Introduction

A selective phosphodiesterase type 4 (PDE4) inhibitor.

Uses for Roflumilast (Systemic)

COPD

Reduction of risk of COPD exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.

Not a bronchodilator and not indicated for relief of acute bronchospasm.

Effects on COPD exacerbations when added to a fixed-combination preparation containing a long-acting β₂-adrenergic agonist and orally inhaled corticosteroid not established.

Roflumilast (Systemic) Dosage and Administration

Administration

Oral Administration

Administer orally once daily without regard to meals.

Dosage

Adults

COPD

Oral

500 mcg once daily.

Special Populations

Dosage adjustment not necessary based on gender or race.

Hepatic Impairment

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

Renal Impairment

Dosage adjustment not necessary.

Geriatric Patients

Dosage adjustment not necessary.

Contraindications

• Moderate or severe hepatic impairment (Child-Pugh class B or C). (See Hepatic Impairment under Cautions and also Special Populations under Pharmacokinetics.)

Warnings/Precautions

Acute Bronchospasm

Not a bronchodilator; do not use for relief of acute bronchospasm.

Psychiatric Events and Suicidality

Increased risk of adverse psychiatric effects; insomnia, anxiety, and depression most frequently reported. Suicidal ideation or behavior, including completed suicide and suicide attempts, also reported.

Carefully weigh the risks and benefits before using the drug in patients with a history of depression and/or suicidal thoughts or behavior. Carefully evaluate the risks and benefits of continuing therapy with roflumilast if such effects occur. Some clinicians recommend avoiding the drug in patients with depression. (See Advice to Patients.)

Weight Loss

Moderate or severe weight loss (defined as 5–10% or >10% of body weight, respectively) reported. Most patients regained some of the lost weight following treatment discontinuance.

Regularly monitor patient’s weight. If unexplained or clinically important weight loss occurs, evaluate weight loss and consider discontinuing roflumilast. Some clinicians avoid use of roflumilast therapy in underweight patients.

Interactions

Concomitant use with potent CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin) not recommended. (See Specific Drugs under Interactions.)

Specific Populations

Pregnancy

Category C.

Do not use during labor and delivery. Effect on preterm labor or labor at term in humans unknown; however, labor and delivery disrupted in animals.

Lactation

Roflumilast and/or its metabolites distributed into milk in rats. Distribution likely into human milk. Effects in breast-fed infants not established. Do not use in nursing women.

Pediatric Use

Safety and efficacy not established in pediatric patients; COPD does not occur in children.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults. Clinical experience has not revealed age-related differences, but increased sensitivity cannot be ruled out. Dosage adjustment not necessary.

Hepatic Impairment

Consider the risks and benefits of using roflumilast in patients with mild hepatic impairment (Child-Pugh class A). Contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh class B or C). (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Diarrhea, weight loss, nausea, headache, back pain, influenza, insomnia, dizziness, decreased appetite.

Administration

Oral Administration

Administer orally once daily without regard to meals.

Dosage

Adults

COPD

Oral

500 mcg once daily.

Special Populations

Dosage adjustment not necessary based on gender or race.

Hepatic Impairment

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

Renal Impairment

Dosage adjustment not necessary.

Geriatric Patients

Dosage adjustment not necessary.

Metabolized by CYP3A4 and CYP1A2 to roflumilast N-oxide; roflumilast N-oxide metabolized mainly by CYP3A4, to a lesser extent by CYP2C19 and extrahepatic CYP1A, and glucuronidated.

Roflumilast and roflumilast N-oxide do not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4/5, or 4A9/11.

Roflumilast does not induce CYP isoenzymes 1A2, 2A6, 2C9, 2C19, or 3A4/5 and is a weak inducer of CYP2B6.

Roflumilast and roflumilast N-oxide do not inhibit the P-glycoprotein transport system.

Drugs Affecting Hepatic Microsomal Enzymes

Potent CYP3A4 inducers: Decrease systemic exposure and may reduce the therapeutic efficacy of roflumilast. Concomitant use not recommended.

CYP3A4 inhibitors or inhibitors of both CYP3A4 and CYP1A2: May result in increased systemic exposure to roflumilast and increased adverse effects. Carefully weigh risk of concurrent use against benefit.

Specific Drugs