Prescription ·Strong evidence ·Reviewed May 2026
Roflumilast is an oral selective phosphodiesterase-4 inhibitor used to reduce COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations. It is not a bronchodilator and is not for acute bronchospasm; key risks are diarrhea, nausea, weight loss, insomnia, anxiety, depression, and suicidal ideation.
The bottom line
Evidence rating strong. Most-documented uses: reduced risk of copd exacerbations in severe copd with chronic bronchitis, adjunctive anti-inflammatory therapy for patients with frequent exacerbations, potential reduction in steroid- or hospitalization-requiring exacerbations. 3 sources indexed (2009–2026), with 4 interaction records on file.
Core mechanism
Roflumilast and its active N-oxide metabolite inhibit phosphodiesterase-4 in inflammatory and structural cells relevant to COPD. This increases intracellular cyclic AMP and reduces release of pro-inflammatory mediators, leading to decreased airway inflammation and exacerbation frequency. The drug is metabolized mainly through CYP3A4 and CYP1A2 pathways, so strong enzyme inducers can reduce exposure.1,2
May be taken with or without food. Monitor weight and mood after initiation and dose escalation.
St. John's Wort can induce CYP3A4 and may reduce roflumilast exposure, potentially decreasing COPD exacerbation prevention.
Recommendation: Avoid St. John's Wort unless the prescriber specifically approves and monitors clinical response.
Caffeinated green tea extract may compound roflumilast-associated insomnia, anxiety, tremor, or appetite suppression.
Recommendation: Avoid high-caffeine extracts if insomnia, anxiety, palpitations, or weight loss occurs.
Quercetin can inhibit some CYP enzymes and transporters in vitro, which could make roflumilast tolerability less predictable.
Recommendation: Use cautiously when starting or stopping high-dose quercetin; monitor diarrhea, nausea, weight loss, and mood symptoms.
Berberine may affect CYP enzymes and P-glycoprotein, creating theoretical exposure changes for roflumilast.
Recommendation: Avoid adding high-dose berberine without clinician review if roflumilast adverse effects or severe COPD instability are present.
Numbered references. Citations throughout the page link here.
Trials showed reduced moderate or severe COPD exacerbations in selected patients with chronic bronchitis phenotype.
Guidelines position roflumilast as add-on therapy for severe COPD with chronic bronchitis and exacerbations despite inhaled therapy.
Labeling describes indication, 500 mcg daily dosing, optional 250 mcg starter period, contraindication in moderate or severe liver impairment, psychiatric warnings, and weight monitoring.
This page is educational. Do not start, stop, or change a supplement or medication based on it without checking with a qualified healthcare professional.
Use this with your stack
Add it to your stack, see how it interacts with everything else you take, and get a Stack Score that updates the moment it does.
NutriStack is an informational and organizational tool, not a medical service, and not a substitute for professional advice. Always consult a qualified healthcare professional before starting, stopping, or changing any supplement or medication.
