Roflumilast - A phosphodiesterase-4 inhibitor licensed for add-on therapy in severe COPD

Swiss Medical Weekly

Volumn 142, Issue JULY, 2012, Pages

  Taegtmeyer, Anne B ^a   Leuppi, Jörg D ^b   Kullak Ublick, Gerd A ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

Add on therapy; Chronic bronchitis; COPD; Phosphodiesterase 4 inhibitor; Roflumilast

Indexed keywords

ALUMINUM MAGNESIUM HYDROXIDE; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BRONCHODILATING AGENT; BUDESONIDE; CIMETIDINE; CORTICOSTEROID; ENOXACIN; ERYTHROMYCIN; FLUVOXAMINE; FORMOTEROL; KETOCONAZOLE; MIDAZOLAM; MONTELUKAST; RIFAMPICIN; ROFLUMILAST; SALBUTAMOL; SALMETEROL; SILDENAFIL; THEOPHYLLINE; TIOTROPIUM BROMIDE; WARFARIN; AMINOPYRIDINE DERIVATIVE; BENZAMIDE DERIVATIVE; CYCLOPROPANE DERIVATIVE; PHOSPHODIESTERASE IV INHIBITOR;

ADD ON THERAPY; ANOREXIA; AREA UNDER THE CURVE; BACKACHE; BODY WEIGHT; BRONCHITIS; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL PRACTICE; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG HALF LIFE; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; FOOD AND DRUG ADMINISTRATION; FORCED EXPIRATORY VOLUME; HEADACHE; HUMAN; HYPERTENSION; INFLUENZA; INSOMNIA; KIDNEY FAILURE; LIVER FAILURE; PLASMA CONCENTRATION-TIME CURVE; PNEUMONIA; PRACTICE GUIDELINE; REVIEW; RHINOPHARYNGITIS; SIDE EFFECT; SMOKING; UPPER RESPIRATORY TRACT INFECTION; VOMITING; DRUG COMBINATION; DRUG INTERACTION; SEVERITY OF ILLNESS INDEX;

AMINOPYRIDINES; BENZAMIDES; CYCLOPROPANES; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; HUMANS; PHOSPHODIESTERASE 4 INHIBITORS; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; SEVERITY OF ILLNESS INDEX;

EID: 84864552152     PISSN: 14247860     EISSN: None     Source Type: Journal    
DOI: 10.4414/smw.2012.13628     Document Type: Review

References (47)

1. Bridevaux PO, Probst-Hensch NM, Schindler C, et al. Prevalence of airflow obstruction in smokers and never-smokers in Switzerland. Eur Respir J. 2010;36(6):1259-69.
2. Leuppi JD, Miedinger D, Chhajed PN, et al. Quality of spirometry in primary care for case finding of airway obstruction in smokers. Respiration. 2010;79(6):469-74.
3. Mathers CD, Boerma T, Ma Fat D. Global and regional causes of death. Br Med Bull. 2009;92:7-32.
4. Siva R, Green RH, Brightling CE, et al. Eosinophilic airway inflammation and exacerbations of COPD: a randomised controlled trial. Eur Respir J. 2007;29(5):906-13. (Pubitemid 46711894)
5. Nussbaumer-Ochsner Y, Rabe KF. Systemic manifestations of COPD. Chest. 2011;139(1):165-73.
6. GOLD. Global strategy for the diagnosis, management and prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2011. Available from: http://wwwgoldcopdorg/. 2011.
7. Pinner NA, Hamilton LA, Hughes A. Roflumilast: a phosphodiesterase-4 inhibitor for the treatment of severe chronic obstructive pulmonary disease. Clin Ther. 2012;34(1):56-66.
8. Lipworth BJ. Phosphodiesterase-4 inhibitors for asthma and chronic obstructive pulmonary disease. Lancet. 2005;365(9454):167-75. (Pubitemid 40091808)
9. Tashkin DP, Celli B, Senn S, et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008;359(15):1543-54.
10. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med. 2007;356(8):775-89. (Pubitemid 46294610)
11. Scherr A, Schafroth Torok S, Jochmann A, et al. Response to add-on inhaled corticosteroids in COPD based on airway hyperresponsiveness to mannitol. Chest. 2012 Mar 29.
12. Jochmann A, Neubauer F, Miedinger D, et al. General practitioner's adherence to the COPD GOLD guidelines: baseline data of the Swiss COPD Cohort Study. Swiss Med Wkly. 2010 Apr 21.
13. Hatzelmann A, Morcillo EJ, Lungarella G, et al. The preclinical pharmacology of roflumilast - a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2010;23(4):235-56.
14. Torphy TJ. Phosphodiesterase isozymes: molecular targets for novel antiasthma agents. Am J Respir Crit Care Med. 1998;157(2):351-70. (Pubitemid 28090521)
15. FDA. Centre for Drug Evaluation and Research. Application number 022522Orig1s000. Medical Review(s). Available at http://wwwaccessdatafdagov/ drugsatfda-docs/nda/2011/022522Orig1s000MedRpdf. Last accessed 9th March 2012.
16. Daliresp®. Full prescribing information, revised September 2011. Forest Pharmaceuticals, St Louis. 2011.
17. Rennard SI, Calverley PM, Goehring UM, et al. Reduction of exacerbations by the PDE4 inhibitor roflumilast - the importance of defining different subsets of patients with COPD. Respir Res. 2011;12:18.
18. Gauvreau GM, Boulet LP, Schmid-Wirlitsch C, et al. Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects. Respir Res. 2011;12:140.
19. ClinicalTrials.gov. www.clinicaltrials.gov. [cited 2012 12.03.2012].
20. Rabe KF. Roflumilast for the treatment of chronic obstructive pulmonary disease. Expert Rev Respir Med. 2010;4(5):543-55.
21. Grootendorst DC, Gauw SA, Baan R, et al. Does a single dose of the phosphodiesterase 4 inhibitor, cilomilast (15 mg), induce bronchodilation in patients with chronic obstructive pulmonary disease? Pulm Pharmacol Ther. 2003;16(2):115-20. (Pubitemid 36369401)
22. Daxas R. Product Information. Nycomed AG, Dübendorf, Switzerland. 2012.
23. Grootendorst DC, Gauw SA, Verhoosel RM, et al. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007;62(12):1081-7. (Pubitemid 350206202)
24. Hohlfeld JM, Schoenfeld K, Lavae-Mokhtari M, et al. Roflumilast attenuates pulmonary inflammation upon segmental endotoxin challenge in healthy subjects: a randomized placebo-controlled trial. Pulm Pharmacol Ther. 2008;21(4):616-23. (Pubitemid 351982014)
25. Bethke TD, Bohmer GM, Hermann R, et al. Dose-proportional intraindividual single- and repeated-dose pharmacokinetics of roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor. J Clin Pharmacol. 2007;47(1):26-36. (Pubitemid 44973995)
26. Bethke TD, Lahu G. High absolute bioavailability of the new oral phosphodiesterase-4 inhibitor roflumilast. Int J Clin Pharmacol Ther. 2011;49(1):51-7.
27. Tenor H HA, Beume R, Lahu G, Zech K, Bethke T. Pharmacology, clinical efficacy and tolerability of phosphodiesterase-4 inhibitors: impact of human pharmacokinetics. In: Francis SH et al. (eds). In "Phosphodiesterases as drug targets, handbook of experimental pharmacology 204". Berlin Heidelberg: Springer-Verlag; 2011.
28. Rabe KF. Update on roflumilast, a phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease. Br J Pharmacol. 2011;163(1):53-67.
29. Nassr N, Lahu G, von Richter O, et al. Lack of a pharmacokinetic interaction between steady-state roflumilast and single-dose midazolam in healthy subjects. Br J Clin Pharmacol. 2007;63(3):365-70.
30. Eckermann G, Lahu G, Nassr N, et al. Absence of pharmacokinetic interaction between roflumilast and digoxin in healthy adults. J Clin Pharmacol. 2011 Jan 21.
31. Hermann R, Nassr N, Lahu G, et al. Steady-state pharmacokinetics of roflumilast and roflumilast N-oxide in patients with mild and moderate liver cirrhosis. Clin Pharmacokinet. 2007;46(5):403-16. (Pubitemid 46686466)
32. Bethke TD, Hartmann M, Hunnemeyer A, et al. Influence of renal impairment on the pharmacokinetics of oral roflumilast: an open-label, parallel-group, single-center study. Int J Clin Pharmacol Ther. 2011;49(8):491-9.
33. Briggs G FR, Yaffe S. Drugs in pregnancy and Lactation. 6th ed: Lippincott Williams and Wilkins; 2002.
34. Neville KA, Szefler SJ, Abdel-Rahman SM, et al. Single-dose pharmacokinetics of roflumilast in children and adolescents. J Clin Pharmacol. 2008;48(8):978-85. (Pubitemid 352009491)
35. Bateman ED, Rabe KF, Calverley PM, et al. Roflumilast with longacting beta2-agonists for COPD: influence of exacerbation history. Eur Respir J. 2011;38(3):553-60.
36. Rabe KF, Bateman ED, O'Donnell D, et al. Roflumilast - an oral antiinflammatory treatment for chronic obstructive pulmonary disease: a randomised controlled trial. Lancet. 2005;366(9485):563-71. (Pubitemid 41140331)
37. Vestbo J, Prescott E, Almdal T, et al. Body mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: findings from the Copenhagen City Heart Study. Am J Respir Crit Care Med. 2006;173(1):79-83. (Pubitemid 43069791)
38. Calverley PM, Rabe KF, Goehring UM, et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009;374(9691):685-94.
39. Gupta S. Side-effects of roflumilast. Lancet. 2012;379(9817):710-1; author reply 1-2.
40. Lahu G, Huennemeyer A, Herzog R, et al. Effect of repeated dose of erythromycin on the pharmacokinetics of roflumilast and roflumilast Noxide. Int J Clin Pharmacol Ther. 2009;47(4):236-45.
41. Lahu G, Huennemeyer A, von Richter O, et al. Effect of single and repeated doses of ketoconazole on the pharmacokinetics of roflumilast and roflumilast N-oxide. J Clin Pharmacol. 2008;48(11):1339-49.
42. Lahu G, Nassr N, Herzog R, et al. Effect of steady-state enoxacin on single-dose pharmacokinetics of roflumilast and roflumilast N-oxide. J Clin Pharmacol. 2011;51(4):586-93.
43. Bohmer GM, Gleiter CH, Morike K, et al. No dose adjustment on coadministration of the PDE4 inhibitor roflumilast with a weak CYP3A, CYP1A2, and CYP2C19 inhibitor: an investigation using cimetidine. J Clin Pharmacol. 2011;51(4):594-602.
44. von Richter O, Lahu G, Huennemeyer A, et al. Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. Clin Pharmacokinet. 2007;46(7):613-22. (Pubitemid 47025361)
45. Nassr N, Huennemeyer A, Herzog R, et al. Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects. Br J Clin Pharmacol. 2009;68(4):580-7.
46. Calverley PM, Sanchez-Toril F, McIvor A, et al. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;176(2):154-61. (Pubitemid 47057851)
47. Fabbri LM, Calverley PM, Izquierdo-Alonso JL, et al. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009;374(9691):695- 703.