Dosing and uses of Daliresp (roflumilast)
Adult dosage forms and strengths
tablet
- 500mcg
Chronic Obstructive Pulmonary Disease
Reduction of frequency of exacerbations or worsening of symptoms
500 mcg PO once daily
Dosing Modifications
Renal impairment
- No dosage adjustment required
Hepatic impairment
- Mild (Child-Pugh class A): Not sufficiently studied; AUCs of roflumilast and roflumilast N-oxide are increased by 51% and 24%, respectively; benefits of administration must be weighed against risks
- Moderate-to-severe (Child-Pugh class B or C): Contraindicated
Administration
May be taken with or without food
Pediatric dosage forms and strengths
Safety and efficacy not established
Daliresp (roflumilast) adverse (side) effects
1-10%
Diarrhea (9.5%)
Weight loss (7.5%)
Nausea (4.7%)
Headache (4.4%)
Back pain (3.2%)
Insomnia (2.4%)
Decreased appetite (2.1%)
Dizziness (2.1%)
1-10%
Abdominal pain (1-2%)
Anxiety (1-2%)
Depression (1-2%)
Dyspepsia (1-2%)
Gastritis (1-2%)
Muscle spasms (1-2%)
Rhinitis (1-2%)
Sinusitis (1-2%)
Tremor (1-2%)
Urinary tract infection (1-2%)
Vomiting (1-2%)
Frequency not defined
Suicidality
Postmarketing Reports
Hypersensitivity reactions including angioedema, urticaria, rash
Gynecomastia
Warnings
Contraindications
Hypersensitivity
Moderate-to-severe liver impairment (Child-Pugh class B or C)
Cautions
Not indicated for relief of acute bronchospasm; drug is not bronchodilator
Psychiatric events, including suicidality, reported (monitor for emergence or worsening of insomnia, mood disturbance, or anxiety)
Monitor for clinically significant weight loss; this may be reversible upon discontinuance
Use with strong cytochrome P450 enzyme inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin) not recommended
Pregnancy and lactation
Pregnancy category: C
Lactation: Probable that roflumilast, its metabolites, or both are excreted into milk; avoid use
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Daliresp (roflumilast)
Mechanism of action
Selective phosphodiesterase (PDE)-4 inhibitor; PDE-4 inhibition leads to accumulation of intracellular cyclic adenosine monophosphate (cAMP) in lung tissue and is thought to be underlying mechanism of action
Absorption
80% absorbed
Peak plasma time: 1 hr (range, 0.5-2 hr); active metabolite, 8 hr
Distribution
Protein bound: 99%
Vd: 2.9 L/kg
Metabolism
Extensively metabolized via phase I (CYP450) and phase II (conjugation) reactions; N-oxide metabolite is only major metabolite observed in human plasma; together, roflumilast and roflumilast N-oxide account for 87.5% of total dose administered in plasma
Biotransformation of roflumilast to N-oxide metabolite is mediated by CYP1A2 and CYP3A4
Elimination
Half-life: Roflumilast, 17 hr; N-oxide metabolite, 30 hr
Clearance: 9.6 L/hr
Excretion: Urine (70%)
