Severe Chronic Obstructive Pulmonary Disease (COPD) Associated with Chronic Bronchitis and History of Exacerbations (see Chronic Obstructive Pulmonary Disease, [[Chronic Obstructive Pulmonary Disease]])
Clinical Effects
Roflumilast Increases Pre/Postbronchodilator FEV1 and FVC
Roflumilast Decreases Frequency of Moderate-Severe COPD Exacerbations
Clinical Efficacy
Cardiovascular Safety of Roflumilast in COPD (Chest, 2013) [MEDLINE]
Roflumilast Decreased the Rates of Non-Fatal Acute MI and Non-Fatal Stroke
REACT Trial in Patients with Severe COPD and Chronic Bronchitis Who are at Risk of Frequent and Severe Exacerbations Despite Inhaled Corticosteroids/LABA/Tiotropium (Lancet, 2015) [MEDLINE]
Phosphodiesterase Type 4 is the Predominant cAMP-Metabolizing Enzyme Found in Inflammatory/Immune Cells: this explains the anti-inflammatory properties of these agent
Anti-Inflammatory Effects
Decreases Inflammatory Mediators
Decreased Expression of Cell Surface Markers
Inhibition of Apoptosis
Metabolism
Hepatic: phase I cytochrome P450 (CYP) reactions (isoenzymes 1A2 and 3A4) and phase II conjugation
Pharmacokinetics
Half-Life: 17 hrs
Administration
PO: 500 ug qday
Dose Adjustment
Hepatic: none (although liver disease may lead to decreased clearance)
Renal: none
Drug Interaction
Avoid Roflumilast Use with CYP3A4 Inhibitors
Clarithromycin
Erythromycin
Grapefruit
Itraconazole
Ketoconazole
Pomegranate
Protease Inhibitors: ritonavir, etc
Avoid Roflumilast Use with Dual CYP3A4 and CYP1A2 Inhibitors
Cardiovascular safety in patients receiving roflumilast for the treatment of COPD. Chest. 2013; 144(3):758–765 [MEDLINE]
Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial. Lancet. 2015 Mar 7;385(9971):857-66. doi: 10.1016/S0140-6736(14)62410-7. Epub 2015 Feb 13 [MEDLINE]
Roflumilast: a review of its use in the treatment of COPD. Int J Chron Obstruct Pulmon Dis. 2016 Jan 6;11:81-90. doi: 10.2147/COPD.S89849. eCollection 2016 [MEDLINE]