advisable if coadministration is medically necessary.
    Prochlorperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Promethazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Promethazine; Dextromethorphan: (Contraindicated) Dextromethorphan products are contraindicated in patients taking selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), due to the risk of serious and possibly fatal drug interactions, including serotonin syndrome. Patients should read nonprescription product labels carefully. Before initiating selegiline after using dextromethorphan, a sufficient amount of time is advisable for clearance of dextromethorphan. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Promethazine; Phenylephrine: (Contraindicated) The product label for phenylephrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Phenylephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Propofol: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Propoxyphene: (Contraindicated) Coadministration of propoxyphene and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with propoxyphene. After stopping treatment with propoxyphene, a time period equal to 4 to 5 half-lives of propoxyphene or any active metabolite should elapse before starting therapy with selegiline.
    Protriptyline: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Pseudoephedrine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Pseudoephedrine; Triprolidine: (Contraindicated) The product label for pseudoephedrine contraindicates use with monoamine oxidase inhibitors (MAOIs) due to the risk of hypertensive crisis. Selegiline is a selective monoamine oxidase inhibitor type B; however, the selectivity of the drug decreases with increasing doses. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Pseudoephedrine should generally not be used concurrently with MAOIs or within 14 days before or after their use. (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and triprolidine. Concurrent use may result in additive CNS depression.
    Pyrilamine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and pyrilamine. Concurrent use may result in additive CNS depression.
    Quazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Quetiapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Racepinephrine: (Contraindicated) The product label for racepinephrine contraindicates use with monoamine oxidase inhibitors (MAOIs), including selegiline, due to the risk of hypertensive crisis. The manufacturers of selegiline products recommend caution and monitoring of blood pressure during concurrent use with sympathomimetics. Racepinephrine should generally not be used concurrently with MAOIs or within 14 days before or after their use.
    Ramelteon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and ramelteon. Concurrent use may result in additive CNS depression.
    Rasagiline: (Contraindicated) Both rasagiline and selegiline are selective monoamine oxidase type B inhibitors (MAO-B inhibitors), and concurrent use is contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with rasagiline. After stopping treatment with rasagiline, a time period equal to 4 to 5 half-lives of rasagiline or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors simultaneously. Concurrent use may also represent duplicative therapy.
    Remifentanil: (Major) Avoid concomitant use of remifentanil in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Remimazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Reserpine: (Moderate) Closely monitor for increased blood pressure during concomitant use of selegiline and reserpine. Coadministration can cause hypertension and increased excitation. Reserpine depletes intracellular catecholamines by initially causing their release from bound stores, so the acute administration of reserpine to patients currently taking an MAOI can lead to hypertensive crisis.
    Rifampin: (Moderate) Use caution if selegiline and rifampin are used concomitantly. Although rifampin is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Rifapentine: (Moderate) Use caution if selegiline and rifapentine are used concomitantly. Although rifapentine is a strong CYP3A4 inducer and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate its effect, if any, on the effectiveness of selegiline.
    Risperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Rizatriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering rizatriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with rizatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue rizatriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
    Safinamide: (Contraindicated) Both safinamide and selegiline are selective monoamine oxidase type B inhibitors (MAO-B inhibitors), and concurrent use is contraindicated. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with safinamide. After stopping treatment with safinamide, a time period equal to 4 to 5 half-lives of safinamide or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors simultaneously. Concurrent use may also represent duplicative therapy.
    Secobarbital: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) Selegiline concentrations may be increased by the coadministration of oral contraceptives containing estrogens and progestins. The metabolism of selegiline appears to be decreased by the presence of oral contraceptives. Dose reductions in selegiline may be necessary in patients on ethinyl estradiol or hormonal combined contraceptive agents in order to limit the risk of increased MAO type B inhibition.
    Selective norepinephrine reuptake inhibitors: (Contraindicated) Selective norepinephrine reuptake inhibitors are contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a selective norepinephrine reuptake inhibitor. After stopping treatment with the reuptake inhibitor, a time period equal to 4 to 5 half-lives of the reuptake inhibitor or any active metabolite should elapse before starting therapy with selegiline.
    Selective serotonin reuptake inhibitors: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Serotonin norepinephrine reuptake inhibitors: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Serotonin-Receptor Antagonists: (Moderate) Concomitant use of selegiline and serotonin receptor antagonists may increase the risk of serotonin syndrome. Monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Sertraline: (Contraindicated) Selective serotonin reuptake inhibitors (SSRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SSRI. With the exception of fluoxetine, a time period equal to 4 to 5 half-lives of the SSRI or any active metabolite should elapse after discontinuing treatment with the SSRI and before starting therapy with selegiline. Because of the long half-life of fluoxetine and its active metabolite, at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of treatment with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Sevoflurane: (Moderate) Although CNS depression is a desired effect of general anesthetics, patients also receiving selegiline should be closely monitored for additive effects that may prolong recovery after administration of general anesthetics.
    Sibutramine: (Contraindicated) Sibutramine is contraindicated for use with monoamine oxidase inhibitors, such as selegiline, due to the risk of serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with sibutramine. After stopping treatment with sibutramine, a time period equal to 4 to 5 half-lives of sibutramine or any active metabolite should elapse before starting therapy with selegiline.
    Sodium Oxybate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and sodium oxybate. Concurrent use may result in additive CNS depression.
    Solriamfetol: (Contraindicated) The concurrent use of noradrenergic drugs, such as solriamfetol, and monoamine oxidase inhibitors (MAOIs), such as selegiline, or use of solriamfetol within 14 days of MAOI therapy is contraindicated due to the increased risk for hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure.
    St. John's Wort, Hypericum perforatum: (Contraindicated) Concomitant use of selegiline and St. John's Wort is contraindicated due to the risk of serotonin syndrome.
    Sufentanil: (Major) Avoid concomitant use of sufentanil in patients receiving selegiline or within 14 days of stopping treatment with selegiline due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Sumatriptan: (Contraindicated) Because of the potential risk and severity of serotonin syndrome, use of sumatriptan with or within 2 weeks of discontinuing transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets is contraindicated. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with sumatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment.
    Sumatriptan; Naproxen: (Contraindicated) Because of the potential risk and severity of serotonin syndrome, use of sumatriptan with or within 2 weeks of discontinuing transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets is contraindicated. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with sumatriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment.
    Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and selegiline. Dosage adjustments may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants.
    Tapentadol: (Contraindicated) Tapentadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs), such as selegiline, within the previous 14 days. Concomitant use may result in serious adverse effects including serotonin syndrome, additive CNS depression, or hypotension.
    Tedizolid: (Major) Avoid concomitant use of selegiline and tedizolid. Although interactions with monamine oxidase inhibitors (MAOIs) were not evaluated in clinical trials, caution is warranted with the concurrent use of tedizolid and MAOIs due to the potential risk of severe hypertensive crisis and possibly serotonin syndrome. Consider if another antibiotic would be appropriate for the patient. Tedizolid is an oxazolidinone-class antibacterial that is also a weak reversible, non-selective inhibitor of MAO. Serotonin syndrome has been reported when another oxazolidinone-class antibacterial has been administered with certain serotonergic agents.
    Temazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Tetrabenazine: (Contraindicated) Tetrabenazine use is contraindicated in patients who are receiving or have received MAOI therapy, such as selegiline, 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.
    Tetrahydrozoline: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and tetrahydrozoline. Although tetrahydrozoline is only used by ophthalmic and nasal routes, the use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued immediately and therapy to lower blood pressure should be instituted immediately.
    Thiethylperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Thiopental: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and barbiturates. Concurrent use may result in additive CNS depression. Although barbiturates are CYP3A4 inducers and selegiline is a CYP3A4 substrate, adequate studies have not been conducted to evaluate their effect, if any, on the effectiveness of selegiline.
    Thioridazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to thiothixene. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
    Tramadol: (Contraindicated) Coadministration of tramadol and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with tramadol. After stopping treatment with tramadol, a time period equal to 4 to 5 half-lives of tramadol or any active metabolite should elapse before starting therapy with selegiline. Consider the use of an alternate opioid if urgent use for pain is needed.
    Tramadol; Acetaminophen: (Contraindicated) Coadministration of tramadol and selegiline is contraindicated due to a risk for serotonin syndrome. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with tramadol. After stopping treatment with tramadol, a time period equal to 4 to 5 half-lives of tramadol or any active metabolite should elapse before starting therapy with selegiline. Consider the use of an alternate opioid if urgent use for pain is needed.
    Tranylcypromine: (Contraindicated) Non-selective monoamine oxidase inhibitors (MAOIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an MAOI. After stopping treatment with an MAOI, a time period equal to 4 to 5 half-lives of the MAOI or any active metabolite should elapse before starting therapy with selegiline. Hypertensive crisis has occurred in patients receiving selective MAO-B inhibitors and non-selective MAOIs simultaneously.
    Trazodone: (Contraindicated) Trazodone is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with trazodone. After stopping treatment with trazodone, a time period equal to 4 to 5 half-lives of trazodone or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
    Triazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and benzodiazepines. Concurrent use may result in additive CNS depression.
    Tricyclic antidepressants: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Trifluoperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and selegiline may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic to the phenothiazine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. Additive hypotensive effects are also possible.
    Trimipramine: (Contraindicated) Tricyclic antidepressants (TCAs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a TCA. After stopping treatment with a TCA, a time period equal to 4 to 5 half-lives of the TCA or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and such antidepressants simultaneously.
    Triprolidine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and triprolidine. Concurrent use may result in additive CNS depression.
    Tryptophan, 5-Hydroxytryptophan: (Major) Avoid use together if possible. The combination of tryptophan supplements and selegiline may lead to increased levels of serotonin and serotonin syndrome. Tryptophan is a serotonin precursor. Selegiline is a MAO-B inhibitor. In the postmarketing period, potentially life-threatening serotonin syndrome has been reported in patients treated with selected serotonergic agents concomitantly with selegiline. There are also reports of tryptophan and MAO inhibitor interactions in the literature.
    Valbenazine: (Major) Avoid the use of valbenazine with monoamine oxidase inhibitors (MAOIs), including selegiline. Concomitant use of valbenazine with MAO inhibitors, including selegiline, may result in an increased 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: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and valerian. Concurrent use may result in additive CNS depression.
    Valproic Acid, Divalproex Sodium: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and valproic acid. Concurrent use may result in additive CNS depression.
    Venlafaxine: (Contraindicated) Serotonin norepinephrine reuptake inhibitors (SNRIs) are contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with an SNRI. After stopping treatment with an SNRI, a time period equal to 4 to 5 half-lives of the SNRI or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonin-augmenting antidepressants simultaneously. Monitor for serotonergic side effects during therapy transitions.
    Vilazodone: (Contraindicated) Vilazodone is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with vilazodone. After stopping treatment with vilazodone, a time period equal to 4 to 5 half-lives of vilazodone or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
    Viloxazine: (Contraindicated) Selective norepinephrine reuptake inhibitors are contraindicated for use with selegiline because of a possible increased risk of hypertensive crisis. At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with a selective norepinephrine reuptake inhibitor. After stopping treatment with the reuptake inhibitor, a time period equal to 4 to 5 half-lives of the reuptake inhibitor or any active metabolite should elapse before starting therapy with selegiline.
    Vortioxetine: (Contraindicated) Vortioxetine is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with vortioxetine. After stopping treatment with vortioxetine, a time period equal to 4 to 5 half-lives of vortioxetine or any active metabolite should elapse before starting therapy with selegiline. Serotonin syndrome has occurred in patients receiving selective MAO-B inhibitors and serotonergic antidepressants simultaneously.
    Yohimbine: (Major) Selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor), should not be used concurrently with or in rapid succession of drugs that possess MAO-inhibiting activity, such as yohimbine, due to the risk of hypertensive crisis. 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. At least 14 days should elapse between the discontinuation of selegiline and the initiation of another drug with MAOI activity, and a time period of 4 to 5 half-lives should elapse following the discontinuation of yohimbine and the initiation of selegiline.
    Zaleplon: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.
    Ziprasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or selegiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and selegiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with selegiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
    Zolmitriptan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering zolmitriptan with transdermal selegiline, orally disintegrating selegiline tablets, and high doses of oral selegiline capsules and tablets. Since selegiline oral tablets and capsules selectively inhibit MAO-B at recommended doses, no interaction with zolmitriptan would be expected with normal prescription use. However, MAO-B selectivity decreases with increasing doses, therefore, an interaction may occur with high dose treatment. Serotonin syndrome has been reported during concurrent use of serotonin-receptor agonists and monoamine oxidase inhibitors (MAOIs). Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue zolmitriptan and selegiline and initiate symptomatic treatment if serotonin syndrome occurs.
    Zolpidem: (Moderate) Monitor for excessive sedation and somnolence during coadministration of selegiline and anxiolytics, sedatives, and hypnotics. Concurrent use may result in additive CNS depression.

    PREGNANCY AND LACTATION

    Pregnancy

    Because there are no adequate and well-controlled studies of selegiline use in pregnant women, oral selegiline should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. The available data on transdermal selegiline in pregnant women are not sufficient to provide information on the risk of drug-associated adverse outcomes during pregnancy. When treating a pregnant woman for depression with transdermal selegiline, the potential risks of taking a monoamine oxidase inhibitor (MAOI), particularly the risk of hypertensive crisis during pregnancy, should be weighed against the established benefits of treating depression with an antidepressant. Selegiline has a low molecular weight and would be expected to cross the placenta. A case report of oral selegiline used in a pregnant woman who continued the drug throughout gestation noted no teratogenic defects or developmental delays in a healthy male infant over a 10-year period. However, animal studies suggest the potential for neurological changes. Decreases in fetal weight, delayed ossification, and embryo-fetal post-implantation lethality have been noted during the period of organogenesis in animal studies at doses up to 60 times the maximum recommended human dose (MRHD). Slight increases in visceral malformations have been seen during the period of embryo-fetal development in animal studies at doses up to 64 times the MRHD. An increase in stillborn pups and post-implantation loss has been seen in rat studies. Throughout lactation and post-weaning periods, decreases in pup weight, retarded pup physical development, and retarded pup neurobehavioral and sexual development were seen at all doses up to 60 times the MRHD. These findings suggest persistent effects on the offspring of treated dams. A no-effect dose was not established for developmental toxicity. It is not known how these animal findings relate to effects in pregnant women. Selegiline has no established use in labor and delivery. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to selegiline; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1-866-961-2388.

    It is unknown if selegiline is excreted into human breast milk, effects the breast-fed infant, or effects milk production. Selegiline has a low molecular weight (188 for the free base) and would be expected to cross into human breast milk. During treatment with the oral capsule or tablet formulations of selegiline, a decision should be made whether to discontinue the drug or discontinue breast-feeding, taking into account the importance of the drug to the mother. Consideration should be given to discontinuing the use of all but absolutely essential drug treatments in nursing women. Because of the potential for serious adverse effects in a breast-fed infant, including hypertensive crisis, the manufacturer for the orally disintegrating tablets recommends against breast-feeding during treatment and for 7 days after the final dose. The manufacturer for transdermal selegiline recommends against breast-feeding during treatment with transdermal selegiline and for 5 days after the final dose. A case report describes maternal use of oral selegiline 10 mg/day, levodopa 400 mg, and benserazide 100 mg daily throughout pregnancy and for 3 days while breast-feeding; the child was followed for 10 years and no developmental abnormalities were found. Although rasagiline may be considered as an alternative therapy to selegiline for the adjunct treatment of Parkinson's disease in breast-feeding women, safety data are lacking. In addition, both rasagiline and selegiline can inhibit prolactin secretion, and thus, interference with proper lactation is possible. Psychotropic medications affect neurotransmitter function in the developing central nervous system, and therefore, the accurate prediction of long-term adverse effects may not be possible. Alternatives to selegiline for the treatment of depression may be considered. 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 preferable to other antidepressants when initiating antidepressant therapy in a breast-feeding mother.

    MECHANISM OF ACTION

    Selegiline is an irreversible inhibitor of the monoamine oxidase (MAO) enzyme system. MAO exists as 2 catabolic isoenzymes, MAO-A and MAO-B. The neurotransmitters serotonin and norepinephrine are primarily catabolized by MAO-A and dopamine is primarily catabolized by MAO-B. In addition to their role in the catabolism of monoamines in the CNS, MAOs are also important in the catabolism of exogenous amines found in a variety of foods and drugs. MAO in the gastrointestinal tract is primarily type A, and provides protection from systemic absorption of exogenous amines with vasopressor actions, such as tyramine, which can cause hypertensive crisis if absorbed intact. Selegiline is considered a selective MAO-B inhibitor, although selectivity decreases as the dose increases. Restrictions on intake of dietary tyramine during selegiline administration vary according to formulation and dose. Two of the metabolites, amphetamine and methamphetamine, may interfere with neuronal uptake and enhance the release of some neurotransmitters (e.g., norepinephrine, dopamine, serotonin). However, the extent to which these metabolites contribute to the therapeutic effects of selegiline is unknown. Selegiline has demonstrated affinity at the adrenergic alpha 2B receptor. No affinity has been noted at dopamine receptors, adrenergic B3, glutamate, muscarinic, nicotinic, or rolapram receptor/sites.
     
    Transdermal selegiline: The mechanism of action of transdermal selegiline as an antidepressant is thought to occur from potentiation of monoamine neurotransmitters (e.g., dopamine, serotonin, norepinephrine) in the CNS resulting from its inhibition of MAO-A and MAO-B. When administered in a transdermal patch, targeted inhibition of MAO-A and MAO-B in the CNS is seen. In vitro studies have shown that transdermal selegiline exhibits antidepressant properties only at doses that inhibit both MAO-A and MAO-B activity in brain. Intestinal MAO is predominantly type A, while in the brain both isoenzymes exist. Clinical trials of transdermal selegiline demonstrated a preservation of MAO-A in the intestinal mucosa and liver, allowing for the breakdown of dietary tyramine and the prevention of gastric absorption of dietary tyramine only at a selegiline dose of 6 mg/24 hour. Higher therapeutic doses (i.e., 9 mg/24 hours and 12 mg/24 hours) must be used with tyramine diet restrictions. Effects resulting from transdermal selegiline administration may also occur through its metabolites. However, transdermal dosing results in significantly higher exposure to selegiline with significantly lower exposure for all metabolites relative to oral administration.
     
    Oral selegiline: At doses used in Parkinson's disease, selegiline typically exhibits a greater affinity for MAO-B. At higher doses, MAO is blocked non-selectively, predisposing patients to the risks (e.g., hypertensive crisis) of traditional MAOIs (e.g., phenelzine) that block both MAO-B and MOA-A. Therefore, the dose limits established for specific oral selegiline products should not be exceeded. An increase in tyramine sensitivity for blood pressure responses appears to begin at a dose of 5 mg/day of selegiline orally disintegrating tablets (ODT); however, the precise dose at which selegiline ODT becomes a non-selective inhibitor of all MAO enzymes in individual patients is unknown. Oral selegiline tablets can ordinarily be used safely without dietary restrictions at doses where it presumably selectively inhibits MAO-B (e.g., 10 mg/day); however, it should be noted that a few cases of hypertensive reactions have been reported at the recommended dose.

    PHARMACOKINETICS

    Selegiline is available as an oral tablet, oral capsule, orally disintegrating tablet (ODT), and transdermal patch. Approximately 85% to 90% of plasma selegiline is reversibly bound to plasma proteins. Selegiline rapidly penetrates the blood-brain barrier. Although platelet MAO-B activity returns to the normal range within 5 to 7 days of discontinuation of oral selegiline, the link between platelet and brain MAO-B inhibition is not fully understood nor is the relationship of MAO-B inhibition to the clinical effect. Selegiline is extensively metabolized to N-desmethylselegiline and L-methamphetamine. Both of these metabolites may subsequently be converted to L-amphetamine. The metabolites are further converted to their hydroxymetabolites. Transdermal dosing results in significantly higher exposure to selegiline with significantly lower exposure for all metabolites when compared to oral dosing. In a kinetic evaluation, approximately 10% of a radiolabeled transdermal dose was recovered in the urine and 2% recovered in feces, with at least 63% of the dose unabsorbed. The remaining 25% of the transdermal dose was unaccounted for. Selegiline ODT produces a smaller fraction of the administered dose recoverable as the metabolites than the conventional, swallowed formulation of selegiline. Following a single oral or ODT dose, the mean elimination half-life of selegiline was 1.3 to 2 hours. At steady-state, the elimination half-life increased to 10 hours. After IV administration, the half-lives of selegiline and its 3 metabolites (N-desmethylselegiline, L-amphetamine, and L-methamphetamine) ranged from 18 to 25 hours. Following hepatic metabolism, selegiline is excreted primarily in the urine as metabolites (mainly as L-methamphetamine and L-amphetamine) and as a small amount in the feces.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, CYP3A5, CYP2B6, CYP2A6, CYP2D6, CYP2C9
    Selegiline is a substrate for CYP2B6, CYP2C9 and CYP3A4/5. In vitro studies indicate that CYP2B6, CYP2C9, CYP3A4 and CYP3A5 appear to be the major isoenzymes involved in the formation of L-methamphetamine from selegiline, with CYP2A6 having a minor role. CYP2A6, CYP2B6, CYP3A4, and CYP3A5 appear to contribute to the formation of L-amphetamine from N-desmethylselegiline. A potent CYP3A inhibitor, itraconazole, had no effect on the pharmacokinetics of selegiline (single 10 mg oral, swallowed dose). Although adequate studies to investigate the effect of CYP3A4-inducers on selegiline have not been performed, drugs that induce CYP3A4 (e.g., phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution.
     
    In vitro studies have demonstrated that selegiline is not an inhibitor of CYP450 enzymes. Selegiline shows competitive inhibitory action at CYP2D6, CYP3A4/5, CYP2C19, and CYP2B6. However, all inhibitory effects of selegiline occur at concentrations that are several orders of magnitude higher than concentrations seen clinically. Selegiline and two of its metabolites, methamphetamine and desmethylselegiline, have little or no potential to induce CYP1A2 and CYP3A4/5 under clinical conditions.

    Oral Route

    Oral Tablet or Capsule: Following administration of the tablet or capsule dosage form, selegiline is readily absorbed from the GI tract and crosses the blood/brain barrier; however, the absolute bioavailability is unknown. The extent of systemic exposure to selegiline at a given dose varies significantly among individuals. Peak serum concentrations are found in 0.5 to 2 hours. Mean maximum plasma concentrations of 1.12 ng/mL are reached for the oral 5 mg selegiline tablets (given as 5 mg PO twice daily). The bioavailability of selegiline is increased 3 to 4 fold when it is taken with food. The peak plasma levels of the 3 metabolites (N-desmethylselegiline, L-amphetamine and L-methamphetamine) following a single oral dose of 10 mg are from 4 to almost 20 times greater than that of the maximum plasma concentration (Cmax) of selegiline. The maximum concentrations of amphetamine and methamphetamine, however, are far below those ordinarily expected to produce clinically important effects. The duration of action of selegiline depends on the time required to regenerate MAO type B. Like phenelzine, the effects of selegiline are cumulative, with beneficial effects seen in a few days to several months depending on the condition being treated and individual response.
    Orally Disintegrating Tablet (ODT): Following administration of the orally disintegrating tablet, disintegration and absorption occur rapidly. Detectable levels of selegiline from selegiline ODT have been measured 5 minutes after administration. Selegiline ODT is more rapidly absorbed (time to maximal concentration or Tmax range 10 to 15 minutes) than from the swallowed 5 mg selegiline tablet (Tmax range 40 to 90 minutes). When selegiline ODT is taken with food, the Cmax and AUC of selegiline are about 60% of those seen when selegiline ODT is taken in the fasted state. Since selegiline ODT is placed on the tongue and absorbed through the oral mucosa, the intake of food and liquid should be avoided 5 minutes before and after administration. The pre-gastric absorption from selegiline ODT and the avoidance of first-pass metabolism results in higher concentrations of selegiline and lower concentrations of the metabolites compared to the 5 mg swallowed tablet. Mean maximum plasma concentrations of 3.34 and 4.47 ng/mL are reached after single dose of 1.25 and 2.5 mg selegiline ODT, respectively, compared to 1.12 ng/mL for the swallowed 5 mg selegiline tablets (given as 5 mg bid). Plasma Cmax and AUC of selegiline ODT are dose proportional. Steady state is achieved after 8 days. Following a single dose, the median elimination half-life is 1.3 hours at the 1.25 mg dose. Under steady-state conditions, the median elimination half-life increases to 10 hours. Selegiline ODT produces a smaller fraction of the administered dose recoverable as the metabolites than the conventional swallowed formulation of selegiline.

    Other Route(s)

    Transdermal Route
    With transdermal application, roughly 25 to 30% (range: 10% to 40%) of the selegiline content is delivered systemically over a 24-hour period. The degree of drug absorption may variably be one-third higher than the average amounts of transdermal doses of 6 mg/24 hours to 12 mg/24 hours. Transdermal administration avoids first-pass metabolism and results in much higher bioavailability compared to the oral dose form (74% vs. 4%). Additionally, substantially lower metabolite (L-desmethylselegiline, L-amphetamine, L-methamphetamine) concentrations are seen, compared to oral dosing. Steady-state plasma concentrations are achieved within 5 days. Transdermal selegiline does not accumulate in and is not metabolized in the skin and does not undergo extensive first-pass metabolism. In one study, steady-state selegiline plasma concentrations indicated selegiline concentration-time profiles were comparable when transdermal selegiline is applied to the upper torso or upper thigh, and absorption from these two sites of administration was equivalent.