Eldepryl

Eldepryl (selegiline hydrochloride) represents a cornerstone in the adjunctive treatment of Parkinson’s disease, offering a targeted mechanism to enhance dopaminergic activity within the central nervous system. As a selective monoamine oxidase-B (MAO-B) inhibitor, it is specifically designed to delay the need for levodopa therapy in newly diagnosed patients and, when combined with levodopa, to reduce the required dosage and mitigate the motor fluctuations associated with long-term treatment. Its well-established efficacy profile and neuroprotective potential make it a critical component in the neurologist’s arsenal for optimizing functional outcomes and quality of life. This expert review details the pharmacological characteristics, clinical applications, and essential safety information surrounding this specialized therapeutic agent.

Features

• Active Ingredient: Selegiline hydrochloride
• Pharmacological Class: Selective, irreversible monoamine oxidase-B (MAO-B) inhibitor
• Available Formulations: 5 mg oral tablets and capsules
• Mechanism of Action: Inhibits the breakdown of dopamine in the brain by blocking MAO-B enzyme activity
• Bioavailability: Rapidly absorbed orally, with extensive first-pass metabolism
• Half-life: Approximately 10 hours for selegiline; active metabolites (amphetamine, methamphetamine) have longer half-lives
• Dosing Flexibility: Can be administered as a single daily dose or divided doses, typically with breakfast and lunch

Benefits

• Prolongs Dopaminergic Activity: By inhibiting dopamine metabolism, it effectively increases and sustains synaptic dopamine levels, enhancing motor control.
• Delays Levodopa Initiation: Monotherapy in early Parkinson’s disease can postpone the need for levodopa by several months, potentially delaying associated complications.
• Reduces ‘Off’ Time: As an adjunct to levodopa, it decreases the duration and severity of off periods, providing more consistent symptom control throughout the day.
• Permits Lower Levodopa Doses: Allows for reduction of levodopa dosage by approximately 10-30%, potentially minimizing dose-dependent adverse effects like dyskinesias.
• Potential Neuroprotective Effects: Theoretical capacity to reduce oxidative stress and neuronal damage through diminished formation of toxic dopamine metabolites.
• Simplified Dosing Regimen: Once or twice-daily dosing supports medication adherence and patient convenience.

Common use

Eldepryl is primarily indicated for the treatment of Parkinson’s disease, both as monotherapy in the early stages of the condition and as adjunctive therapy with levodopa/carbidopa in more advanced cases. In monotherapy, it is particularly valuable for newly diagnosed patients who exhibit mild symptoms, where it can provide symptomatic relief while potentially modifying disease progression. As an adjunct, it is most commonly prescribed when patients begin to experience motor fluctuations (“wearing-off” phenomena) despite optimized levodopa regimens. Off-label, it has been investigated for cognitive enhancement in dementia and as an adjunct in major depressive disorder, though these uses lack formal FDA approval and require careful specialist supervision.

Dosage and direction

For monotherapy in Parkinson’s disease, the recommended initial dosage is 5 mg administered orally twice daily, with breakfast and lunch. The maximum daily dose should not exceed 10 mg. When used as adjunctive therapy with levodopa/carbidopa, the initial dose is typically 5 mg twice daily. After 2-3 days of treatment, a gradual reduction of the levodopa dose (by approximately 10-30%) may be attempted to optimize therapeutic effect while minimizing adverse reactions. Administration with meals may reduce the risk of gastrointestinal upset. Doses should not be taken in the evening or late afternoon due to the potential for insomnia and other stimulant-like effects from metabolites. Dosage adjustments in renal or hepatic impairment have not been systematically studied, but caution is advised.

Precautions

Patients should be carefully monitored for the development of hypertension, particularly during initial dose titration. Orthostatic hypotension may occur, requiring caution when rising from sitting or lying positions. Due to its metabolic conversion to amphetamine-like compounds, Eldepryl may cause CNS stimulation including insomnia, anxiety, agitation, or hallucinations—particularly in elderly patients or those with pre-existing psychiatric conditions. Regular assessment for signs of impulse control disorders (e.g., pathological gambling, hypersexuality) is recommended. Use with extreme caution in patients with cardiovascular disease, history of peptic ulcer, or epilepsy. Periodic liver function tests may be advisable during prolonged therapy. Patients should be advised that effects may be potentiated by alcohol consumption.

Contraindications

Eldepryl is contraindicated in patients with known hypersensitivity to selegiline or any component of the formulation. Concomitant use with meperidine is absolutely contraindicated due to risk of serotonin syndrome and severe hypertensive reactions. Concurrent administration with other MAO inhibitors (including linezolid and intravenous methylene blue) is contraindicated. Should not be used with sympathomimetic amines (including amphetamines, cold remedies containing decongestants), tryptophan, or St. John’s wort. Contraindicated in patients with pheochromocytoma due to risk of hypertensive crisis. Not recommended in patients with severe hepatic impairment or active peptic ulcer disease.

Possible side effect

• Common (>10%): Nausea, dizziness, dry mouth, insomnia, abdominal pain
• Less common (1-10%): Orthostatic hypotension, confusion, hallucinations, vivid dreams, arrhythmias, diaphoresis, rash, constipation
• Rare (<1%): Hypertensive crisis (particularly with tyramine-containing foods or contraindicated medications), serotonin syndrome, angina pectoris, peripheral edema, alopecia, leukopenia
• Behavioral effects: Impulse control disorders, agitation, anxiety, mood changes
• Motor effects: Increased dyskinesias when used with levodopa, dystonia

Drug interaction

Eldepryl exhibits significant pharmacokinetic and pharmacodynamic interactions. Most critically, concomitant use with serotonergic agents (SSRIs, SNRIs, tricyclic antidepressants, tramadol, tapentadol) dramatically increases risk of serotonin syndrome—a minimum 5-week washout period is required after discontinuing Eldepryl before initiating these agents. Sympathomimetics (including decongestants like pseudoephedrine) may precipitate hypertensive crisis. Opioids, particularly meperidine, are contraindicated. Concurrent use with other MAO inhibitors is prohibited. Tyramine-rich foods (aged cheeses, cured meats, fermented products) may cause hypertensive reactions, though the risk is lower with selective MAO-B inhibitors than non-selective MAOIs. Dose adjustments of levodopa are typically required when adding Eldepryl. May potentiate effects of CNS depressants including alcohol.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is closer to the time of the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed administration. Particular caution should be exercised with evening doses due to the potential for insomnia; if a midday dose is missed, it should not be taken after 4 PM. Consistent daily administration is important for maintaining stable dopamine levels, so patients should be counseled on adherence strategies.

Overdose

Symptoms of overdose may include severe hypertension, tachycardia, agitation, hallucinations, hyperpyrexia, dilated pupils, tremors, seizures, and coma. Serotonin syndrome manifestations (autonomic instability, neuromuscular abnormalities, mental status changes) may be present, particularly if taken with other serotonergic agents. Hypertensive crisis may lead to intracranial bleeding. Treatment is primarily supportive and symptomatic: activated charcoal may be considered if presented early; benzodiazepines for agitation or seizures; aggressive cooling measures for hyperthermia. Severe hypertension should be managed with carefully titrated short-acting antihypertensives (e.g., nitroprusside, phentolamine). Avoid beta-blockers which may paradoxically worsen hypertension due to unopposed alpha-adrenergic stimulation. Dialysis is not effective due to high protein binding and extensive tissue distribution.

Storage

Store at controlled room temperature (20-25°C or 68-77°F), with excursions permitted between 15-30°C (59-86°F). Keep in the original container with the lid tightly closed to protect from moisture and light. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Do not transfer tablets to other containers that may not provide adequate protection from environmental factors. Discard any medication that shows signs of discoloration, crumbling, or other physical deterioration.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Individual patient responses to medication may vary. Treatment decisions should be made exclusively by qualified healthcare professionals based on comprehensive assessment of the individual patient’s condition, medical history, and concurrent medications. The prescriber should reference the full prescribing information for complete details on indications, dosing, warnings, and precautions. Patients should not initiate, adjust, or discontinue medication without direct medical supervision.

Reviews

“Eldepryl has been transformative in my Parkinson’s management. Adding it to my levodopa regimen reduced my ‘off’ time by approximately two hours daily, providing more consistent mobility throughout the day. The twice-daily dosing is manageable, though I did experience some initial insomnia that resolved with morning and midday dosing.” — M.H., diagnosed 2016

“As a movement disorder specialist, I find Eldepryl invaluable for patients experiencing motor fluctuations. Its MAO-B selectivity offers a favorable risk profile compared to non-selective inhibitors, though careful patient education about drug and food interactions remains essential. Approximately 60-70% of my patients on adjunctive therapy experience meaningful reduction in off periods.” — Dr. A. Reynolds, Neurologist

“The transition to including Eldepryl was challenging initially due to increased dyskinesias, but after careful levodopa dose reduction, the benefits became apparent. I appreciate the potential neuroprotective aspects, though I understand this remains theoretical. The requirement to avoid certain medications requires vigilance but is manageable with proper guidance.” — T.S., patient since 2019