Pharmacy & Therapeutics - February 2009 - (Page 94)

MEETING HIGHLIGHTS: ASHG becoming a more realistic possibility, given that more than a 50% variation can be accounted for by demographics and SNPs in genes encoding VKORC1, CYP 2C9, and CYP 4F2. Pharmaceutical Approval Update continued from page 91 Inducing PGC-1α Expression in Huntington’s Disease May Slow Neuronal Dysfunction and Neurodegeneration • Albert R. La Spada, MD, PhD, Director, Center for Neurogenetics and Neurotherapeutics, and Associate Professor of Laboratory Medicine, Medical Genetics, Pathology, and Neurology, University of Washington, Seattle, Wash. Huntington’s disease is an autosomal dominant neurological disorder, characterized by uncoordinated movements and cognitive decline that affect almost 40,000 individuals in the U.S. The pathogenesis of this disease results from the expansion of a CAG (glutamine) sequence in the huntingtin (htt) gene; the mutation produces a polyglutamine protein (polyQ) that misfolds and is not susceptible to degradation by proteasomes. There is no cure for HD, although some recent studies have highlighted the importance of mitochondrial function in maintaining neuronal function. In their earlier work, Dr. La Spada and his associates had found that polyQ-expanded htt was localized to the nucleus and disrupted the transcription necessar y for mitochondrial biogenesis and oxidative phosphorylation. The transcription co-activator PGC-1α, a key regulator of mitochondrial biogenesis, seems to be the main target for transcription interference. More recently, Dr. La Spada’s team sought to determine whether inducing PGC-1α could improve neurodegeneration in Huntington’s disease in a mouse model. Based on motor tests, preliminary results indicated that restoring PGC-1α does ameliorate HD progression. In addition, the overexpression of PGC-1α led to a reduced buildup of misfolded htt proteins in the brains of transgenic mice. These findings indicate that htt protein indirectly interferes with PPAR-γ, a peroxisome proliferator-activator receptor that is positively modulated by PGC-1α. Dr. La Spada said the results imply that potential new therapies are already available and are currently being used in humans. PPAR-γ is, in fact, a possible therapeutic target. Currently, PPAR-γ agonists are being developed and studied in human clinical trials. In addition, all-trans-retinoic acid, a systemic antineoplastic and topical dermatological agent, induces PPAR-γ to mediate pro-survival signaling. The researchers were excited about the results of their study, because “the findings could ultimately lead to the first potential treatment for this currently fatal disease.” I (1%) in the fenofibrate group. In the Coronary Drug Project, more clofibrate patients experienced definite or suspected fatal or nonfatal PE or thrombophlebitis compared with the placebo group (5.2% vs. 3.3% at five years). Dosage and Administration: TriLipix is available in strengths of 45 mg and 135 mg. Before receiving this medication, either alone or with a statin, patients should follow a lipidlowering diet and should continue with this diet during treatment. The capsules can be taken without regard to meals. Serum lipids should be monitored periodically. The maximum dose is 135 mg once daily. Coadministration with statins for mixed dyslipidemia. TriLipix 135 mg may be coadministered with a statin in patients with mixed dyslipidemia. For convenience, the daily dose may be taken at the same time as a statin. Coadministration with the maximum dose of a statin has not been evaluated and should be avoided unless the benefits are expected to outweigh the risks. Severe hypertriglyceridemia. The initial dose of TriLipix is 45 to 135 mg once daily. The dosage should be tailored according to each patient’s response and should be adjusted, if necessary, following repeated lipid determinations at fourweek to eight-week intervals. The maximum dose is 135 mg once daily. Primary hyperlipidemia or mixed dyslipidemia. The TriLipix dose is 135 mg once daily. Impaired renal function. TriLipix should be initiated at a dose of 45 mg once daily in patients with mild-to-moderate renal impairment. The dose should be increased only after an evaluation of the effects on renal function and lipid levels at this dose. TriLipix should be avoided in patients with severely impaired renal function. Elderly patients. The dose depends on the patient’s renal function. Commentar y: TriLipix, a delayed-release capsule, can be used along with diet to help lower triglyceride and LDL-C levels and to raise HDL-C levels. This drug is the first fibrate to be approved for use in combination with a statin. The active component in TriLipix is the same as in TriCor, an older formulation of Abbott’s fenofibric acid. The newer formulation comprises fenofibric acid, a binder, and optional excipients. In clinical studies of almost 2,700 patients with mixed dyslipidemia, TriLipix was more effective in controlling the three lipids when used with a statin compared with the use of the statin alone. TriLipix has not been shown to prevent heart disease or heart attacks. It is not indicated for patients with liver, gallbladder, or severe kidney disease; nursing mothers; or those allergic to any ingredient in the product. Source: www.rxabbott.com I 94 P&T® • February 2009 • Vol. 34 No. 2 http://www.rxabbott.com

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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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