Considerations for Daliresp (roflumilast) Use in Hospice

Managing drug therapy in terminally ill COPD patients can certainly be challenging. Patients may be resistant to changing long-term medication regimens.1 Patients and caregivers may even interpret medication adjustments as giving up, patient abandonment, or as a suggestion that death is imminent.1 In this patient population, especially, some medications that were once effective may no longer provide adequate symptom relief and many of these drugs have significant cost implications. One medication that often raises questions about how to proceed once patients elect hospice care is Daliresp (roflumilast).

Daliresp is an oral phosphodiesterase-4 (PDE4) inhibitor that reduces inflammation in the lungs.2 Its labeled indication is to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.3

Available literature suggests that Daliresp probably doesn’t provide significant benefit at the end of life. It reduces exacerbations in patients with severe COPD by 0.3 per year (number needed to treat =    24 patients x 1 year).3,4 A Cochrane Review of PDE4 inhibitors concluded that this drug class provides a small benefit compared to placebo in improving lung function and reducing the likelihood of COPD exacerbations. The clinical relevance of these benefits at the end of life is highly questionable.5

There are other factors that may weigh in favor of deprescribing Daliresp. It’s not a bronchodilator and doesn’t provide acute symptom relief.2,3,6 Aside from not reducing symptoms, Daliresp hasn’t been shown to improve quality of life or prolong survival.5,7 It can also cause adverse effects which may warrant deprescribing, including weight loss, diarrhea, depression, and mood swings.

Daliresp is contraindicated in patients with liver impairment and there are clinically significant drug interactions when combined with strong cytochrome P450 enzyme inducers and CYP3A4 / CYP1A2 inhibitors.3,4,6 Additionally, it shouldn’t be used in combination with theophylline due to overlapping mechanisms of action.2,3,6

Not only are there clinical questions about Daliresp’s role at end of life, but it’s also expensive – over $400/month. It certainly makes sense to consider deprescribing Daliresp at the end of life, especially since it doesn’t reduce symptoms, improve quality of life, or prolong survival.

Written by:

John Corrigan, PharmD

Clinical Pharmacist, OnePoint Patient Care

John’s primary responsibilities as a clinical pharmacist at OnePoint Patient Care are staff and partner education, medication utilization reviews, and assisting with formulary development and maintenance. He attended the University of Iowa for both undergraduate studies and pharmacy school. He earned a PharmD from the University of Iowa College of Pharmacy in 2013. He was first introduced to hospice and OnePoint Patient Care as a 4th year pharmacy student, completing a 5-week elective clinical hospice pharmacy rotation. He started his employment with OnePoint Patient Care as a staff pharmacist in 2014. He transitioned to his current role, as a clinical pharmacist, in the spring of 2019.

References:

  1. Hospice Medication Deprescribing Toolkit. National Hospice and Palliative Care Organization. November 2020. Version 1.0 Accessed July 28, 2022. https://www.nhpco.org/resources/publications/
  2. Global Strategy for the diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Global Initiative for Chronic Obstructive Lung 2022 Report. Accessed February 2, 2022. https://goldcopd.org/2022-gold-reports-2/
  3. Daliresp – roflumilast Package Insert. AstraZeneca Pharmaceuticals LP; 2011, revised March 2019. Accessed February 1, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/022522s003lbl.pdf
  4. Martinez F, Calverley P, Goehring UM, Brose M, Fabbri L, Rabe K. Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicenter randomized controlled Lancet. 2015;385:857-866. doi:10.1016/S0140-6736(14)62410-7
  5. Janjua S, Fortescue R, Poole Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease (Review). Cochrane Database of Systematic Reviews. 2020, Issue 5. Art. No.:CD002309. doi:10.1002/14651858.CD002309.pub6.
  6. In: Lexi-Drugs, Lexicomp. Wolters Kluwer Health, Inc.; 2022. Updated January 31, 2022. Accessed February 1, 2022.
  7. Wedzica J, Calverley P, Albert R, Anzueto A, Criner G, Hurst J, et Prevention of COPD exacerbations: a European Respiratory Society / American Thoracic Society Guideline. Eur Respir J. 2017; 50:1602265. doi:10.1183./13993033.02265-2016