Selective MAO-B inhibitors have low potential for the tyramine effect


Selective MAO-B Inhibitors Have Low Potential for the Tyramine Effect

Despite accumulating data to suggest that administration of rasagiline (Azilect) at approved dosages is safe without dietary modification, some patients, physicians (nonmovement disorder specialists), and pharmacists have expressed safety concerns owing to the tyramine dietary precautions that appear in the manufacturer's package insert.1 To address these concerns, deMarcaida et al. published some additional safety data on rasagiline in their article, “Effects of Tyramine Administration in Parkinson's Disease Patients Treated With Selective MAO-B Inhibitor Rasagiline.”2

deMarcaida et al. reported the results of tyramine challenges in 110 patients from the TEMPO and PRESTO* studies who had Parkinson's disease and were treated with rasagiline monotherapy (1–2 mg/day) or rasagiline (0.5–1 mg/day) in combination with levodopa.2–4 Results were reassuring in that no patient receiving rasagiline monotherapy (n = 38) had changes in blood pressure or heart rate that were suggestive of a tyramine interaction. However, among the 55 patients treated in the combination therapy group, 3 receiving rasagiline 0.5 mg/day showed systolic blood pressure elevations of more than 30 mm Hg over three consecutive measurements after the tyramine challenge. Although these changes did not occur in a time course typically suggestive of tyramine ingestion, the possibility that the delayed gastric emptying or intestinal absorption associated with PD altered the time course, cannot be ruled out.

It is of more than passing interest in determining whether this rise in systolic blood pressure seen in the PRESTO study is of true clinical significance. Further study of blood pressure changes in patients treated with selective monoamine oxidase type-B (MAO-B) inhibitors may be needed to ensure that we are not inadvertently elevating our patients' systolic blood pressure. The recent revelation of valvular abnormalities associated with pergolide after so many years of regular use shows the value of postmarketing drug surveillance of trends suggested in premarketing trials.

Some selective MAO inhibitors at higher dosages may be associated with the tyramine response. Oral selegiline (Deprenyl), another selective inhibitor of MAO-B for Parkinson's disease, loses its selectivity when administered at doses greater than 20 mg/day.5 The safety of another recently approved MAO-B inhibitor, Zydis selegiline (Zelapar), an orally disintegrating formulation of selegiline absorbed through the buccal mucosa, was also examined after an oral tyramine challenge.6 In an open-label, randomized, parallel-group study, 24 patients were given Zydis selegiline 1.25 mg/day or conventional selegiline 10 mg/day for 14 days and were challenged with tyramine 400 mg. In all patients receiving conventional selegiline 10 mg, the threshold dose of tyramine required to elicit the pressor response was significantly reduced (from 400 to 200 mg; P < 0.0001). Unlike conventional selegiline tablets (10 mg dose), Zydis selegiline 1.25mg did not potentiate the tyramine effect before or after 14 days of treatment.6 A similar study with the Zydis selegiline 2.5 mg dose would be advisable. Moreover, although no rise in systolic blood pressure was seen in the premarketing studies of Zydis selegiline, it may also be wise to evaluate blood pressure changes in currently treated patients. Emsam, the transdermal selegiline patch for major depression, is not administered through a gastric delivery route. Although higher doses have shown a loss of selective MAO-B inhibition, the results of a recent tyramine challenge showed that Emsam is safe to use at the recommended starting dose (6 mg/24 hour) without dietary tyramine restriction.7 However, this study did not assess the safety of available higher doses of Emsam.

The valuable contribution of selective MAO-B inhibition in the treatment of patients with Parkinson's disease is accompanied by a robust safety profile demonstrated over almost 30 years of clinical use. Further investigation into the long-term safety of the newer agents Azilect and Zelapar will provide clearer assurances concerning effects on blood pressure, as well as potential for interactions with diet and other medications, such as antidepressants.

Stuart H. Isaacson MD*, * Parkinson's C.O.R.E., Institute of Boca Raton, Boca Raton, Florida, USA.


  • *

    TEMPO, Rasagiline Mesylate [TVP-1012] in Early Monotherapy for Parkinson's Disease Outpatients; PRESTO, Parkinson's Rasagiline: Efficacy and Safety in the Treatment of “Off.”