WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck today announced that the U.S. Food and Drug Administration (FDA) has approved DULERA® (mometasone furoate and formoterol fumarate dihydrate) Inhalation Aerosol, a new fixed-dose combination asthma treatment for patients 12 years of age and older. DULERA is not indicated for the relief of acute bronchospasm. DULERA combines an inhaled corticosteroid (mometasone furoate) with a long-acting beta2-agonist (formoterol fumarate). The approval of DULERA is based, in part, on Phase III studies that evaluated the safety and efficacy of DULERA in patients 12 years of age and older with persistent asthma.
“Asthma control is an important treatment goal and DULERA provides a new option for physicians to help manage this chronic condition in appropriate patients.” “Despite the advances made in the treatment of asthma in recent years, many patients may still not be well-controlled on their current therapies,” said Michael S. Blaiss, M.D., clinical professor of pediatrics and medicine at the University of Tennessee Health Science Center, Memphis, Tennessee. “Asthma control is an important treatment goal and DULERA provides a new option for physicians to help manage this chronic condition in appropriate patients.”
DULERA is indicated for the treatment of asthma in patients 12 years of age and older. DULERA is not indicated for the relief of acute bronchospasm.
Long-acting beta2-adrenergic agonists (LABA), such as formoterol, one of the active ingredients in DULERA, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, DULERA should only be used for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue DULERA) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use DULERA for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.
“As a leader in researching and developing new treatments for respiratory diseases, including asthma, Merck is committed to bringing forth medicines that help meet the needs of healthcare professionals and their patients,” said James E. Fish, M.D., executive director, Global Scientific Affairs, Merck Research Laboratories. “DULERA represents an important part of this ongoing commitment.”
DULERA is a pressurized metered-dose inhaler with a built-in numeric counter that shows the number of remaining doses. DULERA will be available for patients 12 years of age and older in two strengths: DULERA 100 mcg/5 mcg and DULERA 200 mcg/5 mcg. Each inhalation contains 5 mcg of formoterol fumarate and either 100 mcg or 200 mcg of mometasone furoate. The recommended starting dose is based on prior asthma therapy. The maximum daily recommended dose is two inhalations of DULERA 200 mcg/5 mcg twice daily every day in the morning and evening. DULERA is expected to be available in retail pharmacies nationwide by the end of July 2010.
Clinical Trials - Lung Function Measures
The approval of DULERA is supported, in part, by two randomized clinical trials (Trial 1, Trial 2) lasting 12 to 26 weeks in duration. These trials involved a total of 1,509 patients 12 years of age and older with persistent asthma uncontrolled on medium or high dose inhaled corticosteroids. These studies included a 2 to 3-week run-in period with mometasone furoate to establish a certain level of asthma control.
Trial 1 compared DULERA 100 mcg/5 mcg (n=191) to its individual components, mometasone furoate 100 mcg (n=192) and formoterol 5 mcg (n=202), and placebo (n=196). Trial 2 compared DULERA 200 mcg/5 mcg (n=255) with DULERA 100 mcg/5 mcg (n=233) and mometasone furoate 200 mcg (n=240). All medications were given as two inhalations twice daily by metered dose inhalers.
Results from both clinical trials showed patients receiving DULERA (100 mcg/5 mcg or 200 mcg/5 mcg) experienced significant improvement from baseline in lung function (mean area under the concentration-time curve for forced expiratory volume in 1 second, measured from 0 to 12 hours [FEV1 AUC0-12h]) at week 12, a primary efficacy endpoint in the trials, compared to mometasone furoate (Trial 1 and 2) and placebo (Trial 1). In Trial 1, these differences were maintained through week 26.
The change in mean trough FEV1 from baseline to week 12 was assessed as another endpoint in both trials. In Trial 1, a significantly greater increase in the mean trough FEV1 was observed for DULERA 100 mcg/5 mcg compared to formoterol 5 mcg (the primary treatment comparison) as well as to placebo. In trial 2, a greater numerical increase in the mean trough FEV1 were was observed for DULERA 200 mcg/5 mcg compared to DULERA 100 mcg/5 mcg and mometasone furoate 200 mcg.
Clinical Trials - Clinically Judged Deteriorations in Asthma or Reduction in Lung Function
Clinically judged deteriorations in asthma or reductions in lung function were assessed in Trial 1 as another primary endpoint to evaluate the contribution of mometasone furoate 100 mcg to DULERA 100 mcg/5 mcg (primary treatment comparison DULERA vs. formoterol). Deteriorations in asthma were defined as any of the following: a 20 percent decrease in FEV1; a 30 percent decrease in peak expiratory flow (PEF) on two or more consecutive days; emergency treatment, hospitalization, or treatment with systemic corticosteroids or other asthma medications not allowed per protocol. Fewer patients who received DULERA 100 mcg/5 mcg reported an event compared to patients who received formoterol 5 mcg (p<0.001).
In Trial 2, clinically judged deterioration in asthma or reduction in lung function was also assessed as an additional endpoint. Fewer patients who received DULERA 200 mcg/5 mcg or DULERA 100 mcg/5 mcg compared to mometasone furoate 200 mcg alone reported an event, using the same definition as Trial 1.
Clinical Trials - Safety Data
The most common treatment-emergent adverse events were nasopharyngitis, sinusitis and headache. These adverse events were reported at an incidence of greater than or equal to 3.0 percent and more commonly than placebo. Oral candidiasis has been reported in clinical trials at an incidence of 0.7 percent in patients using DULERA 100 mcg/5 mcg, 0.8 percent in patients using DULERA 200 mcg/5 mcg and 0.5 percent in the placebo group. Similar safety outcomes were observed in a long-term 52-week trial of patients 12 years of age and older receiving DULERA (100 mcg/5 mcg or 200 mcg/5 mcg) or active comparator. Dysphonia was observed at a higher frequency in the longer term treatment trial at a reported incidence of 7/141 (5%) patients receiving DULERA 100 mcg/5 mcg and 5/130 (3.8%) patients receiving DULERA 200 mcg/5 mcg.
Important Safety Information about DULERA®
WARNING: ASTHMA-RELATED DEATH Long-acting beta2-adrenergic agonists (LABA), such as formoterol, one of the active ingredients in DULERA, increase the risk of asthma-related death. Data from a large placebo-controlled U.S. study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of the LABA, including formoterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.
When treating patients with asthma, prescribe DULERA only for patients with asthma not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue DULERA) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use DULERA for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids.
DULERA is contraindicated in the primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required. DULERA is contraindicated in patients with known hypersensitivity to any of the ingredients in DULERA.
DULERA is NOT a rescue medication and does NOT replace fast-acting inhalers to treat acute symptoms. Increasing use of inhaled, short-acting beta2-agonists is a marker for deteriorating asthma. In this situation, the patient requires immediate re-evaluation with reassessment of the treatment regimen.
Patients using DULERA should not use additional formoterol or other long-acting inhaled beta2-agonists for any reason.
DULERA should be used with caution in patients with tuberculosis, fungal, bacterial, viral (including chicken pox or measles), or parasitic infections; or ocular herpes simplex infections because of the potential for worsening of these infections. A more serious or even fatal course of chickenpox or measles can occur in susceptible patients.
Particular care is needed for patients who are transferred from systemically active corticosteroids to DULERA. Deaths due to adrenal insufficiency have occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.
Mometasone furoate, a component of DULERA, will often help control asthma symptoms with less suppression of HPA function than therapeutically equivalent oral doses of prednisone. Since mometasone furoate is absorbed into the circulation and can be systemically active at higher doses, the beneficial effects of DULERA in minimizing HPA dysfunction may be expected only when recommended dosages are not exceeded and individual patients are titrated to the lowest effective dose.
Because of the possibility of systemic absorption of inhaled corticosteroids, patients treated with DULERA should be observed carefully for any evidence of systemic corticosteroid effects. Particular care should be taken in observing patients postoperatively or during periods of stress for evidence of inadequate adrenal response.
It is possible that systemic corticosteroid effects such as hypercorticism and adrenal suppression (including adrenal crisis) may appear in a small number of patients, particularly when mometasone furoate is administered at higher than recommended doses over prolonged periods of time. If such effects occur, the dosage of DULERA should be reduced slowly, consistent with accepted procedures for reducing systemic corticosteroids and for management of asthma symptoms.
Caution should be exercised when considering the coadministration of DULERA with long-term ketoconazole and other known strong CYP3A4 inhibitors, or in patients being treated with MAO inhibitors or tricyclic antidepressants.
Discontinue DULERA and institute alternative therapy if paradoxical bronchospasm occurs.
Excessive beta-adrenergic stimulation has been associated with central nervous system and cardiovascular effects. DULERA should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids, including mometasone furoate, a component of DULERA.
Inhaled corticosteroids, including DULERA, may cause a reduction in growth velocity when administered in pediatric patients.
Glaucoma, increased intraocular pressure, and cataracts have been reported following the use of long-term inhaled corticosteroids, including mometasone furoate, a component of DULERA.
DULERA, like other medications containing sympathomimetic amines, should be used with caution in patients with convulsive disorders or thyrotoxicosis; and in patients who are unusually responsive to sympathomimetic amines. Doses of the related beta2-agonist albuterol, when administered intravenously, have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.
Beta2-agonist medications may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. Clinically significant changes in blood glucose and/or serum potassium were seen infrequently during clinical studies with DULERA at recommended doses.
The most common treatment-emergent adverse events reported in = three percent of patients and more common than placebo included nasopharyngitis, sinusitis, and headache.
About Asthma
Asthma is a chronic lung disease characterized by inflammation of the air passages, resulting in the temporary narrowing of the airways. Asthma symptoms can be triggered by allergens or irritants and can include difficulty breathing, wheezing, coughing, shortness of breath and chest tightness.
About Merck
Today’s Merck is a global healthcare leader. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com.
Forward-Looking Statement
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The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the U.S. and internationally and the exposure to litigation and/or regulatory actions.
Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2009 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see attached Full Prescribing Information including Boxed Warning for DULERA. Full prescribing information is also available at www.spfiles.com/pidulera.pdf
DULERA® is a trademark of Schering Corp., a subsidiary of Merck & Co., Inc.
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use DULERA safely and effectively. See full prescribing information for DULERA.
DULERA® 100 mcg/5 mcg (mometasone furoate 100 mcg and formoterol fumarate dihydrate 5 mcg) Inhalation Aerosol
DULERA® 200 mcg/5 mcg (mometasone furoate 200 mcg and formoterol fumarate dihydrate 5 mcg) Inhalation Aerosol
FOR ORAL INHALATION
Initial U.S. Approval: 2010
WARNING: ASTHMA-RELATED DEATH See full prescribing information for complete boxed warning.
-- Long-acting beta2-adrenergic agonists (LABA), such as formoterol, one of the active ingredients in DULERA, increase the risk of asthma-related death. Data from a large placebo-controlled U.S. study that compared the safety of another LABA (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of the LABA, including formoterol. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.
-- When treating patients with asthma, prescribe DULERA only for patients with asthma not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue DULERA) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use DULERA for patients whose asthma is adequately controlled on low or medium dose inhaled corticosteroids. (1.1, 5.1)
INDICATIONS AND USAGE
DULERA is a combination product containing a corticosteroid and a long-acting beta2-adrenergic agonist indicated for:
•Treatment of asthma in patients 12 years of age and older. (1.1) Important limitations:
•Not indicated for the relief of acute bronchospasm. (1.1) DOSAGE AND ADMINISTRATION
For oral inhalation only.
Treatment of asthma in patients =12 years: 2 inhalations twice daily of DULERA 100 mcg/5 mcg or 200 mcg/5 mcg. Starting dosage is based on prior asthma therapy. (2.2)
DOSAGE FORMS AND STRENGTHS
Inhalation aerosol containing a combination of mometasone furoate (100 or 200 mcg) and formoterol fumarate dihydrate (5 mcg) per actuation. (3)
CONTRAINDICATIONS
•Primary treatment of status asthmaticus or acute episodes of asthma requiring intensive measures. (4.1) •Hypersensitivity to any of the ingredients of DULERA. (4.2) WARNINGS AND PRECAUTIONS
•Asthma-related death: Long-acting beta2-adrenergic agonists increase the risk. Prescribe only for recommended patient populations. (5.1)
•Deterioration of disease and acute episodes: Do not initiate in acutely deteriorating asthma or to treat acute symptoms. (5.2)
•Use with additional long-acting beta2-agonist: Do not use in combination because of risk of overdose. (5.3)
•Localized infections: Candida albicans infection of the mouth and throat may occur. Monitor patients periodically for signs of adverse effects on the oral cavity. Advise patients to rinse the mouth following inhalation. (5.4)
•Immunosuppression: Potential worsening of existing tuberculosis, fungal, bacterial, viral, or parasitic infection; or ocular herpes simplex infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. Use with caution in patients with these infections because of the potential for worsening of these infections. (5.5)
•Transferring patients from systemic corticosteroids: Risk of impaired adrenal function when transferring from oral steroids. Taper patients slowly from systemic corticosteroids if transferring to DULERA. (5.6)
•Hypercorticism and adrenal suppression: May occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue DULERA slowly. (5.7)
•Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Risk of increased systemic corticosteroid effects. Exercise caution when used with DULERA. (5.8)
•Paradoxical bronchospasm: Discontinue DULERA and institute alternative therapy if paradoxical bronchospasm occurs. (5.9)
•Patients with cardiovascular disorders: Use with caution because of beta-adrenergic stimulation. (5.11)
•Decreases in bone mineral density: Monitor patients with major risk factors for decreased bone mineral content. (5.12)
•Effects on growth: Monitor growth of pediatric patients. (5.13)
•Glaucoma and cataracts: Monitor patients with change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts closely. (5.14)
•Coexisting conditions: Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. (5.15)
•Hypokalemia and hyperglycemia: Be alert to hypokalemia and hyperglycemia. (5.16)
ADVERSE REACTIONS
Most common adverse reactions (reported in =3% of patients) included:
•Nasopharyngitis, sinusitis and headache. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Schering Corporation, a subsidiary of Merck & Co., Inc., at 1-800-526-4099 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
•Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir): Use with caution. May cause increased systemic corticosteroid effects. (7.1)
•Adrenergic agents: Use with caution. Additional adrenergic drugs may potentiate sympathetic effects. (7.2)
•Xanthine derivatives and diuretics: Use with caution. May potentiate ECG changes and/or hypokalemia. (7.3, 7.4)
•MAO inhibitors, tricyclic antidepressants, and drugs that prolong QTc interval: Use with extreme caution. May potentiate effect on the cardiovascular system. (7.5)
•Beta-blockers: Use with caution and only when medically necessary. May decrease effectiveness and produce severe bronchospasm. (7.6)
USE IN SPECIFIC POPULATIONS
•Hepatic impairment: Monitor patients for signs of increased drug exposure. (8.6)
