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

DALIRESP safety profile

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

In 8 controlled COPD studies:

Most common adverse reactions with DALIRESP1

  • The safety data described below reflect exposure of 4438 patients to DALIRESP 500 mcg once daily in four 1-year placebo-controlled trials, two 6-month placebo-controlled trials, and two 6-month drug add-on trials. In these trials, 3136 ansd 1232 COPD patients were exposed to DALIRESP 500 mcg daily for 6 months and 1-year, respectively1


Adverse reactions reported by ≥2% of DALIRESP patients and greater than placebo1

Adverse
Reaction

DALIRESP
(N=4438)(%)

Placebo
(N=4192)(%)

Diarrhea

9.5

2.7

Weight loss

7.5

2.1

Nausea

4.7

1.4

Headache

4.4

2.1

Back pain

3.2

2.2

Influenza

2.8

2.7

Insomnia

2.4

1.0

Dizziness

2.1

1.1

Decreased
appetite

2.1

0.4


In these controlled COPD studies:

  • Overall rate of discontinuation due to adverse reactions was 14.8% for DALIRESP and 9.9% for placebo1

The safety profile of DALIRESP reported in Trial 9 was consistent with the key pivotal studies.1

Psychiatric Adverse Reactions

  • 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 reported at higher rates in the DALIRESP vs placebo-treated groups 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.


    • 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 health care 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


Weight Loss Adverse Reaction

  • In addition to weight loss being reported as a common adverse reaction, 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 lost1


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


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


See Additional 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:

Duration of events was evaluated among all patients who experienced diarrhea (N=203) and nausea (N=103)2

Duration of Diarrhea and Nausea Over Time2

Duration of Diarrhea and Nausea Over Time Duration of Diarrhea and Nausea Over Time Duration of Diarrhea and Nausea Over Time

*Includes 1 additional patient in the roflumilast group whose diarrhea was ongoing.
Includes 1 additional patient in the placebo group whose nausea was ongoing.

In the two 1-year pivotal studies:

  • Diarrhea and nausea were among the 3 most common adverse reactions reported by patients taking DALIRESP in clinical trials1

  • For the majority of patients who reported diarrhea and/or nausea, it was mild to moderate and generally lasted less than 4 weeks2

    • For some patients, diarrhea and nausea persisted beyond 4 weeks. In rare instances, diarrhea was a serious adverse reaction that occurred more frequently with DALIRESP than placebo2

In the 8 controlled COPD studies:

  • Overall rate of discontinuation due to adverse reactions was 14.8% for DALIRESP and 9.9% for placebo1

    • Discontinuation rates due to diarrhea and nausea were 2.4% and 1.6%, respectively


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


See Additional Important Safety Information

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

Drug Interaction Profile

Before prescribing DALIRESP:
It is important to ask your patients if they are taking any concomitant medications before prescribing DALIRESP.

In drug interaction studies:
Drug interaction studies were performed with roflumilast and other drugs likely to be coadministered or drugs commonly used as probes for pharmacokinetic interaction.1

See the findings below:

NOT RECOMMENDED1

Strong cytochrome P450 enzyme inducers
(including rifampicin, phenobarbital, carbamazepine and phenytoin)

Concomitant use with these medications is not recommended as they decrease systemic exposure
and may reduce the therapeutic effectiveness of DALIRESP.

USE WITH CAUTION1

CYP3A4 inhibitors and dual inhibitors of CYP1A2 and CYP3A4 (including erythromycin, ketoconazole, fluvoxamine, enoxacin and cimetidine)

Oral contraceptives containing gestodene and ethinyl estradiol

Concomitant use with these medications may increase DALIRESP systemic exposure and may result in increased adverse reactions.
The risk of concurrent use should be weighed carefully against the benefit.

NO SIGNIFICANT INTERACTION1

Salbutamol (albuterol)
Formoterol
Budesonide
Theophylline
Montelukast

Digoxin
Warfarin
Sildenafil
Midazolam
Maalox


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


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

  2. Data on file, 3117725. AZPLP.