Roflumilast

Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors of phosphodiesterase 4 (PDE4). Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic-3',5'-adenosine monophosphate (cyclic AMP)-metabolizing enzyme in lung tissue) activity leads to accumulation of intracellular cyclic AMP.

• Roflumilast tablets is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Limitations of Use Roflumilast tablets is not a bronchodilator and is not indicated for the relief of acute bronchospasm.ICD-10: J20.9, J44.9

• The use of roflumilast tablets is contraindicated in the following condition: Moderate to severe liver impairment (Child-Pugh B or C) [see Clinical Pharmacology ( 12.3 ) and Use in Specific Populations ( 8.6 )].contraindicated

The maintenance dose of roflumilast tablets is one 500 micrograms (mcg) tablet per day, with or without food. Starting treatment with a dose of Roflumilast tablets 250 mcg once daily for 4 weeks and increasing to Roflumilast tablets 500 mcg once daily thereafter may reduce the rate of treatment discontinuation in some patients [ see Clinical Studies ( 14.1 ) ]. However, 250 mcg per day is not the effective (therapeutic) dose. The maintenance dose for patients with COPD is one 500 mcg tablet per day, with or without food. Starting treatment with a dose of Roflumilast tablets 250 mcg once daily for 4 weeks and increasing to roflumilast tablets 500 mcg once daily thereafter may reduce the rate of treatment discontinuation in some patients.( 2 )

Acute Bronchospasm: Do not use for the relief of acute bronchospasm. ( 5.1 ) Psychiatric Events including Suicidality: 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. Carefully weigh the risks and benefits of treatment with roflumilast tablets in patients with a history of depression and/or suicidal thoughts or behavior. ( 5.2 ) Weight Decrease: Monitor weight regularly. If unexplained or clinically significant weight loss occurs, evaluate weight loss and consider discontinuation of roflumilast tablets. ( 5.3 ) Drug Interactions: Use with strong cytochrome P450 enzyme inducers (e.g., rifampicin, phenobarbital, carbamazepine, phenytoin) is not recommended. ( 5.4 ) 5.1 Treatment of Acute Bronchospasm Roflumilast tablets is not a bronchodilator and should not be used for the relief of acute bronchospasm. 5.2 Psychiatric Events including Suicidality Treatment with roflumilast tablets is associated with an increase in psychiatric adverse reactions. In 8 controlled clinical trials 5.9% (263) of patients treated with roflumilast tablets 500 mcg daily reported psychiatric adverse reactions compared to 3.3% (137) treated with placebo.

The following adverse reactions are described in greater detail in other sections: Psychiatric Events Including Suicidality [see Warnings and Precautions (5.2) ] Weight Decrease [see Warnings and Precautions (5.3) ] Most common adverse reactions (≥2%) are diarrhea, weight decrease, nausea, headache, back pain, influenza, insomnia, dizziness and decreased appetite. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Adverse Reactions in Clinical Studies Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflect exposure of 4438 patients to roflumilast tablets 500 mcg once daily in four 1year placebo-controlled trials, two 6-month placebo-controlled trials, and two 6-month drug add-on trials [see Clinical Studies (14.1) ]. In these trials, 3136 and 1232 COPD patients were exposed to roflumilast tablets 500 mcg once daily for 6 months and 1 year, respectively. The population had a median age of 64 years (range 40 to 91), 73% were male, 92.9% were Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV 1 ) of 8.9 to 89.1% predicted. In these trials, 68.5% of the patients treated with roflumilast tablets reported an adverse reaction compared with 65.3% treated with placebo.

Nursing Mothers: Roflumilast tablets should not be used by women who are nursing as excretion of roflumilast and/or its metabolites into human milk is probable and there are no human studies that have investigated effects of roflumilast tablets on breast-fed infants. ( 8.2 ) 8.1 Pregnancy Risk Summary There are no randomized clinical studies of roflumilast tablets in pregnant women. In animal reproductive toxicity studies, roflumilast tablets administered to pregnant rats and rabbits during the period of organogenesis produced no fetal structural abnormalities. The highest roflumilast tablets dose in these studies was approximately 30 and 26 times, respectively, the maximum recommended human dose (MRHD). Roflumilast tablets induced post-implantation loss in rats at doses greater than or equal to approximately 10 times the MRHD. Roflumilast tablets induced stillbirth and decreased pup viability in mice at doses corresponding to approximately 16 and 49 times, respectively, the MRHD. Roflumilast tablets has been shown to adversely affect pup post-natal development when dams were treated with the drug during pregnancy and lactation periods in mice at doses corresponding to 49 times the MRHD (see Data). The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S.

Metabolism

Absorption The absolute bioavailability of roflumilast following a 500 mcg oral dose is approximately 80%. Maximum plasma concentrations (C max ) of roflumilast typically occur approximately one hour after dosing (ranging from 0.5 to 2 hours) in the fasted state while plateau-like maximum concentrations of the N-oxide metabolite are reached in approximately eight hours (ranging from 4 to 13 hours).

10.1 Human Experience No case of overdose has been reported in clinical studies with roflumilast tablets. During the Phase I studies of roflumilast tablets, the following symptoms were observed at an increased rate after a single oral dose of 2500 mcg and a single dose of 5000 mcg: headache, gastrointestinal disorders, dizziness, palpitations, lightheadedness, clamminess, and arterial hypotension 10.2 Management of Overdose In case of overdose, patients should seek immediate medical help. Appropriate supportive medical care should be provided. Since roflumilast is highly protein bound, hemodialysis is not likely to be an efficient method of drug removal. It is not known whether roflumilast is dialyzable by peritoneal dialysis.

• Feb 28, 2011NDANDA022522Astrazeneca
• Oct 3, 2018ANDAANDA208236Senores Pharms
• Nov 23, 2018ANDAANDA208213Hetero Labs Ltd Iii
• Mar 22, 2019ANDAANDA208180Micro Labs
• Feb 10, 2022ANDAANDA208303Zydus Pharms
• May 10, 2022ANDAANDA208299Prinston Inc
• Jul 29, 2022NDANDA215985Arcutis
• Dec 15, 2023NDANDA217242Arcutis

1. 1Dyspnoea1,03015%
2. 2Death73611%
3. 3Chronic Obstructive Pulmonary Disease6439.7%
4. 4Diarrhoea5808.7%
5. 5Nausea4857.3%
6. 6Pneumonia4637.0%
7. 7Weight Decreased4426.6%
8. 8Headache4166.3%
9. 9Off Label Use4046.1%
10. 10Drug Ineffective3765.7%
11. 11Cough3565.4%
12. 12Insomnia3204.8%
13. 13Dizziness3044.6%
14. 14Asthma2894.3%
15. 15Fatigue2894.3%

The 10 most recently updated of 136 ClinicalTrials.gov registrations naming Roflumilast as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Efficacy and Safety of Roflumilast in Japanese Patients With Bronchial Asthma (20 to 70 y) (APTA-2217-05).
  Completed · Phase 2 · Phase 3 · Interventional · 450 enrolled · AstraZeneca
  NCT00242307updated 2026-06-10
• An Open-label, Single Center Study Evaluating the Safety and Efficacy of Roflumilast Foam 0.3% in Subjects With Cutaneous Adverse Events Due to Checkpoint Inhibitors
  Not yet recruiting · Phase 2 · Interventional · 20 enrolled · Massachusetts General Hospital
  NCT07639840updated 2026-06-10
• Long-term Study of Safety and Efficacy of Roflumilast in Japanese Patients With Bronchial Asthma (20 to 71 y) (APTA-2217-07).
  Completed · Phase 3 · Interventional · 150 enrolled · AstraZeneca
  NCT00246922updated 2026-06-10
• Effect of Roflumilast as Add-On Therapy in Rheumatoid Arthritis
  Recruiting · Phase 2 · Interventional · 50 enrolled · Horus University
  NCT07632846updated 2026-06-08
• Exercise as an Immune Adjuvant for Allogeneic Cell Therapies
  Recruiting · Early phase 1 · Interventional · 200 enrolled · University of Arizona
  NCT06643221updated 2026-06-05
• Utilization of a Microdevice for Psoriasis and Atopic Dermatitis
  Not yet recruiting · Phase 4 · Interventional · 10 enrolled · University of California, San Francisco
  NCT07352566updated 2026-06-03
• Roflumilast or Azithromycin to Prevent COPD Exacerbations (RELIANCE)
  Completed · Phase 4 · Interventional · 1,032 enrolled · Johns Hopkins University
  NCT04069312updated 2026-06-01
• The Role of Phosphodiesterase Inhibitors in Incretin Secretion
  Completed · Phase 1 · Interventional · 29 enrolled · National Institute on Aging (NIA)
  NCT02363335updated 2026-06-01
• Effect of Roflumilast and Desloratadine as Add-On Therapy in Patients With Rheumatoid Arthritis
  Recruiting · Phase 2 · Interventional · 90 enrolled · Horus University
  NCT07566351updated 2026-05-12
• The Italian Registry of Patients With Chronic Obstructive Pulmonary Disease
  Enrolling by invitation · Observational · 10,000 enrolled · University of Milan
  NCT06652776updated 2026-05-04

Frequently asked questions

How does Roflumilast work?

Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors of phosphodiesterase 4 (PDE4). Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic-3',5'-adenosine monophosphate (cyclic AMP)-metabolizing enzyme in lung tissue) activity leads to accumulation of intracellular cyclic AMP.

What is Roflumilast used for?

According to FDA labeling, Roflumilast carries indications including: Roflumilast tablets is indicated as a treatment to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. Limitations of Use Roflumilast tablets is not a bronchodilator and is not indicated for the relief of acute bronchospasm.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Roflumilast?

Roflumilast is classified as Other antipsoriatics for topical use, Other systemic drugs for obstructive airway diseases, Phosphodiesterase 4 Inhibitor, Phosphodiesterase 4 Inhibitors, Decreased Tracheo-Bronchial Secretions.

What are the brand names for Roflumilast?

Roflumilast is marketed under brand names including Daliresp, Zoryve.

What are the contraindications for Roflumilast?

Roflumilast labeling lists contraindications including: The use of roflumilast tablets is contraindicated in the following condition: Moderate to severe liver impairment (Child-Pugh B or C) [see Clinical Pharmacology ( 12.3 ) and Use in Specific Populations ( 8.6 )].. Always consult the full prescribing information and a clinician.