Treatment Of Chronic Obstructive Pulmonary Disease With Phosphodiesterase-4 Inhibitor
Disclosed is a method of treatment of chronic obstructive pulmonary disease associated with chronic bronchitis in a patient at risk of exacerbations. The method includes administering to a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis and at risk of exacerbations, a maintenance dose of 500 micrograms per day of roflumilast. Also disclosed is a method of increasing pre-bronchodilator FEV 1 or post-bronchodilator FEV 1 in such a patient, and increasing pre-bronchodilator FVC or post-bronchodilator FVC in such a patient. Further disclosed is a method of reducing the rate of exacerbations in such a patient.
1 . A method of treatment of chronic obstructive pulmonary disease associated with chronic bronchitis in a patient at risk of exacerbations, comprising:
administering to a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis and at risk of exacerbations, a maintenance dose of 500 micrograms per day of roflumilast.
2 . A method of treatment of chronic obstructive pulmonary disease, comprising:
identifying a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis; and
administering a maintenance dose to said patient of 500 micrograms per day of roflumilast.
3 . The method of claim 2 , wherein said patient has a non-reversible airway obstruction (post-bronchodilator FEV 1 /FVC ratio of less than or equal to 70%).
4 . The method of claim 3 , wherein said patient further has an FEV 1 of less than or equal to 50% of the predicted FEV 1 .
5 . The method of claim 4 , wherein said patient has had at least one exacerbation during the 12 months prior to administration of roflumilast.
6 . A method of increasing pre-bronchodilator FEV 1 or post-bronchodilator FEV 1 in a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis, comprising:
administering a maintenance dose to a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis of 500 micrograms per day of roflumilast.
7 . The method of claim 6 further comprising,
assessing a first pre-bronchodilator FEV 1 or post-bronchodilator FEV 1 in a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis; and after
administering a maintenance dose to said patient of 500 micrograms per day of roflumilast, subsequently assessing a second pre-bronchodilator FEV 1 or post-bronchodilator FEV 1 , respectively, in said patient.
8 . The method of claim 6 , wherein said patient has a non-reversible airway obstruction (post-bronchodilator FEV 1 /FVC ratio of less than or equal to 70%).
9 . The method of claim 8 , wherein said patient further has an FEV 1 of less than or equal to 50% of the predicted FEV 1 .
10 . The method of claim 9 , wherein said patient has had at least one exacerbation during the 12 months prior to administration of roflumilast.
11 . A method of increasing pre-bronchodilator FVC or post-bronchodilator FVC in a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis, comprising:
administering a maintenance dose to a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis of 500 micrograms per day of roflumilast.
12 . The method of claim 11 , further comprising,
assessing a first pre-bronchodilator FVC or post-bronchodilator FVC in a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis; and after
administering a maintenance dose to said patient of 500 micrograms per day of roflumilast, subsequently assessing a second pre-bronchodilator FVC or post-bronchodilator FVC, respectively, in said patient.
13 . The method of claim 11 , wherein said patient has a non-reversible airway obstruction (post-bronchodilator FEV 1 /FVC ratio of less than or equal to 70%).
14 . The method of claim 13 , wherein said patient further has an FEV 1 of less than or equal to 50% of the predicted FEV 1 .
15 . The method of claim 14 , wherein said patient has had at least one exacerbation during the 12 months prior to administration of roflumilast.
16 . A method of reducing the rate of exacerbations in a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis, comprising:
administering a maintenance dose to a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis of 500 micrograms per day of roflumilast.
17 . The method of claim 16 , further comprising,
assessing a first rate of exacerbations in a patient with a history of chronic obstructive pulmonary disease associated with chronic bronchitis; and after
administering a maintenance dose to said patient of 500 micrograms per day of roflumilast, subsequently assessing a second rate of exacerbations in said patient.
18 . The method of claim 16 , wherein said patient has a non-reversible airway obstruction (post-bronchodilator FEV 1 /FVC ratio of less than or equal to 70%).
19 . The method of claim 18 , wherein said patient further has an FEV 1 of less than or equal to 50% of the predicted FEV 1 .
20 . The method of claim 19 , wherein said patient has had at least one exacerbation during the 12 months prior to administration of roflumilast.
21 . The method of claim 16 wherein said exacerbations are moderate.
22 . The method of claim 16 wherein said exacerbations are severe.
23 . The method of claim 16 , wherein said exacerbations include both moderate and severe exacerbations.
24 . The method of claim 1 , wherein said dose of roflumilast is administered once per day.
25 . The method of claim 24 , wherein said dose of roflumilast is administered orally.
26 . The method of claim 25 , wherein said dose of roflumilast is administered as a tablet.
27 . The method of claim 26 , wherein said tablet is D-shaped.
28 . The method of claim 27 , wherein said tablet is film-coated.
29 . The method of claim 1 , wherein said patient has experienced a history of chronic obstructive pulmonary disease for at least 12 months prior to administration of said roflumilast.
30 . The method of claim 5 , wherein said patient has experienced a history of chronic obstructive pulmonary disease for at least 12 months prior to administration of said roflumilast.
31 . The method of claim 29 , wherein said patient has been treated with a long-acting bronchodilator prior to administration of said roflumilast.
32 . The method of claim 31 , wherein said treatment with said long-acting bronchodilator is continued concurrently with maintenance administration of roflumilast.
33 . The method of claim 31 , wherein said long-acting bronchodilator is selected from the group consisting of tiotropium bromide, tiotropium bromide monohydrate, salmeterol, formoterol, aformoterol and combinations thereof.
34 . The method of claim 31 , wherein said long-acting bronchodilator is selected from the group consisting of salmeterol, tiotropium bromide, tiotropium bromide monohydrate and combinations thereof.
35 . The method of claim 2 , wherein said patient is administered a dose of less than 500 micrograms per day of roflumilast if said patient is being treated with a CYP 1A2 or dual CYP 3A4/1A2 inhibitor.
36 . The method of claim 35 , wherein said CYP 1A2 or dual CYP 3A4/1A2 inhibitor is selected from the group consisting of fluvoxamine, enoxacine and cimetidine and mixtures thereof.
37 . The method of claim 2 , wherein said patient is administered a dose of greater than 500 micrograms per day of roflumilast if said patient is being treated with a cytochrome P450 enzyme inducer.
38 . The method of claim 37 , wherein said cytochrome P450 enzyme is selected from the group consisting of rifampicin, phenobarbital, carbamazepine and phenyloin and mixtures thereof.
39 . The method of claim 2 , wherein said treatment includes concomitant administration of a long-acting beta-2 agonist.
40 . The method of claim 5 , wherein said treatment includes concomitant administration of a long-acting beta-2 agonist.
41 . The method of claim 2 , wherein said treatment excludes concomitant administration of an inhaled corticosteroid.
42 . The method of claim 5 , wherein said treatment excludes concomitant administration of an inhaled corticosteroid.
43 . The method of claim 2 , wherein said treatment includes concomitant administration of an inhaled corticosteroid.
44 . The method of claim 5 , wherein said treatment includes concomitant administration of an inhaled corticosteroid.
45 . A method to reduce the risk of chronic obstructive pulmonary disease exacerbations in patients with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations, comprising:
administering to a patient with severe chronic obstructive pulmonary disease associated with chronic bronchitis and a history of exacerbations,
a dose of 500 micrograms per day of roflumilast.
46 . The method of claim 45 , wherein said dose is administered in tablet form.
47 . The method of claim 45 , wherein said patient has a non-reversible airway obstruction (post-bronchodilator FEV 1 /FVC ratio of less than or equal to 70%).
48 . The method of claim 47 , wherein said patient further has an FEV 1 of less than or equal to 50% of the predicted FEV 1 .
49 . The method of claim 48 , wherein said patient has had at least one exacerbation during the 12 months prior to administration of roflumilast.