Usage
Selegiline is prescribed for the management of symptoms associated with Parkinson’s disease, a progressive nervous system disorder affecting movement. It is also used as an adjunct to levodopa/carbidopa therapy. Selegiline falls under the pharmacological classifications of antiparkinson agent and monoamine oxidase B (MAO-B) inhibitor. It works by selectively and irreversibly inhibiting MAO-B, an enzyme that breaks down dopamine in the brain. This action increases dopamine levels, which helps improve motor control and reduce Parkinsonian symptoms. At higher doses, selegiline loses its selectivity and also inhibits MAO-A.
Alternate Names
Selegiline is also known as selegiline hydrochloride and L-deprenyl. Brand names include Eldepryl®, Zelapar®, Emsam®, and Atapryl®.
How It Works
Pharmacodynamics: Selegiline primarily enhances dopaminergic neurotransmission by inhibiting MAO-B, thus increasing dopamine concentrations in the neuronal synapse. At higher doses, MAO-A inhibition also occurs, affecting other neurotransmitters like serotonin and norepinephrine, potentially increasing the risk of serotonin syndrome and hypertensive crisis.
Pharmacokinetics:
- Absorption: Selegiline is well-absorbed orally. The transdermal patch provides continuous delivery, bypassing first-pass metabolism. The orally disintegrating tablet has rapid absorption.
- Metabolism: Hepatic metabolism primarily via CYP2B6 with minor contributions from other CYP enzymes. Metabolites include desmethylselegiline, amphetamine, and methamphetamine.
- Elimination: Renal excretion of metabolites.
Mode of Action: Selegiline binds irreversibly to MAO-B, preventing it from metabolizing dopamine. This results in increased dopamine availability at the synapse, improving dopaminergic signaling.
Elimination Pathways: Primarily hepatic metabolism followed by renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Conventional Tablets/Capsules: 5 mg twice daily, taken at breakfast and lunch. The maximum daily dose is 10 mg.
- Orally Disintegrating Tablets (Zelapar®): Initially 1.25 mg once daily in the morning without liquid. The dose may be increased to 2.5 mg/day after 6 weeks if inadequate response. No food or drink 5 minutes before and after administration.
- Transdermal Patch (Emsam®): Initial dose is 6 mg/24 hours. The dose can be increased in increments of 3 mg/24 hours every 2 weeks, up to a maximum of 12 mg/24 hours, based on clinical response.
Children:
Selegiline is generally not recommended for children under 12 years of age. For older children, dosing should be determined by a physician on a case-by-case basis.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., 5 mg/day) and titrate up based on response and tolerability.
- Patients with Renal Impairment: For severe renal impairment (CrCl <30 ml/min), the orally disintegrating tablet is not recommended. Caution should be exercised with other formulations.
- Patients with Hepatic Dysfunction: For severe hepatic impairment (Child-Pugh C), the orally disintegrating tablet is not recommended. Caution should be exercised with other formulations.
- Patients with Comorbid Conditions: Close monitoring is required in patients with cardiovascular disease, depression, or other psychiatric disorders.
Clinical Use Cases
Selegiline is not typically indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is primarily used for chronic management of Parkinson’s disease.
Dosage Adjustments
Dose adjustments may be necessary based on patient-specific factors, such as renal or hepatic impairment, comorbid conditions, and concomitant medications.
Side Effects
Common Side Effects:
Nausea, dizziness, lightheadedness, fainting, stomach pain, dry mouth, insomnia, vivid dreams, headache, and hallucinations.
Rare but Serious Side Effects:
Severe allergic reactions (anaphylaxis), hypertensive crisis (especially with tyramine-rich foods), serotonin syndrome (with serotonergic drugs), orthostatic hypotension, arrhythmias, sudden sleep episodes, mental status changes, dyskinesia, extrapyramidal symptoms (muscle spasms, rigidity, tremor).
Long-Term Effects:
Potential long-term effects include impulse control disorders (e.g., gambling, compulsive shopping, hypersexuality) and the development of motor complications (dyskinesia) in Parkinson’s disease patients.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include serotonin syndrome, hypertensive crisis, neuroleptic malignant syndrome (rare), and severe allergic reactions.
Contraindications
- Hypersensitivity to selegiline.
- Concomitant use with meperidine and other opioids.
- Concomitant use of MAO inhibitors (e.g., phenelzine, isocarboxazid, tranylcypromine, linezolid).
- Within 14 days of discontinuing MAO inhibitors, TCAs, or SSRIs.
- Pheochromocytoma.
- Concomitant use with dextromethorphan, cyclobenzaprine, or St. John’s wort.
Drug Interactions
Selegiline interacts with numerous medications, including:
- MAO Inhibitors: Increased risk of hypertensive crisis and serotonin syndrome.
- Opioids (especially meperidine): Increased risk of serotonin syndrome and other serious adverse effects.
- Tricyclic Antidepressants (TCAs) and Selective Serotonin Reuptake Inhibitors (SSRIs): Increased risk of serotonin syndrome.
- Sympathomimetics: Enhanced sympathomimetic effects, potentially leading to hypertension and other cardiovascular effects.
- Tyramine-rich foods: Risk of hypertensive crisis.
- CYP2B6 inhibitors and inducers: May affect selegiline metabolism.
Pregnancy and Breastfeeding
- Pregnancy: Insufficient data to determine risk. Animal studies show developmental toxicity at high doses. Use only if potential benefit outweighs risk.
- Breastfeeding: Selegiline is present in animal milk. It is unknown whether it passes into human milk. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended while using selegiline.
Drug Profile Summary
- Mechanism of Action: Selective MAO-B inhibitor, increasing dopamine levels in the brain. At higher doses, also inhibits MAO-A.
- Side Effects: Nausea, dizziness, insomnia, hallucinations, orthostatic hypotension, hypertensive crisis, serotonin syndrome.
- Contraindications: Hypersensitivity, concomitant use with MAOIs, meperidine, TCAs, SSRIs, and other serotonergic drugs.
- Drug Interactions: Numerous drug interactions, including with MAOIs, opioids, antidepressants, sympathomimetics.
- Pregnancy & Breastfeeding: Insufficient data for pregnancy. Breastfeeding not recommended.
- Dosage: Varies by formulation; see detailed dosage guidelines above.
- Monitoring Parameters: Blood pressure, Parkinsonian symptoms, signs of serotonin syndrome, psychiatric status.
Popular Combinations
Selegiline is often used in combination with levodopa/carbidopa to manage Parkinson’s disease symptoms. This combination can improve motor control and reduce the required dose of levodopa, potentially minimizing levodopa-related side effects.
Precautions
- Evaluate for potential drug interactions.
- Monitor blood pressure and psychiatric status.
- Advise patients about dietary restrictions (tyramine).
- Educate patients about the risk of impulse control disorders.
- Caution in elderly patients and those with renal or hepatic impairment.
- Assess for history of depression and suicidal ideation.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Selegiline?
A: The dosage depends on the formulation and the patient’s condition. See the detailed dosage section above.
Q2: What are the most serious side effects of Selegiline?
A: Hypertensive crisis (especially with tyramine-rich foods), serotonin syndrome (with serotonergic drugs), and severe allergic reactions.
Q3: Can Selegiline be used with other MAO inhibitors?
A: No, concomitant use with other MAO inhibitors is contraindicated due to the risk of hypertensive crisis and serotonin syndrome.
Q4: What foods should be avoided while taking Selegiline?
A: Tyramine-rich foods, such as aged cheeses, cured meats, sauerkraut, and tap beer, should be avoided, especially with higher doses of selegiline, due to the risk of hypertensive crisis.
Q5: Can Selegiline be used during pregnancy?
A: There is insufficient data to determine the safety of selegiline during pregnancy. Animal studies show developmental toxicity at high doses. Use only if the potential benefit outweighs the risk.
Q6: Can Selegiline be used while breastfeeding?
A: Breastfeeding is generally not recommended while using selegiline.
Q7: How does Selegiline interact with antidepressants?
A: Concomitant use with TCAs and SSRIs increases the risk of serotonin syndrome.
Q8: What are the common side effects of Selegiline?
A: Nausea, dizziness, lightheadedness, dry mouth, insomnia, vivid dreams, headache, and hallucinations.
Q9: How does Selegiline work in Parkinson’s disease?
A: It blocks the enzyme MAO-B, increasing dopamine levels in the brain, which helps improve motor control and reduce Parkinsonian symptoms.
Q10: Does Selegiline have any drug interactions with over-the-counter medications?
A: Yes, selegiline can interact with some over-the-counter medications, including decongestants containing sympathomimetics, which could exacerbate cardiovascular effects. Always review a patient’s medication list, including OTC drugs and supplements, before prescribing selegiline.
