Drug Topics - February 11, 2008 - (Page 45) www.drugtopics.com FEBRUARY 11, 2008 DRUG TOPICS 45 CONTINUING EDUCATION An ongoing CE program of The University of Florida College of Pharmacy and DRUG TOPICS E 3C C S DIT RE New drug update of 2007 Joshua G. Chestnutt, Pharm.D., BCPS, Clinical Pharmacist, and Adam D. Landers, Pharm.D., Clinical Pharmacist, Columbus Regional Healthcare System, Columbus, Ga. CE The University of Florida College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education ACPE # 012-999-08001-H04-P ACPE # 012-999-08001-H04-T T his continuing education lesson reviews the new molecular entities (NMEs) approved by the Food & Drug Administration in 2007. Some 78 New Drug Applications (NDAs) were cleared, including 16 NMEs (see Tables 1 and 2). Six notable biological entities were also approved. This makes 2007 with fewer applications approved than any other year in recent history. Of the 78 NDAs reviewed by the FDA in 2007, 71 received standard review, seven received priority review, and five were granted orphan drug status designation. Among the approvals are the first in a new class of antiretrovirals, a transdermal dopamine agonist used in the treatment of Parkinson’s disease, a first medical therapy option available in the treatment of phenylketonuria, and a once-daily cardioselective -blocker. ALISKIREN (Novartis) Tekturna FDA rating: 1-S (S = standard review) Aliskiren is a new antihypertensive agent that acts on the renin-angiotensin-aldosterone system (RAAS) in a novel way. Indication: Aliskiren is indicated for the treatment of hypertension either alone or in combination with other antihypertensive agents. The combination of aliskiren and maximal doses of ACE inhibitors has not been studied sufficiently. Pharmacology and pharmacokinetics: Aliskiren acts on the RAAS by directly inhibiting renin activity. Renin is secreted by the kidneys as a result of decreases in blood volume and renal perfusion. A series of enzymatic reactions results in production of angiotensin II, which increases blood pressure. Angiotensin II provides negative feedback to the system by inhibiting renin release. Aliskiren is unique from ACE inhibitors and ARBs because the increase in plasma renin activity seen with these other classes is absent. In studies, however, a reduction in plasma renin activity did not correlate with blood pressure reduction. When aliskiren is administered orally, peak plasma concentrations are reached within one to three hours. Mean area under the curve (AUC) is decreased by 71% when the drug is taken with high-fat meals. One-fourth of the dose appears unchanged in the urine. CYP3A4 seems to be responsible for the majority of the drug’s metabolism. Precautions: Like all drugs that modify the RAAS, aliskiren should never be used in pregnancy due to the risk of fetal/neonatal morbidity and mortality. It belongs to pregnancy category C for the first trimester and D for the second and third trimester. Aliskiren should not be used in patients who have experienced angioedema with ACE inhibitors or ARBs because of the associated risk. Patients who are volume or salt depleted, and thus have an activated RAAS, should have the underlying condition corrected before aliskiren is initiated to prevent hypotension. Aliskiren should not be used in patients with greater than moderate renal dysfunction or renal artery stenosis because the drug was not studied in these populations. While hyperkalemia is rare when this agent is used alone, greater concern is required based on concomitant factors, such as use with other drugs that increase potassium levels. Drug interactions: Aliskiren is a substrate of CYP3A4. CYP3A4 inhibitors would be expected to increase aliskiren levels. When co-administered with ketoconazole, levels of aliskiren increased substantially. While aliskiren neither inhibits nor induces CYP450 enzymes, a significant reduction in furosemide exposure was seen when co-administered with aliskiren. Adverse effects: Aliskiren was generally well tolerated in trials. Dose-related gastrointestinal (GI) This lesson is no longer valid for CE credit after 2/28/10. To obtain immediate CE credit, take the test online at www.drugtopics.com. Just click on the “Continuing Education” box on the Drug Topics home page, which will take you to the CE site. Log in, find and click on this lesson, and follow the three simple steps. Test results will be displayed immediately and you can print the certificate showing your earned CE credits. The authors disclose that they have no financial relationship with any manufacturer in this area of medicine. For questions concerning PRINT CEs, call (352) 273-6275. For questions concerning ON-LINE CEs, call (866) 261-3558. http://www.drugtopics.com http://www.drugtopics.com
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