Selegiline: Medication Information and Guidelines

Medication Information and Guidelines

Selegiline, also known as L-deprenyl, is a medication primarily used in the treatment of Parkinson’s disease and depression. It belongs to a class of drugs known as monoamine oxidase inhibitors (MAOIs) and works by increasing the levels of certain neurotransmitters in the brain, such as dopamine, norepinephrine, and serotonin. Selegiline is available in various formulations, including oral tablets and transdermal patches.

Recommended Dose and Dosage Regimen

The recommended dose of selegiline varies depending on the indication, patient response, and concomitant medications. For the treatment of Parkinson’s disease, the typical starting dose of oral selegiline is 5 mg taken orally once daily in the morning. The dosage may be gradually increased over time under medical supervision to a maximum of 10 mg per day, divided into two or three doses. For depression, lower doses of selegiline may be used, typically ranging from 5 to 10 mg taken orally once daily.

Frequency of Administration

Selegiline is usually administered once daily in the morning, with or without food, to minimize the risk of insomnia or sleep disturbances associated with its stimulant effects. In some cases, particularly in the treatment of depression, selegiline may be administered in divided doses throughout the day to maintain steady blood levels and optimize therapeutic effects. The transdermal patch formulation of selegiline is applied once daily to clean, dry skin on the upper torso or upper thigh and left in place for 24 hours.

Route of Administration

Selegiline is available for oral administration as tablets and orally disintegrating tablets, as well as in transdermal patch formulations. Oral selegiline is absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism in the liver, resulting in low systemic bioavailability. The transdermal patch delivers selegiline through the skin, bypassing the gastrointestinal tract and liver, and providing more consistent blood levels with reduced risk of gastrointestinal side effects.

Mechanism of Action (MOA)

Selegiline exerts its pharmacological effects primarily by inhibiting the activity of monoamine oxidase type B (MAO-B), an enzyme responsible for the breakdown of dopamine in the brain. By inhibiting MAO-B, selegiline increases the levels of dopamine and other neurotransmitters in the synaptic cleft, enhancing neurotransmission and alleviating symptoms of Parkinson’s disease and depression. Selegiline also has neuroprotective effects and may slow the progression of Parkinson’s disease by reducing oxidative stress and apoptosis in dopaminergic neurons.

Pharmacokinetics (PK)

After oral administration, selegiline is rapidly absorbed from the gastrointestinal tract and undergoes extensive first-pass metabolism in the liver to form metabolites such as L-amphetamine and L-methamphetamine, which contribute to its pharmacological effects. The transdermal patch formulation delivers selegiline through the skin, allowing for more consistent blood levels and reduced variability compared to oral administration. Selegiline and its metabolites are primarily excreted in the urine, with a half-life ranging from 1 to 3 hours for the parent compound and up to 10 hours for metabolites.

Pharmacodynamics (PD)

The pharmacodynamics of selegiline involve its ability to increase the levels of dopamine, norepinephrine, and serotonin in the brain by inhibiting MAO-B activity. By enhancing neurotransmission, selegiline helps to alleviate motor symptoms of Parkinson’s disease such as bradykinesia, rigidity, and tremor, as well as depressive symptoms such as low mood, anhedonia, and fatigue. Selegiline may also have neuroprotective effects by reducing oxidative stress, apoptosis, and inflammation in the brain, which could potentially slow the progression of neurodegenerative disorders.

Primary Indications

1. Parkinson’s Disease: Selegiline is indicated for the treatment of Parkinson’s disease as monotherapy or as adjunctive therapy in combination with levodopa/carbidopa or dopamine agonists. It helps to alleviate motor symptoms of Parkinson’s disease and may reduce the need for levodopa and delay the onset of motor complications such as dyskinesias and motor fluctuations.
2. Depression: Selegiline is used off-label for the treatment of depression, particularly in patients who have not responded to or cannot tolerate other antidepressant medications. It may be used as monotherapy or as adjunctive therapy in combination with selective serotonin reuptake inhibitors (SSRIs) or tricyclic antidepressants (TCAs) to augment antidepressant effects and improve treatment outcomes.

Contraindications

Contraindications to selegiline use include hypersensitivity to selegiline or any component of the formulation, concomitant use of other MAO inhibitors, and the use of meperidine or other opioids with serotonergic properties due to the risk of serotonin syndrome. Selegiline should be used with caution in patients with cardiovascular disease, hypertension, severe hepatic or renal impairment, or a history of psychosis or bipolar disorder, as it may exacerbate these conditions.

Purpose of Taking Medication

The purpose of selegiline therapy is to alleviate symptoms of Parkinson’s disease and depression by increasing the levels of neurotransmitters such as dopamine, norepinephrine, and serotonin in the brain. Selegiline helps to improve motor function, reduce motor fluctuations, and enhance mood and cognition in patients with Parkinson’s disease and depression, thereby improving quality of life and functional outcomes.

Usage Instructions

For oral administration, selegiline tablets should be taken once daily in the morning with or without food, as directed by a healthcare provider. The orally disintegrating tablet formulation may be taken without water and allowed to dissolve on the tongue. For transdermal administration, the selegiline patch should be applied to clean, dry skin on the upper torso or upper thigh once daily and left in place for 24 hours. The patch should not be cut or folded and should be rotated to different application sites to minimize skin irritation.

Precautions and Care

Patients receiving selegiline therapy should be monitored for changes in mood, behavior, and motor function, particularly during dose titration and treatment initiation. Selegiline may potentiate the effects of other dopaminergic medications and increase the risk of serotonin syndrome when used concomitantly with serotonergic agents. Patients should be advised to report any new or worsening symptoms to their healthcare provider promptly.

Dietary Considerations

Dietary restrictions are necessary when taking selegiline due to its interaction with tyramine-containing foods, which can lead to hypertensive crisis or serotonin syndrome. Patients should avoid consuming foods rich in tyramine, such as aged cheeses, cured meats, fermented or pickled foods, and certain beverages (e.g., wine, beer, tap beer). Additionally, patients should be cautious when taking over-the-counter medications, herbal supplements, or dietary supplements that may interact with selegiline.

Possible Side Effects

Common side effects of selegiline may include insomnia, nausea, dry mouth, dizziness, headache, dyskinesias, or agitation. These side effects are usually mild and transient and may improve with continued use or dose adjustment. Rare but serious adverse reactions may include hypertensive crisis, serotonin syndrome, hallucinations, confusion, or orthostatic hypotension. Patients should be advised to seek medical attention if they experience severe or persistent side effects while taking selegiline.

Storage and Disposal

Selegiline tablets or patches should be stored at room temperature away from heat, light, and moisture, and kept out of reach of children and pets. Unused or expired medication should be discarded properly according to local regulations or guidelines for pharmaceutical waste disposal. Patients should not use selegiline beyond the expiration date printed on the packaging, and any unused portions should be disposed of appropriately.

Overdose or Emergency

In case of selegiline overdose or emergency, seek immediate medical attention or contact a poison control center. Overdose may lead to excessive dopaminergic stimulation, hypertensive crisis, serotonin syndrome, or other adverse effects. Treatment of selegiline overdose may involve supportive care to alleviate symptoms, monitoring of vital signs and neurological status, and administration of antidotes or symptomatic treatments as necessary. Healthcare providers should be prepared to manage complications associated with selegiline toxicity or overdose.

Important Note: Always consult with a healthcare professional for personalized medical advice and guidance regarding the use of given drug, especially regarding dosing, administration, and potential side effects. Your healthcare provider can provide tailored recommendations based on your individual medical history, current medications, and specific treatment needs. Never self-adjust your given drug regimen or discontinue treatment without first consulting your healthcare provider. If you have any questions or concerns about given drug or its use, talk to your doctor or pharmacist for further information and assistance.