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

Stem definition	Drug id	CAS RN
antivirals RNA polymerase (NS5B) inhibitors	4811	1190307-88-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: sofosbuvir sovaldi PSI-7977	A uridine monophosphate analog inhibitor of HEPATITIS C VIRUS (HCV) polymerase NS5B that is used as an ANTIVIRAL AGENT in the treatment of CHRONIC HEPATITIS C. Molecular weight: 529.46 Formula: C22H29FN3O9P CLOGP: 0.84 LIPINSKI: 2 HAC: 12 HDO: 3 TPSA: 152.73 ALOGS: -2.81 ROTB: 11 Status: ONP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

sofosbuvir
sovaldi
PSI-7977

A uridine monophosphate analog inhibitor of HEPATITIS C VIRUS (HCV) polymerase NS5B that is used as an ANTIVIRAL AGENT in the treatment of CHRONIC HEPATITIS C.

Molecular weight: 529.46
Formula: C22H29FN3O9P
CLOGP: 0.84
LIPINSKI: 2
HAC: 12
HDO: 3
TPSA: 152.73
ALOGS: -2.81
ROTB: 11

Status: ONP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
0.40	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Hosey CM, Chan R, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Dec. 6, 2013	FDA	GILEAD SCIENCES INC

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
Headache	2717.35	16.84	2375	29714	475977	46177996
Fatigue	2476.06	16.84	2510	29579	606187	46047786
Hepatitis C	1729.95	16.84	468	31621	5850	46648123
Hepatocellular carcinoma	1335.93	16.84	324	31765	2515	46651458
Insomnia	427.06	16.84	545	31544	164379	46489594
Nausea	411.86	16.84	1213	30876	686241	45967732
Genotype drug resistance test positive	364.99	16.84	83	32006	467	46653506
Hepatic encephalopathy	326.66	16.84	153	31936	10004	46643969
Ascites	250.81	16.84	205	31884	36379	46617594
Hepatitis B reactivation	229.94	16.84	71	32018	1443	46652530
Product dose omission issue	212.83	16.84	400	31689	168120	46485853
Hepatic cirrhosis	211.82	16.84	133	31956	15599	46638374
Hepatitis C virus test positive	196.63	16.84	41	32048	141	46653832
Oesophageal varices haemorrhage	184.24	16.84	57	32032	1166	46652807
Anaemia	160.50	16.84	461	31628	255318	46398655
Treatment failure	148.45	16.84	245	31844	92842	46561131
Hepatic cancer recurrent	130.93	16.84	24	32065	31	46653942
Hepatic failure	130.84	16.84	137	31952	33279	46620694
Rheumatoid arthritis	127.44	16.84	10	32079	240205	46413768
Drug hypersensitivity	114.37	16.84	16	32073	243809	46410164
Hepatitis C RNULL positive	113.19	16.84	23	32066	67	46653906
Dyspepsia	108.80	16.84	180	31909	68292	46585681
Product use complaint	100.04	16.84	40	32049	1772	46652201
Toxicity to various agents	96.73	16.84	15	32074	211751	46442222
Liver transplant	95.35	16.84	42	32047	2375	46651598
Cryoglobulinaemia	94.57	16.84	26	32063	344	46653629
Viral load increased	88.78	16.84	34	32055	1341	46652632
Hyperbilirubinaemia	83.28	16.84	64	32025	10374	46643599
Drug intolerance	81.18	16.84	5	32084	147044	46506929
Diarrhoea	78.93	16.84	654	31435	558948	46095025
Hepatic cancer	76.56	16.84	39	32050	3058	46650915
Portal vein thrombosis	75.71	16.84	36	32053	2431	46651542
Irritability	75.08	16.84	96	31993	28850	46625123
Influenza like illness	69.16	16.84	134	31955	57436	46596537
Viral mutation identified	68.51	16.84	31	32058	1868	46652105
Pruritus	58.52	16.84	324	31765	242028	46411945
Maternal exposure during pregnancy	57.56	16.84	178	31911	102371	46551602
Renal impairment	56.39	16.84	144	31945	74228	46579745
Injection site pain	55.27	16.84	5	32084	107147	46546826
Intentional dose omission	55.07	16.84	32	32057	3258	46650715
Hepatitis C RNULL increased	54.50	16.84	14	32075	140	46653833
Exposure via body fluid	53.81	16.84	18	32071	476	46653497
Jaundice	50.09	16.84	79	32010	28766	46625207
Photosensitivity reaction	47.48	16.84	51	32038	12741	46641232
Product use in unapproved indication	47.13	16.84	4	32085	90269	46563704
Blood bilirubin increased	45.30	16.84	83	32006	34101	46619872
Disease progression	45.16	16.84	5	32084	91295	46562678
Varices oesophageal	43.46	16.84	26	32063	2793	46651180
Glomerular filtration rate decreased	42.31	16.84	46	32043	11648	46642325
Therapeutic product effect incomplete	42.10	16.84	3	32086	78150	46575823
Alopecia	41.75	16.84	221	31868	162193	46491780
Therapeutic product effect decreased	39.67	16.84	5	32084	82596	46571377
Hepatorenal syndrome	39.62	16.84	21	32068	1787	46652186
Fall	38.58	16.84	108	31981	328989	46324984
Dry skin	35.95	16.84	84	32005	40932	46613041
Depression	35.53	16.84	219	31870	169885	46484088
Myalgia	35.48	16.84	173	31916	122915	46531058
Hypotension	33.87	16.84	68	32021	232521	46421452
Systemic lupus erythematosus	33.72	16.84	3	32086	65177	46588796
Hepatic pain	33.62	16.84	22	32067	2766	46651207
Intentional overdose	33.57	16.84	3	32086	64941	46589032
Malignant neoplasm progression	33.55	16.84	3	32086	64923	46589050
Deep vein thrombosis	33.46	16.84	7	32082	79766	46574207
Sunburn	33.20	16.84	21	32068	2491	46651482
Arthropathy	32.45	16.84	9	32080	84691	46569282
Injection site erythema	32.33	16.84	6	32083	74421	46579552
Contraindicated product administered	31.57	16.84	8	32081	79939	46574034
Exposure via partner	31.45	16.84	9	32080	139	46653834
Musculoskeletal stiffness	31.41	16.84	14	32075	97979	46555994
Gastric varices haemorrhage	29.66	16.84	8	32081	98	46653875
Joint swelling	29.25	16.84	43	32046	166030	46487943
Ammonia increased	28.85	16.84	24	32065	4353	46649620
Infection	28.32	16.84	30	32059	133562	46520411
Peritonitis bacterial	27.81	16.84	32	32057	8621	46645352
Blood bilirubin abnormal	27.37	16.84	12	32077	671	46653302
Autoimmune hepatitis	26.99	16.84	30	32059	7784	46646189
Hepatectomy	26.98	16.84	7	32082	73	46653900
Osteoarthritis	26.94	16.84	5	32084	62020	46591953
Encephalopathy	26.44	16.84	66	32023	33523	46620450
Pain	26.35	16.84	206	31883	476742	46177231
Memory impairment	26.19	16.84	114	31975	77223	46576750
Remission not achieved	25.65	16.84	7	32082	90	46653883
Psoriasis	25.55	16.84	11	32078	78593	46575380
Condition aggravated	25.41	16.84	85	32004	244967	46409006
Extra dose administered	25.35	16.84	23	32066	4684	46649289
Asthenia	24.67	16.84	324	31765	310751	46343222
Hypersensitivity	24.49	16.84	41	32048	150280	46503693
Virologic failure	24.25	16.84	16	32073	2039	46651934
Constipation	24.06	16.84	203	31886	173894	46480079
C-reactive protein increased	22.87	16.84	6	32083	58584	46595389
Pneumonia	21.96	16.84	160	31929	376160	46277813
Rash	21.83	16.84	355	31734	356157	46297816
Hepatitis B	21.79	16.84	19	32070	3674	46650299
Abdominal distension	21.77	16.84	104	31985	73247	46580726
Chronic hepatitis C	21.37	16.84	7	32082	173	46653800
Pulmonary embolism	21.25	16.84	26	32063	108559	46545414
Decreased appetite	21.23	16.84	215	31874	193621	46460352
Swelling	21.18	16.84	33	32056	124478	46529495
Dizziness	20.84	16.84	339	31750	340075	46313898
Lower respiratory tract infection	20.83	16.84	6	32083	55083	46598890
Neutropenia	20.71	16.84	42	32047	143162	46510811
Chromaturia	20.57	16.84	37	32052	14982	46638991
Thirst	20.36	16.84	31	32058	10945	46643028
Drug interaction	20.23	16.84	221	31868	202873	46451100
Haemoglobin decreased	19.23	16.84	153	31936	128796	46525177
Gait disturbance	19.03	16.84	45	32044	145218	46508755
Inflammation	19.03	16.84	5	32084	48776	46605197
Emotional disorder	19.01	16.84	32	32057	12292	46641681
Hepatitis C RNULL	18.85	16.84	3	32086	0	46653973
Transcatheter arterial chemoembolisation	18.85	16.84	3	32086	0	46653973
Therapy cessation	18.57	16.84	50	32039	26579	46627394
Vomiting	18.22	16.84	423	31666	452371	46201602
Wrong schedule	18.14	16.84	6	32083	153	46653820
Sinusitis	17.97	16.84	39	32050	129729	46524244
Glomerulonephritis	17.97	16.84	12	32077	1561	46652412
Injection site pruritus	17.70	16.84	3	32086	39740	46614233
Chronic hepatic failure	17.62	16.84	8	32081	486	46653487
Hypoxia	17.25	16.84	7	32082	51831	46602142
Migraine	17.08	16.84	94	31995	69932	46584041

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
Hepatitis C	5568.59	15.27	1641	45752	11564	29893521
Fatigue	4247.21	15.27	3689	43704	316984	29588101
Headache	3936.85	15.27	2807	44586	179499	29725586
Hepatocellular carcinoma	2812.58	15.27	904	46489	8706	29896379
Treatment failure	1654.83	15.27	891	46502	33788	29871297
Genotype drug resistance test positive	1268.46	15.27	327	47066	1262	29903823
Drug ineffective	1056.40	15.27	1902	45491	338485	29566600
Insomnia	603.98	15.27	740	46653	92596	29812489
Hepatic cirrhosis	543.64	15.27	330	47063	15669	29889416
Liver transplant	425.64	15.27	162	47231	2640	29902445
Ascites	390.44	15.27	375	47018	35546	29869539
Hepatic encephalopathy	375.48	15.27	250	47143	13942	29891143
Nausea	359.62	15.27	1156	46237	295801	29609284
Product dose omission issue	358.61	15.27	571	46822	91060	29814025
Hepatitis C virus test positive	302.00	15.27	81	47312	376	29904709
Hepatic cancer	242.90	15.27	143	47250	6405	29898680
Viral mutation identified	241.61	15.27	106	47287	2520	29902565
Oesophageal varices haemorrhage	226.38	15.27	106	47287	2945	29902140
Intentional dose omission	218.61	15.27	83	47310	1342	29903743
Hepatitis B reactivation	201.32	15.27	96	47297	2781	29902304
Hepatic cancer recurrent	182.48	15.27	52	47341	314	29904771
Toxicity to various agents	181.75	15.27	31	47362	177152	29727933
Hepatitis C RNULL positive	181.45	15.27	47	47346	185	29904900
Hepatic failure	177.34	15.27	243	47150	33800	29871285
Hypotension	158.11	15.27	60	47333	200505	29704580
Dyspepsia	142.38	15.27	206	47187	30123	29874962
Irritability	125.26	15.27	168	47225	22882	29882203
Hepatitis C RNULL increased	116.23	15.27	37	47356	341	29904744
Febrile neutropenia	113.04	15.27	17	47376	106676	29798409
Pneumonia	108.36	15.27	230	47163	334076	29571009
Hepatorenal syndrome	104.19	15.27	59	47334	2452	29902633
Virologic failure	103.11	15.27	64	47329	3155	29901930
Chronic hepatitis C	98.44	15.27	35	47358	465	29904620
Hyperbilirubinaemia	95.91	15.27	126	47267	16816	29888269
Influenza like illness	90.95	15.27	153	47240	25452	29879633
Hepatic hydrothorax	87.22	15.27	19	47374	26	29905059
Abdominal discomfort	86.76	15.27	219	47174	48572	29856513
Malignant neoplasm progression	85.22	15.27	8	47385	72279	29832806
Portal vein thrombosis	79.66	15.27	56	47337	3408	29901677
Bleeding varicose vein	77.89	15.27	26	47367	282	29904803
Blood bilirubin increased	76.47	15.27	175	47218	36461	29868624
Drug abuse	74.47	15.27	19	47374	82053	29823032
Completed suicide	69.96	15.27	35	47358	99457	29805628
Drug hypersensitivity	67.94	15.27	13	47380	68506	29836579
General physical health deterioration	67.55	15.27	37	47356	99907	29805178
Diarrhoea	66.88	15.27	814	46579	333289	29571796
Varices oesophageal	65.47	15.27	50	47343	3459	29901626
Anaemia	65.22	15.27	556	46837	207436	29697649
Tachycardia	65.14	15.27	18	47375	73721	29831364
Fall	64.88	15.27	118	47275	181754	29723331
Viral load increased	60.70	15.27	44	47349	2810	29902275
Glomerular filtration rate decreased	60.46	15.27	82	47311	11280	29893805
Pyrexia	60.17	15.27	251	47142	294238	29610847
Jaundice	57.91	15.27	146	47247	32340	29872745
Pulmonary embolism	55.65	15.27	27	47366	78108	29826977
Disease progression	54.79	15.27	29	47364	79845	29825240
Peritonitis bacterial	54.40	15.27	78	47315	11300	29893785
Neutropenia	53.74	15.27	75	47318	128465	29776620
Plasma cell myeloma	53.30	15.27	10	47383	53452	29851633
Product use in unapproved indication	51.67	15.27	26	47367	73667	29831418
Ammonia abnormal	50.85	15.27	14	47379	73	29905012
Oxygen saturation decreased	50.67	15.27	5	47388	43435	29861650
Depression	50.58	15.27	279	47114	90158	29814927
Dyspnoea	50.00	15.27	316	47077	332979	29572106
Cardiac failure congestive	49.16	15.27	37	47356	84370	29820715
Therapeutic embolisation	49.16	15.27	19	47374	323	29904762
Product use complaint	47.61	15.27	27	47366	1125	29903960
Therapy cessation	46.66	15.27	85	47308	15052	29890033
Respiratory failure	44.83	15.27	56	47337	100586	29804499
Hepatic pain	44.62	15.27	27	47366	1271	29903814
Coronary artery disease	44.14	15.27	12	47381	49700	29855385
Cryoglobulinaemia	43.09	15.27	17	47376	306	29904779
Abnormal dreams	42.32	15.27	58	47335	8057	29897028
Pruritus	41.26	15.27	324	47069	117880	29787205
Interstitial lung disease	41.07	15.27	22	47371	60175	29844910
Extra dose administered	40.86	15.27	35	47358	2851	29902234
Incorrect product administration duration	40.75	15.27	40	47353	3882	29901203
White blood cell count decreased	40.30	15.27	44	47349	83903	29821182
Dry skin	40.10	15.27	101	47292	22353	29882732
Therapeutic product effect incomplete	39.18	15.27	4	47389	33830	29871255
Asthma	37.73	15.27	6	47387	36168	29868917
Gait disturbance	37.23	15.27	38	47355	74739	29830346
Hyponatraemia	37.18	15.27	31	47362	67171	29837914
Hypoxia	36.47	15.27	15	47378	47839	29857246
Rheumatoid arthritis	36.47	15.27	10	47383	41187	29863898
Neutrophil count decreased	36.30	15.27	11	47382	42443	29862642
C-reactive protein increased	35.87	15.27	12	47381	43461	29861624
Respiratory arrest	35.11	15.27	3	47390	29255	29875830
Therapeutic product effect decreased	34.84	15.27	3	47390	29073	29876012
Deep vein thrombosis	34.61	15.27	27	47366	60474	29844611
Haematuria	34.26	15.27	14	47379	44820	29860265
Remission not achieved	34.07	15.27	10	47383	68	29905017
Focal segmental glomerulosclerosis	34.01	15.27	26	47367	1801	29903284
Sepsis	33.51	15.27	119	47274	146276	29758809
Pancytopenia	33.20	15.27	52	47341	85000	29820085
Myalgia	32.98	15.27	221	47172	76446	29828639
Atrial fibrillation	32.70	15.27	77	47316	108047	29797038
Neuropathy peripheral	32.66	15.27	38	47355	70437	29834648
Gastric varices haemorrhage	32.50	15.27	13	47380	243	29904842
Complications of transplanted lung	32.48	15.27	12	47381	179	29904906
Gene mutation identification test positive	32.24	15.27	12	47381	183	29904902
Encephalopathy	32.09	15.27	118	47275	32087	29872998
Dry mouth	32.01	15.27	94	47299	22756	29882329
Hypokalaemia	31.88	15.27	20	47373	50172	29854913
Platelet count decreased	31.76	15.27	76	47317	106053	29799032
Cardiac failure	31.62	15.27	52	47341	83366	29821719
Pulmonary oedema	31.60	15.27	15	47378	43960	29861125
Erythema	31.54	15.27	46	47347	77405	29827680
Blood pressure decreased	30.96	15.27	18	47375	47057	29858028
International normalised ratio increased	30.35	15.27	19	47374	47720	29857365
Alpha 1 foetoprotein increased	30.20	15.27	17	47376	698	29904387
Hepatic mass	29.66	15.27	19	47374	990	29904095
Electrocardiogram QT prolonged	29.37	15.27	10	47383	35825	29869260
Hepatic neoplasm	29.33	15.27	24	47369	1835	29903250
Dehydration	29.22	15.27	99	47294	123440	29781645
Drug reaction with eosinophilia and systemic symptoms	29.10	15.27	5	47388	28483	29876602
Intentional overdose	28.52	15.27	15	47378	41466	29863619
Genital herpes simplex	28.46	15.27	10	47383	128	29904957
Treatment noncompliance	28.14	15.27	96	47297	25157	29879928
Photosensitivity reaction	28.07	15.27	53	47340	9641	29895444
Ammonia increased	27.89	15.27	34	47359	4207	29900878
Energy increased	27.89	15.27	20	47373	1256	29903829
Injection site pain	27.51	15.27	7	47386	30303	29874782
Flushing	26.40	15.27	7	47386	29485	29875600
Depressed level of consciousness	26.02	15.27	14	47379	38208	29866877
Coma	25.85	15.27	16	47377	40433	29864652
Urinary retention	25.60	15.27	10	47383	32907	29872178
Accidental overdose	25.42	15.27	75	47318	18200	29886885
Cholangiocarcinoma	25.28	15.27	17	47376	962	29904123
Porphyria non-acute	24.43	15.27	13	47380	477	29904608
Cardiac arrest	24.35	15.27	71	47322	92779	29812306
Mobility decreased	23.60	15.27	6	47387	25993	29879092
Hypocalcaemia	23.57	15.27	3	47390	21373	29883712
Stomatitis	23.47	15.27	15	47378	37264	29867821
Anticoagulation drug level below therapeutic	23.29	15.27	14	47379	651	29904434
Genital herpes	23.11	15.27	13	47380	533	29904552
Ectopic kidney	23.09	15.27	7	47386	54	29905031
Thrombocytopenia	23.07	15.27	125	47268	136919	29768166
Biliary colic	22.55	15.27	16	47377	988	29904097
Cardio-respiratory arrest	22.39	15.27	35	47358	57271	29847814
Hepatitis C RNULL	22.34	15.27	6	47387	28	29905057
Liver transplant rejection	22.06	15.27	22	47371	2176	29902909
Diabetic hyperglycaemic coma	21.68	15.27	6	47387	32	29905053
Thought blocking	21.49	15.27	8	47385	122	29904963
Hepatectomy	21.48	15.27	7	47386	70	29905015
Tinnitus	21.41	15.27	65	47328	16023	29889062
Chronic obstructive pulmonary disease	21.22	15.27	25	47368	46101	29858984
Migraine	21.02	15.27	56	47337	12818	29892267
Abdominal pain upper	20.99	15.27	170	47223	62381	29842704
Memory impairment	20.96	15.27	115	47278	37059	29868026
Hepatic fibrosis	20.83	15.27	27	47366	3553	29901532
Bronchitis	20.48	15.27	19	47374	39106	29865979
Intentional product misuse	20.42	15.27	15	47378	34652	29870433
Portal hypertensive gastropathy	20.30	15.27	12	47381	541	29904544
Acute respiratory distress syndrome	20.21	15.27	6	47387	23466	29881619
Pneumonia aspiration	20.19	15.27	18	47375	37762	29867323
Wheezing	20.10	15.27	12	47381	30926	29874159
Hunger	20.07	15.27	17	47376	1363	29903722
Pain in extremity	19.98	15.27	98	47295	110123	29794962
Adverse drug reaction	19.78	15.27	6	47387	23139	29881946
Blood bilirubin abnormal	19.36	15.27	12	47381	590	29904495
Abdominal cavity drainage	19.33	15.27	10	47383	346	29904739
Acute kidney injury	19.32	15.27	311	47082	273531	29631554
Staphylococcal infection	19.25	15.27	12	47381	30212	29874873
Tumour embolism	19.17	15.27	6	47387	52	29905033
Portal hypertension	19.17	15.27	27	47366	3846	29901239
Urticaria	18.91	15.27	36	47357	54570	29850515
Laryngomalacia	18.79	15.27	9	47384	263	29904822
Delirium	18.72	15.27	22	47371	40609	29864476
Serotonin syndrome	18.58	15.27	3	47390	17888	29887197
Respiratory distress	18.49	15.27	15	47378	32957	29872128
Drug intolerance	18.33	15.27	27	47366	45264	29859821
Haematemesis	18.23	15.27	86	47307	26117	29878968
Seizure	18.17	15.27	87	47306	98388	29806697
Urinary tract infection	18.11	15.27	58	47335	73601	29831484
Lymphocyte count decreased	18.08	15.27	4	47389	19051	29886034
Foetal exposure during pregnancy	18.04	15.27	19	47374	36852	29868233
Acute on chronic liver failure	17.74	15.27	7	47386	126	29904959
Gallbladder cancer	17.53	15.27	8	47385	209	29904876
Hydrocholecystis	17.53	15.27	8	47385	209	29904876
Prostate cancer	17.47	15.27	8	47385	23949	29881136
Viral test positive	17.22	15.27	8	47385	218	29904867
Rhabdomyolysis	17.11	15.27	48	47345	63532	29841553
Gastrointestinal tube insertion	17.05	15.27	15	47378	1266	29903819
Coma hepatic	16.97	15.27	10	47383	448	29904637
Hyperkalaemia	16.92	15.27	51	47342	65959	29839126
Eosinophilia	16.79	15.27	7	47386	22153	29882932
Neoplasm progression	16.67	15.27	4	47389	18019	29887066
Increased appetite	16.62	15.27	31	47362	5586	29899499
Anaphylactic reaction	16.62	15.27	12	47381	27970	29877115
Therapeutic response decreased	16.45	15.27	9	47384	24340	29880745
Pleural effusion	16.40	15.27	61	47332	74005	29831080
Unresponsive to stimuli	16.13	15.27	11	47382	26408	29878677
Pneumonitis	16.01	15.27	12	47381	27442	29877643
Respiratory disorder	15.95	15.27	4	47389	17490	29887595
Loss of consciousness	15.91	15.27	68	47325	79307	29825778
Hypersensitivity	15.90	15.27	39	47354	53989	29851096
Myelodysplastic syndrome	15.81	15.27	5	47388	18773	29886312
Pulmonary fibrosis	15.77	15.27	3	47390	15887	29889198
Gastrooesophageal reflux disease	15.71	15.27	96	47297	32159	29872926
Gastric varices	15.65	15.27	9	47384	385	29904700
Hypoglycaemia	15.64	15.27	36	47357	50945	29854140
Product packaging quantity issue	15.42	15.27	11	47382	685	29904400
Pallor	15.39	15.27	7	47386	21042	29884043
Haemophilia	15.39	15.27	4	47389	16	29905069
Myocardial infarction	15.39	15.27	126	47267	125499	29779586

Pharmacologic Action:

Source	Code	Description
ATC	J05AP08	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
ATC	J05AP51	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
ATC	J05AP55	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
ATC	J05AP56	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HCV infections
FDA EXT	N0000175459	Nucleoside Analog
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000998	Antiviral Agents
FDA MoA	N0000191258	RNULL Replicase Inhibitors
FDA EPC	N0000191493	Hepatitis C Virus Nucleotide Analog NS5B Polymerase Inhibitor
CHEBI has role	CHEBI:36044	anti-virus drug
CHEBI has role	CHEBI:50266	prodrugs
CHEBI has role	CHEBI:64924	hepatitis c protease inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Chronic hepatitis C	indication	128302006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	9.07	acidic
pKa2	11.58	acidic
pKa3	2.07	Basic

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
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	June 28, 2021	NEW CHEMICAL ENTITY
400MG;100MG;100MG	VOSEVI	GILEAD SCIENCES INC	N209195	July 18, 2017	RX	TABLET	ORAL	July 18, 2022	NEW CHEMICAL ENTITY
45MG;200MG	HARVONI	GILEAD SCIENCES INC	N205834	Aug. 28, 2019	RX	TABLET	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
90MG;400MG	HARVONI	GILEAD SCIENCES INC	N205834	Oct. 10, 2014	RX	TABLET	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Nov. 15, 2022	INFORMATION ADDED TO THE DOSING SECTION IN REGARD TO THE TREATMENT OF CHRONIC HEPATITIS C VIRUS INFECTION IN PATIENTS WITH SEVERE RENULLL IMPAIRMENT INCLUDING PATIENTS WITH END STAGE RENULLL DISEASE ON DIALYSIS
200MG;50MG	EPCLUSA	GILEAD SCIENCES INC	N208341	March 19, 2020	RX	TABLET	ORAL	March 19, 2023	NEW STRENGTH
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	March 19, 2023	NEW PATIENT POPULATION
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	May 15, 2023	PEDIATRIC EXCLUSIVITY
200MG;50MG	EPCLUSA	GILEAD SCIENCES INC	N208341	March 19, 2020	RX	TABLET	ORAL	July 14, 2023	INFORMATION ADDED TO THE LABELING DESCRIBING A PHASE 2, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY/EFFICACY OF SOFOSBUVIR/VELPATASVIR IN SUBJECTS WITH CHRONIC HCV INFECTION WHO HAVE RECEIVED A LIVER TRANSPLANT
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	July 14, 2023	INFORMATION ADDED TO THE LABELING DESCRIBING A PHASE 2, MULTICENTER, OPEN-LABEL STUDY TO EVALUATE THE SAFETY/EFFICACY OF SOFOSBUVIR/VELPATASVIR IN SUBJECTS WITH CHRONIC HCV INFECTION WHO HAVE RECEIVED A LIVER TRANSPLANT
200MG;50MG	EPCLUSA	GILEAD SCIENCES INC	N208341	March 19, 2020	RX	TABLET	ORAL	Sept. 19, 2023	PEDIATRIC EXCLUSIVITY
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	Sept. 19, 2023	PEDIATRIC EXCLUSIVITY
200MG;50MG	EPCLUSA	GILEAD SCIENCES INC	N208341	March 19, 2020	RX	TABLET	ORAL	Jan. 14, 2024	PEDIATRIC EXCLUSIVITY
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	Jan. 14, 2024	PEDIATRIC EXCLUSIVITY
200MG	SOVALDI	GILEAD SCIENCES INC	N204671	Aug. 28, 2019	RX	TABLET	ORAL	April 7, 2024	FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
400MG	SOVALDI	GILEAD SCIENCES INC	N204671	Dec. 6, 2013	RX	TABLET	ORAL	April 7, 2024	TREATMENT OF CHRONIC HCV GENOTYPE 2 OR 3 INFECTION IN PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER OR WEIGHING AT LEAST 35 KG WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS FOR USE IN COMBINULLTION WITH RIBAVIRIN
90MG;400MG	HARVONI	GILEAD SCIENCES INC	N205834	Oct. 10, 2014	RX	TABLET	ORAL	April 7, 2024	TREATMENT OF PEDIATRIC PATIENTS 12 YEARS OF AGE AND OLDER OR WEIGHING AT LEAST 35 KG WITH CHRONIC HEPATITIS C VIRUS GENOTYPE 1, 4, 5, OR 6 INFECTION WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS
200MG	SOVALDI	GILEAD SCIENCES INC	N204671	Aug. 28, 2019	RX	TABLET	ORAL	Oct. 7, 2024	PEDIATRIC EXCLUSIVITY
400MG	SOVALDI	GILEAD SCIENCES INC	N204671	Dec. 6, 2013	RX	TABLET	ORAL	Oct. 7, 2024	PEDIATRIC EXCLUSIVITY
90MG;400MG	HARVONI	GILEAD SCIENCES INC	N205834	Oct. 10, 2014	RX	TABLET	ORAL	Oct. 7, 2024	PEDIATRIC EXCLUSIVITY
200MG	SOVALDI	GILEAD SCIENCES INC	N204671	Aug. 28, 2019	RX	TABLET	ORAL	Aug. 28, 2026	FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
400MG	SOVALDI	GILEAD SCIENCES INC	N204671	Dec. 6, 2013	RX	TABLET	ORAL	Aug. 28, 2026	FDA HAS NOT RECOGNIZED ORPHAN-DRUG EXCLUSIVITY (ODE) FOR THIS DRUG, BUT IT CONTAINS THE SAME ACTIVE MOIETY OR MOIETIES AS ANOTHER DRUG(S) THAT WAS ELIGIBLE FOR ODE, AND ALSO SHARES ODE-PROTECTED USE(S) OR INDICATION(S) WITH THAT DRUG(S). AN APPLICATION SEEKING APPROVAL FOR THE SAME ACTIVE MOIETY OR MOIETIES, INCLUDING AN ANDA THAT CITES THIS NDA AS ITS BASIS OF SUBMISSION, MAY NOT BE APPROVED FOR SUCH ODE-PROTECTED USE(S) AND INDICATION(S)
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 INFECTION WITH DECOMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 OR 4 INFECTION WHO ARE LIVER TRANSPLANT RECIPIENTS WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
33.75MG;150MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS BETWEEN 3 YEARS OF AGE AND 12 YEARS OF AGE OR WEIGHING 35 KG WITH CHRONIC HEPATITIS C VIRUS (HCV) GENOTYPE 1, 4, 5, OR 6 INFECTION WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 INFECTION WITH DECOMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS 3 YEARS OF AGE AND OLDER WITH CHRONIC HCV GENOTYPE 1 OR 4 INFECTION WHO ARE LIVER TRANSPLANT RECIPIENTS WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS, FOR USE IN COMBINULLTION WITH RIBAVIRIN
45MG;200MG/PACKET	HARVONI	GILEAD SCIENCES INC	N212477	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	TREATMENT OF PEDIATRIC PATIENTS BETWEEN 3 YEARS OF AGE AND 12 YEARS OF AGE OR WEIGHING 35 KG WITH CHRONIC HEPATITIS C VIRUS (HCV) GENOTYPE 1, 4, 5, OR 6 INFECTION WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS
150MG/PACKET	SOVALDI	GILEAD SCIENCES INC	N212480	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	FOR THE TREATMENT OF CHRONIC HEPATITIS C VIRUS (HCV) GENOTYPE 2 OR 3 INFECTION IN PEDIATRIC PATIENTS BETWEEN 3 YEARS OF AGE AND 12 YEARS OF AGE OR WEIGHING 35 KG WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS FOR USE IN COMBINULLTION WITH RIBAVIRIN
200MG/PACKET	SOVALDI	GILEAD SCIENCES INC	N212480	Aug. 28, 2019	RX	PELLETS	ORAL	Aug. 28, 2026	FOR THE TREATMENT OF CHRONIC HEPATITIS C VIRUS (HCV) GENOTYPE 2 OR 3 INFECTION IN PEDIATRIC PATIENTS BETWEEN 3 YEARS OF AGE AND 12 YEARS OF AGE OR WEIGHING 35 KG WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS FOR USE IN COMBINULLTION WITH RIBAVIRIN
200MG;50MG	EPCLUSA	GILEAD SCIENCES INC	N208341	March 19, 2020	RX	TABLET	ORAL	March 19, 2027	TX OF PED PTS 6 YRS OF AGE & OLDER OR WEIGHING AT LEAST 17 KG WITH CHRONIC HEPATITIS C VIRUS GENOTYPE 1, 2, 3, 4, 5, OR 6 INFECTION: WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS; OR WITH DECOMPENSATED CIRRHOSIS FOR USE IN COMBINULLTION WITH RIBAVIRIN
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	March 19, 2027	TX OF PED PTS 6 YRS OF AGE & OLDER OR WEIGHING AT LEAST 17 KG WITH CHRONIC HEPATITIS C VIRUS GENOTYPE 1, 2, 3, 4, 5, OR 6 INFECTION: WITHOUT CIRRHOSIS OR WITH COMPENSATED CIRRHOSIS; OR WITH DECOMPENSATED CIRRHOSIS FOR USE IN COMBINULLTION WITH RIBAVIRIN
200MG;50MG	EPCLUSA	GILEAD SCIENCES INC	N208341	March 19, 2020	RX	TABLET	ORAL	Sept. 19, 2027	PEDIATRIC EXCLUSIVITY
400MG;100MG	EPCLUSA	GILEAD SCIENCES INC	N208341	June 28, 2016	RX	TABLET	ORAL	Sept. 19, 2027	PEDIATRIC EXCLUSIVITY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Genome polyprotein	Polyprotein		POLG_HCVH	INHIBITOR	EC90	6.96		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
NS5B protein	Enzyme		Q8JXU8_9HEPC	INHIBITOR				CHEMBL	CHEMBL

External reference:

ID	Source
D10366	KEGG_DRUG
4032949	VUID
N0000189539	NUI
4032949	VANDF
C2976303	UMLSCUI
CHEBI:85083	CHEBI
CHEMBL1259059	ChEMBL_ID
D000069474	MESH_DESCRIPTOR_UI
7368	IUPHAR_LIGAND_ID
9665	INN_ID
DB08934	DRUGBANK_ID
WJ6CA3ZU8B	UNII
45375806	PUBCHEM_CID
11311503	PUBCHEM_CID
1484911	RXNORM
207812	MMSL
29932	MMSL
d08184	MMSL
015326	NDDF
710806008	SNOMEDCT_US
713645002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Sovaldi	HUMAN PRESCRIPTION DRUG LABEL	1	61958-1501	TABLET, FILM COATED	400 mg	ORAL	NDA	34 sections
Sovaldi Access	HUMAN PRESCRIPTION DRUG LABEL	1	61958-1502	TABLET, FILM COATED	400 mg	ORAL	Export only	34 sections
Sovaldi	HUMAN PRESCRIPTION DRUG LABEL	1	61958-1503	TABLET, FILM COATED	200 mg	ORAL	NDA	34 sections
Sovaldi	HUMAN PRESCRIPTION DRUG LABEL	1	61958-1504	PELLET	150 mg	ORAL	NDA	34 sections
Sovaldi	HUMAN PRESCRIPTION DRUG LABEL	1	61958-1505	PELLET	200 mg	ORAL	NDA	34 sections
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1801	TABLET, FILM COATED	400 mg	ORAL	NDA	36 sections
Harvoni Access	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1802	TABLET, FILM COATED	400 mg	ORAL	Export only	31 sections
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1803	TABLET, FILM COATED	200 mg	ORAL	NDA	36 sections
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1804	PELLET	200 mg	ORAL	NDA	36 sections
Harvoni	HUMAN PRESCRIPTION DRUG LABEL	2	61958-1805	PELLET	150 mg	ORAL	NDA	36 sections
Epclusa	HUMAN PRESCRIPTION DRUG LABEL	2	61958-2201	TABLET, FILM COATED	400 mg	ORAL	NDA	36 sections
Epclusa Access	HUMAN PRESCRIPTION DRUG LABEL	2	61958-2202	TABLET, FILM COATED	400 mg	ORAL	Export only	31 sections
Epclusa	HUMAN PRESCRIPTION DRUG LABEL	2	61958-2203	TABLET, FILM COATED	200 mg	ORAL	NDA	36 sections
Epclusa	HUMAN PRESCRIPTION DRUG LABEL	2	61958-2204	PELLET	200 mg	ORAL	NDA	36 sections
Epclusa	HUMAN PRESCRIPTION DRUG LABEL	2	61958-2205	PELLET	150 mg	ORAL	NDA	36 sections
Vosevi	HUMAN PRESCRIPTION DRUG LABEL	3	61958-2401	TABLET, FILM COATED	400 mg	ORAL	NDA	34 sections
Ledipasvir and Sofosbuvir	HUMAN PRESCRIPTION DRUG LABEL	2	72626-2601	TABLET, FILM COATED	400 mg	ORAL	NDA AUTHORIZED GENERIC	35 sections
Sofosbuvir and Velpatasvir	HUMAN PRESCRIPTION DRUG LABEL	2	72626-2701	TABLET, FILM COATED	400 mg	ORAL	NDA AUTHORIZED GENERIC	35 sections