BLACK BOX WARNING
- neuropsychiatric events including depression and suicidality
roflumilast
Brand: Daliresp
⚠ BBW Prototype Drug
Drug Class: phosphodiesterase-4 inhibitor
Drug Family: PDE-4 inhibitor
Subclass: PDE4 selective inhibitor (anti-inflammatory)
Organ Systems: respiratory
Mechanism of Action
Selective PDE4 inhibitor increasing cAMP in airway smooth muscle and inflammatory cells; reduces neutrophilic and eosinophilic airway inflammation; reduces COPD exacerbations.
phosphodiesterase-4 (PDE4) in airway cells and leukocytes
Indications
- COPD with severe airflow limitation and chronic bronchitis (frequent exacerbator phenotype)
Contraindications
- moderate-severe hepatic impairment
- pregnancy
- history of depression (neuropsychiatric BBW)
- suicidal ideation
Adverse Effects
Common
- diarrhea
- nausea
- headache
- weight loss
- insomnia
Serious
- neuropsychiatric events (depression, suicidal ideation — BBW)
- significant weight loss
Pharmacokinetics (ADME)
| Absorption | ~80% oral bioavailability |
| Distribution | large Vd |
| Metabolism | extensive hepatic CYP3A4 and CYP1A2 to active metabolite roflumilast-N-oxide |
| Excretion | renal (70%) |
| Half-life | 17 hours (parent), 30 hours (metabolite) |
| Onset | 1 hour |
| Peak | 8-12 hours |
| Duration | 24 hours |
| Protein Binding | 99% |
| Vd | 2.9 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inducers (rifampin) | reduce roflumilast efficacy — avoid | major |
| theophylline | potential additive PDE inhibition | minor |
Nursing Considerations
- Reserve for severe COPD (FEV1 <50% predicted) with chronic bronchitis and frequent exacerbations
- Monitor weight monthly — weight loss is common and may preclude use in underweight patients
- Neuropsychiatric monitoring: screen for depression, anxiety, suicidal ideation
- Not bronchodilator — does not improve acute symptoms; reduces exacerbation frequency
Clinical Pearls
- PDE4 inhibition: increases cAMP in neutrophils, T-cells reducing inflammation — complementary to bronchodilators
- REACT/RE(2)SPOND trials: reduces exacerbations in chronic bronchitis phenotype COPD
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.