WILMINGTON, Del., Nov. 1 /PRNewswire-FirstCall/ -- AstraZeneca announced today that it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for a new product for the management of hypertension. The product is a combination of TOPROL-XL (R) (metoprolol succinate extended-release (ER) and the thiazide diuretic, hydrochlorothiazide (HCT).
TOPROL-XL is already approved in the United States as a treatment for hypertension administered alone and/or in combination with other agents. Additional approved indications include the long-term treatment of angina pectoris, and the treatment of stable, symptomatic (NYHA Class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin. In heart failure, it was studied in patients already receiving ACE inhibitors, diuretics, and, in the majority of cases, digitalis. TOPROL-XL will continue to be available for the treatment of these conditions.
The NDA submission is based in part on the clinical results from the Assessment of TOPROL-XL Taken in Combination with Hydrochlorothiazide (ATTACH) trial, a U.S. multi-center, randomized, double-blind, placebo-controlled, unbalanced factorial study that included 1,571 hypertensive patients and examined a wide range of doses of metoprolol succinate ER, HCT, and their combinations.(1)
Since many hypertensive patients require combination therapy in order to reach optimal blood pressure levels,(2) combining two effective agents into a single drug product may simplify multi-drug treatment regimens.
About Hypertension
An estimated 65 million Americans (one in three adults) have hypertension or high blood pressure.(3) Thirty-one percent of patients with hypertension are unaware they have this condition and among all hypertensive patients, only 31% have their blood pressure under control.(4) Of patients receiving treatment for hypertension 47% do not have their blood pressure properly controlled.(5) The prevalence of hypertension increases with age -- more than 50 percent of men and women ages 60-69 and approximately 75 percent of those age 70 and older have elevated blood pressure.(6)
Lifestyle changes, such as weight loss, exercise, stopping smoking, and dietary adjustments can help reduce elevated blood pressure, and there are a number of classes of antihypertensive medications for those individuals who require drug treatment.(7)
Important Information About TOPROL-XL (R) (metoprolol succinate)
Extended-Release Tablets
TOPROL-XL is a beta1-selective (cardioselective) adrenoceptor-blocking agent, for oral administration, available as extended-release tablets. TOPROL- XL has been formulated to provide a controlled and predictable release of metoprolol for once-daily administration.
Indications for TOPROL-XL include the treatment of hypertension, alone or in combination with other antihypertensives; the long-term treatment of angina pectoris; and the treatment of stable, symptomatic (NYHA Class II or III) heart failure of ischemic, hypertensive, or cardiomyopathic origin. It was studied in patients already receiving ACE inhibitors, diuretics, and, in the majority of cases, digitalis.
TOPROL-XL is contraindicated in severe bradycardia, heart block greater than first degree, cardiogenic shock, decompensated cardiac failure, and sick sinus syndrome (unless a permanent pacemaker is in place) and in patients who are hypersensitive to any component of this product.
Patients taking TOPROL-XL(R) (metoprolol succinate extended-release tablets) should avoid abrupt cessation of therapy. Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, myocardial infarction have occurred. The dosage should be reduced gradually over a one-to-two-week period, and the patient should be carefully monitored. For full Prescribing Information for TOPROL-XL including boxed WARNING, call 1-800-236-9933 or visit http://www.TOPROL-XL.com.
TOPROL-XL should be used with caution in patients who have bronchospastic disease, thyrotoxicosis, peripheral vascular disease, who are undergoing major surgery, or who take calcium channel blockers of the verapamil and diltiazem type.
There is a risk of worsening cardiac failure during up-titration of the dose of TOPROL-XL. Patients need to consult their physicians if they experience signs or symptoms of worsening heart failure such as weight gain or increased shortness of breath.
Patients should be advised to avoid operating automobiles and machinery or engaging in other tasks requiring alertness until the patient’s response to therapy has been determined.
In patients with hypertension and angina pectoris the most common adverse events reported with immediate-release metoprolol tartrate are tiredness (10%), dizziness (10%), depression (5%), diarrhea (5%), pruritus or rash (5%), shortness of breath (3%) and bradycardia (3%).
In patients with heart failure, serious adverse events and adverse events leading to discontinuation of study medication in MERIT-HF at an incidence greater than or equal to 1% in the group receiving TOPROL-XL and greater than placebo by more than 0.5% were dizziness/vertigo (1.8% vs 1.0%), bradycardia (1.5% vs 0.4%), and accident and/or injury (1.4% vs 0.8%).
Important Information About Hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic. It is contraindicated in patients with anuria and in patients who are hypersensitive to any component of this product or to other sulfonamide-derived drugs.
Thiazide diuretics should be used with caution in patients with renal disease, hepatic disease, a history of hypersensitivity reactions, and those with systemic lupus erythematosus. Patients on lithium treatment generally should not take thiazides.
Patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: namely hyponatremia, hypochloremic alkalosis, and hypokalemia.
Thiazides cross the placental barrier and appear in the cord blood. The use of thiazides in pregnant women requires that the anticipated benefit be weighted against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, pancreatitus, thrombocytopenia and possibly other adverse reactions, which have occurred in the adult.
About AstraZeneca
AstraZeneca is a major international health care business engaged in the research, development, manufacture, and marketing of prescription pharmaceuticals and the supply of health care services. It is one of the world’s leading pharmaceutical companies with health care sales of over $21.4 billion and leading positions in sales of gastrointestinal, cardiovascular, respiratory, oncology, and neuroscience products. In the United States, AstraZeneca is a $9.6 billion health care business with more than 12,000 employees. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4Good Index.
For more information about AstraZeneca, please visit: http://www.astrazeneca-us.com.
This press release contains forward-looking statements with respect to the AstraZeneca business. By their nature, forward-looking statements and forecasts involve risks and uncertainties because they relate to events and depend on circumstances that will occur in the future. There are a number of factors that could cause actual results and developments to differ materially. For a discussion of those risks and uncertainties, please see the company’s Annual Report/Form 20-F for 2004.
(1) Papademetriou V, Hainer JW, Sugg J. Combination of Toprol-XL and hydrochlorothiazide: Results of a factorial clinical trial. American Journal of Hypertension 2005;18(5 Pt 2 Suppl S):91A, Abs P237.
(2) Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr., et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206-52.
(3) American Heart Association. The Heart Disease and Stroke Statistics - 2005 Update page. Available at: www.americanheart.org/downloadable/heart/1105390918119HDSStats2005Update.pdf. Accessed October 27, 2005.
(4) Haijar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988-2000. JAMA. 2003;290:199-206.
(5) Ibid.
(6) Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr., et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206-52.
(7) Ibid.
AstraZeneca
CONTACT: Valerie Bomberger of AstraZeneca LP, +1-302-885-4128 orvalerie.bomberger@astrazeneca.com, or Jim Minnick of AstraZeneca LP,+1-302-886-5135 or jim.minnick@astrazeneca.com
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