Drug safety evaluation of roflumilast for the treatment of COPD: a meta-analysis.
BACKGROUND
Roflumilast is the only phosphodiesterase 4 inhibitor approved for the treatment of COPD patients with chronic cough and sputum, and a history of exacerbations, but the compliance to treatment is reduced by poorly tolerated adverse events (AEs).


METHODS
The synthesis of clinical evidences indicates that roflumilast 500μg once-daily increased the risk of AEs, with no impact on the risk of serious AEs (SAEs), compared with placebo. Gastrointestinal AEs were common in patients treated with roflumilast, that may also induce headache, backpain and insomnia. Roflumilast protects against COPD related AEs. The frequency of very SAEs was rare but greater in patients treated with roflumilast than placebo, although factors other than the study drug were related with these SAEs.


CONCLUSIONS
The safety profile of roflumilast administered in combination with further drugs for the treatment of COPD should be investigated through specifically designed RCTs, and the post-marketing surveillance might help to characterize the real risk of very SAEs. Roflumilast may provide more benefit than harm in patients at high risk of severe exacerbations, and the therapy discontinuation may be reduced by a correct education of patients on the generally transient and mild-to-moderate nature of gastrointestinal AEs induced by this drug.
a Department of Systems Medicine , University of Rome Tor Vergata , Rome , Italy.
Paola
P
Rogliani
a Department of Systems Medicine , University of Rome Tor Vergata , Rome , Italy.
Luigino
L
Calzetta
a Department of Systems Medicine , University of Rome Tor Vergata , Rome , Italy.
Mario
M
Cazzola
b Department of Experimental Medicine , Second University of Naples , Naples , Italy.
Maria Gabriella
MG
Matera
D000631:Aminopyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003521:Cyclopropanes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000453:epidemiology; D006801:Humans; D055118:Medication Adherence; D058988:Phosphodiesterase 4 Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D058988:Phosphodiesterase 4 Inhibitors; C424423:Roflumilast
PDE4 inhibitor; Rofllumilast; adverse events; meta-analysis; safety