Roflumilast

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 464383196

| image = Roflumilast structure.svg

| width = 240

| alt =

| image2 = Roflumilast ball-and-stick model.png

| width2 = 240

| alt2 =

| caption =

| pronounce =

| tradename = Daxas, Daliresp, Zoryve, others

| Drugs.com = {{drugs.com|monograph|roflumilast}}

| MedlinePlus = a611034

| DailyMedID = Roflumilast

| pregnancy_AU = B3

| pregnancy_AU_comment =

| pregnancy_category =

| routes_of_administration = By mouth, topical

| class = PDE4 inhibitor

| ATC_prefix = R03

| ATC_suffix = DX07

| ATC_supplemental = {{ATC|D05|AX06}}

| legal_AU = S4

| legal_AU_comment =

| legal_BR =

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| legal_CA = Rx-only

| legal_CA_comment = {{cite web | title=Zoryve Product information | website=Health Canada | date=7 November 2023 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=102624 | access-date=13 July 2024}}

| legal_DE =

| legal_DE_comment =

| legal_NZ =

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| legal_UK = POM

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| legal_US = Rx-only

| legal_US_comment =

| legal_EU = Rx-only

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| bioavailability = 79%

| protein_bound = 99%

| metabolism = Hepatic via CYP1A2 & CYP3A4

| metabolites =

| onset =

| elimination_half-life = 17 hours (30 hours [active metabolite])

| duration_of_action =

| excretion = Urine (70%)

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 162401-32-3

| CAS_supplemental =

| PubChem = 449193

| IUPHAR_ligand = 6962

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01656

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 395793

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 0P6C6ZOP5U

| KEGG_Ref =

| KEGG = D05744

| ChEBI_Ref = {{ebicite|changed|EBI}}

| ChEBI = 47657

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 193240

| NIAID_ChemDB =

| PDB_ligand = ROF

| synonyms =

| IUPAC_name = 3-(Cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide

| C=17 | H=14 | Cl=2 | F=2 | N=2 | O=3

| SMILES = C1CC1COC2=C(C=CC(=C2)C(=O)NC3=C(C=NC=C3Cl)Cl)OC(F)F

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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)

| StdInChI_comment =

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = MNDBXUUTURYVHR-UHFFFAOYSA-N

| density =

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}}

Roflumilast, sold under the brand name Daxas among others, is a medication used for the treatment of chronic obstructive pulmonary disease, plaque psoriasis, seborrheic dermatitis, and atopic dermatitis. It acts as a selective, long-acting inhibitor of the enzyme phosphodiesterase-4 (PDE-4). It has anti-inflammatory effects.{{cite journal | vauthors = Boswell-Smith V, Spina D | title = PDE4 inhibitors as potential therapeutic agents in the treatment of COPD-focus on roflumilast | journal = International Journal of Chronic Obstructive Pulmonary Disease | volume = 2 | issue = 2 | pages = 121–9 | year = 2007 | pmid = 18044684 | pmc = 2695611 | url = }}{{cite journal | vauthors = Herbert C, Hettiaratchi A, Webb DC, Thomas PS, Foster PS, Kumar RK | title = Suppression of cytokine expression by roflumilast and dexamethasone in a model of chronic asthma | journal = Clinical and Experimental Allergy | volume = 38 | issue = 5 | pages = 847–56 | date = May 2008 | pmid = 18307529 | doi = 10.1111/j.1365-2222.2008.02950.x | s2cid = 19050454 }}{{cite journal | vauthors = Field SK | title = Roflumilast: an oral, once-daily selective PDE-4 inhibitor for the management of COPD and asthma | journal = Expert Opinion on Investigational Drugs | volume = 17 | issue = 5 | pages = 811–8 | date = May 2008 | pmid = 18447606 | doi = 10.1517/13543784.17.5.811 | s2cid = 73241684 }}

It was approved for medical use in the European Union in 2010,{{cite web | title=Daxas EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/daxas | access-date=28 September 2020 | archive-date=12 August 2020 | archive-url=https://web.archive.org/web/20200812193907/https://www.ema.europa.eu/en/medicines/human/EPAR/daxas | url-status=live }} in the United States in 2011,{{cite web | title=Daliresp- roflumilast tablet | website=DailyMed | date=12 March 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9a1d0a8-581f-4f91-a2b8-f419192d0ebf | access-date=28 September 2020 | archive-date=25 March 2021 | archive-url=https://web.archive.org/web/20210325081719/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c9a1d0a8-581f-4f91-a2b8-f419192d0ebf | url-status=live }} and in Canada in 2017.{{cite web | title=Daxas Product information | website=Health Canada | date=20 July 2017 | url=https://health-products.canada.ca/dpd-bdpp/info?lang=eng&code=84447 | access-date=13 July 2024}} It is available as a generic medication.{{cite web | title=2022 First Generic Drug Approvals | website=U.S. Food and Drug Administration (FDA) | date=3 March 2023 | url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/2022-first-generic-drug-approvals | archive-url=https://web.archive.org/web/20230630003602/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/2022-first-generic-drug-approvals | archive-date=30 June 2023 | url-status=live | access-date=30 June 2023}}

Medical uses

Roflumilast is indicated for the treatment of severe chronic obstructive pulmonary disease (COPD), plaque psoriasis,{{cite web | title=Zoryve- roflumilast cream | website=DailyMed | date=16 August 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ec1bb0d1-f38a-4080-831a-68791d1d1fdb | access-date=21 January 2023 | archive-date=21 January 2023 | archive-url=https://web.archive.org/web/20230121062229/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ec1bb0d1-f38a-4080-831a-68791d1d1fdb | url-status=live }}{{cite press release | title=FDA Approves Arcutis' Zoryve (Roflumilast) Cream 0.3% For the Treatment of Plaque Psoriasis in Individuals Age 12 and Older | publisher=Arcutis Biotherapeutics | via=GlobeNewswire | date=29 July 2022 | url=https://www.globenewswire.com/news-release/2022/07/29/2488966/0/en/FDA-Approves-Arcutis-ZORYVE-Roflumilast-Cream-0-3-For-the-Treatment-of-Plaque-Psoriasis-in-Individuals-Age-12-and-Older.html | access-date=1 August 2022 | archive-date=1 August 2022 | archive-url=https://web.archive.org/web/20220801114445/https://www.globenewswire.com/news-release/2022/07/29/2488966/0/en/FDA-Approves-Arcutis-ZORYVE-Roflumilast-Cream-0-3-For-the-Treatment-of-Plaque-Psoriasis-in-Individuals-Age-12-and-Older.html | url-status=live }} seborrheic dermatitis,{{cite web | title=Zoryve- roflumilast aerosol, foam | website=DailyMed | date=20 December 2023 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f9e0b4a9-a227-4947-b00c-41fb18d16589 | access-date=13 July 2024}} and atopic dermatitis,{{cite web |title=FDA Approves Atopic Dermatitis Label Expansion for Arcutis' Zoryve Cream |url=https://www.biospace.com/article/fda-approves-atopic-dermatitis-label-expansion-for-arcutis-zoryve-topical-cream-/ |access-date=13 July 2024 |website=BioSpace }}

It is used in the prevention of exacerbations (lung attacks) in severe chronic obstructive pulmonary disease (COPD).{{cite web | title=Daxas 250 micrograms tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=11 June 2020 | url=https://www.medicines.org.uk/emc/product/9162/smpc | access-date=28 September 2020 | archive-date=19 September 2020 | archive-url=https://web.archive.org/web/20200919164902/https://www.medicines.org.uk/emc/product/9162/smpc | url-status=live }}{{cite web|title=Daliresp : EPAR - Product Information|work=European Medicines Agency|publisher=Takeda GmbH|date=26 September 2013|access-date=18 November 2013|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002398/WC500103078.pdf|archive-date=26 June 2016|archive-url=https://web.archive.org/web/20160626155812/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002398/WC500103078.pdf|url-status=live}}{{cite web|title=roflumilast (Rx) - Daliresp|work=Medscape Reference|publisher=WebMD|access-date=18 November 2013|url=http://reference.medscape.com/drug/daliresp-roflumilast-999626|archive-date=12 September 2017|archive-url=https://web.archive.org/web/20170912145935/http://reference.medscape.com/drug/daliresp-roflumilast-999626|url-status=live}}

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.{{cite journal | vauthors = Spina D | title = PDE4 inhibitors: current status | journal = British Journal of Pharmacology | volume = 155 | issue = 3 | pages = 308–15 | date = October 2008 | pmid = 18660825 | pmc = 2567892 | doi = 10.1038/bjp.2008.307 }}

Society and culture

= Legal status =

In June 2010, it was approved in the European Union for severe COPD associated with chronic bronchitis.{{Cite web |url=http://www.genengnews.com/gen-news-highlights/nycomed-s-anti-inflammatory-gains-approval-in-eu-for-copd/81243622/ |title="Nycomed's Anti-Inflammatory Gains Approval in EU for COPD" |access-date=10 July 2010 |archive-date=24 August 2017 |archive-url=https://web.archive.org/web/20170824222207/http://www.genengnews.com/gen-news-highlights/nycomed-s-anti-inflammatory-gains-approval-in-eu-for-copd/81243622 |url-status=live }} In February 2011, it gained FDA approval in the United States for reducing COPD exacerbations.{{cite web | title=Drug Approval Package: Daliresp Tablets (roflumilast) NDA #022522 | website=U.S. Food and Drug Administration (FDA) | date=24 December 1999 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022522Orig1s000TOC.cfm | access-date=28 September 2020 | archive-date=27 October 2020 | archive-url=https://web.archive.org/web/20201027013611/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022522Orig1s000TOC.cfm | url-status=live }}{{cite press release | url = https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm244989.htm | title = FDA approves new drug to treat chronic obstructive pulmonary disease | date = 1 March 2011 | publisher = U.S. Food and Drug Administration (FDA) | access-date = 16 December 2019 | archive-date = 18 January 2017 | archive-url = https://web.archive.org/web/20170118091136/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm244989.htm | url-status = dead }}

Roflumilast

Medical uses

Adverse effects

Society and culture

= Legal status =

References

Further reading