Roflumilast
PDE4 inhibitors
PDE4 inhibitors
An oral PDE4 inhibitor that reduces flare-ups of severe COPD with chronic bronchitis; it is not a bronchodilator.
Quick facts
- Group
- PDE4 inhibitors
- Target
- Phosphodiesterase 4 (PDE4B, PDE4D)
- Used for
- Reducing the risk of exacerbations
- Key effects
- Diarrhoea and nausea · Headache and dizziness
- Monitor
- Body weight at regular visits · Mood
- ATC
- R03DX07
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows roflumilast bound to the catalytic domain of human phosphodiesterase 4B.
Roflumilast and its active N-oxide metabolite selectively inhibit phosphodiesterase 4, the main enzyme that breaks down cyclic AMP in lung inflammatory and structural cells. Higher cyclic AMP reduces the release of inflammatory mediators and the influx of neutrophils into the airways. The result is fewer exacerbations in severe COPD with chronic bronchitis; lung function improves only slightly and there is no immediate bronchodilation.
- Roflumilast and its N-oxide block PDE4
- Cyclic AMP rises inside inflammatory cells
- Fewer cytokines are released and fewer neutrophils arrive
- COPD flare-ups become less frequent
Indications
- Reducing the risk of exacerbations in severe COPD with chronic bronchitis and a history of exacerbations, added to bronchodilators Chronic obstructive pulmonary disease (COPD) →
Adverse effects
Common
- Diarrhoea and nausea
- Weight loss and decreased appetite
- Headache and dizziness
- Insomnia and back pain
Contraindications
- Moderate to severe liver impairment (Child-Pugh B or C)
- Caution with a history of depression or suicidal thoughts
- Not for relief of acute bronchospasm
Key interactions
- Strong CYP inducers: rifampicin, phenobarbital, carbamazepine, phenytoin
- Lower roflumilast exposure and make it less effective; not recommended
- CYP3A4 or dual CYP3A4/CYP1A2 inhibitors: erythromycin, ketoconazole, fluvoxamine, cimetidine
- Raise roflumilast exposure and side effects
What is monitored
- Body weight at regular visits
- Mood, sleep and suicidal thoughts
- Exacerbation frequency
- Liver function before starting
Administration and safety
- Oral tablet once a day, with or without food
- Some regimens start with a lower dose for a few weeks to improve tolerance
- Not a rescue medicine: the patient keeps a short-acting inhaler
Pregnancy and breastfeeding
There are no adequate human data; it is not used in pregnancy unless the clinician judges the benefit worth the risk, and it is not used during breastfeeding.
Nursing care
- Weigh the patient at each visit and report unexplained weight loss
- Ask about mood, sleep and suicidal thoughts; teach family to report changes
- Explain that diarrhoea and nausea often ease after the first weeks
Pharmacokinetics
- Absorption
- Well absorbed by mouth
- Metabolism
- Liver: CYP3A4 and CYP1A2 form the active N-oxide, which provides most of the effect
- Elimination
- Urine, as metabolites
- Onset and duration
- Benefit on exacerbations builds over weeks to months
Test yourself
Think of the answer, then tap the question to see it.
Is roflumilast a bronchodilator?
No; it is an anti-inflammatory PDE4 inhibitor that reduces exacerbations.
Which COPD phenotype benefits from roflumilast?
Severe COPD with chronic bronchitis and frequent exacerbations.
Which two things are monitored regularly during roflumilast treatment?
Body weight and mood (depression, suicidal thoughts).
Why should rifampicin not be combined with roflumilast?
It induces CYP enzymes, lowers roflumilast exposure and makes it ineffective.
Connections
← Back to the class: PDE4 inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - ROFLUMILAST tablet (DailyMed (U.S. National Library of Medicine), 2026); Roflumilast: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2016); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.