DALIRESP
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DALIRESP (DALIRESP).
Selective phosphodiesterase 4 (PDE4) inhibitor that reduces inflammation by increasing intracellular cAMP levels, thereby inhibiting inflammatory cell activity.
| Metabolism | Primarily hepatic via CYP3A4 and CYP1A2; also metabolized by glucuronidation (UGT1A1, UGT1A3, UGT1A7, UGT1A8, UGT2B7). |
| Excretion | Approximately 70% of the dose is excreted via the feces (primarily as unchanged drug and glucuronide conjugates) and 20% via the urine (mostly as metabolites). |
| Half-life | The terminal elimination half-life is approximately 17-21 hours, supporting once-daily dosing. |
| Protein binding | 97-99% bound, primarily to albumin. |
| Volume of Distribution | Estimated 2.9 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 58-79%, primarily due to first-pass metabolism. |
| Onset of Action | Bronchodilator effect begins within 1-2 hours after oral administration; maximum improvement in lung function may take several days to weeks. |
| Duration of Action | Duration of bronchodilator effect is approximately 24 hours, allowing once-daily dosing. Clinical benefit in COPD requires chronic administration. |
500 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No adjustment required for GFR 30-79 mL/min; insufficient data for GFR <30 mL/min, use with caution |
| Liver impairment | Child-Pugh A: No adjustment; Child-Pugh B: Not recommended; Child-Pugh C: Contraindicated |
| Pediatric use | Not established for patients under 18 years |
| Geriatric use | No specific dose adjustment required, but monitor for adverse effects due to age-related comorbidities |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DALIRESP (DALIRESP).
| Breastfeeding | It is unknown whether roflumilast or its metabolites are excreted in human milk. In animal studies, roflumilast was excreted in the milk of lactating rats at concentrations up to 0.8 times the maternal plasma concentration. The M/P ratio in humans is not determined. Caution should be exercised when administered to a nursing woman, and the decision to breastfeed should consider the importance of the drug to the mother and the potential risk to the infant. |
| Teratogenic Risk | In animal studies, roflumilast (DALIRESP) was not teratogenic in rats or rabbits at doses up to 4 and 2 times the maximum recommended human dose (MRHD), respectively. However, there are no adequate and well-controlled studies in pregnant women. Therefore, DALIRESP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Risk cannot be excluded; FDA Pregnancy Category C. |
■ FDA Black Box Warning
None.
| Serious Effects |
Moderate-to-severe liver impairment (Child-Pugh B or C).
| Precautions | Increased risk of psychiatric events (including suicidality); weight loss; potential drug interactions with CYP3A4 inhibitors or inducers; not for acute bronchospasm. |
Loading safety data…
| Fetal Monitoring | No specific maternal-fetal monitoring requirements are established. General obstetric monitoring is recommended for pregnant women with COPD or other conditions for which DALIRESP is prescribed. |
| Fertility Effects | In animal fertility studies, roflumilast had no effects on mating or fertility at oral doses up to 4 times the MRHD (on a mg/m² basis). There are no human data on fertility effects. |