Drug Topics - December 10, 2007 - (Page 36)

36 DRUG TOPICS DECEMBER 10, 2007 www.drugtopics.com CONTINUING EDUCATION slow the progression of osteoarthritis. Glucosamine decreases inflammation by inhibiting cytokines mediators and interleukin 1-beta. Cytokines mediators normally lead to the stimulation of inflammatory mediators and cartilage destruction. The two interleukins are normally responsible for the gene expression and protein synthesis of the COX-2 enzyme, which is responsible for the production in prostaglandins, which lead to inflammation. A normal therapeutic dose of glucosamine for osteoarthritis patients is 1,500 mg taken daily in three divided doses or 1,500 mg of the long-acting formulation. Glucosamine preparations are normally made up of either the hydrochloride or sulfate salt formulation. It is thought that the sulfate moiety is the more active of the salt formulations, and it is required for the synthesis of articular cartilage. Studies have shown conflicting data over the efficacy of glucosamine in osteoarthritis patients. The Glucosamine/ Chondroitin Arthritis Intervention Trial (GAIT), funded by the National Institutes of Health, looked at the efficacy of glucosamine, chondroitin, and the combination of the two natural products. This five-armed multicenter study looked at 1,583 randomized patients taking glucosamine hydrochloride 500 mg three times daily, chondroitin sulfate 400 mg three times daily, the combination of the two taken three times daily, celecoxib 200 mg taken daily, or placebo. It concluded that the combination product of glucosamine and chondroitin decreased mild to severe knee pain in osteoarthritis patients. However, this study also showed that glucosamine alone or in combination for patients with mild to moderate pain was no better than placebo. Additional studies have shown glucosamine sulfate taken alone led to a decrease in pain by as much as 28% to 48% and increased the patient’s ability to function by as much as 21% to 46%. Disease progression of osteoarthritis has also been studied. One meta-analysis suggested there was a reduced risk of disease progression up to 54% for patients taking this natural product. In contrast to these findings, other studies suggest that taking glucosamine for severe osteoarthritis may not be beneficial, especially for patients who are elderly or overweight. The majority of trials have still shown that glucosamine is likely beneficial for patients with osteoarthritis. Adverse drug reactions associated with glucosamine include GI side effects such as diarrhea, constipation, heartburn, and nausea. Other side effects such as drowsiness, skin reactions, and headache have also been reported. Previously, controversy existed over blood glucose and hemoglobin A1c levels with diabetes patients who were taking glucosamine. Studies have shown patients who took glucosamine up to three months showed no change in A1c levels. Another concern with glucosamine is its effects on cholesterol and lipid levels. Data collected from a three-year study showed that glucosamine did not have a significant effect on lipid levels or any other metabolic complication. Glucosamine has been shown to affect international normalized ratio (INR) values and interact with warfarin administration. High-dose combination therapy such as 3,000 mg of glucosamine and 2,400 mg of chondroitin taken daily in divided doses was found to increase the INR value as well as anticoagulative properties of warfarin. Other drug interactions were considered to be minor and of little concern. Chondroitin: Chondroitin sulfate belongs to a class known as glycosaminoglycans (GAGs). This group is composed of a large molecule of galactosamine and glucuronic acid and is found in ground substance that forms the extracellular matrix of joints. In the body, chondroitin is found in cartilage, bone, skin, and other areas. Chondroitin sulfate is a natural product and is manufactured from sources such as shark and bovine cartilage. This product is thought to promote and maintain the structure and function of cartilage, reduce pain, and have anti-inflammatory activity. Chondroitin is believed to be beneficial in osteoporosis because it is found endogenously in cartilaginous tissue and serves as a substrate in the formation of the joint matrix. Evidence has shown that it also protects against the breakdown of cartilage by inhibiting the enzyme leukocyte elastase, decreasing the infiltration of polymorphonuclear leukocytes, and most important by increasing the synthesis of proteoglycans and hyaluronic acid. Chondroitin is important in osteoarthritis because the interaction between proteoglycans and hyaluronic acid plays a role in the formation of cartilage. A normal therapeutic dose of chondroitin for osteoarthritis is 200 to 400 mg taken two to three times daily. If chondroitin is to be taken as a single dose, 1,000 to 1,200 mg is recommended. As seen with glucosamine, chondroitin appears to have inconsistent data. Since 2005, data have not shown chondroitin to be as effective as previously reported. In 2007, a metaanalysis study focused on 20 different trials with a total of 3,846 patients. The meta-analysis was performed to determine the use of chondroitin for osteoarthritis of the knee or hip. It concluded that chondroitin had a minimal to nonexistent symptomatic pain benefit. This study discourages the routine use of chondroitin in osteoarthritis patients. Other authors still encourage patients to use this natural agent if it is beneficial. As previously discussed in the section of glucosamine, chondroitin used alone in the GAIT study did not decrease mild to moderate pain, but used in combination, it decreased moderate to severe pain better than placebo. Overall, it appears that chondroitin taken alone is less effective than previously reported. Chondroitin is considered to be well tolerated by patients; however, GI pain, nausea, diarrhea, constipation, edema of the lower limbs, and alopecia have been reported. One concern found with this natural product focused on its possible anticoagulant effect. This anticoagulant effect is believed to be a concern because chondroitin is a component of danaparoid, a low molecular weight heparinoid. However, clinical trials have shown no hematological changes in patients taking chondroitin. Chondroitin as well as glucosamine have been shown to af- http://www.drugtopics.com

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Drug Topics - December 10, 2007 Latebreakers Latebreakers in Depth Letters Health-System Edition - Cover Story Clinical Practice Professional Practice Special Report Technology Community Practice Unraveling Medicare 150 Years of American Pharmacy Rx Care In the Pipeline Cover Story: Fair or foul? Self-Care Chains and Business Government and Law Continuing Education: Natural Medicines for Bone Health New Products Advertisers Index Classified Viewpoint

Drug Topics - December 10, 2007

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