Roflumilast (Daliresp)

Indications

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]
      • Roflumilast Decreased Exacerbations/Hospital Admissions

Pharmacology

  • Phosphodiesterase Type 4 Inhibitor (PDE4 Inhibitor) (see Phosphodiesterase Type 4 Inhibitors, [[Phosphodiesterase Type 4 Inhibitors]])
    • 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

Adverse Effects

Gastrointestinal Adverse Effects

Other Adverse Effects


References

  • 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]