roflumilast 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
phosphodiesterase IV (PDE IV) inhibitors 3531 162401-32-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • libertek
  • roflumilast
  • daxas
  • daliresp
  • BY217
  • B9302-107
  • BYK20869
  • Molecular weight: 403.21
  • Formula: C17H14Cl2F2N2O3
  • CLOGP: 3.12
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 1
  • TPSA: 60.45
  • ALOGS: -4.81
  • ROTB: 7
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.50 mg O

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 1.92 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.20 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.01 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 15.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Feb. 28, 2011 EMA
Feb. 28, 2011 FDA ASTRAZENECA PHARMS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Chronic obstructive pulmonary disease 161.89 25.83 78 3539 53357 50548150
Dyspnoea 102.19 25.83 157 3460 547451 50054056
Full blood count abnormal 76.34 25.83 36 3581 23352 50578155
Asthma 72.32 25.83 56 3561 89281 50512226
Wheezing 71.02 25.83 48 3569 61999 50539508
Pneumothorax spontaneous 49.10 25.83 11 3606 645 50600862
Obstructive airways disorder 47.72 25.83 23 3594 15629 50585878
Emphysema 45.83 25.83 19 3598 9074 50592433
Weight decreased 44.47 25.83 66 3551 221179 50380328
Sleep disorder due to a general medical condition 39.18 25.83 16 3601 7355 50594152
Pneumonia 38.70 25.83 84 3533 378317 50223190
Therapeutic product effect incomplete 37.32 25.83 39 3578 91476 50510031
Productive cough 36.12 25.83 30 3587 52664 50548843
Hypercapnia 35.08 25.83 13 3604 4614 50596893
Breath sounds abnormal 34.99 25.83 15 3602 7777 50593730
Adenocarcinoma 34.60 25.83 11 3606 2470 50599037
Polymyalgia rheumatica 33.94 25.83 11 3606 2625 50598882
Respiratory tract infection 32.42 25.83 23 3594 31994 50569513
Bacterial disease carrier 31.49 25.83 8 3609 803 50600704
Bronchial secretion retention 30.91 25.83 9 3608 1504 50600003
Bronchial wall thickening 30.62 25.83 8 3609 897 50600610
Spirometry abnormal 29.88 25.83 6 3611 207 50601300
Lung diffusion disorder 29.76 25.83 5 3612 62 50601445
Diarrhoea 28.26 25.83 99 3518 588377 50013130
Multiple allergies 27.51 25.83 13 3604 8450 50593057
Suicidal ideation 26.96 25.83 26 3591 55359 50546148

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Dyspnoea 158.49 27.84 193 3328 326539 29244467
Chronic obstructive pulmonary disease 121.98 27.84 70 3451 40885 29530121
Weight decreased 75.37 27.84 91 3430 150814 29420192
Product prescribing error 73.64 27.84 38 3483 17938 29553068
Suicidal ideation 46.20 27.84 36 3485 34680 29536326
Cough 43.91 27.84 64 3457 126663 29444343
Decreased appetite 37.33 27.84 64 3457 145278 29425728
Insomnia 35.41 27.84 48 3473 88713 29482293
Diarrhoea 33.70 27.84 101 3420 332597 29238409
Wheezing 32.81 27.84 29 3492 33211 29537795
Asthma 30.39 27.84 28 3493 33821 29537185
Cold sweat 28.62 27.84 16 3505 8826 29562180
Oedema peripheral 28.40 27.84 47 3474 103510 29467496
Death 28.36 27.84 97 3424 341987 29229019
Asthma-chronic obstructive pulmonary disease overlap syndrome 28.14 27.84 8 3513 735 29570271

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Chronic obstructive pulmonary disease 219.58 26.39 112 5503 70936 64422181
Dyspnoea 214.22 26.39 285 5330 718389 63774728
Weight decreased 85.13 26.39 114 5501 285625 64207492
Asthma 81.61 26.39 67 5548 95158 64397959
Product prescribing error 76.37 26.39 44 5571 35225 64457892
Wheezing 67.56 26.39 56 5559 80523 64412594
Full blood count abnormal 58.81 26.39 35 5580 29722 64463395
Emphysema 45.72 26.39 23 5592 14046 64479071
Cough 44.92 26.39 88 5527 302060 64191057
Suicidal ideation 43.19 26.39 40 5575 66502 64426615
Obstructive airways disorder 42.52 26.39 26 5589 23159 64469958
Decreased appetite 41.89 26.39 82 5533 281207 64211910
Sleep disorder due to a general medical condition 37.57 26.39 17 5598 8217 64484900
Pneumothorax spontaneous 36.90 26.39 10 5605 1056 64492061
Pneumonia 36.45 26.39 119 5496 559457 63933660
Productive cough 36.31 26.39 38 5577 73165 64419952
Sputum discoloured 35.26 26.39 21 5594 17835 64475282
Death 34.47 26.39 106 5509 482599 64010518
Respiratory tract infection 33.42 26.39 27 5588 37380 64455737
Spirometry abnormal 32.63 26.39 8 5607 568 64492549
Bronchial wall thickening 31.16 26.39 10 5605 1897 64491220
Therapeutic product effect incomplete 30.23 26.39 41 5574 103441 64389676
Insomnia 29.80 26.39 58 5557 197778 64295339
Haematochezia 28.61 26.39 32 5583 66341 64426776
Bacterial disease carrier 28.27 26.39 8 5607 991 64492126
Breath sounds abnormal 26.42 26.39 15 5600 11654 64481463

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC R03DX07 RESPIRATORY SYSTEM
DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
Other systemic drugs for obstructive airway diseases
FDA MoA N0000182960 Phosphodiesterase 4 Inhibitors
FDA EPC N0000182961 Phosphodiesterase 4 Inhibitor
CHEBI has role CHEBI:49167 anti-asthmatic drugs
CHEBI has role CHEBI:68844 phosphodiesterase IV inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Severe chronic obstructive pulmonary disease indication 313299006
COPD Associated with Chronic Bronchitis indication
Suicidal thoughts contraindication 6471006
Mood swings contraindication 18963009
Depressive disorder contraindication 35489007
Hepatic failure contraindication 59927004
Weight loss contraindication 89362005
Suicidal contraindication 267073005




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 10.92 acidic
pKa2 2.32 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
250MCG DALIRESP ASTRAZENECA N022522 Jan. 23, 2018 RX TABLET ORAL 8536206 March 8, 2024 TREATMENT TO REDUCE THE RISK OF COPD EXACERBATIONS IN PATIENTS WITH SEVERE COPD ASSOCIATED WITH CHRONIC BRONCHITIS AND A HISTORY OF EXACERBATIONS
250MCG DALIRESP ASTRAZENECA N022522 Jan. 23, 2018 RX TABLET ORAL 8604064 March 8, 2024 TREATMENT TO REDUCE THE RISK OF COPD EXACERBATIONS IN PATIENTS WITH SEVERE COPD ASSOCIATED WITH CHRONIC BRONCHITIS AND A HISTORY OF EXACERBATIONS
500MCG DALIRESP ASTRAZENECA N022522 Feb. 28, 2011 RX TABLET ORAL 8536206 March 8, 2024 TREATMENT TO REDUCE THE RISK OF COPD EXACERBATIONS IN PATIENTS WITH SEVERE COPD ASSOCIATED WITH CHRONIC BRONCHITIS AND A HISTORY OF EXACERBATIONS
500MCG DALIRESP ASTRAZENECA N022522 Feb. 28, 2011 RX TABLET ORAL 8604064 March 8, 2024 TREATMENT TO REDUCE THE RISK OF COPD EXACERBATIONS IN PATIENTS WITH SEVERE COPD ASSOCIATED WITH CHRONIC BRONCHITIS AND A HISTORY OF EXACERBATIONS

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Phosphodiesterase 4 Enzyme INHIBITOR IC50 9.10 CHEMBL CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4B Enzyme IC50 9.40 CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme IC50 9.46 CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4D Enzyme IC50 9.57 CHEMBL
Phosphodiesterase Enzyme Ki 5.50 CHEMBL

External reference:

IDSource
4030722 VUID
N0000182732 NUI
D05744 KEGG_DRUG
4030722 VANDF
C0965618 UMLSCUI
CHEBI:47657 CHEBI
ROF PDB_CHEM_ID
CHEMBL193240 ChEMBL_ID
DB01656 DRUGBANK_ID
C424423 MESH_SUPPLEMENTAL_RECORD_UI
449193 PUBCHEM_CID
6962 IUPHAR_LIGAND_ID
7598 INN_ID
0P6C6ZOP5U UNII
1091836 RXNORM
180364 MMSL
27361 MMSL
d07684 MMSL
013499 NDDF
448971002 SNOMEDCT_US
714680006 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Daliresp HUMAN PRESCRIPTION DRUG LABEL 1 0310-0088 TABLET 250 ug ORAL NDA 27 sections
Daliresp HUMAN PRESCRIPTION DRUG LABEL 1 0310-0095 TABLET 500 ug ORAL NDA 27 sections