Roflumilast

Roflumilast, sold under the brand name Daxas among others, is a medication used for the treatment of chronic obstructive pulmonary disease,^[4] plaque psoriasis,^[5] seborrheic dermatitis,^[6] and atopic dermatitis.^[5] It acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4).^[10] It has anti-inflammatory effects.^[10][11][12]

Roflumilast

Clinical data
Trade names	Daxas, Daliresp, Zoryve, others
AHFS/Drugs.com	Monograph
MedlinePlus	a611034
License data	US DailyMed: Roflumilast
Pregnancy category	AU: B3
Routes of administration	By mouth, topical
Drug class	PDE4 inhibitor
ATC code	R03DX07 (WHO) D05AX06 (WHO)
Legal status
Legal status	AU: S4 (Prescription only) CA: ℞-only[1][2] UK: POM (Prescription only)[3] US: ℞-only[4][5][6] EU: Rx-only[7]
Pharmacokinetic data
Bioavailability	79%[4][3][8][9]
Protein binding	99%[4][3][8][9]
Metabolism	Hepatic via CYP1A2 & CYP3A4[4][3][8][9]
Elimination half-life	17 hours (30 hours [active metabolite])[4][3][8][9]
Excretion	Urine (70%)[4][3][8][9]
Identifiers
IUPAC name 3-(Cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
CAS Number	162401-32-3 N
PubChem CID	449193
IUPHAR/BPS	6962
DrugBank	DB01656 Y
ChemSpider	395793 N
UNII	0P6C6ZOP5U
KEGG	D05744
ChEBI	CHEBI:47657 N
ChEMBL	ChEMBL193240 N
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) N Key:MNDBXUUTURYVHR-UHFFFAOYSA-N N
NY (what is this?)  (verify)

It was approved for medical use in the European Union in 2010,^[7] in the United States in 2011,^[4] and in Canada in 2017.^[1] It is available as a generic medication.^[13]

Medical uses

Roflumilast is indicated for the treatment of severe chronic obstructive pulmonary disease (COPD),^[4] plaque psoriasis,^[5][14] seborrheic dermatitis,^[6] and atopic dermatitis,^[5][15]

It is used in the prevention of exacerbations (lung attacks) in severe chronic obstructive pulmonary disease (COPD).^{[3][4][7][8][9]}

Adverse effects

Common (1–10% incidence) adverse effects include diarrhea, weight loss, nausea, headache, insomnia, decreased appetite, abdominal pain, rhinitis, sinusitis, urinary tract infection, and depression.^{[4][3][8][9][16]}

Society and culture

Legal status

In June 2010, it was approved in the European Union for severe COPD associated with chronic bronchitis.^[7][17] In February 2011, it gained FDA approval in the United States for reducing COPD exacerbations.^[18][19]

References

1. "Daxas Product information". Health Canada. 20 July 2017. Retrieved 13 July 2024.
2. "Zoryve Product information". Health Canada. 7 November 2023. Retrieved 13 July 2024.
3. "Daxas 250 micrograms tablets - Summary of Product Characteristics (SmPC)". (emc). 11 June 2020. Archived from the original on 19 September 2020. Retrieved 28 September 2020.
4. "Daliresp- roflumilast tablet". DailyMed. 12 March 2020. Archived from the original on 25 March 2021. Retrieved 28 September 2020.
5. "Zoryve- roflumilast cream". DailyMed. 16 August 2022. Archived from the original on 21 January 2023. Retrieved 21 January 2023.
6. "Zoryve- roflumilast aerosol, foam". DailyMed. 20 December 2023. Retrieved 13 July 2024.
7. "Daxas EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 12 August 2020. Retrieved 28 September 2020.
8. "Daliresp : EPAR - Product Information" (PDF). European Medicines Agency. Takeda GmbH. 26 September 2013. Archived (PDF) from the original on 26 June 2016. Retrieved 18 November 2013.
9. "roflumilast (Rx) - Daliresp". Medscape Reference. WebMD. Archived from the original on 12 September 2017. Retrieved 18 November 2013.
10. 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.
11. 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.
12. 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.
13. "2022 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 3 March 2023. Archived from the original on 30 June 2023. Retrieved 30 June 2023.
14. "FDA Approves Arcutis' Zoryve (Roflumilast) Cream 0.3% For the Treatment of Plaque Psoriasis in Individuals Age 12 and Older" (Press release). Arcutis Biotherapeutics. 29 July 2022. Archived from the original on 1 August 2022. Retrieved 1 August 2022 – via GlobeNewswire.
15. "FDA Approves Atopic Dermatitis Label Expansion for Arcutis' Zoryve Cream". BioSpace. Retrieved 13 July 2024.
16. 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.
17. ""Nycomed's Anti-Inflammatory Gains Approval in EU for COPD"". Archived from the original on 24 August 2017. Retrieved 10 July 2010.
18. "Drug Approval Package: Daliresp Tablets (roflumilast) NDA #022522". U.S. Food and Drug Administration (FDA). 24 December 1999. Archived from the original on 27 October 2020. Retrieved 28 September 2020.
19. "FDA approves new drug to treat chronic obstructive pulmonary disease" (Press release). U.S. Food and Drug Administration (FDA). 1 March 2011. Archived from the original on 18 January 2017. Retrieved 16 December 2019.

Further reading

• 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. Archived (PDF) from the original on 28 August 2019. Retrieved 24 June 2019.