Pharmacy & Therapeutics - May 2008 - (Page 280) DRUG FORECAST continued from page 273 Table 2 Characteristics of Drugs Used to Treat Very High Triglyceride Levels Lovaza Dose Price* Total cholesterol Triglycerides LDL-C HDL-C 4 g daily $153.98 Niacin (Niaspan) 1–2 g at bedtime $120.98–$241.97 Gemfibrozil (Lopid) 600 mg twice daily $15.99 Fenofibrate (TriCor) 145 mg daily $118.52 ↓9.7% ↓44.9% ↑44.5% ↑9.1% ↓25% ↓20%–50% ↓5%–25% ↑15%–35% ↓15% ↓20%–50% ↓5%–20% ↑10%–20% ↓15% ↓20%–50% ↓5%–20% ↑10%–20% LDL-C = low-density lipoprotein-cholesterol; HDL-C = high-density lipoprotein-cholesterol. * Cash price for a 30-day supply of the stated dose as of April 14, 2008. (From Drugstore.com.48) Data from prescribing information for Lovaza, TriCor, Lopid, and Niaspan.9,43–45 McClaskey and Michalets reported on a subdermal hematoma that developed after a fall in an elderly patient who had been taking high-dose omega-3 fatty acids (6 g/day) with war farin (Cou madin, Bristol-Myers Squibb) and aspirin. Patients receiving this combination should be monitored carefully.41 It is unknown whether Lovaza, a Pregnancy Category C agent, is excreted in human milk. Caution must be exercised for women who are breast-feeding.8–10 Fibric Acids The mechanism of action by which fibric acids reduce TG remains unclear, but it may be mediated by peroxisome proliferator-activated receptors (PPARs), which regulate gene transcription. This results in increased TG clearance and decreased hepatic TG synthesis.43,44 Niacin Niacin’s mechanism of action is not well defined, but it may involve several actions that result in lower TG, higher HDL-C, and a lower prevalence of small, dense particles of LDL-C. Niacin inhibits access of free fatty acid to adipose tissue, suppresses hepatic assembly and release of VLDL-C, and increases lipoprotein lipase activity.45 There are less expensive over-thecounter niacin products than Niaspan, a prescription product, but they cause considerably more flushing. Flushing is a prostaglandin-mediated response and may be reduced by taking a sustainedrelease formulation product like Niaspan or an aspirin, 81 to 325 mg, at a minimum of 30 minutes before the niacin dose.45 DOSAGE AND ADMINISTRATION Lovaza is available as a 1-g oil-filled capsule. In addition to containing omega-3 and omega-6 fatty acids, it includes alphatocopherol 4 mg in a carrier of partially hydrogenated vegetable oils (2.2 mg per 1-mg capsule), including soybean oil.42 The recommended dose is 4 g by mouth daily with meals for the treatment of very high TG levels. The dose can be taken as 4 g once daily or 2 g twice daily. Dividing doses and taking the medication with meals can help reduce gastrointestinal adverse effects.8–10 The dose is 1 to 2 g daily for the off-label use of preventing CHD.19 Table 2 lists therapeutic agents that can reduce very high TG levels, along with their doses, retail prices for a onemonth supply, and the effects on lipids. dietary supplements of fish oils do not undergo as rigorous a purification process and have a “fishier” taste. Because nonprescription fish oils do not contain the same high levels of EPA and DHA, they are less potent than Lovaza; an average of 12 to 20 capsules is equal to four capsules of Lovaza. Taking more capsules has the potential to increase caloric consumption by approximately 100 calories per day.46 For example, the amount of EPA and DHA in four capsules of Lovaza is equivalent to 12 capsules of Member’s Mark Omega 3 Fish Oil (Sam’s Club), to 16 capsules of Walgreen’s Fish Oil Concentrate or General Nutrition Centers Fish Body Oil, and to 20 capsules of Nature’s Bounty Salmon Oil. Fish consumption is another option, but the amount needed to consume to equal 4 g of Lovaza would be extreme and not feasible because of safety concerns regarding exposure to environmental pollutants such as mercury.46 FORMULARY CONSIDERATIONS Gemfibrozil (Lopid) is a safe, costeffective therapy for hypertriglyceridemia, and it should be recommended as a first-line therapy for TG levels above 500 mg/dL. Advantages of gemfibrozil include low cost, less need for titration, and good tolerability. A disadvantage is its potential drug interaction with statins. Because of their higher cost, fenofibrate (TriCor), niacin (Niaspan), and Lovaza are all reasonable second-line options in patients who do not respond to or who are intolerant of gemfibrozil. For very high TG levels, the ATP III guidelines recommend a fibric acid to be used as a first-line drug, niacin as a second-line drug, and omega-3 fatty acids as an adjunct.1 If a patient’s TG level is 200 to 499 Statins Statins reduce TG levels by only 7% to 30%, so they can be used when TG levels are below 400 mg/dL.1 ALTERNATIVE THERAPIES NCEP ATP III guidelines recommend therapeutic lifestyle changes, including a decreased intake of saturated fats and cholesterol, exercise, smoking and alcohol cessation, niacin, fibric acids, omega3 fatty acids, and statins—all as options for treating hypertriglyceridemia. It is unlikely that diet and lifestyle changes alone can lower very high TG levels to less than 500 mg/dL.1 Dietary Supplements Several nonprescription omega-3 fatty acid products are classified as dietary supplements. Because the FDA does not regulate these supplements, the potency and purity of ingredients are not guaranteed. Fish oil used in the manufacture of Lovaza undergoes an intense purification process that includes removal of pesticides, cholesterol, fatty acids, and by-products. Most 280 P&T® • May 2008 • Vol. 33 No. 5 http://Drugstore.com
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