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

Stem definition	Drug id	CAS RN
human origin	5237	1189541-98-7

Description:

Molecule	Description
Synonyms: sarilumab REGN88 SAR153191 kevzara	Sarilumab is a human recombinant monoclonal antibody of the IgG1 subclass. Sarilumab is produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Sarilumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes, and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis. Based on encouraging results in China with a similar drug, tocilizumab, a phase 2/3 US study evaluating efficacy and safety of sarilumab in patients hospitalized with severe COVID-19 was performed. At the moment, there are insufficient data to recommend either for or against use of sarilumab for hospitalized patients with COVID-19. Molecular weight: Formula: CLOGP: LIPINSKI: None HAC: None HDO: None TPSA: ALOGS: ROTB: None

Molecule

Description

Synonyms:

sarilumab
REGN88
SAR153191
kevzara

Sarilumab is a human recombinant monoclonal antibody of the IgG1 subclass. Sarilumab is produced by recombinant DNA technology in Chinese Hamster Ovary cell suspension culture. Sarilumab binds to both soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R), and has been shown to inhibit IL-6-mediated signaling through these receptors. IL-6 is a pleiotropic pro-inflammatory cytokine produced by a variety of cell types including T- and B-cells, lymphocytes, monocytes, and fibroblasts. IL-6 has been shown to be involved in diverse physiological processes such as T-cell activation, induction of immunoglobulin secretion, initiation of hepatic acute phase protein synthesis, and stimulation of hematopoietic precursor cell proliferation and differentiation. IL-6 is also produced by synovial and endothelial cells leading to local production of IL-6 in joints affected by inflammatory processes such as rheumatoid arthritis. Based on encouraging results in China with a similar drug, tocilizumab, a phase 2/3 US study evaluating efficacy and safety of sarilumab in patients hospitalized with severe COVID-19 was performed. At the moment, there are insufficient data to recommend either for or against use of sarilumab for hospitalized patients with COVID-19.

Molecular weight:
Formula:
CLOGP:
LIPINSKI: None
HAC: None
HDO: None
TPSA:
ALOGS:
ROTB: None

Drug dosage:

Dose	Unit	Route
14.30	mg	P

ADMET properties:

None

Approvals:

Date	Agency	Company
June 23, 2017	EMA	sanofi-aventis groupe
May 22, 2017	FDA	SANOFI SYNTHELABO
Sept. 27, 2017	PMDA	SANOFI KK

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
Rheumatoid factor positive	1414.09	62.46	710	37771	49149	50517494
Anti-cyclic citrullinated peptide antibody positive	1343.92	62.46	771	37710	69816	50496827
Hand deformity	1098.27	62.46	772	37709	99427	50467216
Wound	1092.54	62.46	786	37695	105008	50461635
Synovitis	1053.39	62.46	819	37662	123046	50443597
Glossodynia	1014.94	62.46	779	37702	114790	50451853
Pericarditis	1013.20	62.46	670	37811	78019	50488624
Hepatic enzyme increased	986.98	62.46	823	37658	136557	50430086
Pemphigus	983.67	62.46	777	37704	119389	50447254
Discomfort	959.05	62.46	734	37747	107646	50458997
Systemic lupus erythematosus	925.20	62.46	801	37680	139821	50426822
Joint swelling	903.50	62.46	1017	37464	244269	50322374
Arthropathy	760.36	62.46	756	37725	157150	50409493
Infusion related reaction	756.67	62.46	779	37702	168778	50397865
Drug intolerance	681.68	62.46	834	37647	218270	50348373
Swelling	634.94	62.46	771	37710	200101	50366542
Abdominal discomfort	614.99	62.46	815	37666	230826	50335817
Treatment failure	612.74	62.46	632	37849	137005	50429638
Alopecia	612.29	62.46	837	37644	244210	50322433
Contraindicated product administered	557.46	62.46	624	37857	148334	50418309
Maternal exposure during pregnancy	546.75	62.46	639	37842	159139	50407504
Product use issue	525.06	62.46	606	37875	148869	50417774
Hypersensitivity	514.53	62.46	720	37761	214441	50352202
Duodenal ulcer perforation	460.60	62.46	335	38146	45276	50521367
Helicobacter infection	450.31	62.46	342	38139	49360	50517283
Condition aggravated	420.31	62.46	783	37698	296275	50270368
Hip arthroplasty	385.60	62.46	257	38224	30172	50536471
Rash	330.63	62.46	898	37583	436573	50130070
Knee arthroplasty	318.68	62.46	244	38237	35602	50531041
Rheumatic fever	311.31	62.46	181	38300	16686	50549957
Swollen joint count increased	291.55	62.46	166	38315	14707	50551936
Therapeutic product effect decreased	253.74	62.46	406	38075	135644	50430999
Pain	249.17	62.46	981	37500	577922	49988721
General physical health deterioration	243.94	62.46	409	38072	142025	50424618
Blister	238.67	62.46	309	38172	85109	50481534
Death	223.68	62.46	5	38476	325374	50241269
Drug ineffective	206.04	62.46	1188	37293	818145	49748498
Type 2 diabetes mellitus	199.59	62.46	183	38298	34192	50532451
Blood cholesterol increased	186.78	62.46	220	38261	54995	50511648
Fall	184.52	62.46	20	38461	334912	50231731
Diarrhoea	159.36	62.46	129	38352	588347	49978296
Acute kidney injury	158.63	62.46	3	38478	228055	50338588
Anaemia	155.87	62.46	9	38472	252447	50314196
Musculoskeletal stiffness	154.44	62.46	317	38164	128164	50438479
Hypotension	153.07	62.46	6	38475	235463	50331180
Dyspnoea	145.77	62.46	122	38359	547486	50019157
Adverse drug reaction	142.13	62.46	192	38289	55030	50511613
Toxicity to various agents	139.53	62.46	5	38476	212494	50354149
Intentional product use issue	136.98	62.46	225	38256	76693	50489950
Injury	136.53	62.46	177	38304	48748	50517895
Back pain	124.01	62.46	12	38469	220018	50346625
Live birth	120.71	62.46	100	38381	16308	50550335
Asthenia	118.96	62.46	47	38434	318995	50247648
Adverse event	113.87	62.46	153	38328	43610	50523033
Constipation	113.42	62.46	7	38474	185701	50380942
Cough	108.96	62.46	25	38456	241239	50325404
Oral discomfort	107.01	62.46	70	38411	7947	50558696
Arthralgia	102.10	62.46	625	37856	438077	50128566
Vomiting	89.16	62.46	133	38348	460625	50106018
Weight decreased	86.76	62.46	30	38451	221215	50345428
Pneumonia	85.75	62.46	97	38384	378304	50188339
Product use in unapproved indication	84.98	62.46	236	38245	115583	50451060
Insomnia	81.18	62.46	17	38464	174848	50391795
Haemoglobin decreased	80.11	62.46	4	38477	127212	50439431
Blood pressure increased	78.40	62.46	6	38475	133126	50433517
Mobility decreased	77.46	62.46	181	38300	79767	50486876
Urinary tract infection	77.08	62.46	37	38444	223983	50342660
Seizure	76.54	62.46	3	38478	117871	50448772
Drug tolerance decreased	76.21	62.46	60	38421	9100	50557543
Fatigue	75.70	62.46	845	37636	706756	49859887
Anxiety	73.30	62.46	22	38459	177584	50389059
Thrombocytopenia	71.78	62.46	7	38474	127666	50438977
Tremor	71.13	62.46	4	38477	114899	50451744
Feeling abnormal	70.24	62.46	7	38474	125485	50441158
Dizziness	69.85	62.46	97	38384	346272	50220371
Pyrexia	69.42	62.46	114	38367	380089	50186554
Irritable bowel syndrome	67.78	62.46	132	38349	51309	50515334
Abdominal pain	67.20	62.46	49	38432	236179	50330464
Atrial fibrillation	64.69	62.46	3	38478	101742	50464901
Myalgia	64.46	62.46	9	38472	124310	50442333
Sleep disorder due to general medical condition, insomnia type	64.22	62.46	98	38383	31349	50535294
Nausea	63.99	62.46	298	38183	705100	49861543
Liver injury	63.40	62.46	86	38395	24720	50541923
Tachycardia	63.24	62.46	3	38478	99760	50466883
Retinitis	62.65	62.46	30	38451	1857	50564786

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
Joint swelling	83.21	41.15	37	872	49593	29524025
Arthralgia	63.59	41.15	44	865	139573	29434045
Drug ineffective	60.51	41.15	64	845	363106	29210512
Pain	49.11	41.15	41	868	171391	29402227

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
Rheumatoid factor positive	1089.13	61.87	439	25523	34499	64438271
Anti-cyclic citrullinated peptide antibody positive	1045.21	61.87	472	25490	49090	64423680
Pemphigus	945.00	61.87	469	25493	60232	64412538
Hand deformity	935.97	61.87	471	25491	62300	64410470
Wound	931.68	61.87	501	25461	75976	64396794
Systemic lupus erythematosus	924.74	61.87	501	25461	77111	64395659
Glossodynia	913.78	61.87	468	25494	64228	64408542
Synovitis	831.29	61.87	509	25453	98581	64374189
Pericarditis	818.84	61.87	430	25532	62086	64410684
Discomfort	754.59	61.87	445	25517	80433	64392337
Joint swelling	734.08	61.87	641	25321	214741	64258029
Hepatic enzyme increased	707.81	61.87	510	25452	129433	64343337
Arthropathy	691.51	61.87	489	25473	120478	64352292
Alopecia	608.29	61.87	515	25447	165175	64307595
Swelling	590.15	61.87	499	25463	159719	64313051
Abdominal discomfort	528.62	61.87	496	25466	181826	64290944
Contraindicated product administered	527.55	61.87	397	25565	107432	64365338
Maternal exposure during pregnancy	525.34	61.87	378	25584	95506	64377264
Infusion related reaction	518.61	61.87	469	25493	163998	64308772
Drug intolerance	515.68	61.87	496	25466	187496	64285274
Treatment failure	471.64	61.87	384	25578	116432	64356338
Hypersensitivity	407.23	61.87	446	25516	196006	64276764
Product use issue	403.78	61.87	394	25568	151321	64321449
Helicobacter infection	378.03	61.87	219	25743	38143	64434627
Duodenal ulcer perforation	377.04	61.87	211	25751	34414	64438356
Hip arthroplasty	322.76	61.87	162	25800	21189	64451581
Blister	282.68	61.87	245	25717	80722	64392048
Condition aggravated	266.87	61.87	510	25452	371916	64100854
Knee arthroplasty	262.89	61.87	153	25809	26846	64445924
Pain	249.84	61.87	629	25333	552882	63919888
Rash	247.73	61.87	559	25403	457990	64014780
Rheumatic fever	239.10	61.87	102	25860	9192	64463578
Therapeutic product effect decreased	231.77	61.87	258	25704	115093	64357677
Swollen joint count increased	216.54	61.87	90	25872	7599	64465171
Drug ineffective	185.60	61.87	746	25216	839501	63633269
Death	171.69	61.87	5	25957	482700	63990070
Acute kidney injury	158.49	61.87	5	25957	449235	64023535
Type 2 diabetes mellitus	147.89	61.87	117	25845	33903	64438867
General physical health deterioration	143.47	61.87	278	25684	204147	64268623
Blood cholesterol increased	138.37	61.87	133	25829	49933	64422837
Adverse drug reaction	137.56	61.87	127	25835	45337	64427433
Drug interaction	131.49	61.87	3	25959	362080	64110690
Adverse event	130.65	61.87	116	25846	39373	64433397
Hypotension	128.32	61.87	6	25956	380968	64091802
Injury	127.65	61.87	134	25828	55858	64416912
Irritable bowel syndrome	124.08	61.87	110	25852	37259	64435511
Musculoskeletal stiffness	121.99	61.87	195	25767	123011	64349759
Arthralgia	119.67	61.87	420	25542	441840	64030930
Live birth	113.01	61.87	65	25897	11139	64461631
Anaemia	112.90	61.87	11	25951	378669	64094101
Fall	110.03	61.87	18	25944	416808	64055962
Intentional product use issue	109.95	61.87	162	25800	95202	64377568
Sleep disorder due to general medical condition, insomnia type	109.16	61.87	88	25874	26182	64446588
Exposure during pregnancy	107.44	61.87	144	25818	77531	64395239
Muscle injury	88.10	61.87	78	25884	26359	64446411
Dyspnoea	85.91	61.87	98	25864	718576	63754194
Folliculitis	81.37	61.87	79	25883	29998	64442772
Mobility decreased	78.32	61.87	131	25831	85709	64387061
Constipation	75.91	61.87	4	25958	229333	64243437
Asthenia	75.70	61.87	39	25923	428005	64044765
Retinitis	74.59	61.87	29	25933	2056	64470714
Pneumonia	73.90	61.87	70	25892	559506	63913264
Ill-defined disorder	70.80	61.87	88	25874	43964	64428806
Diarrhoea	70.72	61.87	114	25848	722590	63750180
Somnolence	69.17	61.87	3	25959	203642	64269128
Fibromyalgia	66.65	61.87	77	25885	35654	64437116
Back pain	65.50	61.87	11	25951	250160	64222610
Oral discomfort	64.69	61.87	41	25921	8365	64464405
Fatigue	64.30	61.87	517	25445	748213	63724557
Cough	63.93	61.87	21	25941	302127	64170643
Product use in unapproved indication	62.32	61.87	184	25778	176434	64296336

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L04AC14	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Interleukin inhibitors
FDA MoA	N0000190478	Interleukin 6 Receptor Antagonists
FDA EPC	N0000190480	Interleukin-6 Receptor Antagonist

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

Disease	Relation	SNOMED_ID	DOID
Rheumatoid arthritis	indication	69896004	DOID:7148
Bacterial infectious disease	contraindication	87628006

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Interleukin-6 receptor	Membrane receptor	P08887 P40189	IL6RA_HUMAN IL6RB_HUMAN	ANTIBODY BINDING	Kd	11.10		IUPHAR	DRUG LABEL

External reference:

ID	Source
NU90V55F8I	UNII
C3885145	UMLSCUI
CHEMBL2108730	ChEMBL_ID
DB11767	DRUGBANK_ID
D10161	KEGG_DRUG
7999	IUPHAR_LIGAND_ID
1923319	RXNORM
257686	MMSL
32766	MMSL
d08592	MMSL
735231009	SNOMEDCT_US
763522001	SNOMEDCT_US
4036706	VANDF
017137	NDDF
C000592401	MESH_SUPPLEMENTAL_RECORD_UI
9476	INN_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
KEVZARA	HUMAN PRESCRIPTION DRUG LABEL	1	0024-5908	INJECTION, SOLUTION	150 mg	SUBCUTANEOUS	BLA	28 sections
KEVZARA	HUMAN PRESCRIPTION DRUG LABEL	1	0024-5910	INJECTION, SOLUTION	200 mg	SUBCUTANEOUS	BLA	28 sections
KEVZARA	HUMAN PRESCRIPTION DRUG LABEL	1	0024-5920	INJECTION, SOLUTION	150 mg	SUBCUTANEOUS	BLA	28 sections
KEVZARA	HUMAN PRESCRIPTION DRUG LABEL	1	0024-5922	INJECTION, SOLUTION	200 mg	SUBCUTANEOUS	BLA	28 sections