Roflumilast

Take the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

If you take too much roflumilast, call your local Poison Control Center or seek emergency medical attention right away.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Administration

Oral Administration

Administer orally once daily without regard to meals.1

Dosage

Adults

500 mcg once daily.1

Special Populations

Dosage adjustment not necessary based on gender or race.1

Hepatic Impairment

Dosage of 500 mcg once daily not studied in patients with hepatic impairment.1 Consider the risks and benefits of using roflumilast in patients with mild hepatic impairment (Child-Pugh class A).1 Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C).1 (See Special Populations under Pharmacokinetics.)

Renal Impairment

Dosage adjustment not necessary.1

Geriatric Patients

Dosage adjustment not necessary.1

• Selective inhibitor of PDE4, a major enzyme involved in the metabolism of cyclic adenosine-3′,5′-monophosphate (cAMP) in lung tissue.1 2 3 4 5 6 7 8 9

• Exact mechanism(s) of therapeutic action in patients with COPD not fully elucidated; thought to be related to the effects of increased cAMP in lung cells.1 8 9

• Increased cAMP concentrations can lead to activation of protein kinase A, resulting in phosphorylation and inactivation of target transcription factors and reduction of cellular inflammatory activity.2 9 Anti-inflammatory effect may account for efficacy of roflumilast; available data are limited and inconclusive regarding such effects in humans.6 7 8

• Reduced number of neutrophils and eosinophils in sputum of patients with COPD and number of total cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid in healthy individuals; clinical importance unknown.1 7

• Not a bronchodilator.1 8

• Importance of patients reading the manufacturer’s patient information (medication guide) prior to initiation of therapy and each time the prescription is refilled.1

• Importance of informing patients that roflumilast is not a bronchodilator and should not be used for the relief of acute bronchospasm.1

• Risk of adverse psychiatric effects (e.g., insomnia, anxiety, depression, suicidal ideation or behavior).1 Importance of advising patients, their families, and caregivers to be alert for the emergence or worsening of insomnia, anxiety, depression, suicidal thoughts, or other mood changes, and to contact a clinician if such changes occur.1

• Risk of weight loss.1 Importance of patients being regularly monitored for weight loss.1 Importance of patients informing a clinician if weight loss occurs.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, vitamins, and herbal supplements, as well as any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

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. No dosage adjustment is necessary.

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. Roflumilast is contraindicated in patients with moderate or severe liver impairment (Child-Pugh class B or C).

Moderate to severe hepatic impairment (Child-Pugh class B or C)

Canadian labeling: Additional contraindication (not in US labeling): Hypersensitivity to roflumilast or any component of the formulation

COPD: Oral: 500 mcg once daily

No dosage adjustment necessary.

Concerns related to adverse effects:

• Arrhythmia: Supraventricular arrhythmias including atrial fibrillation have been reported.

• Gastrointestinal effects: May cause weight loss and/or diarrhea (sometimes severe); weight loss usually observed within 6 months of initiating therapy and diarrhea within 4 weeks. Instruct patients to monitor weight regularly. Avoid initiation of therapy or discontinue therapy with unexplained/pronounced weight loss.

• Neuropsychiatric: Neuropsychiatric effects (eg, anxiety, depression) have been reported with use; rarely, suicidal behavior/ideation and completed suicide were reported. Avoid use 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.

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: Systemic exposure may be increased in patients with mild hepatic impairment; use in moderate to severe impairment is contraindicated.

Other warnings/precautions:

• Appropriate use: Not indicated for relieving acute bronchospasms or for use as monotherapy of COPD; use only as adjunctive therapy to bronchodilator therapy.

To reduce the risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations: 500 mcg orally once a day, with or without food