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

Stem definition	Drug id	CAS RN
HIV protease inhibitors	1601	192725-17-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: lopinavir aluviran koletra	An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A. Molecular weight: 628.81 Formula: C37H48N4O5 CLOGP: 6.09 LIPINSKI: 2 HAC: 9 HDO: 4 TPSA: 120 ALOGS: -5.51 ROTB: 15 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

lopinavir
aluviran
koletra

An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.

Molecular weight: 628.81
Formula: C37H48N4O5
CLOGP: 6.09
LIPINSKI: 2
HAC: 9
HDO: 4
TPSA: 120
ALOGS: -5.51
ROTB: 15

Status: OFP

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

Drug dosage:

Dose	Unit	Route
0.80	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)	2.20 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	24.22 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Approvals:

Date	Agency	Company	Orphan
Sept. 15, 2000	FDA

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
Exposure during pregnancy	1679.26	50.79	409	1490	24810	2331376
Abortion spontaneous	918.67	50.79	225	1674	13220	2342966
Foetal exposure during pregnancy	723.03	50.79	156	1743	5096	2351090
Stillbirth	540.12	50.79	99	1800	1342	2354844
Abortion induced	510.94	50.79	109	1790	3327	2352859
Maternal exposure during pregnancy	417.28	50.79	124	1775	14739	2341447
Premature baby	349.84	50.79	79	1820	3125	2353061
Foetal death	349.09	50.79	72	1827	1840	2354346
Premature labour	219.15	50.79	50	1849	2056	2354130
Live birth	208.63	50.79	44	1855	1247	2354939
Pregnancy	203.50	50.79	62	1837	7887	2348299
Viral mutation identified	193.26	50.79	32	1867	223	2355963
Anaemia	192.83	50.79	88	1811	34704	2321482
Premature rupture of membranes	187.98	50.79	38	1861	868	2355318
Caesarean section	172.19	50.79	47	1852	4034	2352152
Drug interaction	146.47	50.79	69	1830	29094	2327092
Drug resistance	142.88	50.79	37	1862	2587	2353599
Immune reconstitution inflammatory syndrome	131.80	50.79	30	1869	1214	2354972
Foetal growth restriction	123.51	50.79	28	1871	1112	2355074
Vomiting	116.40	50.79	81	1818	71521	2284665
Virologic failure	109.04	50.79	20	1879	266	2355920
Skull malformation	105.68	50.79	17	1882	96	2356090
Pre-eclampsia	100.55	50.79	25	1874	1479	2354707
Hepatitis	87.30	50.79	31	1868	6306	2349880
Premature delivery	86.14	50.79	26	1873	3174	2353012
Diarrhoea	83.78	50.79	71	1828	83493	2272693
Cushing's syndrome	83.39	50.79	19	1880	770	2355416
Spina bifida	81.41	50.79	14	1885	125	2356061
Patent ductus arteriosus	80.85	50.79	18	1881	656	2355530
Pyrexia	80.62	50.79	58	1841	53650	2302536
Viral load increased	78.49	50.79	15	1884	252	2355934
Cerebral ventricle dilatation	76.25	50.79	14	1885	187	2355999
HIV infection	74.54	50.79	13	1886	127	2356059
Normal newborn	73.96	50.79	19	1880	1281	2354905
Portal hypertension	73.19	50.79	16	1883	535	2355651
Lipodystrophy acquired	70.70	50.79	14	1885	285	2355901
Abdominal pain	70.29	50.79	45	1854	34329	2321857
Trisomy 21	67.93	50.79	12	1887	127	2356059
Nausea	67.72	50.79	72	1827	112117	2244069
Pulmonary tuberculosis	65.65	50.79	16	1883	869	2355317
Oligohydramnios	64.35	50.79	16	1883	944	2355242
Placental disorder	63.29	50.79	13	1886	320	2355866
Ventricular septal defect	61.86	50.79	15	1884	797	2355389
Placenta praevia	61.23	50.79	12	1887	231	2355955
Placental insufficiency	60.52	50.79	12	1887	246	2355940
Acute kidney injury	60.40	50.79	38	1861	28084	2328102
Coarctation of the aorta	59.90	50.79	11	1888	147	2356039
Gestational diabetes	58.51	50.79	16	1883	1371	2354815
Polydactyly	56.76	50.79	10	1889	104	2356082
Dysmorphism	55.01	50.79	12	1887	397	2355789
Mitochondrial cytopathy	54.02	50.79	9	1890	65	2356121
Treatment noncompliance	53.89	50.79	21	1878	5513	2350673
Congenital anomaly	52.97	50.79	12	1887	473	2355713
Genotype drug resistance test positive	52.36	50.79	9	1890	80	2356106

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
Foetal exposure during pregnancy	710.10	36.90	186	2373	6173	1738049
Lipodystrophy acquired	614.95	36.90	102	2457	271	1743951
Mitochondrial toxicity	452.72	36.90	72	2487	130	1744092
Exposure during pregnancy	389.28	36.90	98	2461	2719	1741503
Eyelid ptosis	353.66	36.90	71	2488	666	1743556
Diarrhoea	345.50	36.90	194	2365	53658	1690564
Premature baby	341.03	36.90	89	2470	2853	1741369
Immune reconstitution inflammatory syndrome	338.21	36.90	78	2481	1471	1742751
Progressive external ophthalmoplegia	284.22	36.90	41	2518	19	1744203
Drug interaction	282.38	36.90	137	2422	27821	1716401
Diplopia	246.56	36.90	67	2492	2503	1741719
Hyperlipidaemia	190.06	36.90	53	2506	2176	1742046
Pyrexia	180.26	36.90	122	2437	46278	1697944
Vomiting	176.14	36.90	112	2447	38203	1706019
Nausea	171.70	36.90	123	2436	51073	1693149
Weight decreased	152.63	36.90	85	2474	22668	1721554
Anaemia	152.56	36.90	93	2466	29364	1714858
Kaposi's sarcoma	148.89	36.90	36	2523	831	1743391
Hyperlactacidaemia	142.00	36.90	30	2529	366	1743856
Depression	138.94	36.90	72	2487	16597	1727625
Hypertriglyceridaemia	137.01	36.90	36	2523	1173	1743049
Trisomy 21	136.63	36.90	24	2535	97	1744125
Acute kidney injury	133.19	36.90	91	2468	34853	1709369
Abdominal pain	129.77	36.90	75	2484	21415	1722807
Pancytopenia	124.05	36.90	59	2500	11298	1732924
Fanconi syndrome	123.21	36.90	26	2533	315	1743907
Blood triglycerides increased	122.02	36.90	39	2520	2561	1741661
Osteonecrosis	117.13	36.90	42	2517	3920	1740302
Liver disorder	113.11	36.90	45	2514	5591	1738631
Congenital anomaly	111.83	36.90	25	2534	403	1743819
Drug resistance	109.82	36.90	38	2521	3192	1741030
Cryptorchism	104.74	36.90	23	2536	340	1743882
Cerebral toxoplasmosis	102.72	36.90	20	2539	156	1744066
Renal failure	100.29	36.90	62	2497	19955	1724267
Renal impairment	99.06	36.90	52	2507	12262	1731960
Renal tubular disorder	98.84	36.90	26	2533	849	1743373
General physical health deterioration	98.76	36.90	53	2506	13065	1731157
Cushing's syndrome	98.16	36.90	24	2535	580	1743642
Polydactyly	97.64	36.90	20	2539	207	1744015
Hepatic cirrhosis	97.14	36.90	33	2526	2620	1741602
Asthenia	94.89	36.90	74	2485	34596	1709626
Abdominal distension	94.03	36.90	41	2518	6403	1737819
Lactic acidosis	92.71	36.90	38	2521	5091	1739131
Pneumocystis jirovecii pneumonia	91.69	36.90	31	2528	2425	1741797
Hypokalaemia	91.20	36.90	40	2519	6334	1737888
Dysphagia	90.57	36.90	46	2513	10122	1734100
Cardiac murmur	90.25	36.90	26	2533	1196	1743026
Viral load increased	88.80	36.90	22	2537	562	1743660
Portal hypertension	85.29	36.90	22	2537	664	1743558
Osteoporosis	84.06	36.90	26	2533	1529	1742693
Progressive multifocal leukoencephalopathy	82.71	36.90	26	2533	1613	1742609
Ventricular septal defect	82.54	36.90	22	2537	756	1743466
Abdominal hernia	81.98	36.90	19	2540	362	1743860
Headache	78.39	36.90	66	2493	34310	1709912
Hepatitis	77.09	36.90	33	2526	4922	1739300
Maternal drugs affecting foetus	73.64	36.90	22	2537	1149	1743073
HIV-associated neurocognitive disorder	72.40	36.90	13	2546	61	1744161
Virologic failure	70.39	36.90	17	2542	389	1743833
Atypical mycobacterial infection	66.98	36.90	14	2545	161	1744061
Gamma-glutamyltransferase increased	66.50	36.90	30	2529	5068	1739154
Blood alkaline phosphatase increased	65.95	36.90	30	2529	5165	1739057
Cytomegalovirus chorioretinitis	65.80	36.90	16	2543	377	1743845
Blood lactic acid increased	65.80	36.90	19	2540	880	1743342
Aspartate aminotransferase increased	63.28	36.90	37	2522	10719	1733503
Oral candidiasis	62.86	36.90	20	2539	1289	1742933
Gastritis	62.86	36.90	25	2534	3092	1741130
Lymphadenopathy	62.66	36.90	27	2532	4087	1740135
Pneumonia	61.77	36.90	66	2493	46116	1698106
Thrombocytopenia	61.56	36.90	47	2512	21202	1723020
Jaundice	61.54	36.90	30	2529	6032	1738190
Lipoatrophy	60.69	36.90	12	2547	102	1744120
Dehydration	59.99	36.90	43	2516	17615	1726607
Oesophageal candidiasis	59.95	36.90	16	2543	552	1743670
Decreased appetite	58.83	36.90	48	2511	23823	1720399
Alanine aminotransferase increased	58.76	36.90	37	2522	12241	1731981
Diabetes mellitus	57.82	36.90	30	2529	6878	1737344
Mycobacterium avium complex infection	57.81	36.90	14	2545	324	1743898
Ascites	57.76	36.90	28	2531	5558	1738664
Ophthalmoplegia	57.26	36.90	13	2546	225	1743997
Hepatic function abnormal	57.15	36.90	30	2529	7044	1737178
Viral mutation identified	56.25	36.90	14	2545	364	1743858
HIV infection	55.91	36.90	13	2546	251	1743971
Gastrointestinal disorder	55.82	36.90	26	2533	4722	1739500
Acquired immunodeficiency syndrome	55.38	36.90	11	2548	96	1744126
Blood bilirubin increased	54.95	36.90	28	2531	6182	1738040
Hypophosphataemia	54.72	36.90	18	2541	1290	1742932
Nephropathy toxic	53.54	36.90	19	2540	1713	1742509
Blood cholesterol increased	53.21	36.90	22	2537	3004	1741218
Hyponatraemia	53.03	36.90	31	2528	8969	1735253
Foetal growth restriction	52.48	36.90	15	2544	669	1743553
Malaise	51.85	36.90	49	2510	29516	1714706
Oesophageal atresia	51.80	36.90	10	2549	74	1744148
Myocardial infarction	51.44	36.90	47	2512	27127	1717095
Dysmorphism	50.64	36.90	13	2546	384	1743838
Nervous system disorder	50.58	36.90	20	2539	2434	1741788
C-reactive protein increased	50.52	36.90	26	2533	5859	1738363
Low set ears	50.47	36.90	10	2549	86	1744136
Small for dates baby	49.82	36.90	14	2545	587	1743635
Neuropathy peripheral	49.63	36.90	30	2529	9223	1734999
Kidney malformation	49.00	36.90	9	2550	49	1744173
Fanconi syndrome acquired	48.47	36.90	13	2546	457	1743765
Mitochondrial cytopathy	48.40	36.90	9	2550	53	1744169
Hypercholesterolaemia	47.98	36.90	16	2543	1196	1743026
Coronary artery disease	47.91	36.90	30	2529	9816	1734406
Gastroschisis	46.88	36.90	8	2551	26	1744196
Leukopenia	46.78	36.90	28	2531	8452	1735770
Cachexia	46.63	36.90	15	2544	1001	1743221
Atrial septal defect	46.20	36.90	16	2543	1342	1742880
Volvulus	45.48	36.90	11	2548	253	1743969
Dyslipidaemia	45.44	36.90	14	2545	811	1743411
Encephalitis	44.96	36.90	15	2544	1123	1743099
Hepatitis C	44.70	36.90	19	2540	2777	1741445
Proteinuria	44.39	36.90	19	2540	2825	1741397
Tachypnoea	44.37	36.90	18	2541	2340	1741882
Rash	44.23	36.90	51	2508	38642	1705580
Sepsis	43.51	36.90	37	2522	19401	1724821
Syphilis	43.25	36.90	9	2550	101	1744121
HIV associated nephropathy	43.13	36.90	7	2552	15	1744207
Hepatic steatosis	42.78	36.90	18	2541	2566	1741656
Femoral neck fracture	42.77	36.90	12	2547	500	1743722
Exomphalos	42.75	36.90	8	2551	49	1744173
Hepatic failure	41.96	36.90	23	2536	5880	1738342
Bone marrow failure	41.83	36.90	22	2537	5178	1739044
Herpes zoster	41.55	36.90	21	2538	4552	1739670
Hyperbilirubinaemia	41.46	36.90	17	2542	2270	1741952
Anogenital warts	41.03	36.90	9	2550	132	1744090
Congenital hearing disorder	40.96	36.90	7	2552	23	1744199
Stillbirth	40.78	36.90	8	2551	65	1744157
Caesarean section	40.59	36.90	12	2547	603	1743619
Varices oesophageal	40.31	36.90	12	2547	618	1743604
Hepatosplenomegaly	40.18	36.90	12	2547	625	1743597
Liver function test abnormal	39.84	36.90	22	2537	5704	1738518
Dyspnoea	39.55	36.90	56	2503	52003	1692219
Neutropenia	39.31	36.90	34	2525	18226	1725996
Adrenal insufficiency	38.52	36.90	14	2545	1351	1742871
Opportunistic infection	38.00	36.90	10	2549	326	1743896
Seizure	37.94	36.90	35	2524	20406	1723816
Cough	37.84	36.90	34	2525	19163	1725059

Pharmacologic Action:

Source	Code	Description
ATC	J05AR10	ANTIINFECTIVES FOR SYSTEMIC USE ANTIVIRALS FOR SYSTEMIC USE DIRECT ACTING ANTIVIRALS Antivirals for treatment of HIV infections, combinations
FDA EPC	N0000175889	Protease Inhibitor
FDA MoA	N0000185503	P-Glycoprotein Inhibitors
FDA MoA	N0000190114	Cytochrome P450 3A Inhibitors
FDA MoA	N0000190107	Organic Anion Transporting Polypeptide 1B1 Inhibitors
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	D065692	Cytochrome P-450 CYP3A Inhibitors
MeSH PA	D065607	Cytochrome P-450 Enzyme Inhibitors
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D017320	HIV Protease Inhibitors
MeSH PA	D065606	Metabolic Side Effects of Drugs and Substances
MeSH PA	D011480	Protease Inhibitors
CHEBI has role	CHEBI:36044	antiviral drug

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Human immunodeficiency virus infection	indication	86406008	DOID:526
Coronavirus infection	off-label use	186747009
Prevention of HIV Infection after Exposure	off-label use
Hyperbilirubinemia	contraindication	14783006	DOID:2741
Cirrhosis of liver	contraindication	19943007	DOID:5082
Complete atrioventricular block	contraindication	27885002
Hereditary factor VIII deficiency disease	contraindication	28293008	DOID:12134
Torsades de pointes	contraindication	31722008
Hereditary factor IX deficiency disease	contraindication	41788008	DOID:12259
Hypokalemia	contraindication	43339004
Conduction disorder of the heart	contraindication	44808001
Chronic type B viral hepatitis	contraindication	61977001
Diabetes mellitus	contraindication	73211009	DOID:9351
Hyperglycemia	contraindication	80394007	DOID:4195
Cardiomyopathy	contraindication	85898001	DOID:0050700
Prolonged QT interval	contraindication	111975006
Chronic hepatitis C	contraindication	128302006
Structural disorder of heart	contraindication	128599005
Liver function tests abnormal	contraindication	166603001
Hypomagnesemia	contraindication	190855004
Second degree atrioventricular block	contraindication	195042002
Acute pancreatitis	contraindication	197456007	DOID:2913
Disease of liver	contraindication	235856003	DOID:409
Mixed hyperlipidemia	contraindication	267434003
Hypertriglyceridemia	contraindication	302870006
Breastfeeding (mother)	contraindication	413712001
Myocardial ischemia	contraindication	414795007	DOID:3393
Congenital long QT syndrome	contraindication	442917000
First Degree Atrioventricular Heart Block	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	12.03	acidic
pKa2	12.72	acidic

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])	Bioact source	MoA source
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		IC50	4.99	CHEMBL
Potassium voltage-gated channel subfamily H member 2	Ion channel	Q12809	KCNH2_HUMAN		IC50	5.07	CHEMBL
Pol polyprotein	Enzyme		Q72874_9HIV1	INHIBITOR	Ki	10.40	CHEMBL	CHEMBL
Gag-Pol polyprotein	Polyprotein		POL_HV1BR				WOMBAT-PK
CAAX prenyl protease 1 homolog	Enzyme		FACE1_MOUSE		IC50	4.74	CHEMBL
Protease	Enzyme		Q9YQ12_9HIV1		IC50	7.60	CHEMBL

External reference:

ID	Source
4021228	VUID
N0000179581	NUI
C0674432	UMLSCUI
D01425	KEGG_DRUG
2494G1JF75	UNII
7798	INN_ID
129475001	SNOMEDCT_US
d04716	MMSL
15774	MMSL
195088	RXNORM
4021228	VANDF
387067003	SNOMEDCT_US
008874	NDDF
CHEMBL729	ChEMBL_ID
AB1	PDB_CHEM_ID
DB01601	DRUGBANK_ID
CHEBI:31781	CHEBI
D061466	MESH_DESCRIPTOR_UI
92727	PUBCHEM_CID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	0074-0522	TABLET, FILM COATED	100 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	0074-1575	TABLET, FILM COATED	100 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	0074-2605	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	0074-3956	SOLUTION	80 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	0074-6799	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Lopinavir-Ritonavir	HUMAN PRESCRIPTION DRUG LABEL	2	0527-1947	SOLUTION	80 mg	ORAL	ANDA	19 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	11819-342	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	21695-362	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	53808-0276	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	54868-5566	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	55289-947	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Lopinavir and Ritonavir	HUMAN PRESCRIPTION DRUG LABEL	2	65015-299	GRANULE	40 mg	ORAL	Export only	1 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	66336-624	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	68258-1972	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections
Kaletra	HUMAN PRESCRIPTION DRUG LABEL	2	70518-0091	TABLET, FILM COATED	200 mg	ORAL	NDA	18 sections