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FDA APPROVES NEW COPD DRUG: ROFLUMILAST

5 de março de 2011

FDA approves new drug for COPD

(PULMAOSANEWS) The Food and Drug Administration (FDA) approved the Roflumilast (Daxas ®), a new drug that prevents and reduces the frequency of exacerbations, acting in the elevation of intracellular cyclic AMP (cAMP), preventing worsening symptoms of lung disease obstructive pulmonary disease (COPD), which is now the third leading cause of death in the United States.
COPD is an  umbrella term that homes two lung diseases: pulmonary emphysema and chronic bronchitis. The COPD disease results from chronic inflammation of the airways caused by inhalation of toxic products whose main generator factor is tobacco smoking.

Pathophysiology:

Environmental pollution and smoking mainly promote migration of inflammatory cells (macrophages, neutrophils, CD8, and dendritic cells) to the lung. These are deposited in the airways, causing chronic local and systemic damage. These cells are already present since the early stages of COPD, and its population will increase as the COPD patient continues to smoke and thus causing the perpetuation and worsening of inflammation. [Fig1].

Fig 1-Cigarette causes an "inflammatory cascade"and generates COPD.

It is this constant aggression, caused by continued smoking, which impairs the lung function and leads to the development of comorbidities such as heart failure, osteoporosis, pulmonary hypertension, etc, that cause the worsening of COPD symptoms that can range from shortness of breath, chronic cough and sputum over .

An exacerbation (acute worsening) of COPD can last up to several weeks, resulting in worsening of dyspnea (breathlessness), decline in lung function, increased risk of death, and anxiety and fall in the general.
Thus, the concentration of inflammatory cells is directly proportional to time and the evolution of the COPD disease.

Therefore, in a patient classified as GOLD 4 (FEV1 <35%), the number of inflammatory Cells is much higher than in patients with GOLD 1 /FEV = 80% [Fig2].

Fig2-Inflammation is present in any state classification of COPD (GOLD)

The constant action of inflammatory cells cause damage in the pulmonary and bronchial architecture, resulting in obstructive bronchiolitis, and destruction of bronchial bronchial cilia, fibrosis, which results in retention of secretions (mucus) and lung emphysema (hyperinflation) (Fig.3)
The cascade of inflammatory events is mediated by secondary messengers such as intracellular cAMP – Involved in the “fine adjustment” of inflammatory cells, in mucus production and in the bronchi remodeling (fibrosis of the airways). CAMP is degraded by a enzyme named Phosphodiesterase 4.
Thus, maintenance of high concentrations of intracellular cAMP in its active form, exerts a regulatory restraint and it inhibits the inflammatory reaction.

Mechanism of Action

The Roflumilast is a potent inhibitor of the enzyme Phosphodiesterase type 4 (PDE-4). This causes an immediate increase in intracellular cAMP-Activity, reducing inflammation process.
Roflumilast is recommended for people with severe COPD (FEV1 <50%  or GOLD 3), treating the symptoms of cough and excess mucus associated with chronic bronchitis. Therefore, the Roflumilast is not intended to treat emphysema, another form of COPD.

The Roflumilast should not be used to treat episodes of acute / COPD exacerbation (acute bronchospasm), and is not recommended for people younger than 18 years.
The safety and efficacy of Roflumilast was demonstrated in two Phase 3 clinical studies that included more than 1,500 patients aged over 40 years.
The FDA approved Roflumilast, with the warning that patients may present potential risks associated with mental health, including changes in mood, thought or behavior, as well as unexplained weight loss.
The most common side effects reported by those receiving Roflumilast include diarrhea, nausea, headache, insomnia, pain in the dorsal region, appetite loss  and dizziness.
ANVISA (Brazilian Agency for Sanitary Vigilance) also approved the Daxas ® in February 2011.

The Roflumilast is marketed by Forest Pharmaceuticals / Nycomed, a subsidiary of Forest Laboratories in the United States.

Sources:

PULMAOSANEWS- PULMAOSA- Lungs, Your Atmosphere, your Life!®

FDA- Food And Drugs Administration

Forest Pharmaceuticals

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