EP Lab Digest - December 2007 - (Page 25)

DECEMBER EP PHARMACOLOGY Overview on Shire and the Discontinuation of ® Ethmozine : After the Heart Rhythm Society Intervenes, the Company Changes its Decision Bruce D. Lindsay, MD, FHRS, President, Heart Rhythm Society Director of Clinical Electrophysiology, Barnes-Jewish Hospital,Washington University School of Medicine, and Professor of Medicine at Washington University in St. Louis St. Louis, Missouri arketed by Shire under the name Ethmozine®, morizine hydrochloride has been available in the United States as an antiarrhythmic medication for approximately 20 years. It is used in the treatment of both supraventricular and ventricular arrhythmias, most often when other treatments have failed, are poorly tolerated, or are contraindicated. On July 30, 2007, Shire posted a notice on the U.S. Food and Drug Administration’s Web site under the heading “Drugs to be Discontinued” that Ethmozine® would be discontinued on August 28, 2007. Given that Ethmozine® is used in patients with life-threatening arrhythmias and has no generic alternative, the Heart Rhythm Society (HRS) contacted Shire to attempt to change the decision in a manner that would protect patients and provide adequate time for physicians to safely adjust treatment. M reason was to suppress sustained ventricular arrhythmias in patients with implantable cardioverter defibrillators (ICDs). In such cases, these patients would be at increased risk for ICD shocks if their treatment was withdrawn. Shire’s decision to discontinue the drug was based on business interests.The number of patients who were taking Ethmozine® when Shire made its decision was relatively small, so their decision to discontinue marketing ® Ethmozine can be understood. However, the relatively short interval between this decision and the proposed date to end sales was problematic, because it did not allow physicians enough time to identify which patients were taking Ethmozine® and arrange for alternative management. In a letter dated August 16, 2007, I advised the manufacturer to reconsider its decision in the interest of patient safety. I recognized why Shire had decided to remove the drug from the market, but requested additional time for physicians to contact their patients and arrange for suitable treatment. I advised Shire that patients who were receiving Ethmozine® might need to be hospitalized to evaluate the best alternatives. In some cases, an In the News: Study Shows Vernakalant Hydrochloride is Effective in Conversion to Normal Heart Rhythm in Atrial Fibrillation Patients Following Cardiac Surgery Astellas Pharma US, Inc. announced that the investigational agent vernakalant hydrochloride increased conversion to normal heart rhythm (sinus rhythm [SR]) in patients with AF following coronary artery bypass graft (CABG) or valvular surgeries. The study results were presented at the annual meeting of the American Heart Association. “Postoperative AF is common after cardiac surgery, occurring in up to 40% of patients, and has a significant effect on both the intensive care unit and ablation procedure might be required, or a trial of another drug could be indicated. I also emphasized that effective alternatives to Ethmozine® might be difficult to identify. The decision to withdraw Ethmozine ® without an appropriate transition period could put some patients at risk of an adverse outcome. A conference call was convened with executives from Shire in order to discuss the implications of their decision and the need to modify the initial plan. Shire understood our concerns and was very receptive to recommendations from the Heart Rhythm Society. They agreed to keep Ethmozine ® in stock until December 31, 2007, so that physicians would have sufficient time to identify alternative treatment for patients who might be prone to recurrent arrhythmias. Shire’s revised plan reflects the positive influence HRS can exert on behalf of its members and their patients. I am indebted to the Heart Rhythm Society’s staff, who monitored these problems and facilitated the steps needed for corrective action. For more information, please visit: www.HRSonline.org version of AF/atrial flutter to SR for at least one minute within 90 minutes. Patients demonstrating conversion within 90 minutes were categorized as responders. Other efficacy measures included time to conversion of all responders and percentage of AF patients demonstrating conversion to SR within 90 minutes for one minute. Following CABG or valvular surgery, a significantly higher percentage of patients with AF/atrial flutter given vernakalant (45 percent) demonstrated conversion to SR within 90 minutes compared to patients given placebo (15 percent), p = 0.0002. In the subset of patients with AF at baseline, conversion was observed in 47 percent treated with vernakalant compared with 14 percent given placebo (p = 0.0001). Median time to conversion among vernakalant responders was 12 minutes and SR was maintained for patients with AF/atrial flutter for 24 hours in 60 percent and for seven days in 57 percent. Seventy-five percent of vernakalant responders required only one dose of the drug.Vernakalant is not effective in atrial flutter. The most common adverse events (AEs) in patients given vernakalant were AF (20 percent), nausea (6 percent), constipation (5 percent), weight increase (5 percent) and dyspnea (5 percent). Rates of serious AEs over the entire study were similar with placebo (11 percent) and vernakalant (9 percent). In the first 24 hours, only 2 patients (2 percent) given vernakalant experienced a serious AE (complete AV block and hypotension). There were no deaths or cases of torsade de pointes. The week of August 11, 2007, the Heart Rhythm Society became aware of a decision by Shire Pharmaceuticals to discontinue the production of Ethmozine® (morizine hydrochloride). The stated deadline was August 28, 2007. Sometimes manufacturers decide to withdraw medications from the market because of low volume sales. Under most circumstances, the discontinuation or halt in distribution of a specific pharmaceutical is manageable as there are alternative medications readily available that enable continued treatment with the same results. In some cases, the decision is problematic because patient safety may be compromised if they cannot gain access to the medication.This is especially true when sales of antiarrhythmic drugs are discontinued, because patients could experience adverse consequences from recurrence of their arrhythmias. The abrupt notice by Shire alarmed our members because there was very little time to adapt patient management strategies. Although Ethmozine® had not gained widespread usage, it has unique properties that may suppress heart rhythm disorders when other antiarrhythmic agents have failed, are poorly tolerated, or are contraindicated. I believe that Ethmozine® was used primarily under these circumstances, as opposed to firstline therapy, for treatment of patients with atrial or ventricular arrhythmias. Although there is no definitive data regarding the indications for its use, one overall hospital length of stay,” said Peter Kowey, MD, William Wikoff Smith Chair in Cardiovascular Research at the Main Line Health System. “This study shows that vernakalant may be an effective treatment option for converting AF to SR following CABG or valvular surgeries.” The Atrial arrhythmia Conversion Trial (ACT II) was a randomized, double-bind, placebo-controlled, parallel-group, multinational, multicenter study evaluating the efficacy and safety of vernakalant among patients who experienced AF or atrial flutter within 24 hours to 7 days after cardiac surgery. Patients received vernakalant 3 mg/kg (n=107) or placebo (n=54) infused over 10 minutes.After 15 minutes, a second 10-minute infusion of vernakalant 2 mg/kg or placebo was given if AF or atrial flutter was present. The primary efficacy measure was the percentage of patients with treatment-induced con- http://www.HRSonline.org

Table of Contents Feed for the Digital Edition of EP Lab Digest - December 2007

EP Lab Digest - December 2007 Improved Anatomical Orientation During AF Catheter Ablation: Experience from Leipzig Heart Center One EP Lab’s Solution to the Administration of Deep Sedation Contents Letter from the Editor Spotlight Interview: Northeast Georgia Medical Center Emerging Technologies for the Electrophysiology Lab The Western Atrial Fibrillation Symposium About the PRECEDE-HF Trial: Interview with William T. Abraham, MD, FACP, FACC, FAHA Overview on Shire and the Discontinuation of Ethmozine®: After the Heart Rhythm Society Intervenes, the Company Changes its Decision Minimizing the Risk of Infection at Children’s Sibley Heart Center: Interview with Nicole Jarrell, RNC, MSN, and J. Renee Watson, RN, CIC Is There a Link Between Gasoline Vapors and Brugada Syndrome? Interview with Darko Kranjcec, MD and Hugues Abriel, MD, PhD New Feature! Pacemaker/ICD Puzzle Email Discussion Group Events Calendar Industry News and Products

EP Lab Digest - December 2007

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.