Forest Laboratories, Inc. (JOBS) Receives Decision from FDA for Supplemental New Drug Application for Bystolic(R); FDA Does Not Approve Additional Indication
NEW YORK--(BUSINESS WIRE)--Forest Laboratories, Inc. announced today that the U.S. Food and Drug Administration (FDA) did not approve the additional indication for Bystolic® (nebivolol) tablets as a treatment for stable chronic heart failure (CHF) as requested in the company’s Supplemental New Drug Application (sNDA). Bystolic is currently approved in the US for the treatment of hypertension.
However, FDA added information to the Specific Populations section of the product label under “Heart Failure” stating that in a placebo-controlled trial of 2,128 patients (1,067 with Bystolic, 1,061 placebo) over 70 years of age with chronic heart failure, on which the CHF submission was based, no worsening of heart failure was reported with nebivolol compared to placebo. If heart failure worsens physicians should consider discontinuation of Bystolic.
Forest Laboratories will continue to work closely with the FDA to discuss next steps.
About Bystolic
Bystolic (nebivolol) was approved by the U.S. Food and Drug Administration in 2007 for the treatment of hypertension (chronic high blood pressure). Bystolic is a once-daily medication effective at lowering blood pressure when taken alone or in combination with other high blood pressure medications. It is available in 2.5 mg, 5 mg, 10 mg and 20 mg tablets. In clinical trials, the discontinuation rate due to adverse events was 2.8% for Bystolic versus 2.2% for placebo. Nebivolol is approved and marketed in 60 countries outside of North America.
Important Safety Information
Contraindications
* BYSTOLIC is contraindicated in patients with severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, sick sinus syndrome (unless a permanent pacemaker is in place), severe hepatic impairment (Child-Pugh >B), and in patients who are hypersensitive to any component of this product.
Warnings and Precautions
* Do not abruptly discontinue BYSTOLIC therapy in patients with coronary artery disease. Severe exacerbation of angina and the occurrence of myocardial infarction and ventricular arrhythmias have been reported following the abrupt cessation of therapy with ß-blockers. Myocardial infarction and ventricular arrhythmias may occur with or without preceding exacerbation of the angina pectoris. Caution patients without overt coronary artery disease against interruption or abrupt discontinuation of therapy. As with other ß-blockers , when discontinuation of BYSTOLIC is planned, carefully observe and advise patients to minimize physical activity. Taper BYSTOLIC over 1 to 2 weeks when possible. If the angina worsens or acute coronary insufficiency develops, re-start BYSTOLIC promptly, at least temporarily. * BYSTOLIC was not studied in patients with angina pectoris or who had a recent MI. * In general, patients with bronchospastic diseases should not receive beta blockers. * Because beta-blocker withdrawal has been associated with an increased risk of MI and chest pain, patients already on beta-blockers should generally continue treatment throughout the perioperative period. If BYSTOLIC is to be continued perioperatively, monitor patients closely when anesthetic agents which depress myocardial function, such as ether, cyclopropane, and trichloroethylene, are used. If ß-blocking therapy is withdrawn prior to major surgery, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. The ß-blocking effects of BYSTOLIC can be reversed by ß-agonists, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Additionally, difficulty in restarting and maintaining the heartbeat has been reported with ß-blockers. * ß-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia. Advise patients subject to spontaneous hypoglycemia and diabetic patients receiving insulin or oral hypoglycemic agents about these possibilities. * ß-blockers may mask clinical signs of hyperthyroidism, such as tachycardia. Abrupt withdrawal of beta blockers in these patients may be followed by an exacerbation of symptoms or may precipitate a thyroid storm. * ß-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. * Because of significant negative inotropic and chronotropic effects in patients treated with ß-blockers and calcium channel blockers of the verapamil and dilitiazem type, monitor the ECG and blood pressure in patients treated concomitantly with these agents. * Use caution when BYSTOLIC is co-administered with CYP2D6 inhibitors (quinidine, propafenone, fluoxetine, paroxetine, etc). The dose of BYSTOLIC may need to be reduced. When BYSTOLIC is administered with fluoxetine, significant increases in d-nebivolol may be observed (ie, an 8-fold increase in AUC). * Renal clearance of nebivolol is decreased in patients with severe renal impairment. BYSTOLIC has not been studied in patients receiving dialysis. * Metabolism of nebivolol is impaired in patients with moderate hepatic impairment. BYSTOLIC has not been studied in patients with severe hepatic impairment. * Patients with a history of severe anaphylactic reactions to a variety of allergens may be more reactive to repeated challenge and may be unresponsive to the usual doses of epinephrine while taking beta blockers. * In patients with known or suspected pheochromocytoma, initiate an alpha-blocker prior to the use of any beta-blocker.
Drug Interactions
* BYSTOLIC should not be combined with other beta blockers. * Both digitalis glycosides and ß-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. * BYSTOLIC can exacerbate the effects of myocardial depressants or inhibitors of AV conduction, such as certain calcium antagonists (particularly of the phenylalkylamine [verapamil] and benzothiazepine [diltiazem] classes), or antiarrhythmic agents, such as disopyramide.
Use in Specific Populations
* Use BYSTOLIC during pregnancy only if the potential benefit justifies the potential risk to the fetus. BYSTOLIC is not recommended during nursing. * The safety and effectiveness of BYSTOLIC have not been established in pediatric patients. * In a placebo-controlled trial of 2128 patients (1067 BYSTOLIC, 1061 placebo) over 70 years of age with chronic heart failure receiving a maximum dose of 10 mg per day for a median of 20 months, no worsening of heart failure was reported with nebivolol compared to placebo. However, if heart failure worsens, consider discontinuation of BYSTOLIC.
Adverse Reactions
* The most common adverse events with BYSTOLIC versus placebo (approximately =1% and greater than placebo) were headache, fatigue, dizziness, diarrhea, nausea, insomnia, chest pain, bradycardia, dyspnea, rash, and peripheral edema. The most common adverse events that led to discontinuation of BYSTOLIC were headache (0.4%), nausea (0.2%), and bradycardia (0.2%).
About Forest Laboratories
Forest Laboratories (NYSE: FRX - News) is a U.S.-based pharmaceutical company with a long track record of building partnerships and developing and marketing products that make a positive difference in people’s lives. In addition to its well-established franchises in therapeutic areas of the central nervous and cardiovascular systems, Forest’s current pipeline includes product candidates in all stages of development and across a wide range of therapeutic areas. The Company is headquartered in New York, NY. To learn more about Forest Laboratories, visit www.FRX.com.
Except for the historical information contained herein, this release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements involve a number of risks and uncertainties, including the difficulty of predicting FDA approvals, the acceptance and demand for new pharmaceutical products, the impact of competitive products and pricing, the timely development and launch of new products, and the risk factors listed from time to time in Forest Laboratories’ Annual Report on Form 10-K, Quarterly Report on Form 10-Q, and any subsequent SEC filings.
Contact:
Forest Laboratories, Inc. Frank J. Murdolo, 1-212-224-6714 Vice President - Investor Relations Frank.Murdolo@frx.com