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To reduce the risk of 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

STARTING WITH 250 MCG HELPED SIGNIFICANTLY MORE PATIENTS CONTINUE ON DALIRESP1

12-WEEK STARTING-DOSE TITRATION TRIAL PERCENTAGE OF PATIENTS CONTINUING TREATMENT

82%

Patients initiated on DALIRESP 250 mcg daily for 4 weeks followed by DALIRESP 500 mcg daily for 8 weeks (n=441)

75%

Patients initiated on
DALIRESP 500 mcg daily for
12 weeks (n=443)

  • Primary Endpoint: Percentage of patients discontinuing treatment in patients initiated on DALIRESP 250 mcg daily for 4 weeks followed by DALIRESP 500 mcg daily for 8 weeks (18.4%) compared to those initiated on DALIRESP 500 mcg daily for 12 weeks (24.6%) (Odds Ratio=0.66; 95% CI: 0.47, 0.93; P=0.017)1,2

  • Because this trial was limited to 12 weeks in duration, whether initiation of dosing with DALIRESP 250 mcg improves the long-term tolerability of DALIRESP 500 mcg has not been determined1

See Important Safety Information

OPTIONS FOR STARTING DOSE FLEXIBILITY1

250 mcg tablet250 mcg: STARTING DOSE

  • DALIRESP 250-mcg starting dose should be taken once daily for the first 4 weeks only, with or without food, followed by 500 mcg daily for the remainder of treatment

    • This dosing regimen may help reduce the rate of discontinuation in some patients

  • DALIRESP 250 mcg is not a therapeutic dose

500 mcg tablet500 mcg: STARTING DOSE and THERAPEUTIC DOSE

  • DALIRESP 500 mcg should be taken once daily, with or without food, either:

    • At the initiation of treatment

    • Following 4 weeks with the 250-mcg starting dose

Tablet images are representations and not actual size.

ADDITIONAL IMPORTANT DOSING INFORMATION1

  • No dosage adjustment necessary for adults based on age, gender, or race, or those with renal impairment

  • DALIRESP should not be used during pregnancy, labor and delivery, or by nursing mothers because excretion of roflumilast and/or its metabolites into human milk is probable

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

    • Clinicians should consider the risk-benefit of administering DALIRESP to patients with mild liver impairment (Child-Pugh A)

  • Use with inhibitors of CYP3A4 and dual inhibitors of CYP3A4 and CYP1A2 (eg, erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) or oral contraceptives containing gestodene and ethinyl estradiol may increase roflumilast systemic exposure and result in increased adverse reactions

    • The risk of concurrent use should be weighed carefully against the benefit

  • 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

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

See Important Safety Information

Study Design

Starting-dose Titration Trial Study Design: The tolerability of DALIRESP was evaluated in a 12-week randomized, double-blind, parallel-group trial in patients with severe COPD associated with chronic bronchitis (Trial 10). A total of 1323 patients were randomized to DALIRESP 500 mcg once daily (QD) for 12 weeks (n=443), DALIRESP 500 mcg every other day for 4 weeks followed by DALIRESP 500 mcg QD for 8 weeks (n=439), or DALIRESP 250 mcg QD for 4 weeks followed by DALIRESP 500 mcg QD for 8 weeks (n=441). Primary endpoint was the percentage of patients prematurely discontinuing treatment for any reason.1,2

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 pivotal 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.

Limitations of Use

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

  • DALIRESP 250 mcg is a starting dose for the first 4 weeks of treatment only and is not the effective (therapeutic) dose


Please read full Prescribing Information, including Medication Guide.

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References:

  1. DALIRESP® (roflumilast) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; January 2018.

  2. Watz H, Bagul N, Rabe KF, et al. Use of a 4-week up-titration regimen of roflumilast in patients with severe COPD. Int J Chron Obstruct Pulmon Dis. 2018;13:813-822.