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1 January 2012 page 1 / 11

2 Neurology Advising on this article: Jack J. Chen January 5, 2012 Ocrelizumab reduces disease activity in patients with multiple sclerosis Key Point Ocrelizumab (Roche), an investigational monoclonal antibody that deactivates antibody-producing B cells, reduced the total number of gadolinium-enhancing lesions in patients with relapsing remitting multiple sclerosis (MS). Finer Points An international, multicenter, Phase II trial enrolled 220 patients with relapsing remitting MS, a form of the disease marked by the accumulation of lesions in the brain and spinal cord as well as attacks of worsening neurologic function. Patients received one of four randomly assigned treatments: placebo, ocrelizumab in low doses (600 mg) or high doses (2000 mg), or intramuscular interferon beta-1a (Avonex). Each ocrelizumab treatment consisted of 2 infusions administered 2 weeks apart. Each cycle was 24 weeks. Magnetic resonance imaging (MRI) was used to detect gadolinium-enhancing lesions in the patients. After one treatment cycle of 24 weeks, the number of gadolinium-enhancing lesions (GEL) was 89% (95% CI 68 97; P < ) lower in the low-dose ocrelizumab group than in the placebo group, and 96% (89 99; P < ) lower in the high-dose ocrelizumab group. Patients in both ocrelizumab groups had lower GEL scores than those receiving interferon beta-1a. At 24 weeks, serious adverse events were reported in 4% of patients in the placebo group, 4% of patients in the interferon beta-1a group, and 2% and 6% of patients taking the low and high doses of ocrelizumab. Annualized relapse rates were also 70 80% lower in the ocrelizumab groups than in the placebo group. Our study shows the effectiveness of B-cell depletion with both ocrelizumab doses in reducing MRI and clinical disease activity, combined with a favourable short-term safety profile, the researchers concluded. What you need to know Ocrelizumab is a recombinant, humanized, monoclonal antibody that selectively targets CD20-positive B cells. Previous data suggested that T cells controlled inflammation in MS, but recent evidence indicates that B cells may also control inflammation. There are safety concerns with disease-modifying therapies for MS, noted the authors of an accompanying editorial. Therapeutic potency will have to be balanced against early or late risk, both known and unknown. The equation is difficult to solve, the editorialists wrote, adding that the typical 2- to 3-year clinical trial for new MS agents should be extended to at least 5 years if the endpoint is to delay the disease from moving from relapsing remitting to progressive. What your patients need to know In clinical trials, a new biological agent called ocrelizumab has shown promise in patients with relapsing-remitting multiple sclerosis without raising any safety concerns. This means that a new treatment may some day be available for the disease. First, though, the drug must be tested in larger, longer clinical trials. page 2 / 11

3 Sources Kappos L et al. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011;378: Chataway J et al. Multiple sclerosis quenching the flames of inflammation [editorial]. Lancet. 2011;378: page 3 / 11

4 Respiratory Advising on this article: Devra K. Dang January 9, 2012 Azithromycin reduces COPD exacerbations Key Point In patients with chronic obstructive pulmonary disease (COPD), adding a daily dose of azithromycin to usual treatment decreased the frequency of exacerbations and improved quality of life. Finer Points In a randomized, prospective, placebo-controlled trial, 1,142 patients with COPD at 17 sites in the U.S. received azithromycin 250 mg daily or placebo for 1 year to determine if the agent would help reduce acute exacerbations. The primary outcome was time to first acute exacerbation of COPD. Patients were excluded if they had asthma, resting tachycardia, prolonged QTc interval, or hearing impairment, or were concurrently using medications that could increase QTc interval or risk of torsades de pointes (except amiodarone). Among patients who received azithromycin, the median time to the first exacerbation was 266 days (95% CI, ), compared with 174 days (95% CI, ) among patients who received placebo (P < 0.001). In the azithromycin group, the frequency of exacerbations was 1.48 exacerbations per patient year, compared to 1.83 per patient year in the placebo group (P = 0.01). The hazard ratio for having an acute exacerbation of COPD during a patient year in the azithromycin group was 0.73 (95% CI, ; P < 0.001). Patients who took azithromycin had a higher incidence of hearing loss (25%) than those in the placebo group (20%). Adding azithromycin to the usual care regimen in patients who have had an acute COPD exacerbation within the previous year or who require supplemental oxygen therapy was a valuable option, the study authors concluded, based on their analysis of loss of lung function, risk of death, quality of life, and cost of care. However, patients should be monitored for hearing loss. The safety of azithromycin therapy after 1 year is unstudied, as is the impact of long-term azithromycin therapy on bacterial resistance. What you need to know Macrolide antibiotics have antibacterial, immunomodulatory, and antiinflammatory effects. Previous research has yielded mixed results as to whether macrolide antibiotics, including azithromycin, are beneficial to patients with acute exacerbations of COPD. The long-term use of antibiotics does not come without its drawbacks, noted Nikolaos M. Siafakas, MD, PhD, in an accompanying editorial. Hearing loss was more common in the azithromycin group and macrolide-resistant bacteria colonized the airway more frequently. However, the decreased frequency of exacerbations in the azithromycin group and the improvement in the quality of life tip the scales toward the benefits of azithromycin treatment, Saifakas wrote, noting that local antibiotic resistance patterns should be closely monitored. What your patients need to know Adding azithromycin to usual treatment decreased acute exacerbations in patients with COPD and improved their quality of life. Antibiotic use was linked to hearing loss in some patients. Long-term use of azithromycin may increase the risk of antibiotic resistance, and this could patients at risk for developing difficult-to-treat infections. Sources page 4 / 11

5 Albert RK et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365: Siafakas NM. Preventing exacerbations of COPD advice from Hippocrates [editorial]. N Engl J Med. 2011;365: page 5 / 11

6 Supplemental Approvals Generic Name (Trade Name Company) January 3, 2012 Uses/Notes Prevention of invasive disease caused by Streptococcus pneumoniae Pneumococcal 13-valent conjugate vaccine [Diphtheria CRM197 Protein] (Prevnar 13 Wyeth, Pfizer) Expanded use for older adults FDA has granted Prevnar 13 accelerated approval for active immunization of adults 50 years and older for the prevention of invasive disease caused by 13 different serotypes of Streptococcus pneumoniae, according to an agency news release. The vaccine is already approved for use in children ages 6 weeks through 5 years. According to FDA, data from a randomized, multicenter trial in adult patients 50 years and older in the United States and Europe showed that Prevnar 13 induced antibody levels for 12 common serotypes of Streptococcus pneumoniae that were either comparable with or higher than the levels induced by the Pneumovax 23 (Merck) vaccine. FDA also noted that the safety of Prevnar 13 has been evaluated in about 6,000 patients 50 years and older, with commonly reported adverse reactions being pain, redness, and swelling at the injection site; limitation of movement of the injected arm; fatigue; headache; chills; decreased appetite; generalized muscle pain; and joint pain. These reactions are similar to those reported with the Pneumovax 23 vaccine. page 6 / 11

7 Supplemental Approvals Generic Name (Trade Name Company) January 4, 2012 Uses/Notes Management of acute attacks of hereditary angioedema (HAE) C1 esterase inhibitor [human] CSL Behring announced that FDA has approved a label expansion for its C1 esterase inhibitor (Berinert CSL Behring) [human] Berinert to include self-administration for the treatment of acute attacks of HAE. The new label also Self-administration now an option expands the use of the product for life-threatening laryngeal HAE attacks. The drug was originally approved in October 2009 for the treatment of acute abdominal or facial attacks of HAE in adolescent and adult patients. Berinert is administered as an intravenous infusion, traditionally by a health professional. With proper training, however, patients can safely self-administer the drug. The manufacturer recommended that self-administration be considered for all patients. Approval of self-administration was based on data from clinical studies in which intervention with Berinert at the onset of an abdominal or facial HAE attack was shown to provide significantly faster relief (median onset of relief 48 min vs. more than 4 h with placebo). In addition, data from a nonplacebo extension study showed that use of the drug to treat laryngeal attacks provided a median onset of relief of 15 minutes. page 7 / 11

8 Alerts and Recalls Generic Name (Trade Name Company) Uses/Notes January 9, 2012 Doripenem FDA reminded clinicians that doripenem should not be used for the treatment of any type of pneumonia or in (Doribax Janssen) doses greater than 500 mg every 8 hours. The agency cited a trial which terminated early in patients with Do not use for pneumonia ventilator-associated pneumonia after results demonstrated excess mortality and a numerically poorer clinical cure rate among patients treated with doripenem compared with those treated with imipenem cilastatin. FDA noted that doripenem is still considered safe and effective for its approved indications, which include treatment of adults with complicated intra-abdominal infections and complicated urinary tract infections including pyelonephritis. The agency is continuing to review data from the above trial and will communicate any new information that results from this investigation. page 8 / 11

9 Alerts and Recalls Generic Name (Trade Name Company) Uses/Notes January 9, 2012 Various OTC products Novartis Consumer Health announced a voluntary recall of various OTC products as a precautionary measure (Excedrin, NoDoz, Bufferin, Gas-X because the products may contain stray tablets, Prevention Novartis Consumer Health) capsules, or caplets from other Novartis products or broken or chipped tablets. The recall affects all lots of Stray and broken tablets prompt recall select bottle packaging configurations of Excedrin and NoDoz products with expiry dates of December 20, 2014, or earlier as well as Bufferin and Gas-X Prevention products with expiry dates of December 20, 2013, or earlier. These OTC products were distributed nationwide to wholesalers and retailers. Novartis Consumer Health is currently notifying its distributors and customers and is arranging for return of all recalled products. Patients that have any of the products being recalled should stop using the products and contact the Novartis Consumer Relationship Center at for information on how to return the affected products and receive a full refund. Patients can also access additional information about this recall by visiting Novartis reported that its Lincoln, NE, facility has voluntarily suspended operations and shipments to accelerate maintenance and other improvement activities at the site. page 9 / 11

10 Alerts and Recalls Generic Name (Trade Name Company) Uses/Notes January 9, 2012 Various opiates FDA released a safety alert today advising health professionals and patients that certain opiate products (Various trade names Endo manufactured for Endo Pharmaceuticals by Novartis Pharmaceuticals) Consumer Health may have pills, tablets, or caplets mixed in from different prescription products. This alert Opiate products also affected by Novartis recall follows a Novartis voluntary recall of various OTC products due to stray and broken tablets. Endo Pharmaceuticals reports that they are aware of only three product mix-ups with respect to these products since 2009; all three were detected by pharmacists. Endo is not aware of any patient having experienced a confirmed product mix-up, nor any adverse events attributable to a product mix-up. Patients are advised to look at the pills to ensure they all look the same. If a pill that is different in shape, size, color, or markings is found, patients are advised to bring the medicine bottle to their pharmacist and not take any of those pills. Patients who have questions should call their pharmacist, health care provider, or Endo Pharmaceuticals' call center at The following Endo Pharmaceutical products may be affected by the packaging problem: Opana ER (oxymorphone) Opana (oxymorphone) Oxymorphone hydrochloride tablets Percocet (oxycodone/acetaminophen) Percodan (oxycodone/aspirin) Endocet (oxycodone/acetaminophen) Endodan (oxycodone/aspirin) Morphine sulfate extended-release tablets Zydone (hydrocodone/acetaminophen) page 10 / 11

11 Powered by TCPDF ( APhA DrugInfoLine is an official publication of, and is owned and copyrighted by the American Pharmacists Association, the national professional society of pharmacists. Materials in APhA DrugInfoLine do not neces- sarily represent the policy, recommendations, or endorsement of APhA. The publisher, authors, editors, reviewers, and contributors have taken care to ensure that information contained in APhA DrugInfoLine is accurate and current; however, they shall have no liability to any person or entity with regard to claims, losses, or damages caused or alleged to be caused, directly or indirectly, by use of any information contained in the publication. All decisions about drug therapy must be based on the independent judgment of the clinician. Copyright , American Pharmacists Association. All rights reserved. page 11 / 11