Version May 2024
Chronic obstructive pulmonary disease, prevention of exacerbations:
Note: Consider for patients with frequent exacerbations (eg, ≥1 hospital admission per year) despite optimal medical management (Ref).
Oral: 250 mcg once daily for 4 weeks, followed by 500 mcg once daily. The initial dose of 250 mcg once daily is recommended for the first 4 weeks of treatment in an attempt to improve tolerability. However, this is not considered a therapeutic dose and the effect of this approach on long-term tolerability is uncertain.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild impairment (Child-Pugh class A): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.
Moderate to severe impairment (Child-Pugh class B or C): Use is contraindicated.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
2% to 10%:
Central nervous system: Headache (4%), dizziness (2%), insomnia (2%)
Endocrine & metabolic: Weight loss (5% to 10% of body weight: 8% to 20%; >10% loss: 7%)
Gastrointestinal: Diarrhea (10%), nausea (5%), decreased appetite (2%)
Infection: Influenza (3%)
Neuromuscular & skeletal: Back pain (3%)
<2%, postmarketing, and/or case reports: Abdominal pain, anemia, anxiety, arthralgia, arthritis, atrial fibrillation, constipation, depression, dysgeusia, dyspepsia, epistaxis, fatigue, gastritis, gastroesophageal reflux disease, gynecomastia, hematochezia, hypersensitivity, hypersensitivity reaction (including angioedema, urticaria, and rash), increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum AST, limb pain, lung carcinoma, malaise, muscle spasm, myalgia, myasthenia, nervousness, pancreatitis, paresthesia, prostate carcinoma, renal failure, respiratory tract infection, rhinitis, sinusitis, suicidal ideation, suicidal tendencies, suicide, supraventricular cardiac arrhythmia, tremor, urinary tract infection, vertigo, vomiting, weakness
Moderate to severe hepatic impairment (Child-Pugh class B or C).
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to roflumilast or any component of the formulation.
Concerns related to adverse effects:
• Neuropsychiatric: Neuropsychiatric effects (eg, anxiety, depression, insomnia) have been reported with use; rarely, suicidal behavior/ideation and completed suicide were reported. Assess risk versus benefits before prescribing in patients with a history of depression with suicidal behavior/ideations; instruct patients/caregivers to report psychiatric symptoms and consider discontinuation of therapy in such patients.
• Weight loss: Weight loss has occurred; monitor weight regularly. If unexplained or significant weight loss occurs, discontinuation should be considered.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with mild impairment (systemic exposure may be increased); use in moderate to severe impairment is contraindicated.
Other warnings/precautions:
• Appropriate use: Not indicated for relieving acute bronchospasm.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Daliresp: 250 mcg, 500 mcg [contains corn starch]
Generic: 250 mcg, 500 mcg
Yes
Tablets (Daliresp Oral)
250 mcg (per each): $17.75
500 mcg (per each): $17.75
Tablets (Roflumilast Oral)
250 mcg (per each): $15.51 - $15.56
500 mcg (per each): $1.20 - $15.90
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Daxas: 500 mcg [contains corn starch]
Oral: Administer without regard to meals.
An FDA-approved patient medication guide, which is available with the product information and at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022522s006lbl.pdf#page=16, must be dispensed with this medication.
Chronic obstructive pulmonary disease (COPD), prevention of exacerbations: To reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.
Limitations of use: Not indicated for the relief of acute bronchospasm.
Substrate of CYP1A2 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Cimetidine: May increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. Cimetidine may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Moderate) may decrease the serum concentration of Roflumilast (Systemic). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Roflumilast (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Roflumilast (Systemic). Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Enoxacin: May increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Ethinyl Estradiol-Containing Products: May increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. Ethinyl Estradiol-Containing Products may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
FluvoxaMINE: May increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. FluvoxaMINE may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Risk X: Avoid combination
Riociguat: Roflumilast-Containing Products may enhance the hypotensive effect of Riociguat. Risk C: Monitor therapy
Tobacco (Smoked): May decrease the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Viloxazine: May increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. Viloxazine may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
Adverse events were observed in some animal reproduction studies.
It is not known if roflumilast is present in breast milk; however, excretion into human breast milk is likely. Breastfeeding is not recommended by the manufacturer.
Liver function tests; weight (regularly during therapy); new or worsening insomnia, anxiety, depression, suicidal thoughts, or other mood changes.
Roflumilast and its active N-oxide metabolite selectively inhibit phosphodiesterase-4 (PDE4) leading to an accumulation of cyclic AMP (cAMP) within inflammatory and structural cells important in the pathogenesis of COPD. Anti-inflammatory effects include suppression of cytokine release and inhibition of lung infiltration by neutrophils and other leukocytes. Pulmonary remodeling and mucociliary malfunction are also attenuated.
Distribution: Vd: 2.9 L/kg
Protein binding: 99%; N-oxide metabolite: 97%
Metabolism: Hepatic via CYP3A4 and CYP1A2 to active N-oxide metabolite; also undergoes conjugation
Bioavailability: ~80%
Half-life elimination: 17 hours; N-oxide metabolite: 30 hours
Time to peak: ~1 hour (delayed by food); N-oxide metabolite: ~8 hours
Excretion: Urine (~70% as metabolites)
Altered kidney function: In patients with severe renal impairment, roflumilast and N-oxide metabolite AUCs were decreased by 21% and 7%, respectively, and Cmax was reduced 16% and 12%, respectively.
Hepatic function impairment: The AUC of roflumilast and the N-oxide metabolite were increased by 51% and 24%, respectively, in Child-Pugh class A subjects and by 92% and 41%, respectively, in Child-Pugh class B subjects as compared with healthy subjects. The Cmax of roflumilast and the N-oxide metabolite was increased by 3% and 26%, respectively, in Child-Pugh class A subjects and by 26% and 40%, respectively, in Child-Pugh class B subjects.
Older adult: The roflumilast AUC and Cmax increased 27% and 16%, respectively, and the N-oxide metabolite AUC and Cmax increased 19% and 13%, respectively, in elderly patients.
Sex: The roflumilast and N-oxide metabolite AUC increased 39% and 33%, respectively, in healthy women when compared with healthy men.
Race/ethnicity: The AUC and Cmax of roflumilast and the N-oxide metabolite increased in white, black, Hispanic, and Japanese patients.
Cigarette smoking: The AUC of roflumilast in smokers was 13% less than in nonsmokers while the AUC of the N-oxide metabolite in smokers was 17% more than in nonsmokers.
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