Selegiline is an inhibitor of monamine oxidase used in the treatment of depression and as adjunctive therapy in combination with levodopa and carbidopa in the therapy of Parkinson disease. Selegiline has been associated with a low rate of serum enzyme elevations during treatment, but has not been linked to instances of clinically apparent acute liver injury.
Selegiline (se le' ji leen) is a specific inhibitor of monamine oxidase (MAO) type B, which is a major enzyme in the pathway of dopamine and levodopa metabolism. As a result, selegiline results in an increase in the bioavailability of levodopa, enhancing and increasing the duration of its effects in Parkinson disease. Selegiline is also an antidepressant, its mechanism of action being inhibition of dopamine reuptake from the synaptic cleft. Selegiline was approved for use in the United States in 2006, the first MAO-B inhibitor approved for use in the therapy of Parkinson disease as an adjunct to levodopa therapy. Selegiline is available in capsules and tablets of 5 mg generically and under the brand name Eldepryl, the typical dose being 10 mg daily in two divided doses. It is also available in oral disintegrating tablets of 1.25 mg under the brand name Zelapar, which is given once or twice daily. Transdermal patches of selegiline in amounts of 6, 9 and 12 mg/24 hours are available under the brand name Emsam for treatment of depresssion, the usual dose being 6 to 12 mg daily. Common side effects include headache, nausea, dizziness, agitation, delusions, insomnia, orthostatic hypotension, dry mouth, headache and gastrointestinal upset – most of which are attributable to enhanced dopaminergic effects. In higher doses, selegiline can also inhibit MAO-A and, similar to the nonspecific MAO inhibitors, cause increased susceptibility to dietary tyramine inducing hypertensive crises (“cheese effect”).
Selegiline has been reported to cause serum enzyme elevations in up to 40% of patients treated long term. Although the abnormalities were usually mild and self-limiting, they were persistent with continuation of treatment in some patients, ultimately requiring drug discointuation. Selegiline has not been implicated in cases of clinically apparent acute liver injury, but such instances have been reported with other less specific MAO inhibitors.
Likelihood score: E (unlikely cause of clinically apparent liver injury).
Mechanism of Injury
Selegiline is extensively removed from the blood by the liver (first pass metabolism) and undergoes hepatic conjugation and elimination. The pathways of selegiline metabolism have not been well defined.
Outcome and Management
The only liver abnormalities that have attributed to selegiline have been mild and self-limiting elevations in serum enzymes. No instances of acute hepatitis, acute liver failure, chronic hepatitis or vanishing bile duct syndrome have been linked to selegiline use.
Other Drugs in the Subclass, Selective MAO-B Inhibitors: Rasagiline,
REPRESENTATIVE TRADE NAMES
Selegiline – Generic, Atapryl®, Eldepryl®
Product labeling at DailyMed, National Library of Medicine, NIH
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updated: 21 July 2017
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