SELEGILINE

brands

Class

• Neuroscience-based Nomenclature: dopamine, serotonin, norepinephrine enzyme inhibitor
• Transdermal: tissue selective monoamine oxidase (MAO) inhibitor (MAO-A and MAO-B inhibitor in brain and relatively selective MAO-B inhibitor in gut)
• Oral: selective MAO-B inhibitor

SELEGILINE commonly prescribed for

(Bold for FDA approved)

How SELEGILINE works

• Transdermal selegiline (recommended doses): in the brain, irreversibly inhibits both MAO-A and MAO-B from breaking down norepinephrine, serotonin, and dopamine, which boosts noradrenergic, serotonergic, and dopaminergic neurotransmission

• Transdermal selegiline (recommended doses): in the gut, is a relatively selective irreversible inhibitor of MAO-B (intestine and liver), reducing the chances of dietary interactions

• Oral: at recommended doses, selectively and irreversibly blocks MAO-B, which presumably boosts dopaminergic neurotransmission

• Oral: above recommended doses, irreversibly blocks both MAO-A and MAO-B from breaking down norepinephrine, serotonin, and dopamine while simultaneously blocking metabolism of tyramine in the gut

• Thus, high-dose oral administration is not tissue selective and is not MAO-A sparing in the gut, and may interact with tyramine- containing foods to cause hypertension

How long until SELEGILINE works

• Onset of therapeutic actions in depression with transdermal administration is usually not immediate, but often delayed 2–4 weeks or longer following adequate dosing

• If it is not working for depression within 6–8 weeks, it may require a dosage increase or it may not work at all

• May continue to work in depression for many years to prevent relapse of symptoms

• Can enhance the actions of levodopa in Parkinson’s disease within a few weeks of initiating oral dosing

• Theoretical slowing of functional loss in both Parkinson’s disease and Alzheimer disease is a provocative possibility under investigation and would take many months or more than a year to observe

Notable Side Effects

• Transdermal: application-site reactions, headache, insomnia, diarrhea, dry mouth

• Oral: exacerbation of levodopa side effects, especially nausea, dizziness, abdominal pain, dry mouth, headache, dyskinesia, confusion, hallucinations, vivid dreams

Life Threatening Side Effects

• Transdermal: hypertensive crisis was not observed with preliminary experience in clinical trials, even in patients who were not following a low-tyramine diet

• Oral: hypertensive crisis (especially when MAOIs are used with certain tryaminecontaining foods or prohibited drugs) – reduced risk at low oral doses compared to nonselective MAOIs

• Theoretically, when used at high doses may induce seizures and mania as do nonselective MAOIs

weight gain

unusual

sedation

unusual

What to do about SELEGILINE side effects

• Wait

• Wait

• Wait

• Lower the dose

• Switch after appropriate washout to an SSRI or newer antidepressant (depression)

• Switch to other antiparkinsonian therapies (Parkinson’s disease)

usual dosage range

• Depression (transdermal): 6 mg/24 hours– 12 mg/24 hours

• Depression (oral): 30–60 mg/day

• Parkinson’s disease/Alzheimer disease: 5–10 mg/day

Dosage Forms

• Transdermal patch 20 mg/20 cm2 (6 mg/24 hours), 30 mg/30 cm2 (9 mg/24 hours), 40 mg/40cm2 (12 mg/24 hours)

• Capsule 5 mg

• Tablet 5 mg scored

• Orally disintegrating tablet 1.25 mg

long term use

• Long-term use has not been systematically studied although generally recommended for chronic use as for other antidepressants

habit forming

• Lack of evidence for abuse potential with transdermal selegiline despite its metabolism to l-amphetamine and l-methamphetamine

• Dependence to other MAOIs reported but rare

Renal Impairment

• No dose adjustment necessary for transdermal administration in patients with mild to moderate renal impairment

• Use oral administration with caution – drug may accumulate in plasma in patients with renal impairment

• Oral administration may require lower than usual adult dose

Hepatic Impairment

• No dose adjustment necessary for transdermal administration in patients with mild to moderate hepatic impairment

• Oral administration may require lower than usual adult dose

Cardiac Impairment

• May require lower than usual adult dose

• Observe closely for orthostatic hypotension

Elderly

• Recommended dose for patients over 65 years old is 20 mg oral and 6 mg/day transdermal

• Dose increases in the elderly should be made with caution and patients should be observed for postural changes in blood pressure throughout treatment

• Reduction in the risk of suicidality with antidepressants compared to placebo in adults age 65 and older

Children and Adolescents

• Not recommended for use in children under 18

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Carefully weigh the risks and benefits of pharmacological treatment against the risks and benefits of nontreatment with antidepressants and make sure to document this in the patient’s chart

• Monitor patients face-to-face regularly, particularly during the first several weeks of treatment

Pregnancy

• Effective June 30, 2015, the FDA requires changes to the content and format of pregnancy and lactation information in prescription drug labels, including the elimination of the pregnancy letter categories; the Pregnancy and Lactation Labeling Rule (PLLR or final rule) applies only to prescription drugs and will be phased in gradually for drugs approved on or after June 30, 2001

• Controlled studies have not been conducted in pregnant women

• Not generally recommended for use during pregnancy, especially during first trimester

• Should evaluate patient for treatment with an antidepressant with a better risk/benefit ratio

Breast Feeding

• Some drug is found in mother’s breast milk

• Immediate postpartum period is a highrisk time for depression, especially in women who have had prior depressive episodes, so drug may need to be reinstituted late in the third trimester or shortly after childbirth to prevent a recurrence during the postpartum period

• Should evaluate patient for treatment with an antidepressant with a better risk/benefit ratio