Roflumilast (Systemic)

Brand names: Daliresp
Drug class: Antineoplastic Agents

Usage of 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.

Relate drugs

How to use Roflumilast (Systemic)

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.

Warnings

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.

    What other drugs will affect Roflumilast (Systemic)

    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

    Drug

    Interaction

    Comments

    Albuterol

    No clinically important pharmacokinetic interactions observed with orally inhaled albuterol

    No dosage adjustment recommended

    Antacids (aluminum hydroxide/magnesium hydroxide)

    No clinically important pharmacokinetic interactions observed

    No dosage adjustment recommended

    Anticonvulsants (carbamazepine, phenobarbital, phenytoin)

    Decreased systemic exposure and possible reduced therapeutic efficacy of roflumilast

    Concomitant use not recommended

    Budesonide

    No clinically important pharmacokinetic interactions observed with orally inhaled budesonide

    No dosage adjustment recommended

    Cimetidine

    Increased peak plasma concentrations and AUC of roflumilast; decreased peak plasma concentrations and increased AUC of roflumilast N-oxide

    Use concomitantly with caution; weigh risk of concurrent use against benefit

    Digoxin

    No clinically important pharmacokinetic interactions observed

    No dosage adjustment recommended

    Enoxacin (no longer commercially available in US)

    Increased peak plasma concentrations and AUC of roflumilast; decreased peak plasma concentrations and increased AUC of roflumilast N-oxide

    Use concomitantly with caution; weigh risk of concurrent use against benefit

    Erythromycin

    Increased peak plasma concentrations and AUC of roflumilast; decreased peak plasma concentrations and increased AUC of roflumilast N-oxide

    Use concomitantly with caution; weigh risk of concurrent use against benefit

    Fluvoxamine

    Increased peak plasma concentrations and AUC of roflumilast; decreased peak plasma concentrations and increased AUC of roflumilast N-oxide

    Use concomitantly with caution; weigh risk of concurrent use against benefit

    Formoterol

    No clinically important pharmacokinetic interactions observed with orally inhaled formoterol

    No dosage adjustment recommended

    Ketoconazole

    Increased peak plasma concentrations and AUC of roflumilast; decreased peak plasma concentrations and increased AUC of roflumilast N-oxide

    Use concomitantly with caution; weigh risk of concurrent use against benefit

    Midazolam

    No clinically important pharmacokinetic interactions observed with oral midazolam

    No dosage adjustment recommended

    Montelukast

    No clinically important pharmacokinetic interactions observed

    No dosage adjustment recommended

    Oral contraceptives (fixed combination of gestodene [not commercially available in US] and ethinyl estradiol)

    Increased peak plasma concentrations and AUC of roflumilast; decreased peak plasma concentrations and increased AUC of roflumilast N-oxide

    May increase risk of adverse effects

    Use concomitantly with caution; weigh risk of concurrent use against benefit

    Rifampin

    Decreased peak plasma concentrations and AUC of roflumilast; increased peak plasma concentrations and decreased AUC of roflumilast N-oxide

    Possible reduced efficacy of roflumilast

    Concomitant use not recommended

    Sildenafil

    No clinically important pharmacokinetic interactions observed

    No dosage adjustment recommended

    Theophylline

    No clinically important pharmacokinetic interactions observed

    No dosage adjustment recommended; however, some clinicians do not recommend concomitant use

    Warfarin

    No clinically important pharmacokinetic interactions observed

    No dosage adjustment recommended

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