Study Results Supported Removal of Dietary Tyramine Restriction from Azilect® Prescribing Information
KANSAS CITY, Mo.--(BUSINESS WIRE)-- Teva Neuroscience Inc. today announced the publication of a study demonstrating the selectivity of Azilect® (rasagiline tablets) for inhibition of MAO-B (monoamine oxidase-B) at the maximum approved dose of 1 mg/day. The data was published in the Journal of Clinical Pharmacology OnlineFirst on May 5, 2010.
This study was submitted to the Food and Drug Administration (FDA) and became the basis for the change in prescribing information that removed the broad dietary tyramine restriction, reflecting reduced concerns regarding the use of Azilect® together with certain medications, including many over-the-counter cough/cold medications. Confirmation of the MAO-B selectivity of Azilect® that is shown in this study is significant as MAO inhibitors that are non-selective interfere with the breakdown and elimination of tyramine in the body, which can induce hypertensive reactions. Selective MAO-B inhibitors, like Azilect®, do not generally interfere with tyramine breakdown and elimination at recommended doses.
“Multiple studies have demonstrated that Azilect® may play an important role in the treatment of Parkinson’s disease, both as monotherapy and as adjunctive therapy,” said Daniel Kremens, M.D., assistant professor of neurology and co-director of the Parkinson's disease and Movement Disorders Division at Jefferson Medical College of Thomas Jefferson University in Philadelphia. “With the confirmation of Azilect® as a selective MAO-B inhibitor, and the change in the official prescribing information about dietary tyramine, a potential treatment barrier has been removed. Patients and physicians can continue to focus on what’s important - managing the disease.”
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. Elevated levels of tyramine can cause a serious increase in blood pressure. Ingestion of very high levels (e.g., more than 150 mg) of tyramine by patients taking MAO inhibitors, including Azilect®, should be avoided.
An estimated five million people worldwide have Parkinson’s disease, an age-related degenerative disorder of the brain that can cause tremors, stiffness, slowness of movement and impaired balance.
About the Tyramine Study
The tyramine study was a double-blind, placebo-controlled, randomized, dose-ranging study of Azilect® (rasagiline) using a positive control (phenelzine), a known nonselective 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, were randomized to receive 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. This study was sponsored by Teva Neuroscience, Inc.
Azilect® 0.5 and 1mg tablets (rasagiline tablets) are indicated for the treatment of the signs and symptoms of Parkinson’s disease both as initial monotherapy and as adjunct to levodopa later in the disease. Azilect® is currently available in 39 countries, including the US, Canada, Israel, Mexico, and all EU countries.
IMPORTANT SAFETY INFORMATION ABOUT AZILECT®
Do not take Azilect® if you are taking meperidine as it could result in a serious reaction such as coma or death. Also, do not take Azilect® with tramadol, methadone, propoxyphene, dextromethorphan, St. John’s wort, or cyclobenzaprine. You also should not take Azilect® with other monoamine oxidase inhibitors (MAOIs).
Inform your physician if you are taking, or planning to take, any prescription or over-the-counter drugs, especially antidepressants and ciprofloxacin. If you have moderate to severe liver disease, you should not take Azilect®. You should not exceed a dose of 1 mg per day of Azilect® in order to prevent a possibly dangerous increase in blood pressure. All PD patients should be monitored for melanoma (skin cancer) on a regular basis.
Side effects seen with Azilect® alone are flu syndrome, joint pain, depression, and indigestion; and when taken with levodopa are uncontrolled movements (dyskinesia), accidental injury, weight loss, low blood pressure when standing, vomiting, anorexia, joint pain, abdominal pain, nausea, constipation, dry mouth, rash, abnormal dreams, and fall.
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.
Please visit http://azilect.com/PrescribingInformation.pdf.ashx for additional, important information.
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., (NASDAQ: TEVA) headquartered in Israel, is among the top 15 pharmaceutical companies in the world and is the leading generic pharmaceutical company. The company develops, manufactures and markets generic and innovative pharmaceuticals and active pharmaceutical ingredients. Over 80 percent of Teva’s sales are in North America and Western Europe.
About Teva Neuroscience
Teva Neuroscience is dedicated to investigating, developing and marketing ground-breaking products and technologies, with emphasis on cutting-edge treatments for patients who are living with neurological conditions, including multiple sclerosis (MS) and Parkinson’s disease (PD). Therapies marketed by Teva Neuroscience include Copaxone® (glatiramer acetate injection) for relapsing-remitting multiple sclerosis (RRMS) and Azilect® (rasagiline tablets) for the treatment of PD.
Teva Neuroscience’s suite of innovative products continues to demonstrate the company’s commitment to fulfilling unmet medical needs and has helped the company evolve into a global leader in RRMS. Teva Neuroscience is a North American subsidiary of Teva Pharmaceutical Industries Ltd., the world’s largest generic drug company. Teva Neuroscience is proud of the role it plays in providing effective treatment options to patients worldwide. For more information, please visit www.tevaneuro.com or www.tevaclinicaltrials.com.
Teva's Safe Harbor Statement under the U.S. Private Securities Litigation Reform Act of 1995:
This release contains forward-looking statements, which express the current beliefs and expectations of management. Such statements involve a number of known and unknown risks and uncertainties that could cause our future results, performance or achievements to differ significantly from the results, performance or achievements expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to: our ability to successfully develop and commercialize additional pharmaceutical products, the introduction of competing generic equivalents, the extent to which we may obtain U.S. market exclusivity for certain of our new generic products and regulatory changes that may prevent us from utilizing exclusivity periods, potential liability for sales of generic products prior to a final resolution of outstanding patent litigation, including that relating to the generic versions of Neurontin®, Lotrel®, and Protonix®, current economic conditions, the extent to which any manufacturing or quality control problems damage our reputation for high quality production, the effects of competition on our innovative products, especially Copaxone® sales, dependence on the effectiveness of our patents and other protections for innovative products, especially Copaxone®, the impact of consolidation of our distributors and customers, the impact of pharmaceutical industry regulation and pending legislation that could affect the pharmaceutical industry, our ability to achieve expected results though our innovative R&D efforts, the difficulty of predicting U.S. Food and Drug Administration, European Medicines Agency and other regulatory authority approvals, the uncertainty surrounding the legislative and regulatory pathway for the registration and approval of biotechnology-based products, the regulatory environment and changes in the health policies and structures of various countries, any failures to comply with the complex Medicare and Medicaid reporting and payment obligations, the effects of reforms in healthcare regulation, supply interruptions or delays that could result from the complex manufacturing of our products and our global supply chain, interruptions in our supply chain or problems with our information technology systems that adversely affect our complex manufacturing processes, potential tax liabilities that may arise should our agreements (including intercompany arrangements), be challenged successfully by tax authorities, our ability to successfully identify, consummate and integrate acquisitions and other business combinations (including our pending acquisition of ratiopharm), the potential exposure to product liability claims to the extent not covered by insurance, our exposure to fluctuations in currency, exchange and interest rates, as well as to credit risk, significant operations worldwide that may be adversely affected by terrorism, political or economical instability or major hostilities, our ability to enter into patent litigation settlements and the increased government scrutiny of our agreements with brand companies in both the U.S. and Europe, the termination or expiration of governmental programs and tax benefits, impairment of intangible assets and goodwill, any failure to retain key personnel or to attract additional executive and managerial talent, environmental risks, and other factors that are discussed in our Annual Report on Form 20-F for the year ended December 31, 2009, in this report and in our other filings with the U.S. Securities and Exchange Commission (“SEC”).
Teva Neuroscience Inc.
Denise Bradley, 215-591-8974
KEYWORDS: United States North America Missouri Middle East Israel
INDUSTRY KEYWORDS: Health Biotechnology Clinical Trials Pharmaceutical Other Health