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Selegiline Hydrochloride

Class: Monoamine Oxidase B Inhibitors
VA Class: CN500
Chemical Name: (R)-N,α-Dimethyl-N-2-propynyl-benzeneethanamine hydrochloride
Molecular Formula: C13H17N•ClH
CAS Number: 14611-52-0
Brands: Eldepryl, Zelapar

Medically reviewed on May 7, 2018

Introduction

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

Uses for Selegiline Hydrochloride

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.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 (Alzheimer’s disease, presenile or senile dementia).61 62 63 104 105 106 107 127 128

Selegiline Hydrochloride 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 (Clcr 30–89 mL/minute); individualize dosage.144 Use not recommended in patients with severe renal impairment and those with end-stage renal disease (Clcr <30 mL/minute).144

Geriatric Patients

No specific dosage recommendations.1 144

Cautions for Selegiline Hydrochloride

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 Scr 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

Interactions for Selegiline Hydrochloride

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 Hydrochloride 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

AHFS DI Essentials. © Copyright 2018, Selected Revisions May 7, 2018. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

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

References

1. Somerset Pharmaceuticals, Inc. Eldepryl (selegiline hydrochloride) capsules prescribing information. Morgantown, WV; 2012 Jun.

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. http://www.ncbi.nlm.nih.gov/pubmed/1794016?dopt=AbstractPlus

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

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

8. Anon. Drugs for Parkinson’s disease. Med Lett Drugs Ther. 1993; 35:31-4. http://www.ncbi.nlm.nih.gov/pubmed/8096322?dopt=AbstractPlus

9. Prasad A, Glover V, Goodwin BL et al. Enhanced pressor sensitivity to oral tyramine challenge following high dose selegiline treatment. Psychopharmacology. 1988; 95:540-3. http://www.ncbi.nlm.nih.gov/pubmed/3145523?dopt=AbstractPlus

10. McGrath PJ, Stewart JW, Quitkin FM. A possiblel-deprenyl induced hypersensitive reaction. J Clin Psychopharmacol. 1989; 9:310-1. http://www.ncbi.nlm.nih.gov/pubmed/2504782?dopt=AbstractPlus

11. Ahlskog JE. Treatment of Parkinson’s disease. Postgrad Med. 1994; 95:52-69. http://www.ncbi.nlm.nih.gov/pubmed/8153048?dopt=AbstractPlus

12. Schulz R, Antonin KH, Hoffmann E et al. Tyramine kinetics and pressor sensitivity during monoamine oxidase inhibition by selegiline. Clin Pharmacol Ther. 1989; 46:528-36. http://www.ncbi.nlm.nih.gov/pubmed/2510962?dopt=AbstractPlus

13. Messiha FS. Fluoxetine: adverse effects and drug-drug interactions. J Toxicol Clin Toxicol. 1993; 31:603-30. http://www.ncbi.nlm.nih.gov/pubmed/8254702?dopt=AbstractPlus

14. Suchowersky O, deVries J. Possible interactions between deprenyl and Prozac. Can J Neurol Sci. 1990; 17:352-3. http://www.ncbi.nlm.nih.gov/pubmed/2119870?dopt=AbstractPlus

15. Jermain DM, Hughes PL, Follender AB. Potential fluoxetine–selegiline interaction. Ann Pharmacother. 1992; 26:1300. http://www.ncbi.nlm.nih.gov/pubmed/1421659?dopt=AbstractPlus

16. Toyama SC, Iacono RP. Is it safe to combine a selective serotonin reuptake inhibitor with selegiline? Ann Pharmacother. 1994; 28:405-6. Letter.

17. Dista. Prozac (fluoxetine hydrochloride) prescribing information. In: Physicians’ desk reference. 48th ed. Montvale, NJ: Medical Economics Company; 1994:877-80.

18. Montastruc JL, Chamontin B, Senard JM et al. Pseudophaeochromocytoma in parkinsonian patient treated with fluoxetine plus selegiline. Lancet. 1993; 341:555. http://www.ncbi.nlm.nih.gov/pubmed/8094789?dopt=AbstractPlus

19. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991; 337:246. http://www.ncbi.nlm.nih.gov/pubmed/1670882?dopt=AbstractPlus

20. Zornberg GL, Bodkin JA, Cohen BM. Severe adverse interaction between pethidine and selegiline. Lancet. 1991; 337:246. http://www.ncbi.nlm.nih.gov/pubmed/1670882?dopt=AbstractPlus

21. Asch DA, Parker RM. The Libby Zion case: one step forward or two steps backward? N Engl J Med. 1988; 318:771-5. Letter.

22. Youdim MBH. Pharmacology of MAO B inhibitors: mode of action of (—)deprenyl in Parkinson’s disease. J Neural Transm. 1986; 22(Suppl):91-105.

23. Knoll J. The pharmacology of (—)deprenyl. J Neural Transm. 1986; 22(Suppl):75-89.

24. Riederer P, Youdim MBH. Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J Neurochem. 1986; 46:1359-65. http://www.ncbi.nlm.nih.gov/pubmed/2420928?dopt=AbstractPlus

25. Kalir A, Sabbagh A, Youdim MBH. Selective acetylenic ’suicide’ and reversible inhibitors of monoamine oxidase types A and B. Br J Pharmacol. 1981; 73:55-64. http://www.ncbi.nlm.nih.gov/pubmed/7284698?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2071835&blobtype=pdf

26. Reynolds GP, Elsworth JD, Blau K et al. Deprenyl is metabolized to methamphetamine and amphetamine in man. Br J Clin Pharmacol. 1978; 6:542-4. http://www.ncbi.nlm.nih.gov/pubmed/728327?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1429688&blobtype=pdf

27. Fowler JS, Volkow ND, Logan J et al. Monoamine oxidase B (MAO B) inhibitor therapy in Parkinson’s disease: the degree and reversibility of human brain MAO B inhibition by Ro 19 6327. Neurology. 1993; 43:1984-92. http://www.ncbi.nlm.nih.gov/pubmed/8413955?dopt=AbstractPlus

28. Fowler JS, MacGregor RR, Wolf AP et al. Mapping human brain monoamine oxidase A and B with11C-labeled suicide inactivators and PET. Science. 1987; 235:481-5. http://www.ncbi.nlm.nih.gov/pubmed/3099392?dopt=AbstractPlus

29. Meeker JE, Reynolds PC. Postmortem tissue methamphetamine concentrations following selegiline administration. J Analytic Toxicol. 1990; 14:330-1.

30. Reynolds GP, Riederer P, Sandler M et al. Amphetamine and 2-phenylethylamine in post-mortem parkinsonian brain after (—)deprenyl administration. J Neural Transm. 1978; 43:271-7. http://www.ncbi.nlm.nih.gov/pubmed/745019?dopt=AbstractPlus

31. Elsworth JD, Sandler M, Lees AJ et al. The contribution of amphetamine metabolites of (—)-deprenyl to its antiparkinsonian properties. J Neural Transm. 1982; 54:105-10. http://www.ncbi.nlm.nih.gov/pubmed/6809891?dopt=AbstractPlus

32. Heinonen EH, Myllylä V, Sotaniemi K et al. Pharmacokinetics and metabolism of selegiline. Acta Neurol Scand. 1989; 126:93-9.

33. Arnett CD, Fowler JS, MacGregor RR et al. Turnover of brain monoamine oxidase measured in vivo by positron emission tomography usingl-[11C]deprenyl. J Neurochem. 1987; 49:522-7. http://www.ncbi.nlm.nih.gov/pubmed/3110375?dopt=AbstractPlus

34. Baronti F, Davis TL, Boldry RC et al. Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging. Neurology. 1992; 42:541-4. http://www.ncbi.nlm.nih.gov/pubmed/1549214?dopt=AbstractPlus

35. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food Drug and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to June 30, 1994. Rockville, MD; 1994 Jul.

36. Lieberman A. Long-term experience with selegiline and levodopa in Parkinson’s disease. Neurology. 1992; 42(Suppl 4):32-6. http://www.ncbi.nlm.nih.gov/pubmed/1584430?dopt=AbstractPlus

37. Paulson GW. Management of the patient with newly-diagnosed Parkinson’s disease. Geriatrics. 1993; 48:30-40. http://www.ncbi.nlm.nih.gov/pubmed/8094362?dopt=AbstractPlus

38. Csanda E, Tárczy M. Selegiline in the early and late phases of Parkinson’s disease. J Neural Transm. 1987; 25(Suppl):105-13.

39. Birkmayer W, Birkmayer GD. Effect of (—)deprenyl in long-term treatment of Parkinson’s disease. J Neural Transm. 1986; 22(Suppl):219-25.

40. Lieberman AN, Gopinathan G, Neophytides A et al. Deprenyl versus placebo in Parkinson disease: a double-blind study. N Y State J Med. 1987; 87:646-9. http://www.ncbi.nlm.nih.gov/pubmed/3124027?dopt=AbstractPlus

41. Gaál J, Hermecz I. Medicinal chemistry of present and future MAO-B inhibitors. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:75-108.

42. Polymeropoulos EE. l-deprenyl: a unique MAO-B inhibitor. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:109-124.

43. Magyar K. Pharmacology of monoamine oxidase type B inhibitors. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:125-43.

44. Heinonen EH, Anttila MI, Lammintausta RAS. Pharmacokinetics and clinical pharmacology of selegiline. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:201-13.

45. Paul W, Szelenyi I. Chemical structures and pharmacological features of MAO-B inhibitors. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:339-58.

46. Nickel B, Borbe HO, Szelenyi I. Effect of selegiline and desmethyl-selegiline on cortical electric activity in rats. J Neural Transm. 1990; 32(Suppl):139-44.

47. Borbe HO, Niebch G, Nickel B. Kinetic evaluation of MAO-B-activity following oral administration of selegiline and desmethyl-selegiline in the rat. J Neural Transm. 1990; 32(Suppl):131-7.

48. Somerset Pharmaceuticals. Eldepryl (selegiline hydrochloride) protocol for Parkinson’s disease. Tampa, FL.

49. Poewe W, Gerstenbrand F, Ransmayr G. Experience with selegiline in the treatment of Parkinson’s disease. J Neural Transm. 1987; 25(Suppl):131-5.

50. Golbe LI, Duvoisin RC. Double-blind trial of R-(—)-deprenyl for the “on-off” effect complicating Parkinson’s disease. J Neural Transm. 1987; 25(Suppl):123-9.

51. Elizan TS. (—)-deprenyl combined withl-dopa in the treatment of Parkinson’s disease. In: Szelenyi I, ed. Inhibitors of monoamine oxidase B: pharmacology and clinical use in neurodegenerative disorders. Basel, Switzerland: Birkhäuser Verlag; 1993:277-88.

52. Fischer PA, Baas H. Therapeutic efficacy of R-(—)-deprenyl as adjuvant therapy in advanced parkinsonism. J Neural Transm. 1987; 25(Suppl):137-47.

53. The Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med. 1989; 321:1364-71. http://www.ncbi.nlm.nih.gov/pubmed/2509910?dopt=AbstractPlus

54. The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med. 1993; 328:176-83. http://www.ncbi.nlm.nih.gov/pubmed/8417384?dopt=AbstractPlus

55. Tetrud JW, Langston JW. The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science. 1989; 245:519-22. http://www.ncbi.nlm.nih.gov/pubmed/2502843?dopt=AbstractPlus

56. Scherokman B. Tocopherol and deprenyl for patients with early Parkinson disease. ACP J Club. 1993; May/June:71.

57. Calne DB. Treatment of Parkinson’s disease. N Engl J Med. 1993; 329:1021-7. http://www.ncbi.nlm.nih.gov/pubmed/8366903?dopt=AbstractPlus

58. Olanow CW, Calne D. Does selegiline monotherapy in Parkinson’s disease act by symptomatic or protective mechanisms? Neurology. 1991; 42(Suppl 4):13-26. (IDIS 295409)

59. Olanow CW. The early treatment of Parkinson’s disease. Neurology. 1993; 43:S30-1. http://www.ncbi.nlm.nih.gov/pubmed/8414016?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2429957&blobtype=pdf

60. Ward CD. Does selegiline delay progression of Parkinson’s disease? A critical re-evaluation of the DATATOP study. J Neurol Neurosurg Psychiatr. 1994; 57:217-20. http://www.ncbi.nlm.nih.gov/pubmed/8126510?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1072455&blobtype=pdf

61. Burke WJ, Ranno AE, Roccaforte WH et al. L-deprenyl in the treatment of mild dementia of the alzheimer type: preliminary results. J Am Geriatr Soc. 1993; 41:367-70. http://www.ncbi.nlm.nih.gov/pubmed/8463521?dopt=AbstractPlus

62. Burke WJ, Roccaforte WH, Wengel SP et al. L-deprenyl in the treatment of mild dementia of the alzheimer type: results of a 15-month trial. J Am Geriatr Soc. 1993; 41:1219-25. http://www.ncbi.nlm.nih.gov/pubmed/8227897?dopt=AbstractPlus

63. Schneider LS, Olin JT, Pawluczyk S. A double-blind crossover pilot study of l-deprenyl (selegiline) combined with cholinesterase inhibitor in alzheimer’s disease. Am J Psychiatr. 1993; 150:321-3. http://www.ncbi.nlm.nih.gov/pubmed/8422085?dopt=AbstractPlus

64. Golbe LI. Long-term efficacy and safety of deprenyl (selegiline) in advanced Parkinson’s disease. Neurology. 1989; 39:1109-11. http://www.ncbi.nlm.nih.gov/pubmed/2503769?dopt=AbstractPlus

65. Coleman RJ. Current drug therapy for Parkinson’s disease: a review. Drug Aging. 1992; 2:112-24.

66. Lieberman AN, Gopinathan G, Neophytides A et al. Deprenyl in the treatment of Parkinson’s disease: a specific type B monoamine oxidase inhibitor. N Y State J Med. 1984; 84:13-6. http://www.ncbi.nlm.nih.gov/pubmed/6422358?dopt=AbstractPlus

67. Saint-Cyr JA, Taylor AE, Long AE. Neuropsychological and psychiatric side effects in the treatment of Parkinson’s disease. Neurology. 1993; 43(Suppl 6):S47-52. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2429957&blobtype=pdf

68. Waters CH. Side effects of selegiline (Eldepryl). J Geriatr Psychiatr Neurol. 1992; 5:31-4.

69. Rowland MJ, Bransome ED Jr, Hendry LB. Hypoglycemia caused by selegiline, an antiparkinsonian drug: can such side effects be predicted? J Clin Pharmacol. 1994; 34:80-5. (IDIS 325202)

70. Somerset Pharmaceuticals. Eldepryl (selegiline hydrochloride) product monograph. Tampa, FL; 1990 Oct.

71. Subramanya KS, Motimaya AM, Curry PT et al. Assessment of genotoxicity of two anti-parkinsonian drugs (selegiline hydrochloride and bromocryptine mesylate) in vivo in mouse bone marrow cells. Toxicol Lett. 1993; 66:221-30. http://www.ncbi.nlm.nih.gov/pubmed/8475502?dopt=AbstractPlus

72. Magyar K, Tóthfalusi L. Pharmacokinetic aspects of deprenyl effects. Pol J Pharmacol Pharm. 1984; 36:373-84. http://www.ncbi.nlm.nih.gov/pubmed/6441926?dopt=AbstractPlus

73. The Parkinson Study Group. DATATOP: a multicenter controlled clinical trial in early Parkinson’s disease. Arch Neurol. 1989; 46:1052-60. http://www.ncbi.nlm.nih.gov/pubmed/2508608?dopt=AbstractPlus

74. Gewirtz GR, Sharif Z, Cadet JL et al. Selegiline for neuroleptic-induced parksinsonism. Pharmacopsychiatry. 1993; 26:128-9. http://www.ncbi.nlm.nih.gov/pubmed/7901857?dopt=AbstractPlus

75. Menza MA, Golbe LI. Hypomania in a patient receiving deprenyl (selegiline) after adrenal-striatal implantation for Parkinson’s disease. Clin Neuropharmcol. 1988; 11:549-51.

76. Frankel JP, Kempster PA, Stibe CMH et al. A double-blind, controlled study of high-dose L-deprenyl in the treatment of Parkinson’s disease. Clin Neuropharmacol. 1989; 12: 448-51.

77. Mally J, Kovacs AB, Stone TW. Delayed development of symptomatic improvement by (—)-deprenyl in Parkinson’s disease. J Neurol Sci. 1995; 134:143-5. http://www.ncbi.nlm.nih.gov/pubmed/8747857?dopt=AbstractPlus

78. Koutsilieri E, O’Callaghan JFX, Chen T et al. Selegiline enhances survival and neurite outgrowth of MPP+-treated dopaminergic neurons. Eur J Pharmacol. 1994; 269:R3-4. http://www.ncbi.nlm.nih.gov/pubmed/7895766?dopt=AbstractPlus

79. Carrillo MC, Ivy GO, Milgram NW et al. (—)Deprenyl increases activities of superoxide dismutase (SOD) in striatum of dog brain. Life Sci. 1994; 54:1483-9. http://www.ncbi.nlm.nih.gov/pubmed/8190023?dopt=AbstractPlus

80. Gerlach M, Youdim MBH, Riederer P. Is selegiline neuroprotective in Parkinson’s disease? Gen Pharmacol. 1994; 41:177-88.

81. Iwasaki Y, Ikeda K, Shiojima T et al. Deprenyl enhances neurite outgrowth in cultured rat spinal ventral horn neurons. J Neurol Sci. 1994; 125:11-3. http://www.ncbi.nlm.nih.gov/pubmed/7964880?dopt=AbstractPlus

82. Knoll J, Miklya I. Multiple, small dose administration of (-)deprenyl enhances catecholaminergic activity and diminishes serotoninergic activity in the brain and these effects are unrelated to MAO-B inhibition. Arch Int Pharmacodyn Ther. 1994; 328:1-15. http://www.ncbi.nlm.nih.gov/pubmed/7893186?dopt=AbstractPlus

83. Di Paola R, Uitti RJ. Early detection of Parkinson’s disease: implications for treatment. Drugs Aging. 1996; 9:159-68. http://www.ncbi.nlm.nih.gov/pubmed/8877310?dopt=AbstractPlus

84. Montastruc JL, Rascol O, Senard JM. New directions in the drug treatment of Parkinson’s disease. Drugs Aging. 1996; 9:169-84. http://www.ncbi.nlm.nih.gov/pubmed/8877311?dopt=AbstractPlus

85. Fahn S. Controversies in the therapy of Parkinson’s disease. Adv Neurol. 1996; 69:477-86. http://www.ncbi.nlm.nih.gov/pubmed/8615168?dopt=AbstractPlus

86. Fowler JS, Fazzini E,Volkow ND. Deprenyl and levodopa and Parkinson’s disease progression. Ann Neurol. 1996; 40:267-8. http://www.ncbi.nlm.nih.gov/pubmed/8773616?dopt=AbstractPlus

87. Mahmood I, Marinac JS, Willsie S et al. Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers. Biopharm Drug Dispos. 1995; 16:535-45. http://www.ncbi.nlm.nih.gov/pubmed/8785378?dopt=AbstractPlus

88. Kikura R, Nakahara Y. Hair analysis for drugs of abuse. IX. Comparison of deprenyl use and methamphetamine use by hair analysis. Biol Pharm Bull. 1995; 18:267-72. http://www.ncbi.nlm.nih.gov/pubmed/7742796?dopt=AbstractPlus

89. Lees AJ on behalf of the Parkinson’s Disease Research Group of the United Kingdom. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson’s disease. BMJ. 1995; 311:1602-7. http://www.ncbi.nlm.nih.gov/pubmed/8555803?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2551499&blobtype=pdf

90. Bergus G. Treatment of Parkinson’s disease. J Fam Pract. 1996; 42:457-8. http://www.ncbi.nlm.nih.gov/pubmed/8642360?dopt=AbstractPlus

91. Calne DB. Selegiline in Parkinson’s disease: no neuroprotective effect: increased mortality. BMJ. 1995; 311:1583-4. http://www.ncbi.nlm.nih.gov/pubmed/8555790?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2551489&blobtype=pdf

92. Golbe LI, Lieberman AN, Muenter MD et al. Deprenyl in the treatment of symptom fluctuations in advanced Parkinson’s disease. Clin Neuropharmacol. 1988; 11:45-55. http://www.ncbi.nlm.nih.gov/pubmed/3127050?dopt=AbstractPlus

93. Ahlskog JE. Treatment of early Parkinson’s disease: are complicated strategies justified? Mayo Clin Proc. 1996; 71:659-70.

94. Parkinson’s Disease Research Group in the United Kingdom. Comparisons of therapeutic effects of levodopa, levodopa and selegiline, and bromocriptine in patients with early, mild Parkinson’s disease: three year interim report. BMJ. 1993; 307:469-72. http://www.ncbi.nlm.nih.gov/pubmed/8400928?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1678739&blobtype=pdf

95. Anon. Selegiline in Parkinsonism: a need for radical reappraisal. WHO Drug Info. 1996; 10:21-4.

96. Hughes AJ. Drug treatment of Parkinson’s disease in the 1990s: achievements and future possibilities. Drugs. 1997; 53:195-205. http://www.ncbi.nlm.nih.gov/pubmed/9028741?dopt=AbstractPlus

97. Garcia-Monco JC, Padierna A, Gomez Beldarrain M. Selegiline, fluoxetine, and depression in Parkinson’s disease. Mov Disord. 1995; 10:352. http://www.ncbi.nlm.nih.gov/pubmed/7651457?dopt=AbstractPlus

98. Waters CH. Fluoxetine and selegiline—lack of significant interaction. Can J Neurol Sci. 1994; 21:259-61. http://www.ncbi.nlm.nih.gov/pubmed/8000982?dopt=AbstractPlus

99. Solvay Pharmaceuticals. Luvox (fluvoxamine maleate) tablets prescribing information (dated 1996 Aug). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2723-7.

100. SmithKline Beecham Pharmaceuticals. Paxil (paroxetine hydrochloride) tablets prescribing information. In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2681-6.

101. Pfizer, Inc. Zoloft (sertraline hydrochloride) tablets prescribing information (dated 1996 Apr). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2051-3.

102. Zeneca Pharmaceuticals. Elavil (amitriptyline hydrochloride) tablets and injection prescribing information (dated 1996 May). In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:2945-7.

103. Hoechst Marion Roussel, Inc. Norpramin (desipramine hydrochloride) tablets, USP, prescribing information. In: Physicians’ desk reference. 51st ed. Montvale, NJ: Medical Economics Company Inc; 1997:1273-5.

104. Sano M, Ernesto C, Thomas RG et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. N Engl J Med. 1997; 336:1216-22. http://www.ncbi.nlm.nih.gov/pubmed/9110909?dopt=AbstractPlus

105. Drachman DA, Leber P. treatment of Alzheimer’s disease—searching or a breakthrough, settling for less. N Engl J Med. 1997; 336:1245-7. http://www.ncbi.nlm.nih.gov/pubmed/9110915?dopt=AbstractPlus

106. Small GW, Rabins PV, Barry PP et al. Diagnosis and treatment of Alzheimer disease and related disorders: consensus statement of the American Association for Geriatric Psychiatry, the Alzheimer’s associatioon, and the American geriatric Society. JAMA. 1997; 278:1363-71. http://www.ncbi.nlm.nih.gov/pubmed/9343469?dopt=AbstractPlus

107. American Psychiatric Association. Practice guideline for the treatment of patients with Alzheimer’s disease and other dementias of late life. Am J Psychiatry. 1997; 154(Suppl):1-39.

108. Mahmood I. Clinical pharmacokinetics and pharmacodynamics of selegiline: an update. Clin Pharmacokinet. 1997; 33:91-102. http://www.ncbi.nlm.nih.gov/pubmed/9260033?dopt=AbstractPlus

109. Rohatagi S, Barrett JS, McDonald LJ et al. Selegiline percutaneous absorption in various species and metabolism by human skin. Pharmaceut Res. 1997; 14:50-5.

110. Heinonen EH, Anttila MI, Karnani HL et al. Desmethylselegiline, a metabolite od selegiline, is an irreversible inhibitor of monoamine oxidase type B in humans. J Clin Pharmacol. 1997; 37:602-9. http://www.ncbi.nlm.nih.gov/pubmed/9243353?dopt=AbstractPlus

111. Rohatagi S, Barrett JS, DeWitt KE et al. Integrated pharmacokinetic and metabolic modelng of selegiline and metabolites after transdermal administration. Biopharm Drug Dispos. 1997; 18:567-84. http://www.ncbi.nlm.nih.gov/pubmed/9330778?dopt=AbstractPlus

112. Pfeiffer RF. Antiparkinsonia agents: drug interactions of clinical significance. Drug Saf. 1996; 14:343-54. http://www.ncbi.nlm.nih.gov/pubmed/8800629?dopt=AbstractPlus

113. Korn A, Wagner B, Moritz E et al. Tyramine pressor sensitivity in healthy subnjects during combined treatment with moclobemide and selegiline. Eur J Clin Pharmacol. 1996; 49:273-8. http://www.ncbi.nlm.nih.gov/pubmed/8857072?dopt=AbstractPlus

114. Haberny KA, Walsh SL, Ginn DH et al. Absence of acute cocaine interactions with the MAO-B inhibitor selegiline. Drug Alcohol Depend. 1995; 39:55-62. http://www.ncbi.nlm.nih.gov/pubmed/7587975?dopt=AbstractPlus

115. Hauser RA, Zesiewicz TA. Sertraline for the treatment of depression in Parkinson’s disease. Mov Disord. 1997; 12:756-9. http://www.ncbi.nlm.nih.gov/pubmed/9380061?dopt=AbstractPlus

116. Steur EN, Ballering LA. Moclobemide and selegiline in the treatment of depression in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1997; 63:547. http://www.ncbi.nlm.nih.gov/pubmed/9343144?dopt=AbstractPlus

117. American Psychiatric Association. American Psychiatric Association practice guidelines. Washington, DC: American Psychiatric Association. 1996:98,116.

118. Meperidine (Demerol) interactions: selegiline (Eldepryl). In: Hansten PD, Horn JR. Hansten and Horn’s drug interactions analysis and management. Vancouver, WA: Applied Therapeutics, Inc; 1997:379.

119. Parkinson Study Group. Impact of deprenyl and tocopherol treatment on Parkinson’s disease in DATATOP subjects not requiring levodopa. Ann Neurol. 1996; 39:29-36. http://www.ncbi.nlm.nih.gov/pubmed/8572663?dopt=AbstractPlus

120. Mäki-Ikola O, Heinonen E. Study design problems of DATATOP study analysis. Ann Neurol. 1996; 40:946-7. http://www.ncbi.nlm.nih.gov/pubmed/9007106?dopt=AbstractPlus

121. Penney JB, Shoulson I, Kieburtz K et al for the DATATOP Steering Committee and Investigators. Study design problems of DATATOP study analysis. Ann Neurol. 1996; 40:947-8.

122. Reviewers’ comments (personal observations).

123. Baldessarini RJ. Drugs and the treatment of psychiatric disorders. In: Hardman JG, Limbird LE, Molinoff PB et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 9th ed. New York: McGraw-Hill; 1995:431-59.

124. Parkinson Study Group. Clinical outcome following placebo-controlled withdrawal of deprenyl (selegiline) among levodopa-treated DATATOP subjects. Movement Disord. 1997; 12:838.

125. Parkinson Study Group. Mortality in DATATOP: a multicenter trial in early Parkinson’s disease. Ann Neurol. (in press)

126. Richard IH, Kurlan R, Tanner C et al et al. Serotonin syndrome and the combined use of deprenyl and an antidepressant in Parkinson’s disease. Neurology. 1997; 48:1070-7. http://www.ncbi.nlm.nih.gov/pubmed/9109902?dopt=AbstractPlus

127. Adelman A. Selegiline and vitamin E in Alzheimer’s disease. J Fam Pract. 1997; 45:98-100. http://www.ncbi.nlm.nih.gov/pubmed/9267360?dopt=AbstractPlus

128. Pincus MM. Alpha-tocopherol and Alzheimer’s disease. N Engl J Med. 1997; 337:572. http://www.ncbi.nlm.nih.gov/pubmed/9265106?dopt=AbstractPlus

129. Doody RS, Stevens JC, Beck C et al. Practice parameter: management of dementia (an evidence-based review). Report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2001; 56:1154-66. http://www.ncbi.nlm.nih.gov/pubmed/11342679?dopt=AbstractPlus

130. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.

131. Teva Neuroscience, Inc. Azilect (rasagiline mesylate) tablets prescribing information. Kansas City, MO; 2010 Mar. From DailyMed website. http://dailymed.nlm.nih.gov

133. Eli Lilly and Company. Cymbalta (duloxetine hydrochloride) delayed-release capsules prescribing information. Indianapolis, IN; 2011 Sep.

144. Valeant Pharmaceuticals. Zelapar (selegiline hydrochloride) orally disintegrating tablets prescribing information. Bridgewater. NJ; 2016 Aug.

145. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA. 1985; 254:400-2.

146. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm. 1984; 9:26, 28-30.

147. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201] Fed Regist. 1983; 48:54993-5.

148. Food and Drug Administration.Food additivies permitted for direct addition to food for human consumption; aspartame. Final rule. [21 CFR Part 172] Fed Regist. 1983; 48:31376-82.

149. Anon. Aspartame and other sweeteners. Med Lett Drgus Ther. 1982; 24:1-2.

150. Lew MF, Pahwa R, Leehey M et al. Safety and efficacy of newly formulated selegiline orally disintegrating tablets as an adjunct to levodopa in the management of 'off' episodes in patients with parkinson's disease. Cur Med Res Opin. 2007; 23:741-50.

151. Valeant Pharmaceuticals International, Costa Mesa, CA: Personal communication.

152. Waters CH, Sethi KD, Hauser RA et al. Zydis selegiline reduces off time in parkinsons's disease patients with motor fluctuations: a 3-month, randomized, placebo-controlled study. Mov Disord. 2004; 19:426-32.

153. Food and Drug Administration. Center for Drug Evaluation and Research: Clinical NDA review for Zelapar. From FDA website. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021479s000_MedR_P4.pdf

154. Ondo WG, Sethi KD, Kricorian G. Selegiline orally disintegrating tablets in patients with Parkinson disease and “wearing off” symptoms.Clin Neuropharmacol. 2007; 30:295-300.

155. Poston KL, Waters C. Zydis selegiline in the management of Parkinson's disease. Expert Opin. Pharmacother. 2007; 8:2615-24.

156. Lew MF. Selegiline orally disintegrating tablets for the treatment of Parkinson's disease. Expert Rev. Neurotherapeutics. 2005; 5:705-12.

157. . Drugs for Parkinson's disease. Treat Guidel Med Lett. 2013; 11:101-6. http://www.ncbi.nlm.nih.gov/pubmed/24165688?dopt=AbstractPlus

158. Fernandez HH, Chen JJ. Monoamine oxidase-B inhibition in the treatment of Parkinson's disease. Pharmacotherapy. 2007; 27:174S-185S. http://www.ncbi.nlm.nih.gov/pubmed/18041937?dopt=AbstractPlus

160. Pahwa R, Factor SA, Lyons KE et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006; 66:983-95. http://www.ncbi.nlm.nih.gov/pubmed/16606909?dopt=AbstractPlus

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