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Selegiline: Drug information

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

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Suicidal thoughts and behaviors (transdermal patch):

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.

Brand Names: US
  • Eldepryl [DSC];
  • Emsam;
  • Zelapar
Brand Names: Canada
  • TEVA-Selegiline
Pharmacologic Category
  • Anti-Parkinson Agent, MAO Type B Inhibitor;
  • Antidepressant, Monoamine Oxidase Inhibitor
Dosing: Adult

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 (Parkinson Study Group 1993; manufacturer's labeling).

Discontinuation of therapy: When discontinuing antidepressant treatment that has lasted for >3 weeks, gradually taper the dose (eg, over 2 to 4 weeks) to minimize withdrawal symptoms and detect reemerging symptoms (APA 2010; WFSBP [Bauer 2015]). Reasons for a slower taper (eg, over 4 weeks) include history of antidepressant withdrawal symptoms or high doses of antidepressants (APA 2010; Hirsch 2021). More severe symptoms have been associated with MAOIs; more conservative tapers may be necessary (Haddad 2001; Shelton 2001). If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or decrease dose at a more gradual rate (Shelton 2001). Select patients (eg, those with a history of discontinuation syndrome) on long-term treatment (>6 months) may benefit from tapering over >3 months (WFSBP [Bauer 2015]). Evidence supporting ideal taper rates is limited (Shelton 2001; WFSBP [Bauer 2015]).

Switching antidepressants:

Switching to or from selegiline, another monoamine oxidase inhibitor (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 (APA [Gelenberg 2010]).

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.

Dosing: Kidney Impairment: Adult

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).

Dosing: Hepatic Impairment: Adult

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).

Dosing: Pediatric

Depression: Adolescents >17 years: Transdermal: Refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosing: Kidney Impairment: Pediatric

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).

Dosing: Hepatic Impairment: Pediatric

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).

Dosing: Older Adult

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 (Olanow 2001).

Orally disintegrating tablet: Refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Switching antidepressants: Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as hydrochloride:

Eldepryl: 5 mg [DSC]

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]

Generic Equivalent Available: US

May be product dependent

Dosage Forms: Canada

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

Tablet, Oral, as hydrochloride:

Generic: 5 mg

Medication Guide and/or Vaccine Information Statement (VIS)

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

Administration: Adult

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.

Administration: Pediatric

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.

Use: Labeled Indications

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.

Use: Off-Label: Adult

Parkinson disease, monotherapy

Medication Safety Issues
Sound-alike/look-alike issues:

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

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Unless otherwise noted, the percentage of adverse events is reported for the transdermal patch (ODT = orally disintegrating tablet, Oral = capsule/tablet)

>10%:

Central nervous system: Headache (18%; ODT: 7%; oral: 4%), dizziness (oral: 14%; ODT: 11%), insomnia (12%; ODT: 7%)

Gastrointestinal: Nausea (oral: 20%; ODT: 11%)

Local: Application site reaction (24%)

1% to 10%:

Cardiovascular: Hypotension (3% to 10%; including orthostatic hypotension), hypertension (≥1%; ODT: 3%), chest pain (≥1%; ODT: 2%), palpitations (oral: 2%), peripheral edema (≥1%)

Central nervous system: Pain (ODT: 8%; oral: 2%), confusion (oral: 6%; ODT: 4%), hallucination (oral: 6%; ODT: 4%), vivid dream (oral: 4%), ataxia (<1%; ODT: 3%), drowsiness (ODT: 3%), depression (<1%; ODT: 2%), lethargy (oral: 2%), abnormality in thinking (≥1%), agitation (≥1%), amnesia (≥1%), paresthesia (≥1%)

Dermatologic: Skin rash (4%), acne vulgaris (≥1%), diaphoresis (≥1%), pruritus (≥1%)

Endocrine & metabolic: Weight loss (5%; oral: 2%), hypokalemia (ODT: 2%)

Gastrointestinal: Diarrhea (9%; ODT: 2%; oral: 2%), xerostomia (8%; oral: 6%; ODT: 4%), abdominal pain (oral: 8%), dyspepsia (4%; ODT: 5%), stomatitis (ODT: 5%), constipation (≥1%; ODT: 4%), vomiting (≥1%; ODT: 3%), dental caries (ODT: 2%), dysgeusia (≥1%; ODT: 2%), dysphagia (ODT: 2%), flatulence (≥1%; ODT: 2%), anorexia (≥1%), gastroenteritis (≥1%)

Genitourinary: Urinary retention (oral: 2%), dysmenorrhea (≥1%), sexual disorder (≥1%), urinary frequency (≥1%), urinary tract infection (≥1%), uterine hemorrhage (≥1%)

Hematologic & oncologic: Bruise (≥1%; ODT: 2%)

Neuromuscular & skeletal: Dyskinesia (ODT: 6%), back pain (ODT: 5%; oral: 2%), leg cramps (ODT: 3%; oral: 2%), myalgia (≥1%; ODT: 3%), tremor (<1%; ODT: 3%), neck pain (≥1%)

Otic: Tinnitus (≥1%)

Respiratory: Rhinitis (ODT: 7%), pharyngitis (3%; ODT: 4%), dyspnea (<1%; ODT: 3%), sinusitis (3%), bronchitis (≥1%), cough (≥1%)

Frequency not defined:

Cardiovascular: Atrial fibrillation, bradycardia, cardiac arrhythmia, facial edema, myocardial infarction, peripheral vascular disease, syncope, tachycardia, vasodilation

Central nervous system: Altered sense of smell, behavioral changes, chorea, delusions, depersonalization, emotional lability, euphoria, heatstroke, hostility, hyperesthesia, hypertonia, impulse control disorder (including binge eating, hypersexuality, pathological gambling), loss of balance, mania, migraine, mood changes, myasthenia, myoclonus, oral paresthesia, paranoia, psychoneurosis, twitching, vertigo

Dermatologic: Maculopapular rash, skin hypertrophy, urticaria, vesiculobullous dermatitis

Endocrine & metabolic: Dehydration, hypercholesterolemia, hyperglycemia, hypoglycemia, hyponatremia, increased lactate dehydrogenase, increased libido

Gastrointestinal: Colitis, eructation, gastritis, glossitis, increased appetite, melena, periodontal abscess, sialorrhea

Genitourinary: Benign prostatic hypertrophy, hematuria (females), hernia, mastalgia, pelvic pain, urinary urgency, urination disorder (males; impairment), vaginal hemorrhage, vaginitis, vulvovaginal candidiasis

Hematologic & oncologic: Benign skin neoplasm, breast neoplasm (female), leukocytosis, leukopenia, lymphadenopathy, neoplasm, rectal hemorrhage

Hepatic: Abnormal hepatic function tests, hyperbilirubinemia, increased serum alkaline phosphatase

Hypersensitivity: Tongue edema

Infection: Bacterial infection, candidiasis, fungal infection, parasitic infection, viral infection

Neuromuscular & skeletal: Bradykinesia, hyperkinesia, muscle spasm (generalized), osteoporosis, tenosynovitis

Ophthalmic: Visual field defect

Otic: Otitis externa

Renal: Nephrolithiasis (females), polyuria (females)

Respiratory: Asthma, epistaxis, laryngismus, pneumonia

Miscellaneous: Fever

Contraindications

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).

Canadian labeling: Additional contraindications (not in US labeling): Severe psychosis; severe dementia; active peptic ulcer; extrapyramidal disorders, including excessive tremor or tardive dyskinesia.

Warnings/Precautions

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/addictions 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 may be effective for acute treatment of bipolar major depressive episodes, but should 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.

Metabolism/Transport Effects

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

Drug Interactions

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

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

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

Alpha-/Beta-Agonists (Indirect-Acting): Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Alpha-/Beta-Agonists (Indirect-Acting). While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid combination

Alpha1-Agonists: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Alpha1-Agonists. While linezolid is expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to linezolid specific monographs for details. Risk X: Avoid combination

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

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Amphetamines: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of Amphetamines. While linezolid and tedizolid may interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Risk X: Avoid combination

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

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

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

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

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

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

Benzhydrocodone: May enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of benzhydrocodone is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and frequent titration of small benzhydrocodone. Risk D: Consider therapy modification

Beta2-Agonists: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

CarBAMazepine: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Management: Do not use carbamazepine during, or within 14 days of discontinuing, treatment with a monoamine oxidase inhibitor. Risk X: Avoid combination

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

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

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

ClomiPRAMINE: Selegiline may enhance the serotonergic effect of ClomiPRAMINE. This could result in serotonin syndrome. Risk X: Avoid combination

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

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

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

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

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

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

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

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

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

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

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

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

DOPamine: Monoamine Oxidase Inhibitors may enhance the hypertensive effect of DOPamine. Management: Initiate dopamine at no greater than one-tenth (1/10) of the usual dose in patients who are taking (or have taken within the last 2 to 3 weeks) monoamine oxidase inhibitors. Monitor for an exaggerated hypertensive response to dopamine. Risk D: Consider therapy modification

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

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

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

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

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

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

Estrogen Derivatives (Contraceptive): May increase the serum concentration of Selegiline. Risk C: Monitor therapy

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

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

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

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

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

HYDROcodone: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of HYDROcodone. Management: Consider alternatives to this combination when possible. Risk D: Consider therapy modification

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

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

Imipramine: Selegiline may enhance the serotonergic effect of Imipramine. This could result in serotonin syndrome. Risk X: Avoid combination

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

Iobenguane Radiopharmaceutical Products: Monoamine Oxidase Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination

Ioflupane I 123: Selegiline may diminish the diagnostic effect of Ioflupane I 123. Risk C: Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification

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

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy

Levodopa-Containing Products: May enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Type B). Risk C: Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Nefazodone: Selegiline may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Risk X: Avoid combination

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

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

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

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

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

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

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

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

OXcarbazepine: May enhance the serotonergic effect of Selegiline. Risk X: Avoid combination

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

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

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

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

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

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

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

Pipamperone [INT]: Anti-Parkinson Agents (Monoamine Oxidase Inhibitor) may diminish the therapeutic effect of Pipamperone [INT]. Pipamperone [INT] may diminish the therapeutic effect of Anti-Parkinson Agents (Monoamine Oxidase Inhibitor). Risk C: Monitor therapy

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

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

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

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

Remifentanil: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Remifentanil. Specifically, the risk for opioid toxicity (eg, respiratory depression) may be increased. Remifentanil may enhance the serotonergic effect of Monoamine Oxidase Inhibitors. This could result in serotonin syndrome. Management: The use of remifentanil is not recommended for patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI discontinuation. If coadministration is required, use test doses and titrate small doses of remifentanil frequently. Risk D: Consider therapy modification

Reserpine: Monoamine Oxidase Inhibitors may enhance the adverse/toxic effect of Reserpine. Existing MAOI therapy can result in paradoxical effects of added reserpine (e.g., excitation, hypertension). Management: Monoamine oxidase inhibitors (MAOIs) should be avoided or used with great caution in patients who are also receiving reserpine. Monitor closely for paradoxical effects of reserpine (eg, excitation, hypertension). Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: May enhance the serotonergic effect of Selegiline. This could result in serotonin syndrome. Risk X: Avoid combination

Serotonergic Agents (High Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Risk X: Avoid combination

Serotonergic Agents (Moderate Risk, Miscellaneous): Monoamine Oxidase Inhibitors (Type B) may enhance the serotonergic effect 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 therapy

Serotonergic Non-Opioid CNS Depressants: Selegiline may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Risk X: Avoid combination

Serotonergic Opioids (High Risk): May enhance the serotonergic effect of Monoamine Oxidase Inhibitors (Type B). This could result in serotonin syndrome. Risk X: Avoid combination

Serotonin/Norepinephrine Reuptake Inhibitors: Selegiline may enhance the serotonergic effect of Serotonin/Norepinephrine Reuptake Inhibitors. This could result in serotonin syndrome. Risk X: Avoid combination

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

St John's Wort: Monoamine Oxidase Inhibitors (Type B) may enhance the serotonergic effect of St John's Wort. This could result in serotonin syndrome. Risk X: Avoid combination

SUFentanil: May enhance the adverse/toxic effect of Monoamine Oxidase Inhibitors. Specifically, the risk for serotonin syndrome or opioid toxicities (eg, respiratory depression, coma) may be increased. Management: Sufentanil should not be used with monoamine oxidase (MAO) inhibitors (or within 14 days of stopping an MAO inhibitor) due to the potential for serotonin syndrome and/or excessive CNS depression. Risk X: Avoid combination

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

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

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

Tricyclic Antidepressants: Selegiline may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination

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

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

Food Interactions

Concurrent ingestion of foods rich in tyramine, dopamine, tyrosine, phenylalanine, tryptophan, or caffeine may cause sudden and severe high blood pressure (hypertensive crisis or serotonin syndrome). 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).

Pregnancy Considerations

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]).

Breastfeeding Considerations

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.

Dietary Considerations

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.

Monitoring Parameters

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).

Mechanism of Action

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.

Pharmacokinetics

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.

Pharmacokinetics: Additional Considerations

Renal function impairment: 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.

Geriatric: Systemic exposure is about twice as high in elderly patients when given a single 10 mg oral dose.

Pricing: US

Capsules (Selegiline HCl Oral)

5 mg (per each): $2.30

Patch, 24-hour (Emsam Transdermal)

6 mg/24 hrs (per each): $73.79

9 mg/24 hrs (per each): $73.79

12 mg/24 hrs (per each): $73.79

Tablet, orally-disintegrating (Zelapar Oral)

1.25 mg (per each): $104.60

Tablets (Selegiline HCl Oral)

5 mg (per each): $2.10

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.

Brand Names: International
  • Antiparkin (LU);
  • Brintenal (AR);
  • Cognitive (VN);
  • Deprenyl (FR);
  • Egibren (IT);
  • Eldepryl (AU, BB, BE, CN, DK, FI, GB, IE, LU, LV, NO, SE, TW, UA);
  • Elepril (BR);
  • Endopryl (CY);
  • FP-OD (JP);
  • Jin Si Ping (CN);
  • Julab (LK, TH);
  • Jumax (IN);
  • Jumex (AR, AT, BG, CR, CY, CZ, DO, HN, HR, HU, IT, KR, MY, NI, PT, PY, RU, SI, SK, TH, UA, UY, VE);
  • Jumexil (BR);
  • Mao-B (KR);
  • Moverdin (TR);
  • Movergan (DE, HR);
  • Niar (BR, CR, DO, GT, HN, MX, NI, PA, PY, SV);
  • Parkilyne (ZA);
  • Plurimen (ES);
  • Procythol (GR);
  • Sefmex (HK, MY, TH);
  • Segan (PL, UA);
  • Selecom (IT);
  • Selegil (CO, PE);
  • Selegos (HK, PH, RO, SG);
  • Selezin (TW);
  • Selgene (AU);
  • Selgin (IL, IN, PK);
  • Selgina (CL);
  • Selgres (PL);
  • Siltin (TW);
  • Xilopar (IT, PT);
  • Zelapar (GB)


For country abbreviations used in Lexicomp (show table)

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