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

Stem definition	Drug id	CAS RN
HIV protease inhibitors	254	198904-31-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: BMS-232632 atazanavir reyataz atazanavir sulphate atazanavir sulfate	An azapeptide and HIV-PROTEASE INHIBITOR that is used in the treatment of HIV INFECTIONS and AIDS in combination with other ANTI-HIV AGENTS. Molecular weight: 704.87 Formula: C38H52N6O7 CLOGP: 5.92 LIPINSKI: 3 HAC: 13 HDO: 5 TPSA: 171.22 ALOGS: -5.33 ROTB: 18 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

BMS-232632
atazanavir
reyataz
atazanavir sulphate
atazanavir sulfate

An azapeptide and HIV-PROTEASE INHIBITOR that is used in the treatment of HIV INFECTIONS and AIDS in combination with other ANTI-HIV AGENTS.

Molecular weight: 704.87
Formula: C38H52N6O7
CLOGP: 5.92
LIPINSKI: 3
HAC: 13
HDO: 5
TPSA: 171.22
ALOGS: -5.33
ROTB: 18

Status: OFP

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

Drug dosage:

Dose	Unit	Route
0.30	g	O
0.30	g	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	7 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	8.11 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	64 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Approvals:

Date	Agency	Company	Orphan
March 2, 2004	EMA
June 20, 2003	FDA	BRISTOL MYERS SQUIBB

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
Maternal exposure during pregnancy	1382.73	72.45	321	1680	14542	2341542
Abortion spontaneous	1081.79	72.45	259	1742	13186	2342898
Foetal exposure during pregnancy	1009.32	72.45	207	1794	5045	2351039
Exposure during pregnancy	743.74	72.45	220	1781	24999	2331085
Live birth	598.29	72.45	107	1894	1184	2354900
Premature baby	383.69	72.45	86	1915	3118	2352966
Pregnancy	375.93	72.45	101	1900	7848	2348236
Abortion induced	361.53	72.45	83	1918	3353	2352731
Stillbirth	335.29	72.45	67	1934	1374	2354710
Caesarean section	331.78	72.45	80	1921	4001	2352083
Hyperbilirubinaemia	330.46	72.45	67	1934	1482	2354602
Premature delivery	297.76	72.45	70	1931	3130	2352954
Normal newborn	194.67	72.45	42	1959	1258	2354826
Foetal growth restriction	188.67	72.45	40	1961	1100	2354984
Nephrolithiasis	182.93	72.45	51	1950	4492	2351592
Jaundice	182.05	72.45	53	1948	5455	2350629
Pregnancy on contraceptive	151.07	72.45	27	1974	291	2355793
Congenital naevus	147.31	72.45	20	1981	20	2356064
Hepatitis	141.00	72.45	45	1956	6292	2349792
Blood bilirubin increased	139.99	72.45	43	1958	5302	2350782
Foetal death	137.32	72.45	34	1967	1878	2354206
Renal colic	133.00	72.45	24	1977	274	2355810
Ventricular septal defect	120.17	72.45	26	1975	786	2355298
Low set ears	119.60	72.45	18	1983	56	2356028
Acoustic stimulation tests abnormal	105.78	72.45	15	1986	26	2356058
Pre-eclampsia	104.23	72.45	26	1975	1478	2354606
Supernumerary nipple	100.51	72.45	13	1988	5	2356079
Viral mutation identified	97.35	72.45	18	1983	237	2355847
Patent ductus arteriosus	96.47	72.45	21	1980	653	2355431
Virologic failure	95.29	72.45	18	1983	268	2355816
Lipodystrophy acquired	94.49	72.45	18	1983	281	2355803
Drug resistance	94.36	72.45	27	1974	2597	2353487
Immune reconstitution inflammatory syndrome	93.72	72.45	23	1978	1221	2354863
Eosinophilia	91.05	72.45	27	1974	2943	2353141
Premature rupture of membranes	90.28	72.45	21	1980	885	2355199
Twin pregnancy	89.26	72.45	17	1984	265	2355819
Drug interaction	88.19	72.45	50	1951	29113	2326971
Low birth weight baby	86.77	72.45	20	1981	809	2355275
Premature labour	86.28	72.45	24	1977	2082	2354002
Placental insufficiency	84.46	72.45	16	1985	242	2355842
Oligohydramnios	83.85	72.45	20	1981	940	2355144
Gestational diabetes	81.39	72.45	21	1980	1366	2354718
Placenta praevia	79.11	72.45	15	1986	228	2355856
Polydactyly	76.52	72.45	13	1988	101	2355983
Renal failure	75.68	72.45	38	1963	17311	2338773

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
Nephrolithiasis	772.93	43.08	183	2477	3809	1740312
Hyperbilirubinaemia	630.45	43.08	140	2520	2147	1741974
Foetal exposure during pregnancy	603.09	43.08	165	2495	6194	1737927
Jaundice	490.35	43.08	139	2521	5923	1738198
Renal colic	475.18	43.08	85	2575	377	1743744
Lipodystrophy acquired	425.79	43.08	75	2585	298	1743823
Blood bilirubin increased	372.26	43.08	113	2547	6097	1738024
Drug interaction	253.47	43.08	129	2531	27829	1716292
Immune reconstitution inflammatory syndrome	216.99	43.08	55	2605	1494	1742627
Acute kidney injury	186.71	43.08	114	2546	34830	1709291
Ocular icterus	181.85	43.08	40	2620	574	1743547
Cholelithiasis	169.67	43.08	53	2607	3112	1741009
Renal tubular disorder	162.56	43.08	39	2621	836	1743285
Premature baby	160.76	43.08	50	2610	2892	1741229
Renal failure	154.07	43.08	83	2577	19934	1724187
Hepatitis	146.36	43.08	53	2607	4902	1739219
Osteonecrosis	146.14	43.08	50	2610	3912	1740209
Calculus urinary	144.07	43.08	29	2631	262	1743859
Mitochondrial toxicity	142.03	43.08	27	2633	175	1743946
Nausea	136.32	43.08	109	2551	51087	1693034
Alanine aminotransferase increased	132.44	43.08	64	2596	12214	1731907
Eyelid ptosis	117.23	43.08	29	2631	708	1743413
Lipoatrophy	117.17	43.08	21	2639	93	1744028
Depression	95.30	43.08	57	2603	16612	1727509
Aspartate aminotransferase increased	95.02	43.08	49	2611	10707	1733414
Viral load increased	92.97	43.08	23	2637	561	1743560
Renal impairment	91.55	43.08	50	2610	12264	1731857
Drug resistance	89.53	43.08	33	2627	3197	1740924
Hepatic cirrhosis	84.35	43.08	30	2630	2623	1741498
Hydronephrosis	82.47	43.08	25	2635	1320	1742801
Dysphagia	80.32	43.08	43	2617	10125	1733996
Kaposi's sarcoma	79.33	43.08	22	2638	845	1743276
Pancreatitis	78.98	43.08	38	2622	7149	1736972
Diarrhoea	76.77	43.08	81	2579	53771	1690350
Pyrexia	75.56	43.08	75	2585	46325	1697796
Proteinuria	74.93	43.08	28	2632	2816	1741305
Osteoporosis	74.78	43.08	24	2636	1531	1742590
Myocardial infarction	74.37	43.08	59	2601	27115	1717006
Diplopia	73.96	43.08	27	2633	2543	1741578
Ureterolithiasis	70.99	43.08	17	2643	360	1743761
Blood bilirubin unconjugated increased	70.68	43.08	15	2645	179	1743942
Tubulointerstitial nephritis	70.26	43.08	27	2633	2931	1741190
Fatigue	68.13	43.08	74	2586	50707	1693414
Weight decreased	67.85	43.08	52	2608	22701	1721420
Hepatic steatosis	62.85	43.08	24	2636	2560	1741561
Depressed mood	62.71	43.08	25	2635	2991	1741130
Haematuria	62.57	43.08	33	2627	7527	1736594
Diabetes mellitus	62.46	43.08	32	2628	6876	1737245
Vomiting	62.41	43.08	62	2598	38253	1705868
Fanconi syndrome	62.26	43.08	15	2645	326	1743795
Anaemia	62.04	43.08	55	2605	29402	1714719
Hepatomegaly	61.01	43.08	21	2639	1664	1742457
Exposure during pregnancy	60.84	43.08	24	2636	2793	1741328
Nephropathy toxic	60.44	43.08	21	2639	1711	1742410
Hyperlipidaemia	58.91	43.08	22	2638	2207	1741914
Blood creatinine increased	57.89	43.08	39	2621	13907	1730214
Rash	56.42	43.08	59	2601	38634	1705487
Vanishing bile duct syndrome	56.25	43.08	12	2648	147	1743974
Thrombocytopenia	55.64	43.08	45	2615	21204	1722917
Lymphadenopathy	55.23	43.08	25	2635	4089	1740032
Virologic failure	54.72	43.08	14	2646	392	1743729
Cushing's syndrome	53.75	43.08	15	2645	589	1743532
Blood antidiuretic hormone increased	53.19	43.08	9	2651	26	1744095
Fanconi syndrome acquired	52.69	43.08	14	2646	456	1743665
Pruritus	52.14	43.08	45	2615	23177	1720944
Hypertension	50.51	43.08	41	2619	19407	1724714
Myositis	50.45	43.08	18	2642	1585	1742536
Abdominal pain	48.96	43.08	42	2618	21448	1722673
Enanthema	48.82	43.08	10	2650	99	1744022
Heterotaxia	47.84	43.08	8	2652	21	1744100
Neonatal hyponatraemia	47.84	43.08	8	2652	21	1744100
Liver disorder	47.75	43.08	25	2635	5611	1738510
Hepatitis C	47.30	43.08	20	2640	2776	1741345
Blood creatine phosphokinase increased	47.20	43.08	29	2631	8827	1735294
Wrong dose	45.76	43.08	9	2651	71	1744050
Ventricular septal defect	45.71	43.08	14	2646	764	1743357
Cholestasis	45.20	43.08	21	2639	3644	1740477
Hypertriglyceridaemia	43.50	43.08	15	2645	1194	1742927

Pharmacologic Action:

Source	Code	Description
ATC	J05AE08	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Protease inhibitors
ATC	J05AR15	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HIV infections, combinations
ATC	J05AR23	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HIV infections, combinations
MeSH PA	D019380	Anti-HIV Agents
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D044966	Anti-Retroviral Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D017320	HIV Protease Inhibitors
MeSH PA	D011480	Protease Inhibitors
CHEBI has role	CHEBI:36044	antiviral drug
FDA EPC	N0000175889	Protease Inhibitor
FDA MoA	N0000191272	UGT1A1 Inhibitors
FDA MoA	N0000191269	UDP Glucuronosyltransferases Inhibitors
FDA MoA	N0000182141	Cytochrome P450 3A4 Inhibitors
FDA MoA	N0000190114	Cytochrome P450 3A Inhibitors
FDA MoA	N0000187062	Cytochrome P450 2C8 Inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Human immunodeficiency virus infection	indication	86406008	DOID:526
Prevention of HIV Infection after Exposure	off-label use
Hyperbilirubinemia	contraindication	14783006	DOID:2741
Hepatic failure	contraindication	59927004
Chronic type B viral hepatitis	contraindication	61977001
Diabetes mellitus	contraindication	73211009	DOID:9351
Hyperglycemia	contraindication	80394007	DOID:4195
Hemophilia	contraindication	90935002
Lactic acidosis	contraindication	91273001	DOID:3650
Kidney stone	contraindication	95570007
Chronic hepatitis C	contraindication	128302006
Liver function tests abnormal	contraindication	166603001
Atrioventricular block	contraindication	233917008	DOID:0050820
Disease of liver	contraindication	235856003	DOID:409
Breastfeeding (mother)	contraindication	413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.91	acidic
pKa2	11.57	acidic
pKa3	4.94	Basic
pKa4	1.0	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
EQ 300MG BASE	EVOTAZ	BRISTOL-MYERS SQUIBB	N206353	Jan. 29, 2015	RX	TABLET	ORAL	8148374	Sept. 3, 2029	TREATMENT OF HIV INFECTION USING A COMPOSITION CONTAINING A PHARMACOKINETIC ENHANCER THAT INHIBITS CYTOCHROME P450 MONOOXYGENASE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Cytochrome P450 1A2	Enzyme	P05177	CP1A2_HUMAN		Ki	4.92	WOMBAT-PK
Cytochrome P450 2C9	Enzyme	P11712	CP2C9_HUMAN		Ki	4.92	WOMBAT-PK
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		Ki	5.63	WOMBAT-PK
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		IC50	4.17	CHEMBL
UDP-glucuronosyltransferase 1-1	Enzyme	P22309	UD11_HUMAN		Ki	5.72	WOMBAT-PK
Pol polyprotein	Enzyme		Q72874_9HIV1	INHIBITOR	Ki	9.62	CHEMBL	CHEMBL
Gag-Pol polyprotein	Polyprotein		POL_HV1BR		Ki	8.58	WOMBAT-PK
Reverse transcriptase/RNaseH	Enzyme		Q72547_9HIV1		IC50	7.59	CHEMBL
Protease	Enzyme		Q9YQ12_9HIV1		IC50	8.40	CHEMBL

External reference:

ID	Source
D000069446	MESH_DESCRIPTOR_UI
4024316	VUID
N0000022320	NUI
C1145759	UMLSCUI
D01276	KEGG_DRUG
4MT4VIE29P	UNII
229975-97-7	SECONDARY_CAS_RN
413591007	SNOMEDCT_US
343047	RXNORM
d04882	MMSL
413592000	SNOMEDCT_US
4024316	VANDF
000306	NDDF
CHEMBL1163	ChEMBL_ID
DB01072	DRUGBANK_ID
CHEMBL1200678	ChEMBL_ID
8181	INN_ID
DR7	PDB_CHEM_ID
CHEBI:37924	CHEBI
148192	PUBCHEM_CID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	0003-3622	CAPSULE, GELATIN COATED	300 mg	ORAL	NDA	19 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	0003-3624	CAPSULE, GELATIN COATED	150 mg	ORAL	NDA	19 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	0003-3631	CAPSULE, GELATIN COATED	200 mg	ORAL	NDA	19 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	0003-3638	POWDER	50 mg	ORAL	NDA	19 sections
EVOTAZ	HUMAN PRESCRIPTION DRUG LABEL	2	0003-3641	TABLET	300 mg	ORAL	NDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-5526	CAPSULE	150 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-5527	CAPSULE	200 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	0093-5528	CAPSULE	300 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6875	CAPSULE	300 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	16714-860	CAPSULE	150 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	16714-861	CAPSULE	200 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	16714-862	CAPSULE	300 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	51407-171	CAPSULE	150 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	51407-172	CAPSULE	200 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	51407-173	CAPSULE	300 mg	ORAL	ANDA	18 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	54868-4854	CAPSULE, GELATIN COATED	200 mg	ORAL	NDA	18 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	54868-4857	CAPSULE, GELATIN COATED	150 mg	ORAL	NDA	18 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5838	CAPSULE, GELATIN COATED	300 mg	ORAL	NDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	60687-399	CAPSULE	300 mg	ORAL	ANDA	19 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	65862-710	CAPSULE	100 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	65862-711	CAPSULE	150 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	65862-712	CAPSULE	200 mg	ORAL	ANDA	18 sections
Atazanavir Sulfate	HUMAN PRESCRIPTION DRUG LABEL	1	65862-713	CAPSULE	300 mg	ORAL	ANDA	18 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	67296-1236	CAPSULE, GELATIN COATED	300 mg	ORAL	NDA	18 sections
ATAZANAVIR	HUMAN PRESCRIPTION DRUG LABEL	1	69097-443	CAPSULE, GELATIN COATED	100 mg	ORAL	ANDA	18 sections
ATAZANAVIR	HUMAN PRESCRIPTION DRUG LABEL	1	69097-444	CAPSULE, GELATIN COATED	150 mg	ORAL	ANDA	18 sections
ATAZANAVIR	HUMAN PRESCRIPTION DRUG LABEL	1	69097-445	CAPSULE, GELATIN COATED	200 mg	ORAL	ANDA	18 sections
ATAZANAVIR	HUMAN PRESCRIPTION DRUG LABEL	1	69097-446	CAPSULE, GELATIN COATED	300 mg	ORAL	ANDA	18 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	69189-3624	CAPSULE, GELATIN COATED	150 mg	ORAL	NDA	18 sections
REYATAZ	HUMAN PRESCRIPTION DRUG LABEL	1	69189-3631	CAPSULE, GELATIN COATED	200 mg	ORAL	NDA	18 sections