Selegiline dosing

Zelapar with phenylalanine) Rapid-dissolving selegiline Start with 1.25 mg every morning before breakfast if symptoms continue after 6 weeks, increase dose to 2.5 mg every morning. Avoid food or liquid for 5 minutes before or after the dose... 

Selegiline COCs decrease metabolism of selegiline Increase side effects of selegiline may adjust dose of selegiline if needed... 

Selegiline (deprenyl Eldepryl) is an irreversible MAO-B inhibitor that blocks dopamine breakdown and can modestly extend the duration of action of L-dopa (up to 1 hour). It often permits reduction of L-dopa dose by as much as one-half. 

Accordingto the FDA-approved prescribing information for the transdermal selegiline patch, patients receiving the 6 mg/24 hour dose are not required to modify their diet. However, patients receiving the 9 or 12 mg/24 hour dose are still required to follow the dietary restrictions similar to the other monoamine oxidase inhibitors (MAOIs). 

Yet another MAOI is selegiline (Eldepryl). Unlike the other MAOls, selegiline is seldom used to treat depression. At low doses, selegiline only inhibits the M AO-B enzyme. Therefore, it increases dopamine activity but does not have any pronounced effect on norepinephrine or serotonin. For this reason, it has been less useful as an antidepressant however, its primary use has been to treat Parkinson s disease. Of course, this selectivity for dopamine suggests that it may be helpful for ADHD as well. 

After 2 to 3 days of treatment, attempt to reduce the dose of levodopa/carbidopa. A reduction of 10% to 30% appears typical. Further reductions of levodopa/carbidopa may be possible during continued selegiline therapy. 

Absorption/Distribution - Selegiline is rapidly absorbed approximately 73% of a dose is absorbed maximum plasma concentration occurs 0.5 to 2 hours following administration. 

Metabolism/Excretion-The drug is rapidly metabolized. Over 48 hours, 45% of the dose appeared in the urine as metabolites. Unchanged selegiline is not detected in urine. 

Hypertensive crisis In theory, because MAO-A of the gut is not inhibited, patients treated with selegiline at a dose of 10 mg/day can take medications containing pharmacologically active amines and consume tyramine-containing foods without risk of uncontrolled hypertension. 

Most of the adverse reactions to selegiline are related to actions of increased levels of dopamine, as discussed earlier. At recommended doses, and unlike the nonselective MAO inhibitors used in the treatment of depression, selegiline has little effect on MAO-A and therefore generally does not cause the hypertension associated with the ingestion of tyramine-enriched foods (see Chapter 20). However, at doses higher than those usually recommended, MAO-A may be inhibited, which increases the risk of a tyramine reaction. 

Children with Tourette s syndrome and ADHD refractory to other ADHD medication (n = 29) were treated openly with an average deprenyl dose of 8 mg/ day (Jankovic, 1993). The vast majority of patients (26/29) reported clinical improvement with no serious adverse outcomes. Mild side effects that did not require discontinuation of the drug were noted in six patients. Two patients had exacerbations of their tics. A later controlled trial of low-dose selegiline (10 mg/day) did not demonstrate statistically significant improvement of ADHD symptoms in children with Tourette s syndrome (Feigin et ah, 1996). 

Preliminary studies suggest that MAOIs are effective in juvenile and adult ADHD. In a controlled trial of clorygline (MAOI-A) and tranylcypromine sulfate (mixed), Zametkin et al. (1985) reported a significant reduction in ADHD symptoms with minimal adverse effects. Eeigin et al. (1996) conducted a controlled trial of 10 mg of selegiline (which at low doses is a specific MAOI-B) in children with ADHD and Tourette s syndrome. Selegiline was well tolerated and was associated... 

In open studies of adult ADHD, moderate improvements were reported in studies with pargyline and selegiline (MAOI-Bs) (Wender et ah, 1983, 1985). In a controlled study of selegiline in adult ADHD (Ernst 1996), use of active drug failed to produce results different from those with placebo however, the placebo response was unusually high in that study. In addition, a high dose (60 mg) was more effective than a low dose (20 mg), which suggests that MAOI-A effects may be more helpful in the treatment of ADHD. 

Selegiline is an irreversible but relatively selective inhibitor of MAO-B. An oral preparation is currently marketed as a treatment for Parkinson s disease. An oral dose produces meaningful inhibition of MAO-B but not MAO-A. The concept behind the transdermal patch is to preferentially deliver more selegiline to the brain than to the liver such that meaningful inhibition of both MAO-A and MAO-B is achieved in the brain but only MAO-B inhibition is achieved in the liver. The... 

The MAO-B inhibitor, l-deprenyl, has been approved by the FDA for use in Parkinson s disease. At the lower dose range, it does not interact with tyramine. As mentioned earlier, there is preliminary evidence of antidepressant efficacy for a transdermal delivery system for selegiline. This formulation does not interact with tyramine to produce a hypertensive crisis (181). 

VandenBerg CM, Blob LF, Gerrick G, et al. Blood pressure response produced by a tyramine-enriched meal following multiple dose administration of a 20 cm 120 mg selegiline transdermal system (STS) in healthy male volunteers. 40th Annual Meeting NCDEU, Boca Raton, Florida, 2000(abst). 

MAOIs are classified by their specificity for MAO-A or -B and whether their effects are reversible or irreversible. Phenelzine and tranylcypromine are examples of irreversible, nonselective MAOIs. Moclobemide is a reversible and selective inhibitor of MAO-A but is not available in the USA. Moclobemide can be displaced from MAO-A by tyramine, and this mitigates the risk of food interactions. In contrast, selegiline is an irreversible MAO-B-specific agent at low doses. Selegiline is useful in the treatment of Parkinson s disease at these low doses, but at higher doses it becomes a nonselective MAOI similar to other agents. 

Phenelzine Blockade of MAO-A and MAO-B (phenelzine, nonselective) MAO-B irreversible selective MAO-B inhibition (low dose selegiline) Transdermal absorption of selegiline achieves levels that inhibit MAO-A Major depression unresponsive to other drugs Very slow elimination Toxicity Hypotension, insomnia Interactions Hypertensive crisis with tyramine, other indirect sympathomimetics serotonin syndrome with serotonergic agents, meperidine... 

No gender-related differences in the pharmacokinetics of selegiline were observed following a single oral dose of selegiline 10 mg to 6 elderly males and 6 elderly females between 60 and 85 years old. 

Desmethylselegiline is also an irreversible inhibitor of monoamine oxidase B in humans. There is evidence that the 1-stereoisomers of 1-amphetamine and 1-methamphetamine may have some qualitatively different actions from their d-isomer counterparts, which might result in beneficial clinical effects and could complement any beneficial clinical actions of selegiline itself. Food has no effect on the pharmacokinetics of desmethylselegiline, methamphetamine, and amphetamine. At a dose of 10 mg per day, selegiline is devoid of the cheese effect that is, it does not cause hypertension when taken with tyramine-containing foods such as cheese. 

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