apremilast Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
phosphodiesterase IV (PDE IV) inhibitors	4829	608141-41-9

Description:

Molecule

Description

Molfile Inchi Smiles Synonyms: apremilast CC-10004 otezla

Apremilast is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. The specific mechanism(s) by which apremilast exerts its therapeutic action in psoriatic arthritis patients and psoriasis patients is not well defined. Molecular weight: 460.50 Formula: C22H24N2O7S CLOGP: 1.46 LIPINSKI: 0 HAC: 9 HDO: 1 TPSA: 119.08 ALOGS: -4.13 ROTB: 8 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

Dose	Unit	Route
60	mg	O

ADMET properties:

Property	Value	Reference
CL (Clearance)	2.38 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.32 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	6.03 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Sept. 20, 2019	PMDA	Celgene K.K.
March 21, 2014	FDA	CELGENE CORP
Nov. 20, 2014	EMA

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
Psoriasis	18840.35	26.16	7084	107601	71520	46499857
Diarrhoea	10405.22	26.16	9434	105251	550168	46021209
Nausea	8890.80	26.16	9509	105176	677945	45893432
Headache	6846.76	26.16	7015	107670	471337	46100040
Product dose omission issue	5603.74	26.16	4026	110659	164494	46406883
Psoriatic arthropathy	4853.71	26.16	2168	112517	34211	46537166
Abdominal discomfort	2545.71	26.16	2441	112244	148724	46422653
Drug ineffective	1773.73	26.16	4596	110089	673242	45898135
Adverse drug reaction	1302.46	26.16	988	113697	43374	46528003
Depression	1147.55	26.16	1726	112959	168378	46402999
Therapy non-responder	800.23	26.16	722	113963	40430	46530947
Abdominal pain upper	751.58	26.16	1308	113377	143997	46427380
Weight decreased	726.56	26.16	1599	113086	209250	46362127
Gastric disorder	600.33	26.16	509	114176	26196	46545181
Frequent bowel movements	558.82	26.16	362	114323	12270	46559107
Migraine	550.14	26.16	765	113920	69261	46502116
Acute kidney injury	542.90	26.16	7	114678	235848	46335529
Toxicity to various agents	475.84	26.16	9	114676	211757	46359620
Dyspnoea	463.60	26.16	355	114330	515193	46056184
Anaemia	431.18	26.16	59	114626	255720	46315657
Hypotension	395.91	26.16	52	114633	232537	46338840
Rash	382.90	26.16	1809	112876	354703	46216674
Drug interaction	366.58	26.16	37	114648	203057	46368320
Dyspepsia	355.30	26.16	618	114067	67854	46503523
Pyrexia	338.14	26.16	221	114464	348581	46222796
Neutropenia	326.04	26.16	5	114680	143199	46428178
Tension headache	322.78	26.16	149	114536	2525	46568852
Thrombocytopenia	285.71	26.16	5	114680	126576	46444801
Vomiting	275.09	26.16	1976	112709	450818	46120559
Stress	273.52	26.16	470	114215	51081	46520296
Gastrointestinal disorder	261.20	26.16	500	114185	59076	46512301
Confusional state	255.19	26.16	43	114642	159849	46411528
Insomnia	236.72	26.16	915	113770	164009	46407368
Haemoglobin decreased	236.47	26.16	22	114663	128927	46442450
Oedema peripheral	220.14	26.16	60	114625	159646	46411731
Exposure during pregnancy	220.07	26.16	11	114674	108201	46463176
Faeces soft	217.31	26.16	124	114561	3324	46568053
Overdose	211.83	26.16	9	114676	101970	46469407
Therapeutic response decreased	210.24	26.16	379	114306	42766	46528611
White blood cell count decreased	206.16	26.16	19	114666	112212	46459165
Upper respiratory tract infection	202.32	26.16	468	114217	63088	46508289
Fall	199.50	26.16	313	114372	328784	46242593
Death	198.84	26.16	324	114361	335224	46236153
Therapeutic product effect decreased	195.90	26.16	544	114141	82057	46489320
Cardiac arrest	194.60	26.16	6	114679	90393	46480984
Pancytopenia	193.40	26.16	3	114682	85055	46486322
Pneumonia	193.09	26.16	397	114288	375923	46195454
Pleural effusion	188.29	26.16	3	114682	82949	46488428
Sepsis	185.74	26.16	52	114633	135962	46435415
Seizure	181.69	26.16	40	114645	123014	46448363
Respiratory failure	176.99	26.16	15	114670	94801	46476576
Platelet count decreased	175.76	26.16	20	114665	100004	46471373
Asthenia	174.48	26.16	311	114374	310764	46260613
Maternal exposure during pregnancy	167.09	26.16	26	114659	102523	46468854
Pulmonary embolism	160.89	26.16	35	114650	108550	46462827
Renal failure	155.87	26.16	43	114642	113551	46457826
Disease progression	151.38	26.16	22	114663	91278	46480099
Loss of consciousness	150.34	26.16	40	114645	108198	46463179
Enthesopathy	149.76	26.16	110	114575	4580	46566797
Leukopenia	145.43	26.16	5	114680	68338	46503039
Arthralgia	144.59	26.16	1448	113237	363155	46208222
Deep vein thrombosis	142.56	26.16	15	114670	79758	46491619
Intentional overdose	140.90	26.16	4	114681	64940	46506437
Malignant neoplasm progression	140.85	26.16	4	114681	64922	46506455
Syncope	139.50	26.16	42	114643	104761	46466616
Product supply issue	138.40	26.16	59	114626	819	46570558
Oxygen saturation decreased	137.57	26.16	8	114677	69156	46502221
Drug hypersensitivity	135.49	26.16	245	114440	243580	46327797
Decreased appetite	130.01	26.16	868	113817	192968	46378409
Coma	128.82	26.16	3	114682	58346	46513031
Unevaluable event	128.63	26.16	323	114362	45852	46525525
Tachycardia	125.40	26.16	44	114641	99578	46471799
Injection site pain	122.30	26.16	55	114630	107097	46464280
Cardiac failure	119.99	26.16	25	114660	79923	46491454
Off label use	119.47	26.16	504	114181	379337	46192040
Injection site erythema	118.69	26.16	20	114665	74407	46496970
Somnolence	114.90	26.16	129	114556	156392	46414985
Cardiac failure congestive	114.66	26.16	41	114644	91709	46479668
Hypoxia	113.16	26.16	3	114682	51835	46519542
Chest pain	113.13	26.16	161	114524	176163	46395214
Multiple organ dysfunction syndrome	112.86	26.16	3	114682	51707	46519670
Septic shock	111.27	26.16	8	114677	57885	46513492
Hyperkalaemia	110.45	26.16	3	114682	50706	46520671
Product use in unapproved indication	110.01	26.16	42	114643	90231	46481146
Pruritus	109.00	26.16	989	113696	241363	46330014
Flatulence	108.08	26.16	227	114458	28651	46542726
Therapeutic product effect incomplete	104.96	26.16	425	114260	77728	46493649
Infusion related reaction	104.91	26.16	59	114626	101149	46470228
Gastrointestinal haemorrhage	101.16	26.16	32	114653	77341	46494036
Dehydration	101.03	26.16	147	114538	159393	46411984
Oedema	100.59	26.16	21	114664	67050	46504327
Hypoglycaemia	100.30	26.16	9	114676	54340	46517037
Atrial fibrillation	98.21	26.16	67	114618	103523	46467854
Neuropathy peripheral	97.10	26.16	51	114634	90842	46480535
Plasma cell myeloma	95.53	26.16	3	114682	44475	46526902
Interstitial lung disease	89.41	26.16	13	114672	53936	46517441
Mood altered	87.25	26.16	132	114553	12875	46558502
Pulmonary oedema	85.42	26.16	12	114673	51093	46520284
Hypertension	84.54	26.16	227	114458	196129	46375248
Blood alkaline phosphatase increased	83.90	26.16	3	114682	39606	46531771
Mucosal inflammation	82.39	26.16	3	114682	38973	46532404
Anaphylactic reaction	80.95	26.16	16	114669	53096	46518281
Dysphagia	80.21	26.16	45	114640	77267	46494110
Rebound psoriasis	79.78	26.16	21	114664	50	46571327
Nasopharyngitis	79.38	26.16	648	114037	153350	46418027
Tenosynovitis	79.12	26.16	95	114590	7420	46563957
Alanine aminotransferase increased	78.90	26.16	61	114624	88390	46482987
Muscle spasms	78.66	26.16	545	114140	122568	46448809
Product use issue	78.58	26.16	70	114615	94574	46476803
Delirium	78.23	26.16	3	114682	37225	46534152
Ascites	76.70	26.16	3	114682	36581	46534796
Pulmonary hypertension	75.30	26.16	3	114682	35990	46535387
Mental status changes	73.95	26.16	5	114680	38083	46533294
Weight increased	70.88	26.16	190	114495	164283	46407094
Pemphigus	70.35	26.16	13	114672	45261	46526116
Hyperglycaemia	69.90	26.16	4	114681	35067	46536310
Muscular weakness	69.22	26.16	74	114611	91770	46479607
Blood creatinine increased	69.02	26.16	52	114633	76351	46495026
Liver function test abnormal	68.79	26.16	15	114670	46472	46524905
Paraesthesia	67.85	26.16	115	114570	117322	46454055
Dysarthria	67.11	26.16	7	114678	37491	46533886
Cerebrovascular accident	67.01	26.16	90	114595	100949	46470428
Balance disorder	66.29	26.16	38	114647	64483	46506894
Dyspnoea exertional	65.37	26.16	21	114664	50268	46521109
Pneumonia aspiration	64.90	26.16	3	114682	31602	46539775
Influenza	64.76	26.16	408	114277	88862	46482515
Aspartate aminotransferase increased	64.38	26.16	59	114626	78641	46492736
Blood pressure decreased	64.16	26.16	30	114655	57129	46514248
Coronary artery disease	63.90	26.16	5	114680	33747	46537630
Injury	63.56	26.16	15	114670	44012	46527365
Multiple sclerosis relapse	63.55	26.16	13	114672	42112	46529265
Injection site pruritus	62.65	26.16	11	114674	39732	46531645
Flushing	62.29	26.16	41	114644	64573	46506804
Systemic lupus erythematosus	61.97	26.16	42	114643	65138	46506239
Femur fracture	61.10	26.16	9	114676	36988	46534389
Chronic kidney disease	60.86	26.16	13	114672	40858	46530519
Hepatic failure	60.42	26.16	6	114679	33410	46537967
Injection site swelling	59.70	26.16	13	114672	40314	46531063
Respiratory distress	59.66	26.16	5	114680	31911	46539466
Hallucination	59.59	26.16	24	114661	49927	46521450
Acute respiratory failure	59.08	26.16	3	114682	29135	46542242
Myocardial infarction	58.67	26.16	93	114592	97435	46473942
Glossodynia	58.62	26.16	18	114667	44355	46527022
Dyskinesia	58.58	26.16	3	114682	28922	46542455
Renal impairment	58.22	26.16	58	114627	74314	46497063
Angioedema	57.60	26.16	13	114672	39329	46532048
Adverse reaction	56.97	26.16	84	114601	8006	46563371
Cognitive disorder	56.44	26.16	11	114674	36872	46534505
Thrombosis	56.22	26.16	34	114651	56035	46515342
Vision blurred	55.96	26.16	68	114617	79640	46491737
Intentional product use issue	55.79	26.16	30	114655	52750	46518627
Fluid retention	55.46	26.16	28	114657	51018	46520359
Hepatitis	55.18	26.16	7	114678	32208	46539169
No adverse event	55.00	26.16	9	114676	34222	46537155
Lower respiratory tract infection	54.41	26.16	34	114651	55055	46516322
Discomfort	54.26	26.16	243	114442	46427	46524950
Drug reaction with eosinophilia and systemic symptoms	54.23	26.16	5	114680	29543	46541834
Heart rate decreased	54.08	26.16	7	114678	31716	46539661
Gastrooesophageal reflux disease	54.05	26.16	340	114345	74004	46497373
Red blood cell count decreased	53.73	26.16	8	114677	32615	46538762
Blood creatine phosphokinase increased	52.78	26.16	4	114681	27720	46543657
Medication error	52.27	26.16	7	114678	30904	46540473
Sinus headache	52.10	26.16	61	114624	4639	46566738
Suicide attempt	51.60	26.16	36	114649	55000	46516377
Osteonecrosis	51.11	26.16	3	114682	25741	46545636
Disorientation	50.56	26.16	14	114671	36904	46534473
Arthritis	50.37	26.16	344	114341	76972	46494405
Haematoma	49.85	26.16	9	114676	31863	46539514
Gamma-glutamyltransferase increased	49.56	26.16	9	114676	31731	46539646
Aphasia	49.44	26.16	6	114679	28561	46542816
Hepatotoxicity	49.39	26.16	3	114682	25006	46546371
Gait disturbance	49.13	26.16	187	114498	145076	46426301
Bone erosion	48.60	26.16	85	114600	9358	46562019
Visual impairment	47.76	26.16	56	114629	66633	46504744
Melaena	47.65	26.16	6	114679	27766	46543611
Chills	47.63	26.16	103	114582	95929	46475448
Blood urea increased	47.31	26.16	4	114681	25348	46546029
Hepatic function abnormal	47.24	26.16	13	114672	34408	46536969
Agitation	47.18	26.16	40	114645	55375	46516002
Chest discomfort	47.14	26.16	94	114591	90175	46481202
Urinary incontinence	46.98	26.16	7	114678	28523	46542854
Urinary retention	46.29	26.16	5	114680	26056	46545321
Pancreatitis acute	46.21	26.16	4	114681	24868	46546509
White blood cell count increased	45.48	26.16	26	114659	44193	46527184
Lymphocyte count decreased	45.22	26.16	5	114680	25584	46545793
Memory impairment	45.09	26.16	335	114350	77002	46494375
Haemorrhage	45.03	26.16	41	114644	54828	46516549
Epistaxis	44.99	26.16	55	114630	64250	46507127
Hypoaesthesia	44.90	26.16	146	114539	118723	46452654
Hypothyroidism	44.60	26.16	11	114674	31327	46540050
Hand deformity	43.95	26.16	15	114670	34559	46536818
Rash maculo-papular	43.31	26.16	8	114677	27866	46543511
Haematuria	43.29	26.16	7	114678	26851	46544526
Sinusitis	43.08	26.16	498	114187	129270	46442107
Swelling	42.93	26.16	159	114526	124352	46447025
Cerebral infarction	42.76	26.16	4	114681	23362	46548015
Cerebral haemorrhage	42.29	26.16	9	114676	28362	46543015
Speech disorder	42.13	26.16	18	114667	36149	46535228
Blood sodium decreased	41.75	26.16	3	114682	21723	46549654
Impaired healing	41.68	26.16	19	114666	36724	46534653
Hospitalisation	41.47	26.16	57	114628	63328	46508049
Abortion spontaneous	40.33	26.16	29	114656	43617	46527760
Erythema	40.25	26.16	197	114488	142623	46428754
Red blood cell sedimentation rate	40.23	26.16	34	114651	1739	46569638
Palmoplantar pustulosis	40.17	26.16	19	114666	341	46571036
Device related infection	40.16	26.16	3	114682	21038	46550339
Exostosis	39.94	26.16	82	114603	10181	46561196
Visual acuity reduced	39.90	26.16	4	114681	22109	46549268
Pallor	39.76	26.16	5	114680	23161	46548216
Rhinorrhoea	39.10	26.16	225	114460	47440	46523937
Epilepsy	38.68	26.16	6	114679	23732	46547645
Asthma	38.47	26.16	107	114578	91435	46479942
Lung disorder	38.43	26.16	30	114655	43274	46528103
Rheumatoid arthritis	38.34	26.16	391	114294	239824	46331553
Injection site bruising	38.03	26.16	20	114665	35616	46535761
Cholelithiasis	38.02	26.16	24	114661	38657	46532720
Therapy partial responder	37.97	26.16	52	114633	4630	46566747
Gastroenteritis viral	37.75	26.16	114	114571	18005	46553372
Stevens-Johnson syndrome	37.71	26.16	6	114679	23291	46548086
Mood swings	37.45	26.16	106	114579	16146	46555231
Joint dislocation	37.36	26.16	84	114601	11102	46560275
Constipation	36.92	26.16	263	114422	173834	46397543
Blood potassium decreased	36.89	26.16	24	114661	38039	46533338
Joint stiffness	36.82	26.16	148	114537	26960	46544417
Metastases to liver	36.80	26.16	3	114682	19582	46551795
Arrhythmia	36.53	26.16	20	114665	34821	46536556
Aggression	36.49	26.16	6	114679	22738	46548639
Circulatory collapse	36.31	26.16	5	114680	21619	46549758
Wheezing	35.95	26.16	47	114638	53339	46518038
Haemoptysis	35.73	26.16	10	114675	26179	46545198
Skin exfoliation	35.69	26.16	168	114517	32770	46538607
Transient ischaemic attack	35.22	26.16	21	114664	34882	46536495
Pneumonitis	34.98	26.16	13	114672	28407	46542970
Blood parathyroid hormone decreased	34.54	26.16	48	114637	4333	46567044
Injection site reaction	34.45	26.16	40	114645	47809	46523568
Dry skin	33.89	26.16	194	114491	40822	46530555
Loss of personal independence in daily activities	33.49	26.16	248	114437	56935	46514442
Sleep apnoea syndrome	33.18	26.16	7	114678	22194	46549183
Hallucination, visual	32.86	26.16	3	114682	17870	46553507
Abnormal behaviour	32.81	26.16	6	114679	21052	46550325
Blood pressure fluctuation	32.62	26.16	17	114668	30431	46540946
Orthostatic hypotension	32.57	26.16	10	114675	24648	46546729
Malaise	32.17	26.16	1052	113633	330180	46241197
Urinary tract infection	32.14	26.16	366	114319	219900	46351477
Psychotic disorder	32.07	26.16	8	114677	22613	46548764
Rash pruritic	31.99	26.16	202	114483	44013	46527364
Granuloma skin	31.93	26.16	41	114644	3429	46567948
Defaecation urgency	31.89	26.16	36	114649	2631	46568746
Chronic obstructive pulmonary disease	31.85	26.16	58	114627	57575	46513802
Rash macular	31.84	26.16	112	114573	19148	46552229
Dactylitis	31.52	26.16	25	114660	1168	46570209
Lethargy	31.52	26.16	48	114637	51123	46520254
Multiple allergies	31.20	26.16	61	114624	7310	46564067
Accidental exposure to product	30.79	26.16	7	114678	21074	46550303
Intestinal obstruction	30.33	26.16	13	114672	26062	46545315
General physical health deterioration	30.17	26.16	164	114521	115605	46455772
Proteinuria	29.85	26.16	3	114682	16550	46554827
Tongue disorder	29.72	26.16	59	114626	7151	46564226
Swelling face	29.67	26.16	53	114632	53006	46518371
Underdose	29.57	26.16	6	114679	19552	46551825
Hepatic enzyme increased	29.14	26.16	103	114582	81684	46489693
Adverse event	29.11	26.16	163	114522	34021	46537356
Electrolyte imbalance	28.89	26.16	4	114681	17222	46554155
Cardiomyopathy	28.76	26.16	3	114682	16070	46555307
Amnesia	28.70	26.16	36	114649	41595	46529782
Withdrawal syndrome	28.62	26.16	5	114680	18129	46553248
Alopecia	28.27	26.16	558	114127	161856	46409521
Therapy cessation	28.25	26.16	135	114550	26494	46544883
Dandruff	28.18	26.16	12	114673	166	46571211
Wrong technique in product usage process	28.12	26.16	57	114628	54365	46517012
Blood calcium decreased	27.85	26.16	3	114682	15670	46555707
Bowel movement irregularity	27.71	26.16	38	114647	3387	46567990
Pregnancy	27.65	26.16	136	114549	27001	46544376
Panniculitis	27.62	26.16	50	114635	5654	46565723
Mobility decreased	27.61	26.16	68	114617	60526	46510851
COVID-19	27.32	26.16	104	114581	18471	46552906
Contraindicated product administered	26.96	26.16	103	114582	79844	46491533
Drug resistance	26.95	26.16	5	114680	17363	46554014
Injection site haemorrhage	26.29	26.16	9	114676	20700	46550677
Sinus disorder	26.26	26.16	95	114590	16468	46554909

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
Psoriasis	11562.56	34.13	3889	50588	38617	29859384
Diarrhoea	6345.05	34.13	5007	49470	329096	29568905
Headache	3829.10	34.13	2921	51556	179385	29718616
Product dose omission issue	3805.40	34.13	2247	52230	89384	29808617
Nausea	3408.32	34.13	3366	51111	293591	29604410
Abdominal discomfort	2842.77	34.13	1498	52979	47293	29850708
Drug ineffective	2368.01	34.13	2976	51501	337411	29560590
Psoriatic arthropathy	2314.15	34.13	922	53555	14839	29883162
Depression	819.75	34.13	912	53565	89525	29808476
Adverse drug reaction	818.83	34.13	515	53962	22630	29875371
Abdominal pain upper	665.15	34.13	687	53790	61864	29836137
Therapy non-responder	610.26	34.13	472	54005	28981	29869020
Weight decreased	524.57	34.13	963	53514	149958	29748043
Frequent bowel movements	524.05	34.13	271	54206	8134	29889867
Therapeutic product effect decreased	504.44	34.13	420	54057	28656	29869345
Gastric disorder	414.20	34.13	251	54226	10292	29887709
Acute kidney injury	406.41	34.13	23	54454	273819	29624182
Rash	315.97	34.13	912	53565	190977	29707024
Drug interaction	289.01	34.13	19	54458	199549	29698452
Anaemia	278.53	34.13	28	54449	207964	29690037
Hypotension	265.95	34.13	28	54449	200537	29697464
Faeces soft	262.00	34.13	111	54366	2088	29895913
Gastrointestinal disorder	259.54	34.13	287	54190	27850	29870151
Therapeutic response decreased	257.43	34.13	267	54210	24082	29873919
Pyrexia	253.16	34.13	110	54367	294379	29603622
Dyspepsia	217.58	34.13	272	54205	30057	29867944
Dyspnoea	202.08	34.13	186	54291	333109	29564892
Thrombocytopenia	195.45	34.13	14	54463	137030	29760971
Arthralgia	186.11	34.13	606	53871	135185	29762816
Flatulence	183.01	34.13	194	54283	17935	29880066
Tension headache	176.75	34.13	72	54405	1221	29896780
Pneumonia	175.17	34.13	211	54266	334095	29563906
Febrile neutropenia	167.52	34.13	6	54471	106687	29791314
Mood altered	161.51	34.13	128	54349	8122	29889879
Respiratory failure	156.83	34.13	6	54471	100636	29797365
Haemoglobin decreased	156.12	34.13	14	54463	114084	29783917
Therapeutic product effect incomplete	155.35	34.13	245	54232	33589	29864412
Confusional state	146.46	34.13	33	54444	134801	29763200
Nasopharyngitis	140.11	34.13	322	54155	58527	29839474
Cardiac arrest	139.83	34.13	7	54470	92843	29805158
Migraine	139.30	34.13	143	54334	12731	29885270
Overdose	138.80	34.13	3	54474	84334	29813667
Memory impairment	138.33	34.13	245	54232	36929	29861072
Sepsis	138.19	34.13	47	54430	146348	29751653
Platelet count decreased	135.01	34.13	17	54460	106112	29791889
Enthesopathy	134.61	34.13	77	54400	2829	29895172
Completed suicide	133.98	34.13	13	54464	99479	29798522
Upper respiratory tract infection	130.34	34.13	202	54275	27274	29870727
Blood creatinine increased	122.87	34.13	12	54465	91363	29806638
Pleural effusion	120.46	34.13	3	54474	74063	29823938
Renal failure	118.95	34.13	43	54434	128923	29769078
Pruritus	116.36	34.13	474	54003	117730	29780271
Oedema peripheral	114.69	34.13	26	54451	105806	29792195
Fall	114.07	34.13	98	54379	181774	29716227
Product supply issue	110.21	34.13	34	54443	239	29897762
Discomfort	109.74	34.13	133	54344	14223	29883778
Pancytopenia	109.68	34.13	13	54464	85039	29812962
Pulmonary embolism	108.44	34.13	9	54468	78126	29819875
Seizure	107.09	34.13	24	54453	98451	29799550
Hyperkalaemia	102.58	34.13	4	54473	66006	29831995
Bradycardia	101.72	34.13	4	54473	65522	29832479
Arthritis	100.16	34.13	168	54309	24233	29873768
White blood cell count decreased	98.53	34.13	17	54460	83930	29814071
Tenosynovitis	96.84	34.13	67	54410	3448	29894553
Death	96.48	34.13	331	54146	356952	29541049
Deep vein thrombosis	96.34	34.13	3	54474	60498	29837503
Multiple organ dysfunction syndrome	94.88	34.13	5	54472	63482	29834519
Product use in unapproved indication	93.21	34.13	12	54465	73681	29824320
Gastrointestinal haemorrhage	91.40	34.13	20	54457	83426	29814575
Asthenia	89.09	34.13	167	54310	221123	29676878
Syncope	87.78	34.13	23	54454	84880	29813121
Unevaluable event	84.68	34.13	182	54295	31603	29866398
Tachycardia	84.23	34.13	16	54461	73723	29824278
Plasma cell myeloma	83.88	34.13	3	54474	53459	29844542
Interstitial lung disease	83.33	34.13	7	54470	60190	29837811
Insomnia	82.99	34.13	363	54114	92973	29805028
Disease progression	80.02	34.13	23	54454	79851	29818150
Septic shock	74.37	34.13	13	54464	63594	29834407
Dehydration	73.28	34.13	70	54407	123469	29774532
Hypokalaemia	71.83	34.13	5	54472	50187	29847814
Cardiac failure congestive	71.48	34.13	32	54445	84375	29813626
General physical health deterioration	70.03	34.13	48	54429	99896	29798105
Tongue disorder	69.83	34.13	60	54417	4262	29893739
Renal impairment	68.08	34.13	34	54443	84150	29813851
Neuropathy peripheral	67.51	34.13	22	54455	70453	29827548
Rhinorrhoea	67.35	34.13	129	54348	20625	29877376
Pain	67.25	34.13	540	53937	172101	29725900
Off label use	67.08	34.13	231	54246	249059	29648942
Mood swings	65.49	34.13	75	54402	7551	29890450
Sinus headache	64.69	34.13	33	54444	960	29897041
Loss of consciousness	64.27	34.13	32	54445	79343	29818658
C-reactive protein abnormal	63.91	34.13	64	54413	5529	29892472
Acute myocardial infarction	63.71	34.13	10	54467	52929	29845072
Hypoxia	62.45	34.13	7	54470	47847	29850154
Tendonitis	60.67	34.13	74	54403	7962	29890039
Atrial fibrillation	58.75	34.13	66	54411	108058	29789943
Cardiac failure	58.51	34.13	40	54437	83378	29814623
Infusion related reaction	58.16	34.13	4	54473	40560	29857441
Myocardial infarction	55.75	34.13	89	54388	125536	29772465
Drug intolerance	55.53	34.13	195	54282	45096	29852905
Hepatic function abnormal	55.08	34.13	6	54471	41939	29856062
Treatment failure	54.93	34.13	163	54314	34516	29863485
Alanine aminotransferase abnormal	54.20	34.13	42	54435	2577	29895424
Haematuria	52.76	34.13	9	54468	44825	29853176
Coronary artery disease	52.26	34.13	13	54464	49699	29848302
Synovitis	52.17	34.13	76	54401	9707	29888294
Arthropathy	52.14	34.13	116	54361	20611	29877390
Sinusitis	52.12	34.13	156	54321	33189	29864812
Loss of personal independence in daily activities	51.36	34.13	118	54359	21417	29876584
Leukopenia	51.25	34.13	19	54458	56140	29841861
Oedema	49.78	34.13	9	54468	42984	29855017
Decreased appetite	49.43	34.13	452	54025	149458	29748543
Pulmonary oedema	49.23	34.13	10	54467	43965	29854036
Feeling abnormal	49.07	34.13	219	54258	56537	29841464
Chest pain	48.81	34.13	87	54390	117540	29780461
Blood bilirubin increased	48.72	34.13	5	54472	36631	29861370
Coma	47.86	34.13	8	54469	40441	29857560
Therapy partial responder	47.34	34.13	45	54432	3646	29894355
Mental status changes	46.96	34.13	6	54471	37073	29860928
Blood alkaline phosphatase increased	45.45	34.13	3	54474	31484	29866517
Epistaxis	44.97	34.13	20	54457	52961	29845040
Dyspnoea exertional	44.23	34.13	6	54471	35424	29862577
Encephalopathy	43.87	34.13	4	54473	32201	29865800
Hyperglycaemia	43.85	34.13	6	54471	35194	29862807
Product use issue	42.95	34.13	15	54462	46001	29852000
Chills	42.84	34.13	41	54436	72297	29825704
Dysphagia	42.75	34.13	25	54452	56673	29841328
Stomatitis	42.74	34.13	8	54469	37271	29860730
Muscular weakness	42.68	34.13	32	54445	63613	29834388
Somnolence	42.49	34.13	69	54408	96694	29801307
Blood urea increased	42.47	34.13	4	54473	31377	29866624
Hallucination	42.46	34.13	18	54459	49041	29848960
Lactic acidosis	42.18	34.13	4	54473	31209	29866792
Gamma-glutamyltransferase increased	41.77	34.13	3	54474	29347	29868654
Jaundice	41.76	34.13	5	54472	32481	29865520
Chronic kidney disease	41.54	34.13	9	54468	37829	29860172
Weight increased	39.30	34.13	47	54430	74866	29823135
Bowel movement irregularity	38.74	34.13	33	54444	2316	29895685
Pneumonitis	38.52	34.13	3	54474	27451	29870550
Depressed mood	38.08	34.13	91	54386	16938	29881063
Influenza	37.91	34.13	168	54309	43230	29854771
Rash macular	36.83	34.13	67	54410	10300	29887701
Stress	36.80	34.13	100	54377	20135	29877866
Cerebral infarction	36.67	34.13	3	54474	26370	29871631
Acute respiratory failure	35.78	34.13	3	54474	25847	29872154
Intentional product use issue	35.55	34.13	11	54466	36429	29861572
Cerebrovascular accident	35.28	34.13	61	54416	83416	29814585
Muscle swelling	35.17	34.13	16	54461	359	29897642
Hepatocellular injury	35.13	34.13	3	54474	25468	29872533
Rash maculo-papular	35.04	34.13	3	54474	25415	29872586
Skin fissures	35.03	34.13	37	54440	3402	29894599
Liver function test abnormal	34.72	34.13	7	54470	30943	29867058
Anaphylactic reaction	34.31	34.13	5	54472	27977	29870024
Suicide attempt	34.18	34.13	12	54465	36685	29861316

Pharmacologic Action:

Source	Code	Description
ATC	L04AA32	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Selective immunosuppressants
MeSH PA	D000700	Analgesics
MeSH PA	D018712	Analgesics, Non-Narcotic
MeSH PA	D000893	Anti-Inflammatory Agents
MeSH PA	D000894	Anti-Inflammatory Agents, Non-Steroidal
MeSH PA	D018501	Antirheumatic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D058988	Phosphodiesterase 4 Inhibitors
MeSH PA	D010726	Phosphodiesterase Inhibitors
MeSH PA	D018689	Sensory System Agents
CHEBI has role	CHEBI:35475	non-steroidal anti-inflammatory drugs
CHEBI has role	CHEBI:68844	pde4 inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Psoriasis with arthropathy	indication	33339001
Plaque psoriasis	indication	200965009
Behçet's disease affecting oral mucosa	indication	403443000

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
10MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	July 19, 2022	TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
20MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	July 19, 2022	TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
30MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	July 19, 2022	TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
10MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	April 10, 2023	INFORMATION ADDED TO THE CLINICAL STUDIES SECTION OF THE LABELING REGARDING THE USE OF PLAQUE PSORIASIS OF THE SCALP
20MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	April 10, 2023	INFORMATION ADDED TO THE CLINICAL STUDIES SECTION OF THE LABELING REGARDING THE USE OF PLAQUE PSORIASIS OF THE SCALP
30MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	April 10, 2023	INFORMATION ADDED TO THE CLINICAL STUDIES SECTION OF THE LABELING REGARDING THE USE OF PLAQUE PSORIASIS OF THE SCALP
10MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	July 19, 2026	TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
20MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	July 19, 2026	TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE
30MG	OTEZLA	AMGEN INC	N205437	March 21, 2014	RX	TABLET	ORAL	July 19, 2026	TREATMENT OF ADULT PATIENTS WITH ORAL ULCERS ASSOCIATED WITH BEHCETS DISEASE

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
cAMP-specific 3',5'-cyclic phosphodiesterase 4D	Enzyme	Q08499	PDE4D_HUMAN	INHIBITOR	IC50	7.13		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Enzyme	P27815	PDE4A_HUMAN	INHIBITOR	IC50	7.85		IUPHAR
cAMP-specific 3',5'-cyclic phosphodiesterase 4C	Enzyme	Q08493	PDE4C_HUMAN	INHIBITOR	IC50	6.93		IUPHAR
cAMP-specific 3',5'-cyclic phosphodiesterase 4B	Enzyme	Q07343	PDE4B_HUMAN	INHIBITOR	IC50	7.57		IUPHAR

External reference:

ID	Source
UP7QBP99PN	UNII
D08860	KEGG_DRUG
4033216	VUID
N0000190644	NUI
4033216	VANDF
C1678805	UMLSCUI
CHEBI:78540	CHEBI
A9L	PDB_CHEM_ID
CHEMBL514800	ChEMBL_ID
DB05676	DRUGBANK_ID
11561674	PUBCHEM_CID
8872	INN_ID
C505730	MESH_SUPPLEMENTAL_RECORD_UI
7372	IUPHAR_LIGAND_ID
1492727	RXNORM
213427	MMSL
30225	MMSL
d08247	MMSL
015411	NDDF
703350008	SNOMEDCT_US
714684002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Otezla	HUMAN PRESCRIPTION DRUG LABEL	1	55513-137	TABLET, FILM COATED	30 mg	ORAL	NDA	29 sections
OTEZLA	HUMAN PRESCRIPTION DRUG LABEL	1	59572-631	TABLET, FILM COATED	30 mg	ORAL	NDA	25 sections