Skip to Content

Roflumilast

Pronunciation

(roe FLUE mi last)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Daliresp: 500 mcg

Brand Names: U.S.

  • Daliresp

Pharmacologic Category

  • Phosphodiesterase-4 Enzyme Inhibitor

Pharmacology

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

Metabolism

Hepatic via CYP3A4 and CYP1A2 to active N-oxide metabolite; also undergoes conjugation

Excretion

Urine (~70% as metabolites)

Time to Peak

~1 hour (delayed by food); N-oxide metabolite: ~8 hours

Half-Life Elimination

17 hours; N-oxide metabolite: 30 hours

Protein Binding

99%; N-oxide metabolite: 97%

Special Populations: Renal Function Impairment

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.

Special Populations: 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.

Special Populations: Elderly

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.

Special Populations: Gender

The roflumilast and N-oxide metabolite AUC increased 39% and 33%, respectively, in healthy women when compared with healthy men.

Special Populations: Race

The AUC and Cmax of roflumilast and the N-oxide metabolite increased in white, black, Hispanic, and Japanese patients.

Special Populations Note

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.

Use: Labeled Indications

COPD: To reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations

Contraindications

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.

Dosing: Adult

COPD: Oral: 500 mcg once daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

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.

Administration

Administer without regard to meals.

Storage

Store at 20°C to 25°C (68°F to 77°F), excursions permitted from 15°C to 30°C (59°F to 86°F).

Drug Interactions

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Cimetidine: May increase serum concentrations of the active metabolite(s) of Roflumilast. Cimetidine may increase the serum concentration of Roflumilast. Monitor therapy

Ciprofloxacin (Systemic): May increase the serum concentration of Roflumilast. Monitor therapy

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining strong CYP3A4 inducers with roflumilast. The Canadian product monograph makes no such recommendation but notes that such agents may reduce roflumilast therapeutic effects. Avoid combination

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

FluvoxaMINE: May increase serum concentrations of the active metabolite(s) of Roflumilast. FluvoxaMINE may increase the serum concentration of Roflumilast. Monitor therapy

Immunosuppressants: Roflumilast may enhance the immunosuppressive effect of Immunosuppressants. Exceptions: Beclomethasone (Oral Inhalation); Cytarabine (Liposomal); Fluticasone (Oral Inhalation). Consider therapy modification

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. Avoid combination

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

RifAMPin: May decrease the serum concentration of Roflumilast. Management: Roflumilast U.S. prescribing information recommends against combining rifampin with roflumilast. The Canadian product monograph makes no such recommendation but notes that rifampin may reduce roflumilast therapeutic effects. Avoid combination

Riociguat: Roflumilast may enhance the hypotensive effect of Riociguat. Management: Riociguat is contraindicated with nonselective phosphodiesterase (PDE) inhibitors and PDE type 5 inhibitors. Other types of PDE inhibitors are not contraindicated, but caution is advised and patients should be monitored for hypotension. Monitor therapy

St John's Wort: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

Adverse Reactions

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% (Limited to important or life-threatening): Abdominal pain, anemia, arthritis, atrial fibrillation, depression, dysgeusia, epistaxis, gastritis, gastroesophageal reflux disease, gynecomastia, hematochezia, hypersensitivity, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum AST, lung carcinoma, muscle spasm, myalgia, myasthenia, pancreatitis, paresthesia, prostate carcinoma, renal failure, respiratory tract infection, rhinitis, sinusitis, suicidal ideation, suicidal tendencies, suicide completed, supraventricular cardiac arrhythmia, urinary tract infection

Warnings/Precautions

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Monitoring Parameters

Liver function tests; weight (regularly during therapy); new or worsening insomnia, anxiety, depression, suicidal thoughts, or other mood changes.

Pregnancy Considerations

Adverse events were observed in some animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, nausea, diarrhea, headache, back pain, flu-like symptoms, insomnia, or lack of appetite. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), severe anxiety, excessive weight loss, agitation, irritability, panic attacks, or mood changes (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Hide