Section 03 · Monograph

Selegiline

Reviewed Nov 2026FDA label

Eldepryl / ZelaparMAO-B inhibitor

Indications

Adjunctive treatment in Parkinson's disease patients managed with levodopa/carbidopa who exhibit deterioration in the quality of their therapeutic response (Eldepryl oral capsules; Zelapar orally disintegrating tablets)FDA-labeled
Not shown to be effective as monotherapy without concurrent levodopa/carbidopaFDA-labeled

Irreversible inhibitor of monoamine oxidase type B (MAO-B), the enzyme predominantly responsible for dopamine catabolism in the brain
MAO-B inhibition reduces breakdown of dopamine, increasing dopaminergic activity and potentiating the effect of levodopa
At recommended clinical doses, selectivity for MAO-B (versus MAO-A) is preserved, which limits (but does not eliminate) the tyramine ('cheese reaction') pressor response seen with non-selective MAOIs
Selectivity for MAO-B is lost at higher doses, converting selegiline into a non-selective MAO inhibitor

Eldepryl (oral capsule/tablet): 5 mg twice daily (with breakfast and lunch), total 10 mg/day; doses above 10 mg/day increase risk of non-selective MAO inhibition
Zelapar (orally disintegrating tablet): start 1.25 mg once daily in the morning for at least 6 weeks; may increase to 2.5 mg once daily if inadequate response; maximum 2.5 mg/day
Zelapar administration: place on top of tongue in the morning before eating/drinking; avoid food or liquids for 5 minutes before and after dosing; do not attempt to push the tablet through the foil blister
Doses exceeding the recommended maximum lose MAO-B selectivity and inhibit MAO-A as well, increasing risk of tyramine-related hypertensive reactions

Hepatic impairment (Zelapar): mild-to-moderate — reduce to 1.25 mg daily; severe (Child-Pugh >9) — not recommended

Concomitant use with meperidine or related opioid analgesics (tramadol, methadone, propoxyphene) — risk of serious, potentially fatal serotonin syndrome; allow at least 14 days between discontinuation of selegiline and initiation of these agents
Concomitant or recent use of other MAO inhibitors (selective or non-selective) — risk of hypertensive crisis
Concomitant use with dextromethorphan — risk of psychosis or bizarre behavior
Concomitant use with St. John's Wort or cyclobenzaprine
Concomitant use with antidepressants (SSRIs, SNRIs, tricyclics, tetracyclics) without an adequate washout period — risk of serotonin syndrome

Meperidine and related opioids (tramadol, methadone, propoxyphene): contraindicated — serious/fatal serotonin syndrome; requires 14-day washout
Other antidepressants (SSRIs, SNRIs, tricyclics, tetracyclics, triazolopyridines): risk of serious, potentially fatal serotonin syndrome; avoid combination — allow at least 14 days washout (at least 5 weeks after fluoxetine given its long half-life)
Other MAO inhibitors: contraindicated concurrently or within 14 days — risk of hypertensive crisis
Dextromethorphan: contraindicated — risk of psychosis/bizarre behavior
St. John's Wort and cyclobenzaprine: contraindicated
Sympathomimetic agents (e.g., ephedrine, pseudoephedrine, decongestants): risk of hypertensive reactions
Dietary tyramine: at the recommended selegiline dose, dietary tyramine restriction is generally NOT required, distinguishing it from non-selective MAOIs; however, hypertensive reactions have been reported in some patients ingesting very high-tyramine foods (e.g., aged cheese), and risk increases substantially if the recommended dose is exceeded
Strong CYP3A4/CYP2B6 inducers (phenytoin, carbamazepine, rifampin): may reduce selegiline exposure; use with caution given limited data
Dopamine antagonists (antipsychotics, metoclopramide): may reduce antiparkinsonian efficacy

Nausea, dizziness, constipation, dyskinesia, insomnia, dyspepsia, vomiting, myalgia, rash
Buccal/oropharyngeal mucosal irritation (Zelapar, due to oral disintegrating formulation)
Orthostatic hypotension, more pronounced in elderly patients
Sudden onset of sleep during daily activities, including driving, reported up to a year after treatment initiation
Hallucinations and new or worsening psychotic behavior
Impulse control disorders: pathological gambling, hypersexuality, compulsive spending, binge eating
Hypertension, particularly with doses above the recommended maximum or with serotonergic/sympathomimetic co-administration
Serotonin syndrome (confusion, agitation, hallucinations, autonomic instability, hyperthermia, rigidity, hyperreflexia) with contraindicated combinations
Withdrawal-emergent hyperpyrexia and confusion resembling neuroleptic malignant syndrome with abrupt discontinuation
Increased melanoma risk reported in Parkinson's disease populations generally (not selegiline-specific)

Blood pressure, especially at initiation, dose escalation, and if dietary/drug tyramine exposure is significant or dose exceeds recommended maximum
Orthostatic vital signs, particularly in elderly patients
Mental status and behavior for hallucinations, psychosis, or impulse control symptoms
Daytime somnolence and sudden sleep episodes; counsel regarding driving/hazardous activities
Medication reconciliation to avoid contraindicated opioid, antidepressant, or other MAOI combinations
Buccal mucosa integrity with Zelapar formulation
Hepatic and renal function as clinically indicated
Routine dermatologic skin examinations

Pregnancy: No adequate, well-controlled human studies; animal studies showed developmental toxicity (decreased fetal/postnatal growth and survival) at doses exceeding clinical exposure — use only if potential benefit justifies potential risk to the fetus
Lactation: Selegiline and metabolites are excreted into rat milk at concentrations exceeding maternal plasma; unknown whether excreted into human milk — caution advised and a risk-benefit assessment should be made before breastfeeding