recommended dose (a dose believed to be relatively selective for MAO-B).
The safe use of ZELAPAR at doses above 2.5 mg daily without dietary tyramine
restrictions has not been established.
A pharmacodynamic study showed increased tyramine sensitivity for increasing blood
pressure and decreased selectivity for MAO-B with dosing above the recommended level
(2.5 mg daily) [see Clinical Pharmacology (12.2)].
Uncontrolled hypertension has been reported when taking the recommended dose of
swallowed selegiline and a sympathomimetic medication (ephedrine).
After starting ZELAPAR, monitor patients for new onset hypertension or exacerbation of
hypertension that is not adequately controlled.
5.2 Serotonin Syndrome
Serotonin syndrome and hyperpyrexia have been reported with the combined treatment
of an antidepressant (e.g., selective serotonin reuptake inhibitors-SSRIs, serotonin-
norepinephrine reuptake inhibitors-SNRIs, tricyclic antidepressants, tetracyclic
antidepressants, triazolopyridine antidepressants) and a non-selective MAOI (e.g.,
phenelzine, tranylcypromine) or selective MAO-B inhibitors, such as selegiline
(ELDEPRYL), rasagiline (AZILECT), and Zydis selegiline (ZELAPAR).
Serotonin syndrome is a potentially serious condition, which can result in death. Typical
clinical signs and symptoms include behavioral and cognitive/mental status changes
(e.g., confusion, hypomania, hallucinations, agitation, delirium, headache, and coma),
autonomic effects (e.g., syncope, shivering, sweating, high fever/hyperthermia,
hypertension, hypotension, tachycardia, nausea, diarrhea), and somatic effects (e.g.,
muscular rigidity, myoclonus, muscle twitching, hyperreflexia manifested by clonus, and
tremor).
In the post-marketing period, fatal and non-fatal cases of serotonin syndrome have
been reported in patients treated with antidepressants concomitantly with ZELAPAR
[see Contraindications (4) and Drug Interactions (7.1, 7.2, 7.3)].
Clinical studies of ZELAPAR did not allow concomitant use of any selective serotonin re-
uptake inhibitor (e.g., fluoxetine-Prozac, fluvoxamine-Luvox, paroxetine-Paxil, sertraline,
venlafaxine-Effexor, or nefazodone-Serzone) or any non-selective serotonin reuptake
inhibiting antidepressant drug (except when taken at a low dose and only at night for the
purpose of effective sleep) with ZELAPAR.
Because the mechanisms responsible for these reactions are not fully understood, avoid
the combination of ZELAPAR with any antidepressant. At least 14 days should elapse
between discontinuation of ZELAPAR and initiation of treatment with a SSRI, SNRI,
tricyclic, tetracyclic, or triazolopyridine antidepressant. In patients taking
antidepressants with a long half-life (e.g., fluoxetine and its active metabolite), allow at
least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically
and/or at higher doses) to elapse between discontinuation of fluoxetine and initiation of
ZELAPAR [see Drug Interactions (7.6)].
5.3 Falling Asleep During Activities of Daily Living and Somnolence
Patients with Parkinson’s disease treated with ZELAPAR or other drugs increasing
dopaminergic tone have reported falling asleep while engaged in activities of daily living,