Products
Roflumilast is commercially available in the form of film-coated tablets (Daxas). The drug was approved in many countries in 2011.
Structure and properties
Roflumilast (C17H14Cl2F2N2O3, Mr = 403.2 g/mol) has a nonsteroidal benzamide structure and is unrelated to the glucocorticoids. It exists as a white powder that is practically insoluble in water.
Effects
Roflumilast (ATC R03DX07) has anti-inflammatory properties. The effects are due to selective, potent, and competitive inhibition of phosphodiesterases 4, which are responsible for the degradation of cAMP in inflammatory cells. Inhibition of PD4 increases cAMP and decreases the release of inflammatory mediators and the migration of neutrophils and eosinophils into the airways. Phosphodiesterases are enzymes that hydrolyze cyclic nucleotides and play an important role in signal transduction in cells. Roflumilast is not bronchodilating, unlike theophylline, to which it is pharmacologically related.
Indications
For continuous therapy in adult patients with severe COPD and chronic bronchitis with a history of frequent exacerbations. Treatment is concomitant with bronchodilator therapy (e.g., salmeterol, tiotropium bromide).
Dosage
According to the SmPC. Tablets are taken once daily. The intake is independent of meals and should always take place at the same time of day. The effect is not immediate, but delayed within a few weeks.
Contraindications
- Hypersensitivity
- Moderate to severe liver dysfunction
For complete precautions, see the drug label.
Interactions
Roflumilast is metabolized by CYP3A4 and CYP1A2 to roflumilast-N-oxide. Roflumilast N-oxide is a partially active metabolite; accordingly, roflumilast is one of the so-called limited prodrugs. Corresponding interactions with CYP inhibitors and inducers are possible.
Adverse effects
The most common potential adverse effects include digestive symptoms such as diarrhea, weight loss, nausea, abdominal pain, and central side effects such as headache. Inhibition of PDE4D in the central nervous system causes nausea and vomiting. Roflumilast may cause psychiatric disorders such as sleep disturbances, anxiety, nervousness, and depression.
