selegiline transdermal (Rx)

>10%

Application site reaction (24%)

1-10%

Hypotension (3-10%)

Diarrhea (9%)

Xerostomia (8%)

Weight loss (5%)

Dyspepsia (4%)

Rash (4%)

Pharyngitis (3%)

Sinusitis (3%)

Contraindications

Hypersensitivity

Concurrency with SSRIs, SNRIs, TCAs, bupropion, meperidine, analgesic agents, dextromethorphan, tramadol, methadone, St. John's wort, mirtazapine, cyclobenzaprine, oral selegiline, other MAOIs, sympathomimetic amines, propoxyphene, cold products, weight-reducing preparations that contain vasoconstrictors, carbamazepine, oxcabazapine, and food supplements containing tyrosine, phenylalanine, tryptophan, or caffeine

<12 years of age

Beginning therapy with contraindicated drug < 2 weeks after stopping transdermal selegiline

General anesthesia

Pheochromocytoma

Cautions

Dietary modifications required for patients using 9 mg/24 hr & 12 mg/24 hr patch

Clinical worsening & suicide ideation may occur despite medication in adolescents & young adults (18-24 years)

Compulsive behavior may occur in patients prescribed dopaminergic agents

Orthostatic hypotension may occur with transdermal product

Use caution in hepatic and renal impairment (safety and efficacy not established)

Avoid exposing selegiline transdermal application site to external sources of direct heat (ie, heating pads, electric blankets, heat lamps, saunas, hot tubs, heated water bed, and prolonged direct sunlight)

Use caution in patients with history of mania; activation of mania/hypomania may occur

Monitor blood pressure when used concomitantly with the drugs buspirone, buspirone, amphetamines, or cold products or weight-reducing preparations that contain sympathomimetic amines (e.g., pseudoephedrine, phenylephrine, phenylpropanolamine, and ephedrine)

Development of a potentially life-threatening serotonin syndrome reported with concomitant use of MAOIs with serotonergic drugs; monitor and discontinue therapy if symptoms occur

Selegiline inhibits catabolism of dietary amines, such as tyramine, and has the potential to produce hypertensive crisis following ingestion oftyramine-rich foods or beverages; discontinue therapy if symptoms occur

Pregnancy Category: C

Lactation: unknown; use caution

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Irreversible selective MAO-B inhibitor. The inhibitor causes a decrease in the metabolism of dopamine; selegiline may also increase dopaminergic activity by inhibiting dopamine reuptake at the synapse; transdermal administration can attain higher selegiline blood levels and can effectively inhibit both MAO-A and MAO-B, which in turn blocks catabolism of other centrally active amine neurotransmitters

Pharmacokinetics

Absorption: 25-30%

Distribution: rapid to all body tissues

Protein Bound: 90%

Metabolism: CYP2B6, CYP3A4, CYP2A6, CYP1A2, CYP2C8, CYP2D6

Excretion: Urine (10%), feces (2%)