Pharmacy & Therapeutics - February 2009 - (Page 88)

Pharmaceutical Approval Update These chemotherapeutic agents (cyclophosphamide with or without etoposide) may compromise an individual’s immune system and can affect other organs of the body in a negative manner. Following chemotherapy, the stem cells are released into the bloodstream and are collected in preparation for a transplant. For transplantation to take place, at least two million stem cells per kilogram of body weight must be collected. For many patients, this process can take three or four hours over multiple days to complete. Even then, some patients cannot achieve this number and a transplant is not possible. When patients actually undergo autologous transplantation, they first receive high-dose chemotherapy, radiation, or immunotherapy before they receive their own stem cells back. Because high-dose chemotherapy has a more intense effect when it is associated with transplantation, more cells may be destroyed. In transplantation, one must take care with chemotherapy because of the possibility of total immunosuppression of the patient; too high a dose leaves patients vulnerable to secondary infections and transplant rejection. The status of the disease at the time of transplantation can affect outcome. For diffuse, large-cell lymphoma and follicular NHL, an autologous transplant in first remission may offer the best chance of long-term survival. Whether an autologous transplant is recommended at first remission depends on the type of lymphoma and the patient’s risk factors. Therefore, the aim of plerixafor is to decrease the number of apheresis days; this causes less trauma for patients and also provides economic benefits for transplant centers. Plerixafor may also decrease the need for a second mobilization procedure because of failure to mobilize sufficient numbers of stem cells with G-CSF alone. Sources: www.genzyme.com; www.helpwithcancer.org General considerations. In a large randomized, controlled trial that included patients with type-2 diabetes mellitus, fenofibrate at a dose equivalent to 135 mg of the capsule did not reduce CHD morbidity or mortality rates. Laboratory studies should be performed to establish that lipid levels are abnormal before TriLipix is prescribed. Drug Class: This lipid-regulating agent is sold as a delayedrelease oral capsule. Each capsule contains choline fenofibrate, equivalent to 45 mg or 135 mg of fenofibric acid. The chemical name of choline fenofibrate is ethanaminium,2hydroxy-N,N,N-trimethyl,2-{4-(4-chlorobenzoyl)phenoxy]-2methylpropanoate(1:1). The empirical formula is C22H28ClNO5, and the molecular weight is 421.91. Choline fenofibrate is freely soluble in water. Uniqueness of Drug: The lipid-modifying effects of fenofibric acid have been explained in vivo in transgenic mice and in vitro in human hepatocyte cultures by the activation of peroxisome proliferator activated receptor–α (PPAR-α). Fenofibric acid increases lipolysis and helps eliminate triglyceriderich particles from plasma by activating lipoprotein lipase and by reducing production of Apo CIII, an inhibitor of lipoprotein lipase activity. The resulting decrease in triglycerides produces an alteration in the size and composition of LDL-C from small, dense particles (which are thought to be atherogenic) to large, buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly. Activation of PPAR-α also induces an increase in the synthesis of HDL-C and Apo AI and AII. Warnings and Precautions: Skeletal muscle. Fibrates and statin monotherapy increase the risk of myositis and myopathy and have been associated with rhabdomyolysis. The risk of rhabdomyolysis may be increased when fibrates are coadministered with a statin; a significantly higher rate of this complication is observed with gemfibrozil (Lopid, Pfizer). Prescribers should refer to the respective statin labeling for important drug–drug interactions that increase statin levels and that might increase the risk of rhabdomyolysis. The risk of serious muscle toxicity appears to be increased in elderly patients and in patients with diabetes, renal failure, or hypothyroidism. Myalgia was reported in 3.3% of patients who were treated with TriLipix monotherapy, in 3.1% to 3.5% of patients receiving TriLipix plus statins, and in 4.7% to 6.1% of patients receiving statins alone. Increases in creatine phosphokinase (CPK) to more than five times the upper limit of normal (ULN) did not occur with TriLipix monotherapy but did affect 0.2% to 1.2% of patients treated with TriLipix plus statins, compared with 0.4% to 1.3% of patients using statins alone. Myopathy should be considered in all patients with diffuse myalgias, muscle tenderness or weakness, or markedly elevated CPK levels. Patients should promptly report unexplained muscle pain, tenderness, or weakness, particularly if they also have malaise or fever. CPK levels should be assessed in patients reporting these symptoms, and TriLipix and statin therapy should be discontinued if elevated CPK levels occur or if myopathy or myositis is present. Serum creatinine. Reversible elevations in serum creatinine have been reported in patients receiving TriLipix as continued on page 91 Fenofibric Acid Capsule, Delayed Release (TriLipix) Manufacturer: Abbott Laboratories, Abbott Park, Ill. Indications: Fenofibric acid is indicated as an adjunct to diet in combination with a statin to help reduce serum triglyceride and low-density lipoprotein-cholesterol (LDL-C) levels and to raise high-density lipoprotein-cholesterol (HDL-C) levels in patients with mixed dyslipidemia and coronary heart disease (CHD) or who have other forms of atherosclerosis (peripheral arterial disease, abdominal aortic aneurysm, or carotid artery disease); diabetes; or multiple risk factors that confer a 10-year risk for CHD greater than 20%. Severe hypertriglyceridemia. Improving glycemic control in diabetic patients showing fasting chylomicronemia usually obviates the need for pharmacological inter vention. Markedly elevated levels of triglycerides (above 2,000 mg/dL) may increase the risk of pancreatitis. The effects of the new product in reducing this risk have not been adequately studied. Primary hyperlipidemia or mixed dyslipidemia. The capsule is indicated as adjunctive therapy to diet to reduce elevated LDL-C, total cholesterol, and apolipoprotein B levels and to increase HDL-C levels in patients with primary hyperlipidemia or mixed dyslipidemia. Limitations of use. No incremental benefits of the product on cardiovascular morbidity and mortality over and above that shown for statin monotherapy have been established. 88 P&T® • February 2009 • Vol. 34 No. 2 http://www.genzyme.com http://www.helpwithcancer.org

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Pharmacy & Therapeutics - February 2009 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Pushing an Expanded Role for Pharmacists Better Asthma Management with Advanced Technology Pharmaceutical Approval Update 58th Annual Meeting, American Society of Human Genetics, 2008 American Society of Hematology, 50th Annual Meeting and Exposition 2008 San Antonio Breast Cancer Symposium Stahl’s Essential Psychopharmacology, 3rd Edition Author Guidelines

Pharmacy & Therapeutics - February 2009

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