Dosing & Uses
Dosing Form & Strengths
tablet
- 250mcg
- 500mcg
Chronic Obstructive Pulmonary Disease
Indicated to reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations
500 mcg PO qDay
Starting treatment with 250 mcg PO qDay for 4 weeks and increasing to 500 mcg qDay thereafter may reduce the rate of treatment discontinuation in some patients
NOTE: 250 mcg/day is not the effective (therapeutic) dose
Also see Administration
Dosage 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
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse 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
Drug interaction overview
- Strong CYP3A4 inducers may reduce therapeutic effectiveness of roflumilast; coadministration not recommended
- CYP P450 enzyme inhibitors
- CYP3A4 inhibitors or dual inhibitors that inhibit both CYP3A4 and CYP1A2 simultaneously may increase roflumilast systemic exposure and increase risk for adverse effects
Pregnancy & Lactation
Pregnancy
Data are not available regarding use in pregnant women
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
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%)
Administration
Oral Administration
May take with or without food
May titrate dose from 250 mcg/day to 500 mcg/day (therapeutic dose) over 4 weeks to improve tolerability (see Dosing)
Images
Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
