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

Stem definitionDrug idCAS RN
HIV protease inhibitors 1601 192725-17-0

Description:

MoleculeDescription

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

Drug dosage:

DoseUnitRoute
0.80 g O

ADMET properties:

PropertyValueReference
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 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD

Approvals:

DateAgencyCompanyOrphan
Sept. 15, 2000 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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 termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients 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:

SourceCodeDescription
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)

DiseaseRelationSNOMED_IDDOID
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 levelDissociation constantType (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:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Multidrug resistance protein 1 Transporter IC50 4.99 CHEMBL
Potassium voltage-gated channel subfamily H member 2 Ion channel IC50 5.07 CHEMBL
Pol polyprotein Enzyme INHIBITOR Ki 10.40 CHEMBL CHEMBL
Gag-Pol polyprotein Polyprotein WOMBAT-PK
CAAX prenyl protease 1 homolog Enzyme IC50 4.74 CHEMBL
Protease Enzyme IC50 7.60 CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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