Dulera (mometasone furoate + formoterol fumarate dihydrate) Treatment - Research Paper Example

Dulera (mometasone furoate + formoterol fumarate dehydrate) Treatment Dulera (mometasone furoate + formoterol fumarate dehydrate) was approved by FDA on June 2010 for the treatment of asthma. ‘Dulera Inhalation is a fixed-dose combination of the inhaled corticosteroid mometasone furoate plus the long-acting beta2-argonist formoterol fumarate dehydrate’ (Centerwatch.com 1995-2011). Mercks & Co.’s Dulera inhaler has been approved for people 12 years and older whose asthma isn’t controlled with other medication. Dulera ‘combines a corticosteroid (mometasone furoate) and a long-acting beta agonist (formoterol fumarate). The latter class of drug increases the risk of asthma-related hospitalization in children and teens, so Dulera should only be used by people whose asthma isn’t adequately controlled with a different class of drug’ (Doctors’s lounge 2001-2011). FDA approval of Dulera was based on clinical testing of 12-26 weeks among 1509 people. ‘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 rcommended 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’ (Businesswire 2010). For the method of action, ‘Dulera contains both mometasone furoate and formoterol fumarate, therefore, the mechanisms of actions described for the individual components apply to Dulera. The drugs represent two different classes of medications (a synthetic corticosteroid and a selective long-acting beta2-adrenergic receptor agonist) that have different effects on clinical, physiological, and inflammatory indices of asthma. Mometasone furoate is a corticosteroid demonstrating potent anti-inflammatory activity. The precise mechanism of corticosteroid action on asthma is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory effects on multiple cell types (e.g. mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g. histamine, eicosanoids, leukotrienes, and cytokines) involved in inflammation and in the asthmatic response. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma. Mometasone furoate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor, which is approximately 12 times that of dexamethasone, 7 times that o triamcinolone acetonide, 5 times that of budesonide and 1.5 times that of fluticasone. The clinical significance of these findings is unknown.’ (Businesswire 2010). The other component of Dulera is formoterol fumarate which is ‘a long-acting selective beta2-adrenergic receptor agonist (beta2-agonist. Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies, formoterol has more than 200-fold greater agonist activity at beta2-receptors than at beta1-receptors. Although beta2-receptors are the predominant adrenergic receptors in bronchia smooth muscle and beta1-receptors are the predominant receptors in the heart, there are also beta2-receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors’ (Businesswire 2010). These receptors may raise the possibility that even highly selective beta2-agonists may have cardiac effects. ‘Drug interactions with strong cytochrome P450 3A4 Inhibitors – caution should be exercised when considering the coadministration of Dulera with ketoconazole and other known strong CYP3A4 inhibitors (e.g. ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) because adverse effects related to increased systematic exposure to mometasone furoate may occur’ (Businesswire 2010). For the drug-drug interactions, ‘a single-dose crossover study was conducted to compare the pharmacokinetics of 4 inhalations of the following: mometasone furoate MDI, formoterol MDI, Dulera (mometasone furoate/formoterol fumarate MDI), and mometasone furoate MDI plus formoterol fumarate MDI administered concurrently. The results of the study indicated that there was no evidence of a pharmacokinetic interaction between the two components of Dulera. In a drug interaction study, an inhaled dose of mometasone furoate 400 mcg delivered by a dry powder inhaler was given to 24 healthy subjects twice daily for 9 days and ketoconazole 200 mg were given twice daily concomitantly on days 4 to 9. Mometasone furoate plasma concentrations were 200 pcg/mL on day 9 (211-324 pcg/mL. Mometasone furoate plasma levels appeared to increase and plasma cortisol levels appeared to decrease upon concomitant administration of ketoconazole’ (Businesswire 2010). Dulera also interacts with ‘adrenergic agents. It should be used with caution. ‘Additional adrenergic drugs may potentiate sympathetic effects. Xanthine derivatives and diuretics – use with caution. May potentiate ECG changes and/or hypokalemia. MAO inhibitors, tricycylic antidepressants, and drugs that prolong QTc interval – use with extreme caution. May potentiate cardiovascular system. Beta-blockers – use with caution and only when medically necessary. May decrease effectiveness and produce severe bronchospasm’ (Medilexicom 2010). Indications and usage – Dulera is a combination product containing a corticosteroid and a long-acting beta2-adrenergic agonist indicated for the treatment of asthma in patients 12 years of age and older. It is not indicated however for the relief of acute bronchospasm. Contraindications – primary treatment of status asthmaticus or acute of asthma requiring intensive measures. Hypersensitivity to any of the ingredients of Dulera. Dosage and administration – for oral inhalation only. Treatment of asthma in patients 12 years – 2 inhilations twice daily of Dulera 100 mcg/5mcg or 200mcg/5mcg. Starting dosage is based on prior asthma therapy’ (Businesswire 2010). Adverse effects associated with the use of Dulera may include but are not limited to ‘nasopharyngitis, sinusitis, and headache’ (centerwatch 1995-2011). Serious side effects include ‘thrush in the mouth and throat, immune system effects and a higher chance for infections, fever, feeling tired, pain, nausea, body aches, vomiting, chills, adrenal insufficiency, increased wheezing right after taking Dulera, serious allergic reactions, rash, hives, swelling of the face, mouth, tongue and breathing problems’ Medilexicon 2010). Though some believe that Mometasone shows to be superior to budesonide (advantage dulera) making it a breakthrough drug, but still there are some who are contesting its claim saying that budesonide is a very safe corticosteroid that is used in children as young as age 12 months and is an active ingredient in successful number 1 products. ‘They say Merck will just put additional funds, glossy pi’s and plenty of speaker programs to appropriately distinguish the novel product to surpass either of the competitors but still Dulera is just another me too drug’ (anonymous blog). One quick surprise though, the aerosol fixed dose combination called Dulera has been withdrawn by Merck from the approval cue at the EMEA – the European medicines agency. …’on November 5, 2010, the company advised the European Agency (EMEA) that it was withdrawing the application for marketing authorization for Zenhale, a fixed dose combination of mometasone furoate and formoterol fumarate dehydrate, which has been approved for use in asthma patients 12 years of age and older in the US as Dulera Inhalation Aerosol. The company decided to withdraw the application for Zenhale to address questions outstanding between the company and the committee for Medicinal Products for Human Use of the EMEA. The company expects to resubmit application in the future…’ (New Merck: Revisited 2010). Reference Businesswire (2010 Jun 24), Merck = FDA Approves Merck’s Dulera, Schering Corp., Retrieved www.businesswire.com/news/home. Centerwatch (2010 June), Drug Information: Dulera, Retrieved from www.centerwatch.com. Doctor’s lounge (2010 Jun 24), Dulera Inhaler Approved for Asthma, Journal, Retrieved from www.doctor’slounge.com. Medilexicon (2010), Dulera (mometasone furoate + formoterol fumorate dehydrate), Schering Corp., Retrieved www.medilexicon.com/drugs. New Merck:Reviewed (2010 Nov 8), Merck just withdrew European Zenhale (Dulera Aerosol) Approval Application on Friday, Retrieved www.newmerck.com Read More