FDA Approves First New Anti-Obesity Drug in Years
In this issue: Lorcaserin for weight loss; statins and fatigue; treatment-resistant gonorrhea; hydrocodone classification changes; USPSTF recommendations; and FDA actions.
Magic bullet for weight management?
The FDA has approved lorcaserin, the first new weight loss medication in more than a decade. The drug is approved for chronic weight management in adults with a body mass index of 30 or greater, or 27 or greater in those with weight-related conditions such as high blood pressure, type 2 diabetes, or hypercholesterolemia. Lorcaserin works by activating the serotonin 2C receptor in the brain, which promotes satiety. Approval was based on the results of three randomized, placebo-controlled trials of nearly 8000 obese and overweight patients with and without type 2 diabetes. All participants received lifestyle modification and reduced-calorie diets as well as exercise counseling. Lorcaserin was associated with an average weight loss of 3-3.7% compared to placebo over 1 year. Those with type 2 diabetes experienced favorable changes in glycemic control. There is no evidence of valvulopathy associated with the drug; although serotonin syndrome is a concern, especially when the locaserin is taken with an SSRI or some migraine drugs. The most common side effects include headache, dizziness, fatigue, nausea, dry mouth, and constipation as well as hypoglycemia in diabetic patients. Lorcaserin will be marketed by Arena Pharmaceuticals as Belviq.
Do statins cause fatigue?
Statins may be associated with fatigue and exertional intolerance, according to a small study from UC San Diego. Researchers randomized just over 1000 patients (692 men and 324 women) to simvastatin 20 mg (lipophilic statin), pravastatin 40 mg (hydrophilic statin), or placebo for 6 months. The outcomes were self-ratings of change in baseline in "energy" and "fatigue with exertion." Statin users were more likely to report worsening energy and fatigue compared to placebo (P = 0.002) Fatigue and exertional intolerance was worse with simvastatin compared to pravastatin (simvastatin, P = 0.03; pravastatin, P = 0.01). Women were more severely affected than men. The authors acknowledge that these findings are based on small numbers and findings are provisional. However, they also state that "this is the first randomized evidence of affirming unfavorable statin effects on energy and exertional fatigue." They further suggest that these effects "germane to quality of life, merit consideration when prescribing or contemplating use of statins, particularly in groups without expected morbidity/mortality benefit." (Arch Intern Med published online June 11, 2012. doi: 10.1001/archinternmed.2012.2171). The study also raises the potential issue of increased adverse effects of lipophilic statins such as simvastatin. The various risks and benefits of lipophilicity have been debated for years. It is clear that highly lipophilic statins, such as the now removed cerivastatin (Baycol), may have more muscle toxicity, and may have more CNS adverse effects as well. Of currently marketed statins, simvastatin is the most lipophilic, while pravastatin and rosuvastatin are the least.
Call to action for resistant gonorrhea
The World Health Organization (WHO) is calling for urgent action to prevent the spread of "untreatable gonorrhea" around the world. The concern is based on reports from several countries, including Japan, United Kingdom, Australia, France, Sweden, and Norway, of gonorrhea that is resistant to cephalosporin antibiotics — the last remaining treatment option. According to WHO, more than 100 million people are infected with gonorrhea annually, and the world is faced with "dwindling treatment options." WHO is calling for greater vigilance on the correct use of antibiotics and more research into alternative treatment regimens for gonococcal infections. The agency also calls for increased monitoring and reporting of resistant strains as well as better prevention, diagnosis, and control of gonococcal infections. Single-dose treatment to assure adherence is also important as is the treatment of partners. WHO also stresses education and prevention, with special attention to high-risk groups such as sex workers and men who have sex with men. Cephalosporin-resistant gonorrhea has not been reported in the United States yet, but surveillance systems are in place. According to a recent CDC editorial in the New England Journal of Medicine, "It is time to sound the alarm. During the past 3 years, the wily gonococcus has become less susceptible to our last line of antimicrobial defense..." (N Engl J Med 2012; 366:485-487).
Changes on horizon for hydrocodone drugs
Could Vicodin soon be a Schedule II drug? The answer may be yes depending on congressional action this summer. The U.S. Senate recently passed The FDA Safety and Innovation Act (S 3187) with an amendment to classify all hydrocodone-containing products from Schedule III to Schedule II. The House of Representative's version of the bill did not contain similar language, and the proposal is under consideration for the final bill to be sent to the President for signature later this summer. Meanwhile, lawmakers in New York are moving forward with legislation that would make all hydrocodone-containing drugs Schedule II. If enacted, these laws would categorize hydrocodone containing drugs, such as Vicodin and Norco, in the same group with morphine, oxycodone, and methadone. Schedule II drugs cannot be phoned in, and patients are required to receive a new prescription for each refill. The proposed tightened regulations are in response to the explosion of prescription opioid abuse nationwide. Meanwhile, pharmacy groups, such as the American Pharmacists Association, are opposed to the legislation and are actively lobbying against it, arguing that it is unnecessarily restrictive to patients who legitimately need access to these drugs.
Vitamin D and calcium supplements
The U.S. Preventive Services Task Force (USPSTF) has now recommended that vitamin D and calcium supplements above the usual recommended daily allowances are of no benefit to help prevent bone fractures in healthy older women, and may actually cause harm. In a draft recommendation statement issued in early June, the USPSTF concluded that there is insufficient evidence to recommend vitamin D for prevention of cancer or combined vitamin D and calcium for the prevention of fractures in postmenopausal women or men. They further recommend against daily supplementation of more than 400 IU of vitamin D and 1000 mg of calcium carbonate. Older adults who are at risk for falls may continue to take vitamin D (www.uspreventiveserviestaskforce.org/draftrec3.htm). The draft recommendation was issued just after a study was published showing calcium plus vitamin D supplements appear to be associated with lower mortality in older individuals. In a large meta-analysis, patients receiving both calcium and vitamin D had a 9% reduction in mortality (hazard ratio, 0.91; 95% confidence interval, 0.84-0.98), although vitamin D alone did not affect mortality (J Clin Endocrinol Metab published online May 17, 2012, doi: 10.1210/jc.2011-3328).
The FDA has issued opinions on two oral novel anticoagulants. The agency turned down Janssen's application for approval of rivaroxaban (Xarelto) for the treatment of acute coronary syndrome, at least for now. The FDA did not release the reasons for the decision, but speculation is they want more information from the ATLAS-ACS trial. Rivaroxaban was approved last year for prevention of venous thromboembolism after hip or knee replacement surgery, and also for stroke prevention in patients with non-valvular atrial fibrillation (AF). The FDA also delayed the approval of apixaban (which would represent the third novel oral anticoagulant along with dabigatran and rivaroxaban) for the prevention of stroke and systemic embolism in patients with non-valvular AF. It had been widely speculated that the drug would be approved this spring, especially given that the FDA had granted a priority review for apixaban last November. The delay is similarly due to the need for additional information from the ARISTOTLE trial. Once approved apixaban will be marketed by Bristol-Myers Squibb as Eliquis.
This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study. Questions and comments, call: (404) 262-5404. E-mail: firstname.lastname@example.org.