Roflumilast

Selective phosphodiesterase-4 (PDE-4) inhibitor

ATC code: R03DX07

Brand names: Daxas, Daliresp

Updated 24 Sep 2026 · Methodology

Indications

Severe COPD with emphysema and frequent exacerbations

Second line

Add-on therapy in severe COPD with frequent-exacerbator chronic bronchitis phenotype per 2024. Dose 500 mcg once daily. REACT and RE2SPOND showed 15–20% reduction in exacerbations in patients on triple inhaled therapy (LABA + LAMA + ICS). Not used as monotherapy or replacement for inhaled foundation therapy. Often poorly tolerated due to nausea, diarrhea, and weight loss.

Only in patients with severe COPD (FEV1 below 50%), chronic bronchitis, and frequent exacerbations.

Sources

ICD-10: J44.1 · ICD-11: CA22.0

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Anti-aging and longevity

Not recommended

Roflumilast is a selective phosphodiesterase-4 (PDE4) inhibitor. It is prescribed for severe COPD with a frequent-exacerbation phenotype and chronic bronchitis ( 2024, AEMPS Ficha Técnica). In biohacker circles, roflumilast is occasionally promoted to suppress chronic inflammation and for anti-aging. In healthy adults, no clinical studies of such use exist. The drug has serious risks: pronounced weight loss (5–10% of baseline), GI disturbances (nausea, diarrhea, abdominal pain), neuropsychiatric adverse effects (insomnia, anxiety, depression, suicidal ideation – warning), and sleep disturbances. If roflumilast was recommended to a healthy person, seek a second opinion immediately.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

A selective phosphodiesterase-4 inhibitor mainly expressed in pulmonary inflammatory cells (neutrophils, T-lymphocytes, eosinophils, macrophages). Increases intracellular cAMP, suppressing release of pro-inflammatory cytokines and chemokines. Effect develops over weeks – not a bronchodilator but an anti-inflammatory drug. CYP1A2- and CYP3A4-metabolized to active roflumilast N-oxide (30-hour half-life enables once-daily dosing).

Safety

Contraindications

Roflumilast hypersensitivity
Severe hepatic impairment (Child-Pugh B or C)
History of depression or suicidal ideation
Severe immunological diseases (multiple sclerosis, SLE, progressive multifocal leukoencephalopathy)
Acute infections
Pregnancy and lactation
Age under 18

Serious adverse effects

Depression and suicidal ideation (FDA 2014 warning)
Severe weight loss (over 5%)
Acute pancreatitis (rare)
Arrhythmias
Heart failure

Common adverse effects

Diarrhea (10–20%)
Nausea
Weight loss (mean 2–3 kg)
Headache
Insomnia
Reduced appetite

Pregnancy: can you take Roflumilast?

Contraindicated. Stop in advance when planning pregnancy.

Breastfeeding: can you take Roflumilast?

Contraindicated during lactation.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take once daily at the same time, with or without food. Start-up phase of 4 weeks at 250 mcg for tolerability, then move to 500 mcg. Nausea, diarrhea, and reduced appetite are common in the first weeks – most resolve within 4 weeks. Monitor weight monthly – if more than 5% loss, discuss discontinuation. Monitor mental state – depression and suicidal ideation risk.

Label mentions29 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorCarbamazepine
«La administración de rifampicina, inductora de enzimas del citocromo P450, resultó en una reducción de aproximadamente un 60% de la actividad inhibidora total de la PDE4. Por lo tanto, el uso de…»
AEMPS, section 4.5 · Open on CIMA
MajorCarbamazepine
«Drugs that Induce Cytochrome P450 (CYP) Enzymes: Strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness of roflumilast tablets…»
FDA, section 7 · Open on DailyMed
MajorPhenobarbital
«La administración de rifampicina, inductora de enzimas del citocromo P450, resultó en una reducción de aproximadamente un 60% de la actividad inhibidora total de la PDE4. Por lo tanto, el uso de…»
AEMPS, section 4.5 · Open on CIMA
MajorPhenobarbital
«Drugs that Induce Cytochrome P450 (CYP) Enzymes: Strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness of roflumilast tablets…»
FDA, section 7 · Open on DailyMed
MajorPhenytoin
«La administración de rifampicina, inductora de enzimas del citocromo P450, resultó en una reducción de aproximadamente un 60% de la actividad inhibidora total de la PDE4. Por lo tanto, el uso de…»
AEMPS, section 4.5 · Open on CIMA
MajorPhenytoin
«Drugs that Induce Cytochrome P450 (CYP) Enzymes: Strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness of roflumilast tablets…»
FDA, section 7 · Open on DailyMed
MajorRifampicin
«La administración de rifampicina, inductora de enzimas del citocromo P450, resultó en una reducción de aproximadamente un 60% de la actividad inhibidora total de la PDE4. Por lo tanto, el uso de…»
AEMPS, section 4.5 · Open on CIMA
MajorRifampicin
«Drugs that Induce Cytochrome P450 (CYP) Enzymes: Strong cytochrome P450 enzyme inducers decrease systemic exposure to roflumilast and may reduce the therapeutic effectiveness of roflumilast tablets…»
FDA, section 7 · Open on DailyMed
MajorTheophylline
«Teofilina: No existen datos clínicos que respalden el tratamiento concomitante con teofilina en terapia de mantenimiento. Por lo tanto, no se recomienda el tratamiento concomitante con la teofilina.»
AEMPS, section 4.4 · Open on CIMA
ModerateCYP3A4 inhibitorsclass named in the label
«Drugs that Inhibit Cytochrome P450 (CYP) Enzymes: The co-administration of roflumilast tablets (500 mcg) with CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously…»
FDA, section 7 · Open on DailyMed
ModerateErythromycin
«DRUG INTERACTIONS: Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) will increase roflumilast systemic…»
FDA, section 7 · Open on DailyMed
ModerateFluvoxamine
«DRUG INTERACTIONS: Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) will increase roflumilast systemic…»
FDA, section 7 · Open on DailyMed
Moderatehormonal contraceptivesclass named in the label
«Oral Contraceptives Containing Gestodene and Ethinyl Estradiol: The co-administration of roflumilast tablets (500 mcg) with oral contraceptives containing gestodene and ethinyl estradiol may increase…»
FDA, section 7 · Open on DailyMed
ModerateKetoconazole
«DRUG INTERACTIONS: Use with inhibitors of CYP3A4 or dual inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin, ketoconazole, fluvoxamine, enoxacin, cimetidine) will increase roflumilast systemic…»
FDA, section 7 · Open on DailyMed
Minoranticonceptivos hormonalesclass named in the label
«Estudios clínicos de interacción con los inhibidores de CYP 3A4 eritromicina y ketoconazol han mostrado un aumento del 9% en la actividad inhibidora total del PDE4. La coadministración con teofilina…»
AEMPS, section 4.5 · Open on CIMA
MinorErythromycin
«Estudios clínicos de interacción con los inhibidores de CYP 3A4 eritromicina y ketoconazol han mostrado un aumento del 9% en la actividad inhibidora total del PDE4. La coadministración con teofilina…»
AEMPS, section 4.5 · Open on CIMA
MinorEthinylestradiol
«Estudios clínicos de interacción con los inhibidores de CYP 3A4 eritromicina y ketoconazol han mostrado un aumento del 9% en la actividad inhibidora total del PDE4. La coadministración con teofilina…»
AEMPS, section 4.5 · Open on CIMA
Minorinhibidores del CYP3A4class named in the label
«Estudios clínicos de interacción con los inhibidores de CYP 3A4 eritromicina y ketoconazol han mostrado un aumento del 9% en la actividad inhibidora total del PDE4. La coadministración con teofilina…»
AEMPS, section 4.5 · Open on CIMA
MinorKetoconazole
«Estudios clínicos de interacción con los inhibidores de CYP 3A4 eritromicina y ketoconazol han mostrado un aumento del 9% en la actividad inhibidora total del PDE4. La coadministración con teofilina…»
AEMPS, section 4.5 · Open on CIMA
antiácidosclass named in the label
«La coadministración con un antiácido (combinaciones de hidróxido de aluminio e hidróxido de magnesio) no alteró la absorción ni la farmacocinética de roflumilast ni de su N-óxido.»
AEMPS, section 4.5 · Open on CIMA
Budesonide
«No se han observado interacciones con salbutamol, formoterol y budesónida por vía inhalada, ni con montelukast, digoxina, warfarina, sildenafilo y midazolam por vía oral.»
AEMPS, section 4.5 · Open on CIMA
Digoxin
«No se han observado interacciones con salbutamol, formoterol y budesónida por vía inhalada, ni con montelukast, digoxina, warfarina, sildenafilo y midazolam por vía oral.»
AEMPS, section 4.5 · Open on CIMA
Fluvoxamine
«Estudios de interacción con el inhibidor de CYP1A2/3A4 enoxacina y los inhibidores de la CYP1A2/2C19/3A4 cimetidina y fluvoxamina han mostrado un aumento de la actividad inhibidora total de la PDE4…»
AEMPS, section 4.5 · Open on CIMA
Formoterol
«No se han observado interacciones con salbutamol, formoterol y budesónida por vía inhalada, ni con montelukast, digoxina, warfarina, sildenafilo y midazolam por vía oral.»
AEMPS, section 4.5 · Open on CIMA
inhibidores del CYP1A2class named in the label
«Estudios de interacción con el inhibidor de CYP1A2/3A4 enoxacina y los inhibidores de la CYP1A2/2C19/3A4 cimetidina y fluvoxamina han mostrado un aumento de la actividad inhibidora total de la PDE4…»
AEMPS, section 4.5 · Open on CIMA
Magnesium hydroxide
«La coadministración con un antiácido (combinaciones de hidróxido de aluminio e hidróxido de magnesio) no alteró la absorción ni la farmacocinética de roflumilast ni de su N-óxido.»
AEMPS, section 4.5 · Open on CIMA
Montelukast
«No se han observado interacciones con salbutamol, formoterol y budesónida por vía inhalada, ni con montelukast, digoxina, warfarina, sildenafilo y midazolam por vía oral.»
AEMPS, section 4.5 · Open on CIMA
Sildenafil
«No se han observado interacciones con salbutamol, formoterol y budesónida por vía inhalada, ni con montelukast, digoxina, warfarina, sildenafilo y midazolam por vía oral.»
AEMPS, section 4.5 · Open on CIMA
Warfarin
«No se han observado interacciones con salbutamol, formoterol y budesónida por vía inhalada, ni con montelukast, digoxina, warfarina, sildenafilo y midazolam por vía oral.»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Roflumilast used for?

Roflumilast is evaluated for the following indications with varying evidence strength: Severe COPD with emphysema and frequent exacerbations (evidence tier B), Anti-aging and longevity (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Roflumilast?

Common side effects of Roflumilast (≥ 1 in 100): Diarrhea (10–20%), Nausea, Weight loss (mean 2–3 kg), Headache, Insomnia, Reduced appetite. See the Safety section for uncommon and serious reactions.

Is Roflumilast safe during pregnancy?

Contraindicated. Stop in advance when planning pregnancy.

Is Roflumilast compatible with breastfeeding?

Contraindicated during lactation.

Who should not take Roflumilast?

Roflumilast is contraindicated in: Roflumilast hypersensitivity; Severe hepatic impairment (Child-Pugh B or C); History of depression or suicidal ideation; Severe immunological diseases (multiple sclerosis, SLE, progressive multifocal leukoencephalopathy); Acute infections. Full list in the Safety section.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMALabel dated 10/04/2024
EMALabel dated 07/05/2010
FDA / DailyMedLabel dated 09/01/2026

Other drugs in this group

Salbutamol (Albuterol), Salmeterol, Salmeterol + Fluticasone, Theophylline, Aclidinium, Budesonide/formoterol, Formoterol, Tiotropium