Roflumilast

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Roflumilast
Roflumilast PubChem CID 449193.png
Systematic (IUPAC) name
3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
Clinical data
Trade namesDaxas, Daliresp
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa611034
Licence dataEMA:Link, US FDA:link
Pregnancy cat.
Legal status
RoutesOral
Pharmacokinetic data
Bioavailability79%[1][2][3][4]
Protein binding99%[1][2][3][4]
MetabolismHepatic via CYP1A2 & CYP3A4[1][2][3][4]
Half-life17 hours (30 hours [active metabolite])[1][2][3][4]
ExcretionUrine (70%)[1][2][3][4]
Identifiers
CAS number162401-32-3 N
ATC codeR03DX07
PubChemCID 449193
ChemSpider395793 N
UNII0P6C6ZOP5U YesY
ChEBICHEBI:47657 N
ChEMBLCHEMBL193240 N
Chemical data
FormulaC17H14Cl2F2N2O3 
Mol. mass403.207 g/mol
 N (what is this?)  (verify)
 
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Roflumilast
Roflumilast PubChem CID 449193.png
Systematic (IUPAC) name
3-(cyclopropylmethoxy)-N-(3,5-dichloropyridin-4-yl)-4-(difluoromethoxy)benzamide
Clinical data
Trade namesDaxas, Daliresp
AHFS/Drugs.comConsumer Drug Information
MedlinePlusa611034
Licence dataEMA:Link, US FDA:link
Pregnancy cat.
Legal status
RoutesOral
Pharmacokinetic data
Bioavailability79%[1][2][3][4]
Protein binding99%[1][2][3][4]
MetabolismHepatic via CYP1A2 & CYP3A4[1][2][3][4]
Half-life17 hours (30 hours [active metabolite])[1][2][3][4]
ExcretionUrine (70%)[1][2][3][4]
Identifiers
CAS number162401-32-3 N
ATC codeR03DX07
PubChemCID 449193
ChemSpider395793 N
UNII0P6C6ZOP5U YesY
ChEBICHEBI:47657 N
ChEMBLCHEMBL193240 N
Chemical data
FormulaC17H14Cl2F2N2O3 
Mol. mass403.207 g/mol
 N (what is this?)  (verify)

Roflumilast (trade names Daxas, Daliresp) is a drug that acts as a selective, long-acting inhibitor of the enzyme PDE-4. It has anti-inflammatory effects and is under development as an orally administered drug for the treatment of inflammatory conditions of the lungs such as asthma and 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[edit]

Its primary clinical use is in the prevention of exacerbations in severe COPD.[1][2][3][4]

Adverse effects[edit]

Adverse effects by incidence:[1][2][3][4][11]

Common (1-10% incidence) adverse effects include:

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

Uncommon (0.1-1% incidence) adverse effects include:

  • Hypersensitivity
  • Anxiety
  • Tremor
  • Vertigo
  • Dizziness
  • Palpitations
  • Vomiting
  • Gastritis
  • Gastro-esophageal reflux disease
  • Dyspepsia (indigestion)
  • Muscle spasms and weakness
  • Myalgia
  • Back pain
  • Malaise
  • Asthenia
  • Fatigue

Rare (<0.1% incidence) adverse effects include:

  • Gynaecomastia
  • Angioedema
  • Suicidal ideation and behaviour
  • Nervousness
  • Dysgeusia (a change in taste perception)
  • Respiratory tract infections (excluding pneumonia)
  • Haematochezia
  • Urticaria
  • Gamma-GT increased
  • Aspartate aminotransferase (AST) increased
  • Constipation
  • Blood creatine phosphokinase (CPK) increased

Chemical synthesis[edit]

Chemical synthesis:[12]

Roflumilast syn.png

References[edit]

  1. ^ a b c d e f g "DALIRESP (roflumilast) tablet [Forest Laboratories, Inc.]" (PDF). DailyMed. Forest Laboratories, Inc. August 2013. Retrieved 18 November 2013. 
  2. ^ a b c d e f g "DAXAS 500 micrograms film-coated tablets". electronic Medicines Compendium. Takeda UK Ltd. 9 September 2013. Retrieved 18 November 2013. 
  3. ^ a b c d e f g "Daliresp : EPAR - Product Information" (PDF). European Medicines Agency. Takeda GmbH. 26 September 2013. Retrieved 18 November 2013. 
  4. ^ a b c d e f g "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. 
  12. ^ Amschler, H.; 1998, U.S. Patent 5,712,298.

External links[edit]