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Selegiline (Eldepryl) tablets should not be used at daily doses exceeding those recommended (10 mg/day) because of the risks associated with non-selective inhibition of MAO.

The selectivity of selegiline for MAO-B may not be absolute even at the recommended daily dose of 10 mg a day. Rare cases of hypertensive reactions associated with ingestion of tyramine-containing foods have been reported in patients taking the recommended daily dose of selegiline. The selectivity is further diminished with increasing daily doses. The precise dose at which selegiline becomes a non-selective inhibitor of all MAO is unknown, but may be in the range of 30 to 40 mg a day.

Severe CNS toxicity associated with hyperpyrexia and death have been reported with the combination of tricyclic antidepressants and non-selective MAOIs (Nardil, Parnate). A similar reaction has been reported for a patient on amitriptyline and Selegiline HCl (Eldepryl). Another patient receiving protriptyline and Eldepryl developed tremors, agitation, and restlessness followed by unresponsiveness and death two weeks after this medication was added. Related adverse events including syncope, hypertension, asystole, seizures, diaphoresis, changes in behavioral and mental status, and muscular rigidity have also been reported in some patients receiving Selegiline HCl (Eldepryl) tablets and various tricyclic antidepressants.

Serious, sometimes fatal, reactions with signs and symptoms that may include rigidity, hyperthermia, myoclonus, autonomic instability with rapid fluctuations of the vital signs, and mental status changes that include extreme agitation progressing to delirium and coma have been reported with patients receiving a combination of fluoxetine hydrochloride (PROZAC) and non-selective MAOIs. Similar signs have been reported in some patients on the combination of Eldepryl (10 mg a day) and selective serotonin re-uptake inhibitors including sertraline, fluoxetine and paroxetine.

Since the mechanisms of these reactions are not fully understood, it seems prudent, in general, to avoid this combination of Selegiline Hydrochloride (Eldepryl) and tricyclic antidepressants as well as Eldepryl and selective serotonin re-uptake inhibitors. At least 14 days should elapse between discontinuation of this drug and initiation of treatment with a tricyclic antidepressant or selective serotonin re-uptake inhibitors. Because of the long half-lives of fluoxetine and its active metabolite, at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of treatment with Selegiline Hydrochloride (Eldepryl) tablets.

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