Version July 2025
Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening and for emergence of suicidal thoughts and behaviors.
Selegiline transdermal patch is contraindicated in patients less than 12 years of age because of an increased risk of hypertensive crisis.
Major depressive disorder (unipolar): Transdermal: Initial: Apply 6 mg/24 hours patch once daily. Although the initial dose is the target dose, may increase daily dose based on clinical response in increments of 3 mg/day every 2 weeks up to a maximum of 12 mg/24 hours.
Parkinson disease, adjunctive therapy: Oral:
Capsule, tablet: 5 mg twice daily with breakfast and lunch with concomitant carbidopa/levodopa therapy; maximum: 10 mg/day.
Orally disintegrating tablet: Initial: 1.25 mg once daily with concomitant carbidopa/levodopa therapy for at least 6 weeks; may increase to 2.5 mg once daily based on clinical response and tolerability (maximum: 2.5 mg/day).
Parkinson disease, monotherapy (off-label use): Oral: Capsule, tablet: 5 mg twice daily with breakfast and lunch; maximum: 10 mg/day (Ref).
Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for ≥4 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (Ref). For brief treatment (eg, 2 to 3 weeks) may taper over 1 to 2 weeks; <2 weeks treatment generally does not warrant tapering (Ref). Reasons for a slower taper (eg, over 4 weeks) include history of antidepressant withdrawal symptoms or high doses of antidepressants (Ref). More severe symptoms have been associated with monoamine oxidase inhibitor (MAOIs); more conservative tapers may be necessary (Ref). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Ref). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (Ref). Evidence supporting ideal taper rates is limited (Ref).
Switching antidepressants:
Switching to or from selegiline, another MAOI , or an alternative antidepressant:
Allow 14 days (or a time equal to 4 to 5 half-lives of the drug) to elapse between discontinuing another MAOI or an alternative antidepressant without long half-life metabolites (eg, tricyclic antidepressants, paroxetine, fluvoxamine, venlafaxine) and initiation of selegiline (Ref).
Allow 5 weeks to elapse between discontinuing fluoxetine (with long half-life metabolites) and initiation of selegiline.
Allow 14 days to elapse between discontinuing selegiline and initiation of another MAOI or an alternative antidepressant.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral:
Capsules, tablets: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution.
Orally disintegrating tablet:
CrCl 30 to 89 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: Use is not recommended.
End-stage renal disease: Use is not recommended.
Transdermal:
eGFR ≥15 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
ESRD requiring dialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Oral:
Capsules/tablets: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). Use with caution.
Orally disintegrating tablet:
Mild to moderate impairment (Child-Pugh class A and B): 1.25 mg once daily based on clinical response and tolerability.
Severe impairment (Child-Pugh class C): Use is not recommended.
Transdermal:
Mild to moderate impairment (Child-Pugh class A and B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Major depressive disorder (unipolar): Transdermal: 6 mg/24 hours once daily.
Parkinson disease:
Capsule, tablet: ≤5 mg/day (when combined with levodopa) is recommended by some clinicians to decrease the enhanced dopaminergic side effects (Ref).
Orally disintegrating tablet: Refer to adult dosing.
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
Depression: Adolescents >17 years: Transdermal: Refer to adult dosing.
Discontinuation of therapy: Refer to adult dosing.
Switching antidepressants: Refer to adult dosing.
Adolescents ≥18 years: Transdermal:
eGFR ≥15 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <15 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
ESRD requiring dialysis: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Adolescents ≥18 years: Transdermal:
Mild to moderate impairment (Child-Pugh class A and B): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults administered transdermal patch (TDP), orally disintegrating tablet (ODT), and oral (capsule/tablet: oral) formulations unless otherwise noted.
>10%:
Cardiovascular: Hypotension (ODT: 12% to 21%; TDP: 3% to 10%; including orthostatic hypotension)
Gastrointestinal: Nausea (ODT: 11%; oral: 10%)
Local: Application-site reaction (TDP: 24%; including application-site erythema)
Nervous system: Dizziness (ODT: 11%; oral: ≤7%), headache (TDP: 18%; ODT/oral: 2% to 7%), insomnia (ODT/TDP: 7% to 12%)
1% to 10%:
Cardiovascular: Chest pain (ODT: 2%), hypertension (ODT: 3%), palpitations (oral: 2%), syncope (oral: ≤7%)
Dermatologic: Dermal ulcer, dermatological disorder (ODT: 6%; including contact dermatitis, diaphoresis, fungal dermatitis, herpes simplex dermatitis, pruritus, skin hypertrophy, urticaria, xeroderma), ecchymosis (ODT: 2%), skin rash (ODT/TDP: 4%)
Endocrine & metabolic: Hypokalemia (ODT: 2%), weight loss (TDP: 5%; oral: 2%)
Gastrointestinal: Abdominal pain (oral: 4%), constipation (ODT: 4%), diarrhea (TDP: 9%; ODT/oral: 2%), dyspepsia (TDP: 4%; ODT: 5%), dysphagia (ODT: 2%), flatulence (ODT: 2%), oral mucosa changes (ODT: 10%; including mouth pain, odynophagia, oral mucosa ulcer, oral mucosal erythema), stomatitis (ODT: 5%), vomiting (ODT: 3%), xerostomia (TDP: 8%; ODT/oral: 3% to 4%)
Genitourinary: Sexual disorder (TDP: males: anorgasmia [<1%], decreased libido [<1%], ejaculatory disorder [1%]), urinary retention (oral: 2%)
Nervous system: Ataxia (ODT: 3%), confusion (oral: 3%), depression (ODT: 2%), drowsiness (ODT: 3%), generalized ache or pain (oral: 2%), hallucination (ODT/oral: 3% to 4%; including visual hallucination), lethargy (oral: 2%), pain (ODT: 8%), tremor (ODT: 3%), vivid dream (oral: 2%; including abnormal dreams and nightmares)
Neuromuscular & skeletal: Back pain (ODT: 5%), dyskinesia (ODT: 6%; including exacerbation of dyskinesia), lower back pain (oral: 2%), lower leg pain (oral: 2%), lower limb cramp (ODT: 3%), myalgia (ODT: 3%)
Respiratory: Dyspnea (ODT: 3%), pharyngitis (OTD/TDP: 3% to 4%), rhinitis (ODT: 7%), sinusitis (TDP: 3%)
<1%: Nervous system: Manic reaction (TDP)
Frequency not defined (any formulation):
Cardiovascular: Angina pectoris (including exacerbation of angina pectoris), cardiac arrhythmia, peripheral edema, sinus bradycardia, tachycardia
Dermatologic: Alopecia, skin photosensitivity, unusual facial hair growth
Gastrointestinal: Anorexia, decreased appetite, dysgeusia, gastrointestinal hemorrhage, heartburn, rectal hemorrhage, sore throat
Genitourinary: Benign prostatic hypertrophy, nocturia, urinary frequency, urinary hesitancy
Hematologic & oncologic: Hematoma
Nervous system: Abnormal gait (including festinating gait and freezing of gait), amnesia, apathy, apraxia (increased), asthenia, behavioral changes, chills, chorea, delusions, facial grimace, fatigue, heaviness of the legs, irritability, loss of balance, malaise, migraine, mood changes, myasthenia, numbness of fingers, numbness of toes, overstimulation, personality changes, restlessness, sleep disturbance, sleep driving, speech disturbance, sudden onset of sleep, suicidal ideation, suicidal tendencies, tension, twitching, vertigo
Neuromuscular & skeletal: Bradykinesia, dystonia, muscle cramps, neck stiffness, tardive dyskinesia
Ophthalmic: Blepharospasm, blurred vision, diplopia, supraorbital pain
Otic: Tinnitus
Respiratory: Asthma
Postmarketing (any formulation):
Cardiovascular: Hypertensive crisis (Ito 2001)
Endocrine & metabolic: Increased libido (Shapiro 2006)
Hematologic & oncologic: Decreased white blood cell count (Mizuno 2019)
Nervous system: Agitation (Montastruc 2000), anxiety (Mizuno 2019), atypical sexual behavior (paraphilia) (Shapiro 2006), delirium (Montastruc 2000), disorientation, disturbance in attention (Mizumo 2019), falling (Mizuno 2019), hypoesthesia, involuntary body movements (Montastruc 2000), sedated state (Montastruc 2000), seizure
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (Mizuno 2019)
Hypersensitivity to selegiline or any component of the formulation; concomitant use of meperidine.
Orally disintegrating tablet: Concomitant use or within 14 days of other monoamine oxidase inhibitors or other drugs that are potent inhibitors of monoamine oxidase (including linezolid), or opioids (eg, meperidine, methadone, tramadol); concomitant use with cyclobenzaprine, dextromethorphan, or St John's wort.
Transdermal: Pheochromocytoma; patients <12 years of age; use of carbamazepine, serotonin reuptake inhibitors (including selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors), clomipramine, imipramine, tramadol, propoxyphene, meperidine, methadone, pentazocine, and dextromethorphan (concurrently, within 2 weeks of selegiline discontinuation, or selegiline use within 4 to 5 half-lives [approximately 1 week for most medications; 5 weeks for fluoxetine] of discontinuation of the contraindicated drug).
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Severe psychosis; severe dementia; active peptic ulcer; extrapyramidal disorders, including excessive tremor or tardive dyskinesia.
Major psychiatric warnings (transdermal patch):
• Suicidal thinking/behavior:
- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.
- Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their health care provider if any of these symptoms or worsening depression or psychosis occur.
Concerns related to adverse effects:
• BP effects: Oral formulations: May cause exacerbation of hypertension. May also cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Incidence of orthostatic hypotension may also be increased in older adults and when titrating the dose. Monitor patients for new onset or exacerbation of hypotension, new onset hypertension or hypertension not adequately controlled after starting selegiline.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Somnolence and falling asleep while engaged in activities of daily living (including operation of motor vehicles) have been reported with the orally disintegrating tablet; some cases reported that there were no warning signs for the onset of symptoms. Symptom onset may occur well after initiation of treatment; some events have occurred >1 year after initiation of treatment. Prior to treatment initiation, evaluate for factors that may increase these risks such as concomitant sedating medications and the presence of sleep disorders. Monitor for drowsiness or sleepiness. If significant daytime sleepiness or episodes of falling asleep during activities that require active participation occur (eg, driving, conversations, eating), discontinue selegiline. There is insufficient information to suggest that dose reductions will eliminate these symptoms. If therapy is continued, advise patient to avoid driving and other potentially dangerous activities.
• Dyskinesia: Oral formulations: May potentiate the dopaminergic side effects of levodopa and cause dyskinesia or exacerbate preexisting dyskinesia requiring a reduction of the dose of levodopa.
• Impulse control disorders: Dopaminergic agents used for Parkinson disease have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), uncontrolled spending of money, binge eating, and/or other intense urges. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/substance use disorders and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
• Psychosis: Orally disintegrating tablets: May cause new or worsening mental status and behavioral changes (may be severe) including hallucinations and psychotic-like behavior with initiation of therapy, after dose increases, or during the course of therapy. Symptoms may consist of paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium. Avoid use in patients with a major psychotic disorder.
• Serotonin syndrome: Potentially life-threatening serotonin syndrome (SS) has occurred with concomitant use of serotonergic agents (eg, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, buspirone, St. John's wort, tryptophan) or agents that impair metabolism of serotonin (eg, monoamine oxidase inhibitors [MAOIs] intended to treat psychiatric disorders, other MAOIs [ie, linezolid and IV methylene blue]). Monitor patients closely for signs of SS such as mental status changes (eg, agitation, hallucinations, delirium, coma); autonomic instability (eg, tachycardia, labile BP, diaphoresis); neuromuscular changes (eg, tremor, rigidity, myoclonus); GI symptoms (eg, nausea, vomiting, diarrhea); and/or seizures. Discontinue treatment (and any concomitant serotonergic agent) immediately if signs/symptoms arise.
Disease-related concerns:
• Hepatic impairment: Use oral products with caution in patients with hepatic impairment; dosage adjustments may be necessary with orally disintegrating tablets in patients with mild to moderate hepatic impairment (Child-Pugh class A and B); orally disintegrating tablets are not recommended in patients with severe hepatic impairment (Child-Pugh class C).
• Mania/hypomania: Transdermal patch: May precipitate a shift to mania or hypomania in patients with bipolar disorder. Monotherapy in patients with bipolar disorder should be avoided. Combination therapy with an antidepressant and a mood stabilizer should also be avoided in acute mania or mixed episodes, as well as maintenance treatment in bipolar disorder due to the mood-destabilizing effects of antidepressants (CANMAT [Yatham 2018]; WFSBP [Grunze 2018]). Patients presenting with depressive symptoms should be screened for bipolar disorder. Selegiline is not FDA approved for the treatment of bipolar depression.
• Renal impairment: Use oral products with caution in patients with renal impairment; orally disintegrating tablets are not recommended in patients with severe renal impairment (CrCl <30 mL/minute) and end-stage renal disease.
Special populations:
• Surgical patients: According to many of MAOI manufacturers, use within 10 days prior to elective surgery is contraindicated. The decision to continue or withhold MAOIs must be done in collaboration with the patient's psychiatrist. Currently, an MAO-safe anesthetic technique that excludes the use of meperidine and indirect-acting adrenergic agonists is recommended for patients requiring continued MAOI therapy (Huyse 2006).
Dosage form specific issues:
• Orally disintegrating tablet: May cause irritation of buccal mucosa including swallowing pain, mouth pain, discrete areas of focal reddening, multiple foci of reddening, edema, and/or ulceration.
• Phenylalanine: Orally disintegrating tablet: May contain phenylalanine; use caution in patients with phenylketonuria.
• Transdermal patch: Avoid exposure of application site and surrounding area to direct external heat sources (eg, heating pads, electric blankets, heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight); may increase drug absorption.
Other warnings/precautions:
• Antidepressant discontinuation syndrome: Abrupt discontinuation or interruption of antidepressant therapy has been associated with a discontinuation syndrome. Symptoms arising may vary with antidepressant however commonly include nausea, vomiting, diarrhea, headaches, lightheadedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesias, fatigue, somnolence, and sleep disturbances (eg, vivid dreams, insomnia). Less common symptoms include electric shock-like sensations, cardiac arrhythmias (more common with tricyclic antidepressants), myalgias, parkinsonism, arthralgias, and balance difficulties. Psychological symptoms may also emerge such as agitation, anxiety, akathisia, panic attacks, irritability, aggressiveness, worsening of mood, dysphoria, mood lability, hyperactivity, mania/hypomania, depersonalization, decreased concentration, slowed thinking, confusion, and memory or concentration difficulties. Greater risks for developing a discontinuation syndrome have been associated with antidepressants with shorter half-lives, longer durations of treatment, and abrupt discontinuation. More severe symptoms have also been associated with MAOIs. For antidepressants of short or intermediate half-lives, symptoms may emerge within 2 to 5 days after treatment discontinuation and last 7 to 14 days (APA 2010; Fava 2006; Haddad 2001; Shelton 2001; Warner 2006).
• Antiparkinsonian discontinuation syndrome: Abrupt discontinuation or interruption of antiparkinsonian therapy has been associated with a discontinuation syndrome, which may resemble neuroleptic malignant syndrome; symptoms may include elevated temperature, muscular rigidity, altered consciousness, and autonomic instability.
• Tyramine-containing products: Nonselective MAO inhibition may occur with transdermal delivery and is necessary for antidepressant efficacy. Hypertensive crisis as a result of ingesting tyramine-rich foods is always a concern with nonselective MAO inhibition. Although transdermal delivery minimizes inhibition of MAO-A in the gut, there are limited data with higher transdermal doses; dietary modifications are recommended with doses ≥9 mg/24 hours. Discontinue therapy immediately if hypertensive crisis occurs. With the oral product, MAO-B selective inhibition should not pose a problem with tyramine-containing products as long as the typical oral doses are employed, however, rare hypertensive reactions have been reported. Increased risk of nonselective MAO inhibition occurs with oral capsule/tablet doses >10 mg/day or orally disintegrating tablet doses >2.5 mg/day.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral, as hydrochloride:
Generic: 5 mg
Patch 24 Hour, Transdermal:
Emsam: 6 mg/24 hr (1 ea, 30 ea); 9 mg/24 hr (1 ea, 30 ea); 12 mg/24 hr (1 ea, 30 ea)
Tablet, Oral, as hydrochloride:
Generic: 5 mg
Tablet Disintegrating, Oral, as hydrochloride:
Zelapar: 1.25 mg [contains aspartame; grapefruit flavor]
May be product dependent
Capsules (Selegiline HCl Oral)
5 mg (per each): $1.42 - $2.30
Patch, 24-hour (Emsam Transdermal)
6 mg/24 hrs (per each): $90.08
9 mg/24 hrs (per each): $90.08
12 mg/24 hrs (per each): $90.08
Tablet, orally-disintegrating (Zelapar Oral)
1.25 mg (per each): $115.93
Tablets (Selegiline HCl Oral)
5 mg (per each): $1.00 - $9.60
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 5 mg
Oral: Orally disintegrating tablet: Remove blister from sachet immediately before administering. Do not attempt to push tablet through blister's foil backing; peel backing off and gently remove tablet with dry hands. Administer in morning before breakfast; do not swallow; place on top of tongue and allow to dissolve. Avoid food or liquid 5 minutes before and after administration.
Topical: Transdermal: Apply to clean, dry, intact skin to the upper torso (below the neck and above the waist), upper thigh, or outer surface of the upper arm. Do not apply to skin that is hairy, oily, irritated, broken, scarred, or calloused. Do not place under tight clothing. Apply at the same time each day and rotate application sites. Wash hands with soap and water after handling. Avoid touching the sticky side of the patch. Discard any used or unused patches by folding adhesive ends together and discard properly in trash.
Topical: Transdermal: Apply to clean, dry, intact skin to the upper torso (below the neck and above the waist), upper thigh, or outer surface of the upper arm. Do not apply to skin that is hairy, oily, irritated, broken, scarred, or calloused. Do not place under tight clothing. Apply at the same time each day and rotate application sites. Wash hands with soap and water after handling. Avoid touching the sticky side of the patch. Discard any used or unused patches by folding adhesive ends together and discard properly in trash.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Emsam: http://www.fda.gov/downloads/Drugs/DrugSafety/ucm088589.pdf
Major depressive disorder (unipolar) (transdermal patch): Treatment of unipolar major depressive disorder in adults.
Parkinson disease, adjunctive therapy (oral products): Adjunct in the management of patients with Parkinson disease exhibiting decreased response to carbidopa/levodopa therapy.
Parkinson disease, monotherapy
Selegiline may be confused with Salagen, sertraline, Serzone, Stelazine
Eldepryl may be confused with Elavil, enalapril
Zelapar may be confused with zaleplon, Zemplar, zolpidem, ZyPREXA Zydis
Substrate of CYP1A2 (Minor), CYP2A6 (Minor), CYP2B6 (Minor), CYP2C8 (Minor), CYP2D6 (Minor), CYP3A4 (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits Monoamine Oxidase;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Blood Glucose Lowering Effects: Monoamine Oxidase Inhibitors may increase hypoglycemic effects of Agents with Blood Glucose Lowering Effects. Risk C: Monitor
Alcohol (Ethyl): May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Alfuzosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Alpha-/Beta-Agonists (Indirect-Acting): Monoamine Oxidase Inhibitors may increase hypertensive effects of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid
Alpha1-Agonists: Monoamine Oxidase Inhibitors may increase hypertensive effects of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid
Amifampridine: Agents With Seizure Threshold Lowering Potential may increase neuroexcitatory and/or seizure-potentiating effects of Amifampridine. Risk C: Monitor
Amifostine: Blood Pressure Lowering Agents may increase hypotensive effects of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider Therapy Modification
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor
Amisulpride (Oral): May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Amphetamines: Monoamine Oxidase Inhibitors may increase hypertensive effects of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Risk X: Avoid
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may increase hypotensive effects of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor
Apraclonidine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Apraclonidine. Monoamine Oxidase Inhibitors may increase serum concentration of Apraclonidine. Risk X: Avoid
Arginine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Asenapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Atomoxetine: Monoamine Oxidase Inhibitors may increase neurotoxic (central) effects of Atomoxetine. Risk X: Avoid
Atropine (Ophthalmic): Monoamine Oxidase Inhibitors may increase hypertensive effects of Atropine (Ophthalmic). Risk X: Avoid
Avocado: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Barbiturates: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Benperidol: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Benzhydrocodone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of benzhydrocodone is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and frequent titration of small benzhydrocodone. Risk D: Consider Therapy Modification
Beta2-Agonists: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Beta2-Agonists. Risk C: Monitor
Betahistine: Monoamine Oxidase Inhibitors may increase serum concentration of Betahistine. Risk C: Monitor
Bezafibrate: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Bezafibrate. Risk X: Avoid
Blonanserin: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Blonanserin. Specifically, the risk of seizures may be increased. Risk C: Monitor
Blood Pressure Lowering Agents: May increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Bornaprine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Brexanolone: Selegiline may increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Brimonidine (Ophthalmic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Ophthalmic). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Ophthalmic). Risk C: Monitor
Brimonidine (Topical): May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Brimonidine (Topical): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Brimonidine (Topical). Monoamine Oxidase Inhibitors may increase serum concentration of Brimonidine (Topical). Risk C: Monitor
Bromperidol: May decrease hypotensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase hypotensive effects of Bromperidol. Risk X: Avoid
Buprenorphine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
BuPROPion: Monoamine Oxidase Inhibitors may increase hypertensive effects of BuPROPion. Risk X: Avoid
Butorphanol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
CarBAMazepine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Do not use carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Risk X: Avoid
Carbinoxamine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Carbinoxamine. Specifically, the anticholinergic effects of carbinoxamine may be enhanced and prolonged. Risk X: Avoid
Cariprazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cerebrolysin: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Chlorphenesin Carbamate: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
ChlorproMAZINE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of ChlorproMAZINE. Specifically, the risk of seizures may be increased. Risk C: Monitor
ClomiPRAMINE: Selegiline may increase serotonergic effects of ClomiPRAMINE. This could result in serotonin syndrome. Risk X: Avoid
Clothiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
CloZAPine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of CloZAPine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Cocaine (Topical): May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Codeine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Codeine. Risk X: Avoid
Cyclobenzaprine: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Cyproheptadine: May decrease serotonergic effects of Monoamine Oxidase Inhibitors. Monoamine Oxidase Inhibitors may increase anticholinergic effects of Cyproheptadine. Risk X: Avoid
Deutetrabenazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Deutetrabenazine. Risk X: Avoid
Dexmethylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Dexmethylphenidate. Risk X: Avoid
Dextromethorphan: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This may cause serotonin syndrome. Risk X: Avoid
Diamorphine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Diamorphine. Risk X: Avoid
Diazoxide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Diethylpropion: Monoamine Oxidase Inhibitors may increase hypertensive effects of Diethylpropion. Risk X: Avoid
Difenoxin: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Dihydrocodeine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Management: Consider avoiding use of dihydrocodeine while the patient is taking monoamine oxidase inhibitors (MAOIs) and for 2 weeks after MAOI discontinuation. Risk D: Consider Therapy Modification
Diphenoxylate: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Domperidone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Domperidone. Monoamine Oxidase Inhibitors may decrease therapeutic effects of Domperidone. Domperidone may decrease therapeutic effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
DOPamine: Monoamine Oxidase Inhibitors may increase hypertensive effects of DOPamine. Management: Initiate dopamine at no greater than one-tenth (1/10) of the usual dose in patients who are taking (or have taken within the last 2 to 3 weeks) monoamine oxidase inhibitors. Monitor for an exaggerated hypertensive response to dopamine. Risk D: Consider Therapy Modification
Doxapram: Monoamine Oxidase Inhibitors may increase hypertensive effects of Doxapram. Risk C: Monitor
DroPERidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of DroPERidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
EPINEPHrine (Oral Inhalation): Monoamine Oxidase Inhibitors may increase hypertensive effects of EPINEPHrine (Oral Inhalation). Risk X: Avoid
EPINEPHrine (Systemic): Monoamine Oxidase Inhibitors may increase hypertensive effects of EPINEPHrine (Systemic). Risk C: Monitor
Esketamine (Nasal): May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk C: Monitor
Ethinyl Estradiol-Containing Products: May increase serum concentration of Selegiline. Risk C: Monitor
Fenfluramine: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
FentaNYL: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Fluorodopa F18: Coadministration of Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) and Fluorodopa F18 may alter diagnostic results. Management: Discontinue medications used to treat Parkinson disease, including MAO inhibitors, 12 hours prior to fluorodopa F 18 administration if these medications can be safely withheld. Risk D: Consider Therapy Modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Gepirone: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Guanethidine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Haloperidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Herbal Products with Blood Pressure Lowering Effects: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
HYDROcodone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROcodone. Management: Consider alternatives to this combination when possible. If coadministration is required, use test doses, titrate small doses frequently, and monitor patients closely for evidence of serotonergic and opioid toxicities. Risk D: Consider Therapy Modification
HYDROmorphone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of HYDROmorphone. Management: Coadministration of hydromorphone and monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) is not recommended. If required, use test doses, titrate small doses frequently, and monitor for CNS and respitatory depression. Risk D: Consider Therapy Modification
Hypotension-Associated Agents: Blood Pressure Lowering Agents may increase hypotensive effects of Hypotension-Associated Agents. Risk C: Monitor
Iloperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Iloperidone: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Imipramine: Selegiline may increase serotonergic effects of Imipramine. This could result in serotonin syndrome. Risk X: Avoid
Indoramin: Monoamine Oxidase Inhibitors may increase hypotensive effects of Indoramin. Risk X: Avoid
Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may decrease therapeutic effects of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid
Ioflupane I 123: Coadministration of Selegiline and Ioflupane I 123 may alter diagnostic results. Risk C: Monitor
Iohexol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider Therapy Modification
Isoproterenol: Monoamine Oxidase Inhibitors may increase therapeutic effects of Isoproterenol. Risk C: Monitor
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may increase hypotensive effects of Levodopa-Foslevodopa. Risk C: Monitor
Levodopa-Foslevodopa: May increase orthostatic hypotensive effects of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor
Levomethadone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Levonordefrin: Monoamine Oxidase Inhibitors may increase hypertensive effects of Levonordefrin. Management: Avoid the use of levonordefrin during or within 2 weeks of treatment with a monoamine oxidase inhibitor whenever possible. If levonordefrin cannot be avoided during this period, monitor closely for enhanced or prolonged increases in blood pressure. Risk D: Consider Therapy Modification
Linezolid: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Lormetazepam: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Loxapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Loxapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lumateperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Lurasidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Maprotiline: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Meptazinol: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Meptazinol. Risk X: Avoid
Mequitazine: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Mequitazine. Risk X: Avoid
Metaraminol: Monoamine Oxidase Inhibitors may increase hypertensive effects of Metaraminol. Risk C: Monitor
Metergoline: May decrease antihypertensive effects of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may increase orthostatic hypotensive effects of Metergoline. Risk C: Monitor
Methadone: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Methotrimeprazine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methotrimeprazine. Specifically, monoamine oxidase inhibitors may enhance dopamine blockade, possible increasing the risk for neuroleptic malignant syndrome. Methotrimeprazine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Methyldopa: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Methyldopa. Risk X: Avoid
Methylene Blue: Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid
Methylphenidate: Monoamine Oxidase Inhibitors may increase hypertensive effects of Methylphenidate. Risk X: Avoid
Metoclopramide: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Mianserin: Monoamine Oxidase Inhibitors may increase neurotoxic effects of Mianserin. Risk X: Avoid
Mivacurium: Monoamine Oxidase Inhibitors may increase serum concentration of Mivacurium. Risk C: Monitor
Molindone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Molsidomine: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Monoamine Oxidase Inhibitors (Antidepressant): May increase hypertensive effects of Monoamine Oxidase Inhibitors (Type B). Monoamine Oxidase Inhibitors (Antidepressant) may increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Monoamine Oxidase Inhibitors (Type B): May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Morphine (Systemic): Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Morphine (Systemic). Risk X: Avoid
Naftopidil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nalbuphine: Monoamine Oxidase Inhibitors may increase CNS depressant effects of Nalbuphine. Nalbuphine may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Nalbuphine may increase hypertensive effects of Monoamine Oxidase Inhibitors. Management: Use of nalbuphine is not recommended in patients taking MAOIs, or within 14 days of stopping MAOI therapy. If urgent nalbuphine use is needed, use test doses and frequent titration while monitoring blood pressure, CNS depression, and serotonergic toxicity Risk D: Consider Therapy Modification
Nefazodone: Selegiline may increase serotonergic effects of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid
Nefopam: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Nefopam. Risk X: Avoid
Nicergoline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nicorandil: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Nitroprusside: Blood Pressure Lowering Agents may increase hypotensive effects of Nitroprusside. Risk C: Monitor
Norepinephrine: Monoamine Oxidase Inhibitors may increase hypertensive effects of Norepinephrine. Risk C: Monitor
Normethadone: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Normethadone. Risk X: Avoid
Obinutuzumab: May increase hypotensive effects of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider Therapy Modification
OLANZapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Opipramol: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Opium: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Opium. Risk X: Avoid
OxyCODONE: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: Use of oxycodone is not recommended for patients taking MAOIs or within 14 days of MAOI discontinuation. If combined, use test doses and frequent titration of small doses while monitoring blood pressure, CNS depression, and signs of serotonin syndrome. Risk D: Consider Therapy Modification
OxyMORphone: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Ozanimod: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Paliperidone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pentoxifylline: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Periciazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Perphenazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pheniramine: May increase anticholinergic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Pholcodine: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Phosphodiesterase 5 Inhibitors: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Pimozide: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pimozide. Specifically, the risk of seizures may be increased. Risk C: Monitor
Pipamperone: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Pipamperone. Specifically, the risk of seizures may be increased. Risk X: Avoid
Pizotifen: Monoamine Oxidase Inhibitors may increase anticholinergic effects of Pizotifen. Risk X: Avoid
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Promazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Prostacyclin Analogues: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
QUEtiapine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Quinagolide: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Reboxetine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Reboxetine. Risk X: Avoid
Remifentanil: May increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and titrate small doses of remifentanil frequently. Risk D: Consider Therapy Modification
Reserpine: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Monitor closely for paradoxical effects of reserpine (eg, excitation, hypertension). Risk D: Consider Therapy Modification
RisperiDONE: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor
Selective Serotonin Reuptake Inhibitor: May increase serotonergic effects of Selegiline. This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Agents (High Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Agents (Moderate Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of Serotonergic Agents (Moderate Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor
Serotonergic Non-Opioid CNS Depressants: Selegiline may increase serotonergic effects of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid
Serotonergic Opioids (High Risk): May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Serotonin/Norepinephrine Reuptake Inhibitor: Selegiline may increase serotonergic effects of Serotonin/Norepinephrine Reuptake Inhibitor. This could result in serotonin syndrome. Risk X: Avoid
Sertindole: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sertindole. Specifically, the risk of seizures may be increased. Risk C: Monitor
Sevoflurane: Monoamine Oxidase Inhibitors may increase adverse/toxic effects of Sevoflurane. Specifically, the risk of hemodynamic instability may be increased. Risk C: Monitor
Silodosin: May increase hypotensive effects of Blood Pressure Lowering Agents. Risk C: Monitor
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor
Solriamfetol: Monoamine Oxidase Inhibitors may increase hypertensive effects of Solriamfetol. Risk X: Avoid
St John's Wort: Monoamine Oxidase Inhibitors (Type B) may increase serotonergic effects of St John's Wort. This could result in serotonin syndrome. Risk X: Avoid
SUFentanil: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. Risk X: Avoid
Sulpiride: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tapentadol: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Specifically, the additive effects of norepinephrine may lead to adverse cardiovascular effects. Tapentadol may increase serotonergic effects of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Risk X: Avoid
Tetrabenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Thioridazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Thiothixene: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tiapride: Selegiline may decrease therapeutic effects of Tiapride. Tiapride may decrease therapeutic effects of Selegiline. Management: If treatment with tiapride cannot be avoided in a patient with Parkinson disease, discontinuation of selegiline should be done gradually to minimize the risk for neuroleptic malignant syndrome. Risk D: Consider Therapy Modification
Tricyclic Antidepressants: Selegiline may increase serotonergic effects of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor
Tyrosine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Valbenazine: May increase adverse/toxic effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Viloxazine: May increase hypertensive effects of Monoamine Oxidase Inhibitors. Risk X: Avoid
Ziprasidone: May increase serotonergic effects of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may increase adverse/toxic effects of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor
Concurrent ingestion of foods rich in tyramine, dopamine, tyrosine, phenylalanine, tryptophan, or caffeine may cause sudden and severe high blood pressure (hypertensive crisis or serotonin syndrome). Beverages containing tyramine (eg, hearty red wine and beer) may increase toxic effects. Management: Avoid tyramine-containing foods (aged or matured cheese, air-dried or cured meats including sausages and salamis; fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce, and other soybean condiments). Food’s freshness is also an important concern; improperly stored or spoiled food can create an environment in which tyramine concentrations may increase. Avoid foods containing dopamine, tyrosine, phenylalanine, tryptophan, or caffeine. Avoid beverages containing tyramine (Walker 1996).
Information related to the use of selegiline in pregnant patients for the treatment of depression (Bauer 2017) or Parkinson disease (Olivola 2020; Seier 2017) is limited. Agents other than selegiline may be preferred for the treatment of major depressive disorder or Parkinson disease in pregnant patients (Olivola 2020; WFSBP [Bauer 2013]).
It is not known if selegiline is present in breast milk.
Information related to the use of selegiline in breastfeeding patients is limited (Bauer 2017). Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended by the manufacturer. If selegiline is discontinued, wait 5 days after the final selegiline patch is removed, or 7 days after the last oral disintegrating tablet is taken before breastfeeding.
Avoid or limit tyramine-containing foods/beverages (product and/or dose-dependent). Some examples include aged or matured cheese, air-dried or cured meats (including sausages and salamis), fava or broad bean pods, tap/draft beers, Marmite concentrate, sauerkraut, soy sauce and other soybean condiments. Food’s freshness is also an important concern; improperly stored or spoiled food can create an environment where tyramine concentrations may increase (Walker 1996).
Transdermal: 9 mg/24 hours or 12 mg/24 hours: Avoid tyramine-rich foods or beverages beginning the first day of treatment and for 2 weeks after discontinuation or dose reduction to 6 mg/24 hours.
Orally disintegrating tablet: Do not administer with food or liquid; avoid food or liquid 5 minutes before and after administration.
Some products may contain phenylalanine.
BP; mood and behavior (increased anxiety, presence of mania or agitation); suicidal ideation (especially during the initial 1 to 2 months of therapy or when doses are increased or decreased).
Potent, irreversible inhibitor of monoamine oxidase (MAO). Selegiline has a greater affinity for MAO-B compared to MAO-A (intestinal MAO is predominantly type A; in the brain, both isoenzymes exist). In the CNS, MAO plays a major role in the catabolism of dopamine, serotonin, norepinephrine, and epinephrine. At lower doses, selegiline can serve as a selective inhibitor of MAO-B; however, as selegiline concentrations increase, MAO-B selectivity is lost. Selegiline may increase dopaminergic activity by interfering with dopamine reuptake at the synapse. Effects may also be mediated through its metabolites, including amphetamine and methamphetamine, which interfere with neuronal uptake and enhance release of several neurotransmitters (eg, norepinephrine, dopamine, serotonin). The extent to which these metabolites contribute to the effects of selegiline are unknown. Plasma concentrations achieved via administration of oral dosage forms in recommended doses confer selective inhibition of MAO type B. When administered transdermally, selegiline achieves higher blood levels with significantly lower exposure for all metabolites when compared with oral dosing. Attention to the dose-dependent nature of selegiline’s selectivity is necessary if it is to be used without diet and concomitant drug restrictions.
Onset of action: Depression: Initial effects may be observed within 1 to 2 weeks of treatment, with continued improvements through 4 to 6 weeks (Papakostas 2006; Posternak 2005; Szegedi 2009).
Absorption:
Capsule/tablet: Bioavailability increases 3- to 4-fold when taken with food.
Orally disintegrating tablet: Rapid. Food decreases Cmax and AUC to ~60% of fasting state.
Protein binding: 85% to 90%.
Metabolism: Hepatic, primarily via CYP2B6, CYP2C9, CYP3A4, and CYP2A6 (minor) to active (N-desmethylselegiline, amphetamine, methamphetamine) and inactive metabolites. Capsules/tablets undergo extensive first-pass metabolism, resulting in higher exposure to metabolites compared with other dosage forms (Azzaro 2007).
Bioavailability:
Capsule: 4% (Azzaro 2007).
Orally disintegrating tablet (ODT): Sublingual administration of ODT has greater bioavailability than capsule dependent upon time in buccal cavity. Up to 30% absorption if held for 1 minute without swallowing (Tábi 2013).
Transdermal: 73% (Azzaro 2007).
Half-life elimination:
Oral: 10 hours.
Transdermal: 20 hours (Azzaro 2007).
Time to peak:
Capsule: 0.86 hours (Azzaro 2007).
Orally disintegrating tablet: 10 to 15 minutes.
Transdermal: 20 hours (Azzaro 2007).
Excretion: Urine (primarily metabolites); feces.
Altered kidney function: Orally disintegrating tablets: Patients with moderate renal impairment (CrCl 31 to 50 mL/minute) had a 34% to 67% increase in exposure to the active metabolites methamphetamine and amphetamine. Patients with end-stage renal disease off dialysis had a 4-fold increase in exposure to the active metabolites methamphetamine and amphetamine.
Hepatic function impairment: Orally disintegrating tablets: Patients with mild hepatic impairment (Child-Pugh score 5 to 6) had a 1.5-fold higher AUC and Cmax of selegiline and a 1.4-fold and 1.2-fold higher, respectively, AUC and Cmax of the metabolite desmethylselegiline. In patients with moderate hepatic impairment (Child-Pugh score 7 to 9), AUC of selegiline and desmethylselegiline increased 1.5-fold and 1.8-fold, respectively. Patients with severe hepatic impairment (Child-Pugh score >9) had a 4-fold increased AUC of selegiline, 3-fold increased Cmax of selegiline, 1.25-fold increased AUC of desmethylselegiline and 50% reduced Cmax of desmethylselegiline.
Older adult: Systemic exposure is about twice as high in elderly patients when given a single 10 mg oral dose.
