• PO: Parkinson’s disease (with levodopa or levodopa/carbidopa) in patients who fail to respond to levodopa/carbidopa alone (in combination with levodopa or levodopa/carbidopa).
• Transdermal: Major depressive disorder.

Contraindicated in:

• Hypersensitivity
• Pheochromocytoma
• Major psychotic disorder
• Concurrent use of opioids, other MAO inhibitors, St. John's wort, cyclobenzaprine, or dextromethorphan
• Lactation: Lactation.

Use Cautiously in:

• History of peptic ulcer disease
• Phenylketonuria (orally disintegrating tablets only)
• Elective surgery
• May ↑ risk of suicide attempt/ideation, especially during early treatment or dose adjustment (transdermal only)
• History of mania (transdermal only)
• OB: Safety not established in pregnancy
• Pedi: Safety and effectiveness not established in children
• Geri: ↑risk of orthostatic hypotension in older adults.

CV: orthostatic hypotension.

Derm: Transdermal: application site reactions, acne, ecchymoses, pruritus, sweating.

GI: nausea, abdominal pain, diarrhea, dry mouth.

Neuro: aggression, agitation, confusion, delirium, delusions, disorientation, dizziness, fainting, hallucinations, headache, insomnia, paranoia, psychosis, sedation, SEROTONIN SYNDROME, urges (gambling, sexual), vivid dreams.

Drug-Drug:

• Use with opioid analgesic (e.g. meperidine) or cyclobenzaprine may ↑ risk of serotonin syndrome; concurrent use contraindicated. Selegiline should be discontinued for 2 wk before initiating any of these medications.
• Use with other MAO inhibitors, including linezolid, may ↑ risk of hypertensive crises; concurrent use contraindicated. Selegiline should be discontinued for 2 wk before initiating any other medication with MAO inhibitor properties.
• Use with products containing dextromethorphan may lead to episodes of psychosis or bizarre behavior; concurrent use contraindicated.
• Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SSRIs, SNRIs, fentanyl, buspirone, amphetamines, and triptans may ↑ risk of serotonin syndrome; avoid concurrent use with any antidepressant. Selegiline should be discontinued for 14 days before initiating any antidepressant. Fluoxetine should be discontinued for 5 wk before initiating selegiline.
• May initially ↑ risk of side effects (primarily dyskinesia) of levodopa/carbidopa (dose of levodopa/carbidopa may need to be ↓ by 10–30%).
• Antipsychotics and metoclopramide may ↓ effectiveness.

Drug-Natural Products:

• Use with St. John's wort may ↑ risk of serotonin syndrome; concurrent use contraindicated.

Drug-Food:

• Doses >10 mg/day (tablets/capsules), >2.5 mg/day (orally disintegrating tablets), or >6 mg/24 hr (transdermal) may produce hypertensive reactions with tyramine-containing foods (see Appendix M).

(Generic available)

• Capsules: 5 mg;
• Tablets: 5 mg;
• Orally disintegrating tablets (contain phenylalanine) (Zelapar) (grapefruit-flavor): 1.25 mg;
• Transdermal patch (Emsam): 6 mg/24 hr; 9 mg/24 hr; 12 mg/24 hr;

Parkinson's Disease

• PO (Adults): Capsules or tablets: 5 mg twice daily with breakfast and lunch (some patients may require further dividing of doses — 2.5 mg 4 times daily). Orally disintegrating tablets: 1.25 mg once daily for 6 wk. After 6 wk, may ↑ to 2.5 mg once daily if effect not achieved and patient is tolerating medication.

Depression

• Transdermal (Adults): Apply 6 mg/24-hr patch once daily initially; if necessary, may be ↑ at 2-wk intervals in increments of 3 mg/24-hr patch (max dose = 12 mg/24 hr).

Eldepryl, Emsam, Zelapar

• Following conversion by MAO to its active form, selegiline inactivates MAO by irreversibly binding to it at type B (brain) sites; results in higher levels of monoamine neurotransmitters in the brain (dopamine, serotonin, norepinephrine).

• Increased response to levodopa/dopamine therapy in Parkinson’s disease.
• Decreased symptoms of depression.

Therapeutic Classification: antiparkinson agents, antidepressants

Pharmacologic Classification: monoamine oxidase type b inhibitors

Absorption: Well absorbed following oral administration. 25–30% of patch content is absorbed; levels are higher than those following oral administration because there is less first-pass hepatic metabolism.

Distribution: Widely distributed to tissues; crosses the blood-brain barrier.

Metabolism/Excretion: Mostly metabolized by the liver, primarily by the CYP2A6, CYP2C9, and CYP3A4/5 isoenzymes to N-desmethylselegiline, amphetamine, and methamphetamine as well as inactive metabolites. Primarily excreted in urine as metabolites.

Half-life: Oral: 10 hr; Transdermal: 20 hr.

(beneficial effects in Parkinson’s disease)

ROUTE	ONSET	PEAK	DURATION
PO	2–3 days†	40–90 min†	unknown
Orally disintegrating	5 min†	10–15 min†	unknown
Transdermal	unknown	2 wk†	unknown

† Beneficial effects in Parkinson’s disease; dhara Antidepressant effects

• Instruct patient to take medication as directed. Take missed doses as soon as possible, but not if late afternoon or evening or almost time for next dose. Do not double doses. Caution patient that taking more than the prescribed dose may increase side effects and place patient at risk for hypertensive crisis if foods containing tyramine are consumed (see Appendix M).
• Advise patients taking selegiline 20 mg/day to avoid large amounts of tyramine-containing foods (see Appendix M), alcoholic beverages, large quantities of caffeine-containing beverages, or OTC or herbal cough or cold medications.
• Caution patient and caregiver that selegiline may cause drowsiness and dizziness. Monitor and assist with ambulation and caution patient to avoid driving and other activities requiring alertness until response to medication is known.
• Inform patient and family of the signs and symptoms of MAO inhibitor–induced hypertensive crisis (severe headache, chest pain, nausea, vomiting, photosensitivity, enlarged pupils). Advise patient to notify health care professional immediately if severe headache or any other unusual symptoms occur. At least 14 days should elapse between discontinuation of selegiline and start of MAO inhibitor therapy.
• Caution patient to change positions slowly to minimize orthostatic hypotension.
• Advise patient to notify health care professional of signs and symptoms of serotonin syndrome (mental status changes [agitation, hallucinations, delirium, and coma], autonomic instability [tachycardia, labile BP, dizziness, diaphoresis, flushing, hyperthermia], neuromuscular changes [tremor, rigidity, myoclonus, hyperreflexia, incoordination], seizures, and/or GI symptoms [nausea, vomiting, diarrhea]).
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications. Caution patient to avoid use of St. John's wort and the analgesics meperidine, tramadol, or methadone during therapy.
• Advise patient to notify health care professional if agitation, aggression, delirium, hallucinations, new or increased gambling, sexual, or other intense urges occur.
• Advise patient that increasing fluids, sugarless gum or candy, ice, or saliva substitutes may help minimize dry mouth. Consult health care professional if dry mouth continues for >2 wk.
• Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected. Advise patient to avoid breastfeeding during and for 7 days after final dose.
• Transdermal: Instruct patient to apply patch as directed. Advise patients and caregivers to read the Medication Guide about Using Antidepressants in Children and Teenagers. Inform patient that improvement may be noticed after 1 to several wk of therapy. Advise patient not to discontinue therapy without consulting health care professional.
• Caution patient to avoid alcohol and CNS depressants during and for at least 2 wk after therapy has been discontinued; they may precipitate a hypertensive crisis. Contact health care professional immediately if symptoms of hypertensive crisis develop. Patients taking 9 mg/24 hr or 12 mg/24 hr must avoid foods or beverages containing tyramine (see Appendix M) from the 1st day of the increased dose through 2 wk after discontinuation of selegiline transdermal therapy.
• Advise patient to avoid exposing application site to external sources of direct heat such as heating pads, electric blankets, heat lamps, saunas, hot tubs, heated water beds, and prolonged direct sunlight.
• Caution patient to change positions slowly to minimize orthostatic hypotension. Geriatric patients are at increased risk for this side effect.
• Advise patient referred for MRI test to discuss patch with referring health care professional and MRI facility to determine if removal of patch is necessary prior to test and for directions for replacing patch.
• Advise patients and caregivers to notify health care professional if severe headache, neck stiffness, heart racing or palpitations, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, mania, change in behavior, worsening of depression, or suicidal ideation occur, especially during initial therapy or during changes in dose.
• Advise patient to notify health care professional of medication regimen before treatment or surgery. If possible, therapy should be discontinued at least 2 wk before surgery.

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