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

Stem definition	Drug id	CAS RN
phosphodiesterase IV (PDE IV) inhibitors	3531	162401-32-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: libertek roflumilast daxas daliresp BY217 B9302-107 BYK20869	Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors of phosphodiesterase 4 (PDE4). Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic-3′,5′-adenosine monophosphate (cyclic AMP)-metabolizing enzyme in lung tissue) activity leads to accumulation of intracellular cyclic AMP. While the specific mechanism(s) by which DALIRESP exerts its therapeutic action in COPD patients is not well defined, it is thought to be related to the effects of increased intracellular cyclic AMP in lung cells. 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

Molecule

Description

Molfile Inchi Smiles

Synonyms:

libertek
roflumilast
daxas
daliresp
BY217
B9302-107
BYK20869

Roflumilast and its active metabolite (roflumilast N-oxide) are selective inhibitors of phosphodiesterase 4 (PDE4). Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic-3′,5′-adenosine monophosphate (cyclic AMP)-metabolizing enzyme in lung tissue) activity leads to accumulation of intracellular cyclic AMP. While the specific mechanism(s) by which DALIRESP exerts its therapeutic action in COPD patients is not well defined, it is thought to be related to the effects of increased intracellular cyclic AMP in lung cells.

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:

Dose	Unit	Route
0.50	mg	O

ADMET properties:

Property	Value	Reference
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:

Date	Agency	Company	Orphan
Feb. 28, 2011	EMA
Feb. 28, 2011	FDA	ASTRAZENECA PHARMS

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Chronic obstructive pulmonary disease	186.81	24.13	89	4215	62597	63422121
Dyspnoea	118.63	24.13	181	4123	661132	62823586
Full blood count abnormal	94.22	24.13	45	4259	31672	63453046
Wheezing	87.14	24.13	63	4241	95532	63389186
Asthma	85.47	24.13	70	4234	127491	63357227
Pneumothorax spontaneous	80.09	24.13	17	4287	817	63483901
Emphysema	63.76	24.13	25	4279	10913	63473805
Adenocarcinoma	58.76	24.13	17	4287	2933	63481785
Sleep disorder due to a general medical condition	57.74	24.13	24	4280	12164	63472554
Hypercapnia	56.34	24.13	19	4285	5412	63479306
Polymyalgia rheumatica	54.55	24.13	17	4287	3774	63480944
Productive cough	53.79	24.13	40	4264	63168	63421550
Respiratory tract infection	53.67	24.13	34	4270	41449	63443269
Breath sounds abnormal	49.94	24.13	21	4283	10952	63473766
Obstructive airways disorder	48.47	24.13	25	4279	20674	63464044
Therapeutic product effect incomplete	45.63	24.13	49	4255	125007	63359711
Multiple allergies	45.31	24.13	21	4283	13781	63470937
Pneumonia	45.24	24.13	97	4207	456670	63028048
Death	44.77	24.13	86	4218	374295	63110423
Weight decreased	42.57	24.13	71	4233	276727	63207991
Bacterial disease carrier	37.18	24.13	10	4294	1321	63483397
Sputum discoloured	36.14	24.13	19	4285	16328	63468390
Bronchial wall thickening	36.00	24.13	10	4294	1489	63483229
Bronchial secretion retention	33.96	24.13	11	4293	2762	63481956
Pneumonitis	33.83	24.13	24	4280	35198	63449520
Eosinophilia	32.83	24.13	20	4284	22736	63461982
Hyperthyroidism	32.28	24.13	17	4287	14656	63470062
Lung diffusion disorder	29.46	24.13	5	4299	70	63484648
Spirometry abnormal	29.46	24.13	6	4298	235	63484483
Cough	28.68	24.13	62	4242	292681	63192037
Spinal cord compression	26.01	24.13	10	4294	4138	63480580
Suicidal ideation	25.49	24.13	26	4278	62395	63422323
Diarrhoea	24.98	24.13	105	4199	715261	62769457

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Dyspnoea	186.05	28.20	220	3772	376562	34576377
Chronic obstructive pulmonary disease	166.64	28.20	90	3902	48828	34904111
Product prescribing error	88.70	28.20	46	3946	22881	34930058
Weight decreased	81.22	28.20	100	3892	176201	34776738
Asthma-chronic obstructive pulmonary disease overlap syndrome	54.56	28.20	15	3977	1272	34951667
Cough	50.30	28.20	73	3919	150067	34802872
Asthma	49.25	28.20	40	3952	42616	34910323
Nasal obstruction	48.58	28.20	12	3980	668	34952271
Sinus pain	47.78	28.20	12	3980	715	34952224
Wheezing	43.98	28.20	37	3955	41365	34911574
Suicidal ideation	42.71	28.20	36	3956	40352	34912587
Death	40.69	28.20	118	3874	397931	34555008
Sputum discoloured	40.05	28.20	19	3973	7793	34945146
Emphysema	36.48	28.20	19	3973	9506	34943433
Pulmonary mass	36.45	28.20	21	3971	12791	34940148
Decreased appetite	34.21	28.20	65	3927	166327	34786612
Mycobacterium avium complex infection	33.11	28.20	12	3980	2499	34950440
Oedema peripheral	32.65	28.20	53	3939	119759	34833180
Insomnia	32.53	28.20	49	3943	103858	34849081
Osteopenia	31.80	28.20	14	3978	4835	34948104
Diarrhoea	30.95	28.20	106	3886	389806	34563133
Bronchiectasis	30.40	28.20	17	3975	9784	34943155

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Chronic obstructive pulmonary disease	281.44	26.24	138	6412	85281	79652557
Dyspnoea	255.51	26.24	330	6220	856695	78881143
Asthma	103.70	26.24	87	6463	135008	79602830
Product prescribing error	89.56	26.24	52	6498	44761	79693077
Wheezing	89.23	26.24	75	6475	116589	79621249
Full blood count abnormal	89.03	26.24	50	6500	40424	79697414
Weight decreased	88.23	26.24	126	6424	355072	79382766
Emphysema	77.40	26.24	34	6516	16266	79721572
Pneumothorax spontaneous	62.50	26.24	16	6534	1438	79736400
Sputum discoloured	59.33	26.24	31	6519	21712	79716126
Cough	57.92	26.24	106	6444	366683	79371155
Obstructive airways disorder	56.28	26.24	34	6516	31425	79706413
Death	53.79	26.24	133	6417	566381	79171457
Sleep disorder due to a general medical condition	52.71	26.24	25	6525	14252	79723586
Respiratory tract infection	51.64	26.24	38	6512	48651	79689187
Productive cough	48.19	26.24	47	6503	88284	79649554
Therapeutic product effect incomplete	46.98	26.24	58	6492	141587	79596251
Adenocarcinoma	46.97	26.24	16	6534	3870	79733968
Pneumonia	45.67	26.24	138	6412	660108	79077730
Polymyalgia rheumatica	44.55	26.24	16	6534	4521	79733317
Suicidal ideation	40.48	26.24	40	6510	76300	79661538
Hypercapnia	40.35	26.24	18	6532	8917	79728921
Breath sounds abnormal	38.56	26.24	21	6529	15963	79721875
Multiple allergies	37.64	26.24	18	6532	10442	79727396
Bronchial wall thickening	36.39	26.24	12	6538	2629	79735209
Decreased appetite	35.18	26.24	83	6467	342335	79395503
Bacterial disease carrier	33.80	26.24	10	6540	1536	79736302
Haematochezia	30.84	26.24	37	6513	87608	79650230
Spirometry abnormal	29.05	26.24	8	6542	951	79736887
Nasal obstruction	26.51	26.24	9	6541	2155	79735683
Mycobacterium avium complex infection	26.47	26.24	11	6539	4589	79733249

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
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|

Disease	Relation	SNOMED_ID
Plaque psoriasis	indication	200965009
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 level	Dissociation constant	Type (acidic/basic)
pKa1	10.92	acidic
pKa2	2.32	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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
0.3%	ZORYVE	ARCUTIS	N215985	July 29, 2022	RX	CREAM	TOPICAL	9907788	June 7, 2037	TOPICAL TREATMENT OF PLAQUE PSORIASIS, INCLUDING INTERTRIGINOUS AREAS, IN PATIENTS 12 YEARS OF AGE AND OLDER. (1)
0.3%	ZORYVE	ARCUTIS	N215985	July 29, 2022	RX	CREAM	TOPICAL	11129818	Aug. 25, 2037	TOPICAL TREATMENT OF PLAQUE PSORIASIS, INCLUDING INTERTRIGINOUS AREAS, IN PATIENTS 12 YEARS OF AGE AND OLDER. (1)

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
500MCG	ROFLUMILAST	HETERO LABS LTD III	A208213	Nov. 23, 2018	RX	TABLET	ORAL	April 17, 2023	PATENT CHALLENGE
500MCG	ROFLUMILAST	STRIDES PHARMA	A208247	March 30, 2020	RX	TABLET	ORAL	April 17, 2023	PATENT CHALLENGE
500MCG	ROFLUMILAST	MYLAN	A208257	July 13, 2018	RX	TABLET	ORAL	April 17, 2023	PATENT CHALLENGE
250MCG	ROFLUMILAST	MSN	A208256	Sept. 7, 2022	RX	TABLET	ORAL	April 18, 2023	PATENT CHALLENGE
0.3%	ZORYVE	ARCUTIS	N215985	July 29, 2022	RX	CREAM	TOPICAL	July 29, 2025	NEW PRODUCT

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Phosphodiesterase 4	Enzyme	P27815 Q07343 Q08493 Q08499	PDE4A_HUMAN PDE4B_HUMAN PDE4C_HUMAN PDE4D_HUMAN	INHIBITOR	IC50	9.10	CHEMBL	CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4B	Enzyme	Q07343	PDE4B_HUMAN		IC50	9.40	CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Enzyme	P27815	PDE4A_HUMAN		IC50	9.46	CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4D	Enzyme	Q08499	PDE4D_HUMAN		IC50	9.57	CHEMBL
Phosphodiesterase	Enzyme		Q8WQX9_9TRYP		Ki	5.50	CHEMBL

External reference:

ID	Source
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
358833	MMSL
d07684	MMSL
013499	NDDF
448971002	SNOMEDCT_US
714680006	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Daliresp	HUMAN PRESCRIPTION DRUG LABEL	1	0310-0088	TABLET	250 ug	ORAL	NDA	27 sections
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
Daliresp	HUMAN PRESCRIPTION DRUG LABEL	1	0310-0095	TABLET	500 ug	ORAL	NDA	27 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	0378-1905	TABLET	500 ug	ORAL	ANDA	30 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	13668-476	TABLET	500 ug	ORAL	ANDA	26 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	13668-476	TABLET	500 ug	ORAL	ANDA	26 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	31722-623	TABLET	500 ug	ORAL	ANDA	27 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	31722-623	TABLET	500 ug	ORAL	ANDA	27 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	31722-676	TABLET	250 ug	ORAL	ANDA	27 sections
ROFLUMILAST	HUMAN PRESCRIPTION DRUG LABEL	1	42571-259	TABLET	500 ug	ORAL	ANDA	26 sections
ROFLUMILAST	HUMAN PRESCRIPTION DRUG LABEL	1	42571-259	TABLET	500 ug	ORAL	ANDA	26 sections
ROFLUMILAST	HUMAN PRESCRIPTION DRUG LABEL	1	42571-369	TABLET	250 ug	ORAL	ANDA	26 sections
ROFLUMILAST	HUMAN PRESCRIPTION DRUG LABEL	1	43547-005	TABLET	500 ug	ORAL	ANDA	19 sections
ROFLUMILAST	Human Prescription Drug Label	1	59651-275	TABLET	500 ug	ORAL	ANDA	26 sections
roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	64380-786	TABLET	500 ug	ORAL	ANDA	25 sections
roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	64380-786	TABLET	500 ug	ORAL	ANDA	25 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	68382-624	TABLET	250 ug	ORAL	ANDA	25 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	68382-969	TABLET	500 ug	ORAL	ANDA	25 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	68382-969	TABLET	500 ug	ORAL	ANDA	25 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1673	TABLET	250 ug	ORAL	ANDA	1 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1674	TABLET	500 ug	ORAL	ANDA	1 sections
Roflumilast	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1674	TABLET	500 ug	ORAL	ANDA	1 sections
Roflumilast	Human Prescription Drug Label	1	72205-200	TABLET	500 ug	ORAL	ANDA	25 sections
Roflumilast	Human Prescription Drug Label	1	72205-201	TABLET	250 ug	ORAL	ANDA	25 sections
ZORYVE	HUMAN PRESCRIPTION DRUG LABEL	1	80610-130	CREAM	3 mg	TOPICAL	NDA	27 sections