Selegiline (Monograph)

Brand names: Eldepryl, Zelapar
Drug class: Monoamine Oxidase B Inhibitors
- Antiparkinsonian Agents
- Monoamine Oxidase Inhibitors
- MAO Inhibitors
VA class: CN500
Chemical name: (R)-N,α-Dimethyl-N-2-propynyl-benzeneethanamine hydrochloride
Molecular formula: C₁₃H₁₇N•ClH
CAS number: 14611-52-0

Medically reviewed by Drugs.com on Apr 29, 2024. Written by ASHP.

Introduction

Selective irreversible MAO-B inhibitor.¹ ² ³ ¹⁴⁴ ¹⁵⁸

Parkinsonian Syndrome

Used as adjunctive therapy for symptomatic treatment of parkinsonian syndrome (e.g., parkinsonism, Parkinson disease [paralysis agitans]) in patients who exhibit a deteriorating response to levodopa/carbidopa; designated an orphan drug by FDA for this condition.¹ ² ⁴ ⁵ ⁶ ⁷ ⁸ ³⁴ ³⁵ ³⁶ ³⁷ ³⁸ ³⁹ ⁴⁰ ⁶⁵ ⁶⁶ ⁸⁵ ⁹² ⁹³ ¹⁴⁴ Appears to be most beneficial when used during the early stages of the “wearing off” effect.⁶ ⁷ ³⁶ ³⁸ ⁴⁹ Especially useful in improving “end-of-dose” motor fluctuations.⁵ ⁶ ⁷ ⁴⁹ ⁵¹ ⁸⁵

Has been used as monotherapy in patients with newly diagnosed parkinsonian syndrome^{† [off-label]}.⁵ ⁷ ⁸ ³⁷ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ⁷³ ⁸⁴ ⁸⁵ ⁹³ ¹³⁰ Because selegiline is well tolerated and possibly neuroprotective (i.e., reduces the rate of progression of parkinsonian syndrome³ ⁵ ⁸ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ⁵⁷ ⁵⁸ ⁵⁹ ⁶⁰ ¹³⁰ ), some clinicians initiate therapy with selegiline in such patients, reserving levodopa or another agent (i.e., dopamine agonist) until manifestations become severe enough to warrant more aggressive therapy.⁸ ¹¹ ⁵⁷ ⁶⁵ ¹²² ¹³⁰ However, the manufacturers state that there is no evidence from controlled studies indicating that selegiline provides benefit in the absence of concurrent levodopa therapy.¹ ²

Alzheimer’s Disease

Has been used with equivocal results for the palliative treatment of mild to moderate dementia of the Alzheimer’s type^{† [off-label]} (Alzheimer’s disease, presenile or senile dementia).⁶¹ ⁶² ⁶³ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹²⁷ ¹²⁸

Selegiline Dosage and Administration

Administration

Administer orally.¹ ² ¹⁴⁴

Oral Administration

Administer orally as conventional tablets, capsules, or orally disintegrating tablets.¹ ² ¹⁴⁴

Administer conventional tablets and capsules in 2 equally divided doses daily with breakfast and lunch.¹ ² ⁸ ¹¹

Administer orally disintegrating tablets (Zelapar) once daily in the morning before breakfast.¹⁴⁴ Avoid foods or liquids for 5 minutes prior to and after administration.¹⁴⁴ Do not remove tablets from blister pack until just prior to administration.¹⁴⁴ With dry hands, peel backing off 1 or 2 blister packs (depending on dosage); gently remove tablet(s) and place on tongue where dissolution occurs in seconds.¹⁴⁴ (See Absorption under Pharmacokinetics.)

Dosage

Available as selegiline hydrochloride; dosage expressed in terms of the salt.¹ ¹⁴⁴

Adults

Parkinsonian Syndrome

Adjunctive Therapy with Levodopa

Oral

Conventional tablets and capsules: Usual dosage 5 mg twice daily.¹ ² ⁵ ⁶ ¹¹ Some clinicians suggest initial dosage of 2.5 mg daily;¹²² may increase gradually up to 5 mg twice daily.⁸ Dosages >10 mg daily do not provide additional benefit and may increase risk of adverse effects; generally avoid such dosages.¹ ²

Orally disintegrating tablets: Initially, 1.25 mg once daily for ≥6 weeks.¹⁴⁴ If desired response not achieved by 6 weeks, may increase to 2.5 mg once daily, if tolerated.¹⁴⁴ Dosages >2.5 mg daily do not provide additional benefit and may increase risk of adverse effects; generally avoid such dosages.¹⁴⁴

If dyskinesia develops or is exacerbated during therapy, may reduce dosage of concomitant levodopa.¹ ² ¹⁴⁴ (See Dyskinesia under Cautions.) Manufacturers of conventional oral preparations of selegiline state that dosage reduction of levodopa/carbidopa (usually by 10–30%) may be attempted after 2–3 days of selegiline therapy with further reduction possible during continued therapy.¹ ²

Special Populations

Hepatic Impairment

Conventional oral preparations: Manufacturers make no specific dosage recommendations in patients with hepatic impairment.¹ ²

Orally disintegrating tablets: In patients with mild to moderate hepatic impairment (Child-Pugh score 5–9), reduce dosage to 1.25 mg daily (depending on clinical response); use not recommended in patients with severe hepatic impairment (Child-Pugh score >9).¹⁴⁴

Renal Impairment

Conventional oral preparations: Manufacturers make no specific dosage recommendations in patients with renal impairment.¹ ²

Orally disintegrating tablets: No dosage adjustments required in patients with mild to moderate renal impairment (Cl_cr 30–89 mL/minute); individualize dosage.¹⁴⁴ Use not recommended in patients with severe renal impairment and those with end-stage renal disease (Cl_cr <30 mL/minute).¹⁴⁴

Geriatric Patients

No specific dosage recommendations.¹ ¹⁴⁴

Cautions for Selegiline

Contraindications

Known hypersensitivity to selegiline.¹ ²
Concomitant use with other MAO inhibitors (selective or nonselective), certain opiate agonists (e.g., meperidine, methadone, propoxyphene [no longer commercially available in the US], tramadol), dextromethorphan, St. John’s wort (Hypericum perforatum), and cyclobenzaprine.¹ ² ¹⁴⁴ (See Specific Drugs and Foods under Interactions.)

Warnings/Precautions

Warnings

Risks Associated with Nonselective MAO Inhibition

Risk of serious hypertensive reactions associated with nonselective MAO inhibition.¹ ² ¹⁴⁴ Selectivity for MAO-B is relative.¹ ² ³ At recommended dosages, selegiline inhibits cerebral MAO-B while having little effect on MAO-A in the GI tract and liver.¹ ² ⁴ ⁵ ²² ³² ⁸⁴ At higher dosages, selectivity for MAO-B usually diminishes and the drug will inhibit MAO-B and MAO-A.¹ ² ⁴ ⁵ ²² ³² ¹⁴⁴

Hypertensive crises following ingestion of foods containing large amounts of tyramine (i.e., cheese reaction) have occurred in patients receiving nonselective MAO inhibitors.¹²³ Hypertensive reactions reported rarely in patients receiving recommended dosages of selegiline hydrochloride with tyramine-rich foods or sympathomimetic drugs;¹ as dosage is increased beyond recommended dosages, the likelihood of hypertensive reactions increases.¹ ² ⁵ ⁹ ¹⁰ ¹¹ ¹² ¹¹³ ¹⁴⁴ (See Interactions.)

Use selegiline with caution.¹ Do not exceed recommended dosages.¹ (See Dosage under Dosage and Administration.) The exact dosage at which selegiline hydrochloride becomes a nonselective inhibitor of MAO not known, but may be 30–40 mg daily (with conventional oral preparations) or 5 mg daily (with orally disintegrating tablets).¹ ² ¹⁴⁴ (See Advice to Patients.)

Because of the complexity of the MAO enzyme system, observe patients closely for atypical responses.¹

Serotonin Syndrome

Concomitant use of highly serotonergic drugs (e.g., SSRIs, tricyclic antidepressants) and MAO inhibitors, including selegiline, is potentially hazardous and may result in serotonin syndrome.¹ ² ¹³ ¹⁶ ¹⁷ ⁹⁷ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹¹² Manifestations may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).¹ ¹²⁶ ¹³¹ ¹³³ Generally avoid concomitant use.¹ ² (See Interactions.)

General Precautions

Dyskinesia

Selegiline may exacerbate levodopa-associated adverse effects (e.g., dyskinesia¹ ² ⁵ ⁴⁹ ⁵⁰ ⁶⁴ ⁶⁶ ⁶⁸ ¹⁴⁴ ), presumably by increasing dopaminergic activity; effects generally can be mitigated by reducing levodopa dosage.¹ ² ⁵ ⁶⁸ ¹⁴⁴ (See Adjunctive Therapy with Levodopa under Dosage and Administration.)

Sudden Sleep Episodes

Episodes of falling asleep while engaged in activities of daily living (e.g., driving) reported with dopaminergic drugs, sometimes resulting in accidents.¹⁴⁴

Some patients perceived no warning signs (e.g., excessive drowsiness) and believed they were alert immediately prior to the event.¹⁴⁴

Generally discontinue therapy if a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., driving a motor vehicle, conversations, eating).¹⁴⁴ If the drug is continued, advise patients not to drive and to avoid other potentially dangerous activities.¹⁴⁴

Hypotension

Orthostatic hypotension reported; risk appears to be increased after dosage increases.¹⁴⁴ Incidence higher in geriatric patients.¹⁴⁴

Melanoma

Epidemiologic studies indicate patients with Parkinson disease have a twofold to approximately sixfold greater risk of developing melanoma than the general population.¹ ² Unclear whether increased risk is due to Parkinson disease or other factors (e.g., drugs used to treat the disease).¹ ²

Monitor for melanoma on a frequent and regular basis.¹ ² Manufacturers recommend periodic skin examinations performed by qualified clinicians (e.g., dermatologists).¹ ²

Intense Urges

Intense urges (e.g., urge to gamble, increased sexual urges, other intense urges) and inability to control these urges reported in some patients receiving antiparkinsonian agents that increase central dopaminergic tone (including selegiline).¹ ² ¹⁴⁴ Although causal relationship not established, urges stopped in some cases when dosage was reduced or drug was discontinued.¹ ² ¹⁴⁴

Consider reducing dosage or discontinuing selegiline if a patient develops such urges.¹ ² ¹⁴⁴

Neuroleptic Malignant Syndrome

Symptoms resembling neuroleptic malignant syndrome (NMS) (e.g., muscular rigidity, autonomic instability, altered consciousness) reported with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy.¹⁴⁴ (See Advice to Patients.)

Irritation of Buccal Mucosa

Increased frequency of mild oropharyngeal abnormality (e.g., swallowing pain, mouth pain, discrete areas of focal reddening, multiple foci of reddening, edema, and/or ulceration) reported in patients receiving selegiline orally disintegrating tablets.¹⁴⁴

Phenylketonuria

Warn individuals with phenylketonuria (i.e., homozygous genetic deficiency of phenylalanine hydroxylase) and other individuals who must restrict their intake of phenylalanine that selegiline orally disintegrating tablets (Zelapar) contain aspartame (NutraSweet), which is metabolized in the GI tract to provide about 1.25 mg phenylalanine per tablet.¹⁴⁴ ¹⁴⁵ ¹⁴⁶ ¹⁴⁷ ¹⁴⁸ ¹⁴⁹

Renal Effects

Small increases in S_cr and BUN reported in patients receiving high dosages of selegiline orally disintegrating tablets (10 mg daily).¹⁴⁴

Specific Populations

Pregnancy

Category C.¹ No adequate and well-controlled studies in pregnant women; developmental toxicity observed in animal studies.¹ ² ¹⁴⁴

Lactation

Not known whether selegiline is distributed into milk.¹ ² Use caution.¹⁴⁴ Some manufacturers state to give consideration to discontinuing the use of all but absolutely essential drug therapy in nursing women.¹ ²

Pediatric Use

Safety and efficacy not established.¹ ² ¹⁴⁴

Geriatric Use

Safety and efficacy in geriatric patients not studied specifically to date; however, parkinsonian syndrome, for which safety and efficacy have been established, occurs principally in patients >50 years of age.¹ ² ⁴ ⁵ ⁶ ⁷ ⁸ ³⁴ ³⁵ ³⁶ ³⁷ ³⁸ ³⁹ ⁴⁰ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶

Greater frequency of certain adverse effects (e.g., hypertension, orthostatic hypotension) reported in geriatric patients ≥65 years of age compared with younger patients.¹⁴⁴

Common Adverse Effects

Conventional tablets and capsules: Nausea;¹ ² ⁵ ⁶ ³⁹ ⁵⁰ ⁶⁶ dizziness, lightheadedness, or fainting; abdominal pain; hallucinations; dry mouth; vivid dreams; dyskinesias; headache.¹

Orally disintegrating tablets: Constipation, skin disorders, vomiting, dizziness, dyskinesia, insomnia, dyspnea, myalgia, rash.¹⁴⁴

Many of the adverse effects in patients receiving selegiline plus levodopa result from increased dopaminergic activity and can be mitigated by reducing levodopa dosage; these effects include exacerbation of dyskinesias, confusion, and hallucinations.¹ ² ⁵ ⁴⁹ ⁵⁰ ⁶⁴ ⁶⁶ ⁶⁷ ⁶⁸

Drug Interactions

Metabolized by CYP2B6, CYP3A4, and possibly CYP2A6 (to a lesser extent).¹⁴⁴ Does not inhibit CYP enzymes; little or no potential for inducing CYP1A2 and CYP3A4/5.¹⁴⁴

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

CYP3A4 inhibitors: Pharmacokinetic interactions unlikely.¹⁴⁴

CYP3A4 inducers: Use concomitantly with caution.¹⁴⁴

Specific Drugs and Foods

Drug or Food	Interaction	Comments
Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)	Specific studies not conducted to evaluate effect on pharmacokinetics of selegiline¹⁴⁴	Use concomitantly with caution¹⁴⁴
Antidepressants (e.g., SNRIs, SSRIs, tetracyclics, tricyclics, triazolopyridine derivatives)	Potential for serious, possibly fatal serotonin syndrome¹ ² ¹³ ¹⁶ ¹⁷ ⁹⁷ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹¹² ¹²² ¹²⁶ ¹³¹ ¹⁴⁴	Generally avoid concomitant use¹ ² ¹⁷ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁴⁴ Allow ≥2 weeks to elapse between discontinuance of selegiline and initiation of antidepressant¹ ² ¹⁷ ⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁴⁴ Allow ≥5 weeks to elapse between discontinuance of fluoxetine and initiation of selegiline; consider a longer interval after long-term or high-dosage fluoxetine therapy¹ ² ¹⁷ ¹⁴⁴ Allow ≥2 weeks to elapse between discontinuance of fluvoxamine, paroxetine, or sertraline and initiation of selegiline⁹⁹ ¹⁰⁰ ¹⁰¹ Allow ≥2 weeks to elapse between discontinuance of a tricyclic antidepressant and initiation of selegiline¹⁰² ¹⁰³
Antipsychotic agents (i.e., dopamine antagonists)	Possible reduced efficacy of selegiline¹⁴⁴
Cyclobenzaprine	Potential for serious, possibly fatal serotonin syndrome¹⁴⁴	Concomitant use contraindicated¹⁴⁴
Dextromethorphan	Possible psychosis and bizarre behavior¹⁴⁴	Concomitant use contraindicated¹⁴⁴
Foods, tyramine-containing	Hypertensive reactions reported rarely¹ Nonselective inhibition of MAO increases risk of hypertensive reactions; selectivity for MAO typically decreases as dosage of selegiline is increased above recommended dosages (>10 mg daily with conventional oral preparations or >2.5 mg daily with orally disintegrating tablets)¹ ² ⁵ ⁹ ¹⁰ ¹¹ ¹² ¹¹³ ¹⁴⁴	Do not exceed recommended dosages of selegiline¹ ² ¹⁴⁴ Exercise caution regardless of the dosage;¹ avoid foods and beverages with high tyramine content⁵ ⁹ ¹⁰ ¹² ³² Safe use of selegiline orally disintegrating tablets at dosages >2.5 mg daily without dietary tyramine restrictions not established¹⁴⁴ Consult specialized references on food constituents or a dietician for specific information on the tyramine content of foods and beverages¹²²
Itraconazole	No changes observed in pharmacokinetics of selegiline¹⁴⁴
Levodopa	Potential for exacerbation of levodopa-associated adverse effects in some patients, presumably secondary to increased dopaminergic activity¹ ² ⁵ ⁶⁸ ¹⁴⁴	Reduction of levodopa dosage may mitigate adverse effects¹ ² ⁵ ⁶⁸ ¹⁴⁴ Combination used to therapeutic advantage¹ ² ³⁶ ³⁸ ³⁹ ⁴⁰ ⁵³ ⁵⁴ ⁵⁵ ⁵⁶ ⁶⁶ ⁷³
MAO inhibitors (nonselective or selective)	May increase risk of nonselective MAO inhibition, possibly resulting in hypertensive crisis¹⁴⁴	Concomitant use contraindicated¹⁴⁴ Allow ≥14 days to elapse between discontinuance of selegiline and initiation of other MAO inhibitors¹⁴⁴
Metoclopramide	Possible reduced efficacy of selegiline¹⁴⁴
Nafcillin	Specific studies not conducted to evaluate effect on pharmacokinetics of selegiline¹⁴⁴	Use concomitantly with caution¹⁴⁴
Opiate agonists (e.g., meperidine, methadone, propoxyphene [no longer commercially available in US], tramadol)	Potential for serious, possibly fatal serotonin syndrome¹ ² ⁵ ¹⁹ ²⁰ ¹¹² ¹¹⁸ ¹⁴⁴	Concomitant use with meperidine, methadone, and tramadol contraindicated; allow ≥14 days to elapse between discontinuance of selegiline and initiation of opiate agonist¹ ² ⁵ ¹⁹ ²¹ ¹⁴⁴ Consider discontinuing selegiline 2 weeks prior to scheduled surgery if postoperative meperidine analgesia is possible¹¹²
Rifampin	Specific studies not conducted to evaluate effect on pharmacokinetics of selegiline¹⁴⁴	Use concomitantly with caution¹⁴⁴
St. John's wort (Hypericum perforatum)	Potential for serious, possibly fatal serotonin syndrome¹⁴⁴	Concomitant use contraindicated¹⁴⁴
Sympathomimetic agents (e.g., ephedrine)	Hypertensive crisis reported in at least one patient receiving selegiline hydrochloride 10 mg daily (as a conventional oral preparation) and ephedrine¹ ²

Selegiline Pharmacokinetics

Absorption

Bioavailability

Conventional tablets and capsules: Rapidly absorbed following oral administration; peak plasma selegiline concentrations achieved within 0.5–0.9 hours in fasting individuals.⁸⁶ ⁸⁷ ¹⁰⁸ ¹¹⁰ Undergoes extensive first-pass metabolism in gut wall and liver.¹ ³² ¹⁰⁸ Following single oral 10-mg capsule dose, peak plasma concentrations of the first-pass metabolites (l-desmethylselegiline, l-methamphetamine, and l-amphetamine) are 3- to 20-fold higher than the peak plasma concentrations of selegiline.¹ ¹⁰⁸ ¹¹⁰ At steady state, peak plasma selegiline and metabolite concentrations are increased 2.6- to 4-fold and 1.5- to 2-fold, respectively, compared with values following a single dose.¹ ¹⁰⁸ Oral bioavailability of 10% reported for selegiline hydrochloride conventional tablets.¹⁰⁸

Orally disintegrating tablets: Absorbed more rapidly than conventional tablet formulation; mean peak plasma concentrations achieved within 10–15 minutes following buccal administration of a single 1.25- or 2.5-mg dose.¹⁴⁴ ¹⁵⁵ Peak plasma concentrations and AUC are dose proportional over dosage range of 1.25–10 mg daily and steady state is achieved after 8 days.¹⁴⁴ ¹⁵⁶ Undergoes pregastric absorption through buccal mucosa and substantially bypasses first-pass metabolism, resulting in higher plasma concentrations of selegiline and lower concentrations of metabolites than those achieved with conventional oral formulations.¹⁴⁴ ¹⁵⁵ ¹⁵⁶ Relative bioavailability of selegiline from orally disintegrating tablets is greater than that from conventional formulations.¹⁴⁴ ¹⁵⁰

Food

Conventional tablets and capsules: Food increases oral bioavailability of selegiline 3- to 5-fold but does not appear to affect the pharmacokinetics of the first-pass metabolites.¹ ¹⁰⁸

Orally disintegrating tablets: Presence of food in the GI tract decreases AUC and peak plasma concentrations to approximately 60% of those seen when the drug is administered in the fasted state.¹⁴⁴ (See Dosage and Administration: Administration.)

Special Populations

Following administration of orally disintegrating tablets in patients with mild to moderate hepatic impairment (Child-Pugh 5–9), peak plasma concentrations and systemic exposure of selegiline and desmethylselegiline were increased.¹⁴⁴ In patients with severe hepatic impairment (Child-Pugh >9), these pharmacokinetics parameters were considerably increased (by threefold to fourfold).¹⁴⁴

Following administration of orally disintegrating tablets in patients with renal impairment, including those with end-stage renal disease, peak plasma concentrations and systemic exposure of selegiline and desmethylselegiline were not substantially altered; however, exposure to the methamphetamine and amphetamine metabolites were increased.¹⁴⁴

Following administration of a single 10-mg dose (as conventional tablets) in a limited number of adults ≥60 years of age, systemic exposure was twice that reported in adults 18–30 years of age.¹

Distribution

Extent

Selegiline and its metabolites are widely distributed into body tissues.¹ ² ⁵ ²⁷ ²⁸ ²⁹ ³⁰ ³¹ ³² ⁴⁴

Selegiline and its metabolites cross the blood-brain barrier¹ ² ⁵ ²⁷ ²⁸ ²⁹ ³⁰ ³¹ ³² ⁴⁴ with highest accumulation in thalamus, basal ganglia, mesencephalon, and cingulate gyrus.²⁷ ²⁸

Selegiline and/or its metabolites also detected in the liver²⁹ and hair.⁸⁸

Plasma Protein Binding

Selegiline and/or its metabolites: Up to 94%.⁵ ³¹ ³² ⁴⁴

Elimination

Metabolism

Extensively metabolized, principally in the gut wall and liver, to l-desmethylselegiline and l-methylamphetamine (CYP-mediated) and then to l-amphetamine.¹ ³² ¹⁰⁸ Metabolized by CYP2B6, CYP3A4, and possibly CYP2A6 to a lesser extent.¹⁴⁴ The amphetamine metabolites may be hydroxylated and then conjugated with glucuronic acid.⁵ ³² ⁸⁸ ¹⁰⁸

l-Desmethylselegiline is an irreversible inhibitor of MAO-B,¹ ³² ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁷ ¹¹⁰ but its contribution to MAO-B inhibition during selegiline therapy may be only minor.¹¹⁰ The levorotatory amphetamine isomers are less potent CNS stimulants than the racemic or dextrorotatory isomers.⁵ ²⁶ ⁴⁴

When administered as the orally disintegrating tablet, substantially bypasses first-pass metabolism.¹⁴⁴ ¹⁵⁵ ¹⁵⁶

Elimination Route

Excreted principally in urine as conjugated and unconjugated metabolites¹ ⁵ ¹² ²⁶ ²⁷ ²⁸ ²⁹ ³⁰ ³¹ ³² ⁴⁴ (20–63% as l-methamphetamine, 9–26% as l-amphetamine, and 1% as l-desmethylselegiline).⁵ ¹² ³¹ ⁴⁴

Urinary excretion of amphetamines is enhanced in acidic urine.⁵ ³¹ ⁴⁴

Half-life

Selegiline: Approximately 1.2–2 hours following single oral doses of 10 mg (as conventional oral preparations) or 1.25 mg (as orally disintegrating tablets),¹ ⁸⁷ ¹⁰⁸ ¹⁴⁴ and about 10 hours at steady state.¹ ¹⁰⁸ ¹⁴⁴

Metabolites: 2 hours (l-desmethylselegiline), 20.5 hours (l-methamphetamine), and 17.7 hours (l-amphetamine).² ⁴⁴

Stability

Storage

Oral

Conventional Tablets and Capsules

20–25°C.¹ ²

Orally Disintegrating Tablets

25°C (may be exposed to 15–30°C).¹⁴⁴ Use within 3 months of opening pouch and immediately upon opening individual blister.¹⁴⁴ Store blister tablets in pouch.¹⁴⁴

Actions

Irreversible MAO-B inhibitor.¹ ² ³ ¹⁴⁴ At recommended dosages, inhibits cerebral MAO-B while having little effect on MAO-A in the GI tract and liver.¹ ² ⁴ ⁵ ²² ³² ⁸⁴ At higher dosages (e.g., 30–40 mg daily with conventional oral preparations or 5 mg daily with orally disintegrating tablets), selectivity usually diminishes and the drug will inhibit MAO-B and MAO-A.¹ ² ⁴ ⁵ ²² ³² ¹⁴⁴
Principal physiologic action in the management of parkinsonian syndrome is irreversible inhibition of MAO-B within the nigrostriatal pathways in the CNS,¹ ² ⁴ ⁵ ²² thereby blocking microsomal metabolism of dopamine ¹ ² ⁴ ⁵ ²² and enhancing dopaminergic activity in the substantia nigra.¹ ² ⁴ ⁵ ²² Reduces the amount of levodopa required to maintain optimum dopamine concentrations in the brain of patients with parkinsonian syndrome.¹ ² ⁴ ⁵ ²²
May increase dopaminergic activity by mechanisms other than MAO-B inhibition (e.g., interference with dopamine reuptake at the synapse).¹ ² ⁵ ⁸⁴
May prevent or delay neuronal death by protecting the nigral neurons from damage by oxygen free radicals produced through MAO-B activity.⁴ ⁵ ⁸³ ⁸⁴ ⁸⁵ ¹⁰⁴ ¹⁰⁵
Prevents MAO-B mediated production of the neurotoxin methyl-4-phenylpyridinium ion (MPP⁺) from phenyl-1,2,3,6-tetrahydropyridine (MPTP).⁴ ⁵ ⁸³ ⁸⁴ If an MPTP-like substance contributes to the pathogenesis of parkinsonian syndrome, the inhibition of oxidation of such a substance may protect against its neurotoxic effects.⁴ ⁵ ⁸³ ⁸⁴
The ability to promote neuronal survival and neurite outgrowth and release of dopamine from intact neurons and also to block activation of N-methyl-d-aspartate (NMDA)-sensitive glutamate receptors may contribute to selegiline’s activity.¹ ² ⁴ ⁵ ²² ²³ ⁴³ ⁷⁸ ⁷⁹ ⁸⁰ ⁸¹ ⁸² ⁸³ ⁸⁴ ⁸⁵

Advice to Patients

Risk of serious adverse effects (e.g., hypertensive reactions) at dosages higher than recommended.¹ ² ¹⁴⁴ Importance of not exceeding the recommended dosage.¹ ² ¹⁴⁴
Advise patient that serious adverse reactions (e.g., hypertensive reactions) rarely have occurred even at the recommended dosage when tyramine-containing foods or a sympathomimetic drug was used concomitantly.¹ ² ¹²² Importance of avoiding foods and beverages with a high tyramine content.⁵ ⁹ ¹⁰ ¹² ³² ¹⁴⁴ Advise patients to contact their clinician if they do not feel well after eating foods rich in tyramine.¹⁴⁴
Importance of contacting clinician if signs or symptoms of hypertension (e.g., headache, neck stiffness or soreness, palpitation) or other unusual symptoms occur.¹ ² ¹²²
Risk of somnolence and the possibility of falling asleep during activities of daily living.¹⁴⁴ Patients should avoid driving or engaging in other potentially dangerous activities until the effects on the individual are known.¹⁴⁴
Importance of advising patients that if increased somnolence or new episodes of falling asleep during activities of daily living (e.g., watching television, passenger in a car) occur at any time during therapy, they should not drive or participate in potentially dangerous activities until they have contacted their clinician.¹⁴⁴ Patients should not drive, operate machinery, or work at heights during therapy if they have previously experienced somnolence and/or have fallen asleep without warning prior to use of selegiline.¹⁴⁴
Importance of taking selegiline as prescribed.¹ ² ¹⁴⁴ Importance of advising patients to contact their clinician if they wish to discontinue therapy.¹⁴⁴
Potential for selegiline to exacerbate levodopa-associated adverse effects (e.g., dyskinesia).¹ ² ⁵ ⁶⁸ Possible need for reduction of levodopa dosage following initiation of selegiline.¹ ²
Risk of hallucinations or psychotic-like behavior.¹⁴⁴ Importance of advising patients to promptly report any such events to their clinician.¹⁴⁴
Importance of asking patients whether they have developed any new or increased gambling urges, sexual urges, or other urges while receiving selegiline and of advising them of the importance of reporting such urges.¹⁴⁴
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ ¹⁴⁴
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription (e.g., analgesics, antidepressants) and OTC drugs (e.g., decongestants, dextromethorphan), as well as any concomitant illnesses (e.g., major psychotic disorder).¹ ¹⁴⁴
Importance of informing patients of other important precautionary information.¹ ¹⁴⁴ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Selegiline Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules	5 mg*	Eldepryl	Somerset
			Selegiline Hydrochloride Capsules
	Tablets	5 mg*	Selegiline Hydrochloride Tablets
	Tablets, orally disintegrating	1.25 mg	Zelapar	Valeant

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. Mylan Pharmaceuticals Inc. Selegiline hydrochloride tablets, USP, prescribing information. Morgantown, WV; 2017 Mar.

3. Fleeger CA, ed. USAN 1994: USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc.; 1994:497.

4. Knoll J. Deprenyl (selegiline): the history of its development and pharmacological action. Acta Neurol Scand. 1983; 95(Suppl):57-80.

5. Chrisp P, Mammen GJ, Sorkin EM. Selegiline: a review of its pharmacology, symptomatic benefits and protective potential in Parkinson’s disease. Drugs Aging. 1991; 1:228-48. https://pubmed.ncbi.nlm.nih.gov/1794016

6. Golbe LI, Langston JW, Shoulson I. Selegiline and Parkinson’s disease: protective and symptomatic considerations. Drugs. 1990; 39:646-51. https://pubmed.ncbi.nlm.nih.gov/2112994

7. Fuller MA, Tolbert SR. Selegiline: initial or adjunctive therapy of Parkinson’s disease? DICP Ann Pharmacother. 1991; 25:36-40.

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