print_label | resize_label

For reducing the risk of exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations

DALIRESP efficacy

DALIRESP is not a bronchodilator and is not indicated for the relief of acute bronchospasm

When added to current bronchodilator therapy*

DALIRESP enhanced exacerbation protection1

In the two 1-year pivotal studies:

  • DALIRESP significantly reduced the rate of moderate or severe exacerbations on top of current bronchodilator therapy*1

REDUCTION IN THE RATE OF EXACERBATIONS VERSUS PLACEBO*1

Reduction in the Rate of Exacerbations Versus Placebo Reduction in the Rate of Exacerbations Versus Placebo Reduction in the Rate of Exacerbations Versus Placebo
  • On average, patients treated with DALIRESP and bronchodilators* had significantly fewer moderate or severe exacerbations per patient per year than those treated with placebo and bronchodilators*1,2

  • DALIRESP is not a bronchodilator and should not be used for the relief of acute bronchospasm

CONSISTENT EFFECT WITH CONCOMITANT COPD MEDICATIONS1,2:

Consistent Effect with Concomitant COPD Medications Consistent Effect with Concomitant COPD Medications Consistent Effect with Concomitant COPD Medications

*Patients were allowed to be on LABA or SAMA at stable doses. SABA was allowed for rescue use. In the pooled analysis, the use of concomitant bronchodilators in the placebo group vs DALIRESP group were: LABA (51% vs 49%), SAMA (37% vs 35%), and SABA (99% vs 100%).
Moderate exacerbations were defined as those requiring treatment with systemic corticosteroids, and severe exacerbations were defined as those resulting in hospitalization or death.


For reducing the risk of exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations

For every 5 patients treated,

Adding DALIRESP could prevent 1 additional
exacerbation per year‡3

In pooled data from the two 1-year pivotal studies:

  • The reduction in moderate to severe exacerbations corresponded to an average Number Needed to Treat of 5 patients to prevent 1 additional exacerbation per year‡3

  • DALIRESP is not a bronchodilator and should not be used for the relief of acute bronchospasm

Moderate exacerbations were defined as those requiring treatment with systemic corticosteroids, and severe exacerbations were defined as those resulting in hospitalization or death.
Number Needed to Treat of moderate or severe COPD exacerbations was a secondary endpoint in the two 1-year pivotal studies. Number Needed to Treat is calculated by taking the inverse of the difference between the mean rate of exacerbations per patient per year in each treatment arm.

See Important Safety Information

For reducing the risk of exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations

In the two 1-year pivotal studies:

Statistically significant increase in FEV11,2

  • DALIRESP is not a bronchodilator; this increase was not clinically meaningful4,5

CHANGE FROM BASELINE IN PRE-BRONCHODILATOR FEV1 OVER 12 MONTHS1

Change From Baseline in Pre-Bronchodilator FEV, Over 12 Months Change From Baseline in Pre-Bronchodilator FEV, Over 12 Months Change From Baseline in Pre-Bronchodilator FEV, Over 12 Months
  • On average, patients treated with DALIRESP and bronchodilators* had a statistically significant increase from baseline in FEV1 than those treated with placebo and bronchodilators*1,2

    • At baseline, the DALIRESP patients had a mean pre-bronchodilator FEV1 of 1.01 liters (33% predicted)1

  • Similar results were achieved when measuring lung function by post-bronchodilator FEV1, with an increase of 55 mL over placebo (P<0.0001)1,2

  • DALIRESP is not a bronchodilator and should not be used for the relief of acute bronchospasm

*Patients were allowed to be on LABA or SAMA at stable doses. SABA was allowed for rescue use. In the pooled analysis, the use of concomitant bronchodilators in the placebo group vs DALIRESP group were: LABA (51% vs 49%), SAMA (37% vs 35%), and SABA (99% vs 100%).1

See Important Safety Information

Study Design

A pooled analysis of two identical, 1-year, double-blind, placebo-controlled studies of 3091 patients with severe COPD associated with chronic bronchitis and a history of exacerbations compared DALIRESP (n=1537) and placebo (n=1554). Subjects were current or ex-smokers with a smoking history of ≥20 pack-years, aged >40 with a clinical diagnosis of severe COPD with chronic cough and sputum production. The study included a 4-week run-in period followed by a 1-year treatment period. Subjects could use short-acting β2 agonists (SABAs) as needed and could continue treatment with long-acting β2 agonists (LABAs) or short-acting muscarinic antagonists (SAMAs) at stable doses. The studies were designed to assess the rate of moderate or severe COPD exacerbations and the change from baseline in pre-bronchodilator FEV1.

See Important Safety Information
 

IMPORTANT SAFETY INFORMATION

Contraindications

DALIRESP® (roflumilast) is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C).

Warnings and Precautions

  • DALIRESP is not a bronchodilator and should not be used for the relief of acute bronchospasm

  • Prescribers should advise patients, their caregivers, and families to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts or other mood changes, and if such changes occur, to contact their healthcare provider. Prescribers should carefully evaluate the risks and benefits of continuing treatment if such events occur. Before using DALIRESP in patients with a history of depression and/or suicidal thoughts or behavior, prescribers should carefully weigh the risks and benefits of treatment with DALIRESP

    • Treatment with DALIRESP is associated with an increase in psychiatric adverse reactions.
      In 8 controlled clinical trials 5.9% of patients treated with DALIRESP reported psychiatric adverse reactions vs 3.3% treated with placebo. The most common psychiatric adverse reactions in these studies were insomnia (2.4% vs 1.0%), anxiety (1.4% vs 0.9%), and depression (1.2% vs 0.9%). Three patients treated with DALIRESP experienced suicide-related adverse reactions (one completed suicide and two suicide attempts) compared to one patient (suicidal ideation) treated with placebo. In an additional placebo-controlled 1-year clinical trial (Trial 9), which assessed the effect of DALIRESP when added to a fixed-dose combination of an inhaled corticosteroid and long-acting beta agonist, one patient completed suicide while receiving DALIRESP

  • Patients should have their weight monitored regularly. If unexplained or clinically significant weight loss occurs, weight loss should be evaluated and treatment discontinuation considered

    • In addition to weight loss being reported as a common adverse reaction (7.5% of patients treated with DALIRESP vs 2.1% placebo), weight was prospectively assessed in two 1-year clinical trials. In these studies that compared DALIRESP to placebo, 20% vs 7% experienced moderate weight loss (5-10% of body weight) and 7% vs 2% experienced severe weight loss (>10% body weight). During the follow-up period after discontinuing DALIRESP, the majority of patients regained some of the weight they had lost

  • Use with strong cytochrome P450 enzyme inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended, as they decrease the exposure and may reduce the therapeutic effectiveness of DALIRESP

Adverse Reactions

In 8 controlled clinical trials, the most common adverse reactions (≥2% and greater than placebo) were diarrhea (9.5% vs 2.7%), weight loss (7.5% vs 2.1%), nausea (4.7% vs 1.4%), headache (4.4% vs 2.1%), back pain (3.2% vs 2.2%), influenza (2.8% vs 2.7%), insomnia (2.4% vs 1.0%), dizziness (2.1% vs 1.1%), and decreased appetite (2.1% vs 0.4%). The safety profile of DALIRESP in Trial 9 was consistent with the key pivotal studies.

INDICATION AND USAGE

DALIRESP® (roflumilast) is indicated as a treatment to reduce the risk of Chronic Obstructive Pulmonary Disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. DALIRESP is not a bronchodilator and is not indicated for the relief of acute bronchospasm.


Please see full Prescribing Information, including Medication Guide.


You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.

References:

  1. Calverley PMA, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; for the M2-124 and M2-125 Study Groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009;374:685-694.

  2. DALIRESP Prescribing Information. Wilmington, DE; AstraZeneca Pharmaceuticals LP; August 2017.

  3. Data on file, 3121900. AZPLP.

  4. Cazzola M, MacNee W, Martinez FJ, et al. Outcomes for COPD pharmacological trials: from lung function to biomarkers. Eur Respir J. 2008;31:416-468.

  5. Donohue JF. Minimal clinically important differences in COPD lung function. COPD. 2005;2:111-124.