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Health Canada approves Cymbalta for the management of osteoarthritis
knee pain

Once daily treatment a unique new option
TORONTO, Nov. 7, 2012 /CNW/ - Eli Lilly Canada announced that Health Canada has approved Cymbalta® (duloxetine hydrochloride) for the management of chronic pain associated with osteoarthritis (OA) of the knee, representing a new analgesic treatment option for patients suffering from the condition. Cymbalta is the only serotonin and norepinephrine reuptake inhibitor (SNRI) approved in Canada for the management of chronic pain associated with OA of the knee. Other Cymbalta indications include: major depressive disorder, generalized anxiety disorder, neuropathic pain associated with diabetic peripheral neuropathy, pain associated with fibromyalgia and chronic low back pain. "People with OA of the knee often experience debilitating pain and struggle to find an effective treatment without the safety or addiction concerns of other pain medications," said Dr. Philip Baer, Chair of the Section on Rheumatology of the Ontario Medical Association. "This approval gives healthcare providers an important new option to help patients manage their pain so they can get back to doing the activities they enjoy." OA is a progressive disease that occurs when damaged joint tissues are unable to normally repair themselves, resulting in a breakdown of cartilage and bone. The most commonly affected joints are the hands and weight-bearing joints, including the knees, hips, feet and spine. It is believed that Cymbalta helps enhance the body's natural pain suppressing system by increasing the activity of serotonin and norepinephrine in the brain and spinal cord. Safe and Effective
Taken once daily, the safety and efficacy of Cymbalta in the management of chronic pain
associated with OA of the knee was established in two, randomized, double-blind, placebo-
controlled clinical trials.
Patients randomized to Cymbalta or placebo in a 13-week clinical trial started treatment at a dose of 30mg once daily for one week, then increased to 60mg once daily. After seven weeks of treatment, patients with sub-optimal response to treatment ( In a 10-week, placebo-controlled, flexible-dose study, patients with OA pain of the knee, who had inadequate pain relief from an optimized dose of non-steroidal anti-inflammatory drug (NSAID) therapy for two weeks, received 60/120 mg/day of Cymbalta or placebo. After eight weeks of double-blind treatment, patients treated with Cymbalta added to NSAID experienced significantly greater pain reduction compared with placebo. Furthermore, the studies also showed Cymbalta to be safe and well-tolerated. The most commonly observed adverse events in Cymbalta-treated OA patients included nausea, constipation, dry mouth, fatigue, diarrhea, abdominal pain, dizziness, insomnia, decreased appetite, and erectile dysfunction. Patients may take Cymbalta with or without food; however, food may help to reduce the incidence of initial nausea. The recommended starting dose for Cymbalta is 60mg per day. Osteoarthritis in Canada
Osteoarthritis is the most common form of arthritis. In fact, one in eight Canadians live with it and
almost everyone over 65 years of age has OA in at least one joint. Nearly 1 in 100 (or 300,000)
Canadian adults (age 20+ years) have experienced at least moderate to severe pain due to OA.
Among all cases of OA, it is estimated that 40 per cent of patients have moderate to severe hip and/or knee OA. About Eli Lilly Canada Inc.
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of best-in-class
pharmaceutical products by applying the latest research from its own worldwide laboratories and
from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Indiana,
Lilly provides answers - through medicines and information - for some of the world's most urgent
medical needs. Eli Lilly Canada, headquartered in Toronto, Ontario, employs more than 500
people across the country. Additional information about Eli Lilly Canada can be found at

® Registered trademark owned by Eli Lilly and Company; used under license. References:
i Lane NE, Brandt K, Hawker G, Peeva E, Schreyer E, Tsuji W, et al. OARSI-FDA initiative: defining the disease state of osteoarthritis. Osteoarthritis Cartilage. 2011 May 19(5):478-82 Epub 2011 Mar 23 ii Living Well with Osteoarthritis, Knowing your Treatment Options ccessed: October 18, 2012 iii Cymbalta Product Monograph, Clinical Trials, Eli Lilly Canada, 2012 iv Cymbalta Product Monograph, Clinical Trials, Eli Lilly Canada, 2012 v Frakes EP, Risser RC, Hochberg MC, Wohlreich MM, et al. Duloxetine added to oral nonsteroidal anti-inflammatory drugs for treatment of knee pain due to osteoarthritis. Current Medical Research and Opinion, 2011: 27:12 2361-2372 vi Cymbalta Product Monograph, Clinical Trials, Eli Lilly Canada, 2012 vii Arthritis Network. Impact of Arthritis. Accessed September 11, 2012. viii Ibid. ix Ibid. For further information:
Tonya Johnson Cohn & Wolfe 647.259.3282 Helen Stone Eli Lilly Canada Inc. 416-693-3169

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Contribution of dichloroacetate and trichloroacetate to liver tumor induction in mice by trichloroethylene

Toxicology and Applied Pharmacology 182, 55– 65 (2002) doi:10.1006/taap.2002.9427 Contribution of Dichloroacetate and Trichloroacetate to Liver TumorRichard J. Bull,*,†,2 Gayle A. Orner,* Rita S. Cheng,* Lisa Stillwell,* Anja J. Stauber,†Lyle B. Sasser,* Melissa K. Lingohr,† and Brian D. Thrall*,†* Molecular Biosciences Department, Pacific Northwest National Laboratory, Richland, W

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