Daliresp (roflumilast)

Roflumilast is a selective phosphodiesterase type 4 (PDE4) inhibitor.

Roflumilast and its active metabolite, roflumilast N-oxide, are selective inhibitors of phosphodiesterase type 4 (PDE4), a major enzyme involved in the metabolism of cyclic adenosine-3',5'-monophosphate (cAMP) in lung tissue. Selective inhibition of PDE4 results in accumulation of intracellular cAMP. Although the exact mechanism(s) of therapeutic action of roflumilast in patients with chronic obstructive pulmonary disease (COPD) has not been fully elucidated, it is thought to be related to the effects of increased cAMP in lung cells.

Increased cAMP concentrations can lead to activation of protein kinase A, resulting in phosphorylation and inactivation of target transcription factors, and subsequent reduction of cellular inflammatory activity. An anti-inflammatory effect may account for the clinical efficacy of roflumilast; however, few studies have evaluated the potential anti-inflammatory effects of roflumilast in humans and available data are limited and inconclusive. Roflumilast reduced the number of neutrophils and eosinophils in the sputum of patients with COPD and the number of total cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid in healthy individuals; the clinical importance of these results is unknown.

Roflumilast is not a bronchodilator.

Roflumilast is extensively metabolized via cytochrome P-450 (CYP) and conjugation reactions. A major pathway for roflumilast metabolism is pyridine N-oxidation of roflumilast to roflumilast N-oxide by CYP isoenzymes 3A4 and 1A2. Roflumilast N-oxide is O-dealkylated mainly by CYP3A4, and to a lesser extent by CYP2C19 and extrahepatic CYP1A, and glucuronidated.

The N-oxide metabolite is the only major metabolite detected in human plasma and its pharmacokinetics are distinct from the parent compound. Roflumilast and roflumilast N-oxide together account for most (87.5%) of the administered dose present in plasma. While roflumilast is threefold more potent than roflumilast N-oxide with respect to PDE4 inhibition in vitro, the area under the plasma concentration-time curve (AUC) of roflumilast N-oxide is about tenfold greater than that of roflumilast.

The N-oxide metabolite appears to account for about 90% of the biologic action of roflumilast. Roflumilast was not detected in urine, while a trace amount (less than 1%) of roflumilast N-oxide was detected; other conjugated metabolites were detected in urine. Following IV or oral administration of radiolabeled roflumilast, about 70% of radioactivity was recovered in urine.

The median plasma effective half-lives of roflumilast and roflumilast N-oxide are approximately 17 and 30 hours, respectively.

USES: Roflumilast is used to control and prevent symptoms (wheezing and shortness of breath) caused by ongoing lung disease (chronic obstructive pulmonary disease-COPD which includes bronchitis). It should be used along with other medications (bronchodilators such as salmeterol, ipratropium) to treat COPD. It works by reducing the irritation and swelling of the airways.

Controlling symptoms of breathing problems can decrease time lost from work or school. This medication must be used regularly to be effective. It does not work right away and should not be used to relieve sudden shortness of breath or wheezing.

If sudden breathing problems occur, use your quick-relief inhaler (such as albuterol, also called salbutamol in some countries) as prescribed.

Generic name: roflumilast
Pronunciation: (roe-FLUE-mi-last)

The following indications are listed for Daliresp:

• Prevention Of Bronchospasm With Chronic Bronchitis

No ICD codes are available for this drug.