Tyramine Study

The tyramine study, submitted to the FDA as the basis for the change in the prescribing information, supported the selectivity of Azilect for inhibition of MAO-B at approved doses, 1 mg and 0.5 mg. Non selective MAO inhibitors may interfere with the breakdown and elimination of tyramine in the body, which can induce hypertensive reactions. The tyramine study was a double-blind, placebo-controlled, randomized, dose-ranging study of rasagiline using a positive control (phenelzine), a known non-selective MAO inhibitor, and a comparator drug (selegiline). This study was part of a Phase IV commitment to the FDA at the time of Azilect approval. The study results were based on Tyramine Sensitivity Factor (TSF), which measures the ratio of tyramine pressor dose before (baseline) and after MAO inhibitor administration. In the study, 179 healthy male and female volunteers, aged 40 to 70 years received escalating doses of oral tyramine from 25 mg up to 800 mg administered under fasting conditions. TSF was calculated as the tyramine dose associated with three consecutive increases from baseline in systolic blood pressure (SBP) 30 mm Hg over 10 minutes (tyramine pressor dose) in period one divided by the dose associated with the same change in SBP in period three. Geometric mean TSFs of all doses of rasagiline were substantially lower than the TSF for phenelzine. TSFs of various doses of rasagiline were comparable to those of selegiline and placebo. Azilect (rasagiline tablets) is indicated for the treatment of the signs and symptoms of Parkinson's disease (PD) as initial therapy alone and to be added to levodopa later in the disease. Azilect is now available in 39 countries, including the U.S., Canada, Israel, Mexico and all of the European Union countries, where it is marketed by Teva in collaboration with Lundbeck A/S as part of a long-term strategic alliance. Parkinson's disease is an age-related degenerative disorder of the brain. Symptoms can include: tremor, stiffness, slowness of movement, and impaired balance. An estimated five million people worldwide suffer from the disease, with an average age of onset of about 60 years.