Roflumilast

Roflumilast, sold under the trade name Daxas among others, is a drug that acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-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).[6][7][8][9]

Roflumilast

drugb
Clinical data
Trade names	Daxas, Daliresp, others
AHFS/Drugs.com	Monograph
MedlinePlus	a611034
License data	EU EMA: by INN US DailyMed: Roflumilast US FDA: Roflumilast
Pregnancy category	AU: B3
Routes of administration	By mouth
ATC code	R03DX07 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only UK: POM (Prescription only) [1] US: ℞-only [2] EU: Rx-only [3]
Pharmacokinetic data
Bioavailability	79%[2][1][4][5]
Protein binding	99%[2][1][4][5]
Metabolism	Hepatic via CYP1A2 & CYP3A4[2][1][4][5]
Elimination half-life	17 hours (30 hours [active metabolite])[2][1][4][5]
Excretion	Urine (70%)[2][1][4][5]
Identifiers
IUPAC name 3-(Cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
CAS Number	162401-32-3
PubChem CID	449193
IUPHAR/BPS	6962
DrugBank	DB01656
ChemSpider	395793
UNII	0P6C6ZOP5U
KEGG	D05744
ChEBI	CHEBI:47657
ChEMBL	ChEMBL193240
PDB ligand	ROF (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID8044123
ECHA InfoCard	100.210.960
Chemical and physical data
Formula	C17H14Cl2F2N2O3
Molar mass	403.21 g·mol^−1
3D model (JSmol)	Interactive image
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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In June 2010, it was approved in the European Union for severe COPD associated with chronic bronchitis.[3][10] In February 2011, it gained FDA approval in the United States for reducing COPD exacerbations.[11][12]

Medical uses

Its primary clinical use is in the prevention of exacerbations (lung attacks) in severe chronic obstructive pulmonary disease (COPD).[2][1]>[4][5][3]

Adverse effects

Common (1–10% incidence) adverse effects include:[2][1][4][5][13]

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

References

1. "Daxas 250 micrograms tablets - Summary of Product Characteristics (SmPC)". (emc). 11 June 2020. Retrieved 28 September 2020.
2. "Daliresp- roflumilast tablet". DailyMed. 12 March 2020. Retrieved 28 September 2020.
3. "Daxas EPAR". European Medicines Agency. Retrieved 28 September 2020.
4. "Daliresp : EPAR - Product Information" (PDF). European Medicines Agency. Takeda GmbH. 26 September 2013. Retrieved 18 November 2013.
5. "roflumilast (Rx) - Daliresp". Medscape Reference. WebMD. Retrieved 18 November 2013.
6. 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. PMC 2695611. PMID 18044684.
7. 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 and Experimental Allergy. 38 (5): 847–56. doi:10.1111/j.1365-2222.2008.02950.x. PMID 18307529. S2CID 19050454.
8. Hohlfeld JM, Schoenfeld K, Lavae-Mokhtari M, Schaumann F, Mueller M, Bredenbroeker D, et al. (August 2008). "Roflumilast attenuates pulmonary inflammation upon segmental endotoxin challenge in healthy subjects: a randomized placebo-controlled trial" (PDF). Pulmonary Pharmacology & Therapeutics. 21 (4): 616–23. doi:10.1016/j.pupt.2008.02.002. PMID 18374614.
9. 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. PMID 18447606. S2CID 73241684.
10. "Nycomed's Anti-Inflammatory Gains Approval in EU for COPD"
11. "Drug Approval Package: Daliresp Tablets (roflumilast) NDA #022522". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 28 September 2020. Lay summary (PDF).
12. "FDA approves new drug to treat chronic obstructive pulmonary disease" (Press release). U.S. Food and Drug Administration (FDA). March 1, 2011.
13. Spina D (October 2008). "PDE4 inhibitors: current status". British Journal of Pharmacology. 155 (3): 308–15. doi:10.1038/bjp.2008.307. PMC 2567892. PMID 18660825.

External links

• "Roflumilast". Drug Information Portal. U.S. National Library of Medicine.