FLUOROQUINOLONE FORMULATIONS FOR CYSTIC FIBROSIS
The disclosure provides methods for treating cystic fibrosis with fluoroquinolone formulations.
1 . A method for treating a Pseudomonas aeruginosa pulmonary infection in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising levofloxacin to the high-risk cystic fibrosis patient.
2 . A method for reducing the incidents of a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising levofloxacin to the high-risk cystic fibrosis patient.
3 . A method for extending the time between the onset of pulmonary exacerbations in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising levofloxacin to the high-risk cystic fibrosis patient.
4 . A method for treating a pulmonary bacterial infection in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising levofloxacin to the high-risk cystic fibrosis patient.
5 . A method of treating a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising levofloxacin to the high-risk cystic fibrosis patient.
6 . A method of treating cystic fibrosis in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising levofloxacin to the high-risk cystic fibrosis patient.
7 . A method of reducing a Pseudomonas aeruginosa sputum density in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising levofloxacin to the high-risk cystic fibrosis patient.
8 . The method of any one of claims 1 - 7 , wherein the high-risk patient had at least 3 occurrences of a pulmonary exacerbation in the prior year.
9 . The method of any one of claims 1 - 7 , wherein the high-risk patient had at least 4 occurrences of a pulmonary exacerbation in the prior year.
10 . The method of any one of claims 1 - 7 , wherein the high-risk patient had at least 5 occurrences of a pulmonary exacerbation in the prior year.
11 . The method of any one of claims 2 , 3 , 5 , and 8 - 10 , wherein the pulmonary exacerbation comprises at least four of the following: (i) a change in sputum; (ii) a new or increased hemoptysis; (iii) an increased cough; (iv) increased dyspnea; (v) malaise, fatigue, or lethargy; (vi) a temperature above 38° C.; (vii) anorexia or weight loss; (viii) sinus pain or tenderness; (ix) a change in sinus discharge; (x) a change in physical examination of the chest; (xi) a decrease in pulmonary function by 10% or more from a previously recorded value; and (xii) a radiographic change indicative of pulmonary infection.
12 . The method of any one of claims 2 , 3 , 5 , and 8 - 10 , wherein the pulmonary exacerbation is a pulmonary bacterial infection.
13 . The method of any one of claims 2 , 3 , 5 , and 8 - 10 , wherein the pulmonary exacerbation is a Pseudomonas aeruginosa pulmonary infection.
14 . The method of any one of claims 2 , 3 , 5 , and 8 - 10 , wherein the pulmonary exacerbation is a Pseudomonas pulmonary infection.
15 . The method of any one of claims 2 , 3 , 5 , and 8 - 10 , wherein the pulmonary exacerbation is a Staphylococcus aureus pulmonary infection.
16 . The method of any one of claims 2 , 3 , 5 , and 8 - 10 , wherein the pulmonary exacerbation is a Staphylococcus pulmonary infection.
17 . The method of any one of claims 2 , 3 , 5 , and 8 - 10 , wherein the pulmonary exacerbation is a decrease of 10% or more in the FEV 1 of the predicted value using Hankinson/NHANES III reference equation.
18 . The method of any one of claims 1 - 17 , wherein the high-risk patient has a forced expiratory volume in 1 second (FEV 1 ) between 25 and 85 percent of their predicted values using Hankinson/NHANES III reference equation.
19 . The method of any one of claims 1 - 17 , wherein the high-risk patient had a chronic airway infection with Pseudomonas aeruginosa and had received at least three 28-day courses of an inhaled tobramycin formulation in the prior year.
20 . The method of any one of claims 1 - 17 , wherein the high-risk patient had a chronic airway infection with Pseudomonas aeruginosa and had received at least three 28-day courses of an inhaled aminoglycoside formulation in the prior year, an inhaled monobactam formulation in the prior year, an inhaled polymyxin formulation in the prior year, or a combination of two or more thereof.
21 . The method of any one of claims 1 - 20 , wherein the solution comprises levofloxacin or ofloxacin and a divalent or trivalent cation.
22 . The method of claim 21 , wherein the trivalent cation is aluminum or iron.
23 . The method of any one of claims 1 - 20 , wherein the solution comprises levofloxacin and a divalent cation.
24 . The method of claim 23 , wherein the divalent cation is magnesium, calcium, zinc, copper, or iron.
25 . The method of claim 23 , wherein the divalent cation is magnesium.
26 . The method of any one of claims 1 - 20 , wherein the solution comprises about 75 mg/ml to about 150 mg/ml of levofloxacin and about 150 mM to about 250 mM of a divalent cation.
27 . The method of claim 26 , wherein the divalent cation is magnesium, calcium, zinc, copper, or iron.
28 . The method of claim 26 , wherein the divalent cation is magnesium.
29 . The method of any one of claims 1 - 20 , wherein the solution comprises about 90 mg/ml to about 110 mg/ml of levofloxacin and about 190 mM to about 210 mM of a divalent cation.
30 . The method of claim 29 , wherein the divalent cation is magnesium, calcium, zinc, copper, or iron.
31 . The method of claim 29 , wherein the divalent cation is magnesium.
32 . The method of any one of claims 1 - 20 , wherein the solution comprises about 80 mg/ml to about 120 mg/ml of levofloxacin and about 180 mM to about 220 mM of a divalent cation.
33 . The method of claim 32 , wherein the divalent cation is magnesium, calcium, zinc, copper, or iron.
34 . The method of claim 32 , wherein the divalent cation is magnesium.
35 . The method of any one of claims 1 - 20 , wherein solution comprises about 100 mg/ml of levofloxacin and about 200 mM magnesium chloride.
36 . A method for treating a Pseudomonas aeruginosa pulmonary infection in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising ofloxacin to the high-risk cystic fibrosis patient.
37 . A method for reducing the incidents of a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising ofloxacin to the high-risk cystic fibrosis patient.
38 . A method for extending the time between the onset of pulmonary exacerbations in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising ofloxacin to the high-risk cystic fibrosis patient.
39 . A method for treating a pulmonary bacterial infection in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising ofloxacin to the high-risk cystic fibrosis patient.
40 . A method of treating a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising ofloxacin to the high-risk cystic fibrosis patient.
41 . A method of treating cystic fibrosis in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising ofloxacin to the high-risk cystic fibrosis patient.
42 . A method of reducing a Pseudomonas aeruginosa sputum density in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising ofloxacin to the high-risk cystic fibrosis patient.
43 . The method of any one of claims 36 - 42 , wherein the high-risk patient had at least 3 occurrences of a pulmonary exacerbation in the prior year.
44 . A method for treating a Pseudomonas aeruginosa pulmonary infection in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising a fluoroquinolone to the high-risk cystic fibrosis patient.
45 . A method for reducing the incidents of a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising a fluoroquinolone to the high-risk cystic fibrosis patient.
46 . A method for extending the time between the onset of pulmonary exacerbations in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising a fluoroquinolone to the high-risk cystic fibrosis patient.
47 . A method of reducing a Pseudomonas aeruginosa sputum density in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising a fluoroquinolone to the high-risk cystic fibrosis patient.
48 . A method for treating a pulmonary bacterial infection in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising a fluoroquinolone to the high-risk cystic fibrosis patient.
49 . A method of treating a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising a fluoroquinolone to the high-risk cystic fibrosis patient.
50 . A method of treating cystic fibrosis in a high-risk cystic fibrosis patient in need thereof comprising administering a therapeutically effective amount of an aerosol of a solution comprising a fluoroquinolone to the high-risk cystic fibrosis patient.
51 . The method of any one of claims 44 - 50 , wherein the fluoroquinolone is ciprofloxacin, enoxacin, gatifloxacin, gemifloxacin, lomefloxacin, moxifloxacin, norfloxacin, pefloxacin, sparfloxacin, garenoxacin, sitagloxacin, or DX-619.
52 . The method of any one of claims 44 - 50 , wherein the high-risk patient had at least 3 occurrences of a pulmonary exacerbation in the prior year.
53 . A method for treating a Pseudomonas aeruginosa pulmonary infection in a high-risk cystic fibrosis patient in need thereof comprising administering by inhalation a therapeutically effective amount of a pharmaceutical composition comprising an antibiotic to the high-risk cystic fibrosis patient.
54 . A method for reducing the incidents of a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering by inhalation a therapeutically effective amount of a pharmaceutical composition comprising an antibiotic to the high-risk cystic fibrosis patient.
55 . A method for extending the time between the onset of pulmonary exacerbations in a high-risk cystic fibrosis patient in need thereof comprising administering by inhalation a therapeutically effective amount of a pharmaceutical composition comprising an antibiotic to the high-risk cystic fibrosis patient.
56 . A method for treating a pulmonary bacterial infection in a high-risk cystic fibrosis patient in need thereof comprising administering by inhalation a therapeutically effective amount of a pharmaceutical composition comprising an antibiotic to the high-risk cystic fibrosis patient.
57 . A method of treating a pulmonary exacerbation in a high-risk cystic fibrosis patient in need thereof comprising administering by inhalation a therapeutically effective amount of a pharmaceutical composition comprising an antibiotic to the high-risk cystic fibrosis patient.
58 . A method of treating cystic fibrosis in a high-risk cystic fibrosis patient in need thereof comprising administering by inhalation a therapeutically effective amount of a pharmaceutical composition comprising an antibiotic to the high-risk cystic fibrosis patient.
59 . The method of any one of claims 53 - 58 , wherein the high-risk patient had at least 3 occurrences of a pulmonary exacerbation in the prior year.
60 . The method of any one of claims 53 - 59 , wherein the antibiotic is tobramycin.
61 . The method of any one of claims 53 - 59 , wherein the antibiotic is aztreonam.
62 . The method of claim 61 , wherein the aztreonam is aztreonam lysine.