Study Indicated Rasagiline Selectivity for Inhibiting MAO-B at Maximum Approved Dose
KANSAS CITY, Mo., June 9 /PRNewswire/ -- Teva Neuroscience, Inc. today presented results from a clinical pharmacology study in which AZILECT(R) (rasagiline tablets) did not increase the risk of tyramine sensitivity at the maximum approved dose of 1 mg. The presentation was made during the 13th International Congress of Parkinson's Disease and Movement Disorders in Paris, France. This study assessed the potential risk of hypertensive crisis due to the interaction between high doses of oral tyramine and therapeutic doses of rasagiline, which is indicated both as monotherapy in patients with early Parkinson's disease (PD) and as adjunctive treatment in patients receiving levodopa. The study supported the selectivity of rasagiline for inhibition of MAO-B at currently approved doses.
"We are pleased with the results, which met our primary objectives," said Jon Congleton, general manager of Teva Neuroscience. "This study provides continuing evidence of the value of AZILECT. The results demonstrated a low potential for MAO-A and therefore a selectivity for MAO-B inhibition."
The clinical pharmacology trial was a double-blind, placebo-controlled, randomized, dose-ranging study of rasagiline using a positive control (phenelzine) and a comparator drug (selegiline). The study results were based on the Tyramine Sensitivity Factor (TSF), which measures the ratio of tyramine pressor dose before (baseline) and after MAO inhibitor administration. Geometric mean TSFs of all doses of rasagiline were substantially lower than the TSF for phenelzine, a known nonselective MAO inhibitor. TSFs of various doses of rasagiline were comparable to those of selegiline and placebo.
Tyramine is an amino acid found in certain foods and beverages, including some air-dried and fermented meats, some aged cheeses and most soybean products. Nonselective MAO inhibitors, such as phenelzine sulfate, interfere with the breakdown and elimination of tyramine in the body. Selective MAO-B inhibitors do not interfere with tyramine breakdown and elimination. Patients who take nonselective MAO inhibitors need to be cautious with the foods they eat to prevent an abnormal build-up of tyramine, which could lead to an episode of extremely high blood pressure, potentially leading to stroke or heart attack.
This study was performed as part of a Phase IV commitment to the U.S. Food and Drug Administration (FDA) at the time of AZILECT approval. The results of this study have been submitted to FDA, and Teva Neuroscience intends to work with FDA to appropriately incorporate these results into the label for AZILECT.
About the Study
The tyramine trial was a double-blind, placebo-controlled, randomized, dose-ranging study of rasagiline using a positive control (phenelzine) and a comparator drug (selegiline). In the study, 179 healthy male and female volunteers, aged 40 to 70 years, entered a run-in tyramine challenge test with 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 3 consecutive increases from baseline in SBP >/=30 mm Hg over >/=10 minutes (tyramine pressor dose) in period 1 divided by the dose associated with the same change in SBP in period 3. Nonselective comparator, phenelzine, caused the highest geometric mean TSF of 17.32 +/- 12.76. Geometric mean TSF for rasagiline 1 mg once daily, the maximum approved dose, was 2.03 compared with 1.50 for pooled placebo and 2.47 for selegiline.
AZILECT(R) (rasagiline tablets) is indicated for the treatment of the signs and symptoms of Parkinson's disease (PD) both as initial therapy alone and to be added to levodopa later in the disease.
IMPORTANT SAFETY INFORMATION ABOUT AZILECT
Patients should not take AZILECT if they are taking meperidine as it could result in a serious reaction such as coma or death. Also, patients should not take AZILECT with tramadol, methadone, propoxyphene, dextromethorphan, St. John's wort, mirtazapine, or cyclobenzaprine.
Patients should not take AZILECT with other monoamine oxidase inhibitors (MAOIs), amphetamines, cold remedies containing decongestants and weight-reducing preparations containing pseudoephedrine, phenylephrine, phenylpropanolamine, or ephedrine in order to avoid a possibly dangerous increase in blood pressure.
Patients with moderate to severe liver disease or a tumor of the adrenal gland should not take AZILECT.
In order to prevent a possibly dangerous increase in blood pressure, patients taking AZILECT should avoid foods and beverages high in tyramine content such as aged cheeses, air-dried meats, pickled herring, tap/draft beers, sauerkraut, and soy sauce.
Patients should inform their physician if planning any surgical procedures. Patients should inform their physician if they are taking, or planning to take, any prescription or over-the-counter drugs, especially antidepressants and ciprofloxacin. All PD patients should be monitored for melanoma (skin cancer) on a regular basis.
Side effects seen with AZILECT alone are headache, joint pain, and indigestion; and when taken with levodopa are uncontrolled movements (dyskinesias), accidental injury, nausea, weight loss, constipation, low blood pressure when standing, joint pain, vomiting, dry mouth, rash, and sleepiness.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
About Parkinson's Disease
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.
Teva Pharmaceutical Industries Ltd., headquartered in Israel, is among the top 20 pharmaceutical companies in the world and is the world's leading generic pharmaceutical company. The Company develops, manufactures and markets generic and innovative human pharmaceuticals and active pharmaceutical ingredients, as well as animal health pharmaceutical products. Over 80 percent of Teva's sales are in North America and Europe.
Teva's U.S. innovative product marketing subsidiary, Teva Neuroscience, Inc., promotes AZILECT(R) (rasagiline tablets) in the United States. AZILECT is a registered trademark of Teva Pharmaceutical Industries Ltd. Please visit www.AZILECT.com for additional important information, or see the enclosed additional important information.
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|SOURCE Teva Neuroscience, Inc.|
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