Roflumilast

Roflumilast

Systematic (IUPAC) name
3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
Clinical data
Trade names	Daxas,Daliresp
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a611034
License data	EU EMA: Daxas US FDA: Roflumilast
Pregnancy category	AU: B3 US: C (Risk not ruled out)
Routes of administration	Oral
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) US: ℞-only
Pharmacokinetic data
Bioavailability	79%[1][2][3][4]
Protein binding	99%[1][2][3][4]
Metabolism	Hepatic via CYP1A2 & CYP3A4[1][2][3][4]
Biological half-life	17 hours (30 hours [active metabolite])[1][2][3][4]
Excretion	Urine (70%)[1][2][3][4]
Identifiers
CAS Number	162401-32-3
ATC code	R03DX07 (WHO)
PubChem	CID 449193
IUPHAR/BPS	6962
ChemSpider	395793
UNII	0P6C6ZOP5U
ChEBI	CHEBI:47657
ChEMBL	CHEMBL193240
Chemical data
Formula	C17H14Cl2F2N2O3
Molar mass	403.207 g/mol
SMILES C1CC1COC2=C(C=CC(=C2)C(=O)NC3=C(C=NC=C3Cl)Cl)OC(F)F
InChI InChI=1S/C17H14Cl2F2N2O3/c18-11-6-22-7-12(19)15(11)23-16(24)10-3-4-13(26-17(20)21)14(5-10)25-8-9-1-2-9/h3-7,9,17H,1-2,8H2,(H,22,23,24) Key:MNDBXUUTURYVHR-UHFFFAOYSA-N
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Roflumilast (trade names Daxas, Daliresp) is a drug that acts as a selective, long-acting inhibitor of the enzyme PDE-4 (Phosphodiesterase-4). It has anti-inflammatory effects and is used as an orally administered drug for the treatment of inflammatory conditions of the lungs such as chronic obstructive pulmonary disease (COPD).^[5][6][7][8]

In June 2010, Daxas was approved in the EU for severe COPD associated with chronic bronchitis.^[9] In March 2011, Daliresp gained FDA approval in the US for reducing COPD exacerbations.^[10]

Medical uses

Its primary clinical use is in the prevention of exacerbations (lung attacks) in severe COPD.^[1][2][3][4]

Adverse effects

Common (1–10% incidence) adverse effects include:^{[1][2][3][4][11]}

• Diarrhea
• Weight decreased
• Nausea
• Headache
• Insomnia
• Decreased appetite
• Abdominal pain
• Rhinitis
• Sinusitis
• Urinary tract infection
• Depression

References

1. "DALIRESP (roflumilast) tablet [Forest Laboratories, Inc.]" (PDF). DailyMed. Forest Laboratories, Inc. August 2013. Retrieved 18 November 2013.
2. "DAXAS 500 micrograms film-coated tablets". electronic Medicines Compendium. Takeda UK Ltd. 9 September 2013. Retrieved 18 November 2013.
3. "Daliresp : EPAR - Product Information" (PDF). European Medicines Agency. Takeda GmbH. 26 September 2013. Retrieved 18 November 2013.
4. "roflumilast (Rx) - Daliresp". Medscape Reference. WebMD. Retrieved 18 November 2013.
5. Boswell-Smith, V; Spina, D (2007). "PDE4 inhibitors as potential therapeutic agents in the treatment of COPD-focus on roflumilast". International Journal of Chronic Obstructive Pulmonary Disease 2 (2): 121–9. ISSN 1178-2005. PMC 2695611. PMID 18044684.
6. Herbert, C; Hettiaratchi, A; Webb, DC; Thomas, PS; Foster, PS; Kumar, RK (May 2008). "Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma". Clinical & Experimental Allergy 38 (5): 847–56. doi:10.1111/j.1365-2222.2008.02950.x. ISSN 1365-2222. PMID 18307529.
7. Hohlfeld, JM; Schoenfeld, K; Lavae-Mokhtari, M; Schaumann, F; Mueller, M; Bredenbroeker, D; Krug, N; Hermann, R (August 2008). "Roflumilast attenuates pulmonary inflammation upon segmental endotoxin challenge in healthy subjects: a randomized placebo-controlled trial". Pulmonary Pharmacology & Therapeutics 21 (4): 616–23. doi:10.1016/j.pupt.2008.02.002. ISSN 1094-5539. PMID 18374614.
8. Field, SK (May 2008). "Roflumilast: an oral, once-daily selective PDE-4 inhibitor for the management of COPD and asthma". Expert Opinion on Investigational Drugs 17 (5): 811–8. doi:10.1517/13543784.17.5.811. ISSN 1354-3784. PMID 18447606.
9. "Nycomed's Anti-Inflammatory Gains Approval in EU for COPD"
10. "FDA approves new drug to treat chronic obstructive pulmonary disease" (Press release). U.S. Food and Drug Administration (FDA). March 1, 2011.
11. Spina, D (October 2008). "PDE4 inhibitors: current status". British Journal of Pharmacology 155 (3): 308–15. doi:10.1038/bjp.2008.307. ISSN 1476-5381. PMC 2567892. PMID 18660825.