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

Stem definitionDrug idCAS RN
antineoplastics, daunorubicin derivatives 786 20830-81-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • daunorubicin
  • acetyladriamycin
  • cerubidin
  • daunoblastina
  • daunomycine
  • daunorubicine
  • Leukaemomycin C
  • rubidomycin
  • daunorubicin hydrochloride
  • daunorubicin citrate
  • daunorubicin HCl
A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.
  • Molecular weight: 527.53
  • Formula: C27H29NO10
  • CLOGP: 0.84
  • LIPINSKI: 2
  • HAC: 11
  • HDO: 5
  • TPSA: 185.84
  • ALOGS: -2.93
  • ROTB: 4

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.04 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 2.05 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 32.05 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 47.57 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.06 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 14.24 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Dec. 19, 1979 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
Febrile neutropenia 995.19 61.09 232 1733 10650 2345470
Hypofibrinogenaemia 471.39 61.09 65 1900 85 2356035
Neutropenia 407.82 61.09 134 1831 21414 2334706
Posterior reversible encephalopathy syndrome 367.25 61.09 79 1886 2401 2353719
Sepsis 353.52 61.09 116 1849 18372 2337748
Haematotoxicity 307.27 61.09 60 1905 1107 2355013
Pyrexia 276.37 61.09 130 1835 53578 2302542
Thrombocytopenia 271.05 61.09 96 1869 19035 2337085
Hypotension 248.53 61.09 104 1861 32332 2323788
Colitis 231.75 61.09 63 1902 5163 2350957
Septic shock 199.98 61.09 60 1905 6994 2349126
Hyperbilirubinaemia 199.12 61.09 44 1921 1505 2354615
Acute myeloid leukaemia 194.72 61.09 48 1917 2662 2353458
Multiple organ dysfunction syndrome 178.37 61.09 56 1909 7585 2348535
Pancytopenia 175.25 61.09 61 1904 11391 2344729
Bone marrow failure 163.81 61.09 49 1916 5637 2350483
Pneumonia 160.82 61.09 88 1877 49208 2306912
Alanine aminotransferase increased 155.85 61.09 59 1906 13973 2342147
Blood culture positive 151.90 61.09 31 1934 716 2355404
Pleural effusion 143.92 61.09 53 1912 11615 2344505
Respiratory failure 136.28 61.09 53 1912 13475 2342645
Febrile bone marrow aplasia 136.19 61.09 29 1936 828 2355292
Hypoxia 134.30 61.09 43 1922 6184 2349936
Tachycardia 129.75 61.09 54 1911 16355 2339765
Mucosal inflammation 128.97 61.09 40 1925 5184 2350936
Clostridium difficile colitis 125.22 61.09 32 1933 2047 2354073
Leukopenia 124.52 61.09 46 1919 10150 2345970
Pulmonary oedema 123.29 61.09 42 1923 7321 2348799
Respiratory distress 121.27 61.09 38 1927 5091 2351029
Second primary malignancy 120.55 61.09 27 1938 979 2355141
Cardiotoxicity 120.05 61.09 28 1937 1219 2354901
Acute respiratory distress syndrome 115.12 61.09 33 1932 3259 2352861
Blood bilirubin increased 111.49 61.09 36 1929 5309 2350811
Abdominal pain 110.76 61.09 61 1904 34313 2321807
Tumour lysis syndrome 108.04 61.09 25 1940 1050 2355070
Acute kidney injury 104.82 61.09 55 1910 28067 2328053
Neuropathy peripheral 98.34 61.09 40 1925 11392 2344728
Hyperglycaemia 98.20 61.09 32 1933 4853 2351267
Cerebral venous sinus thrombosis 96.43 61.09 19 1946 364 2355756
Neutropenic sepsis 95.73 61.09 24 1941 1418 2354702
Secondary immunodeficiency 93.77 61.09 15 1950 78 2356042
Haemophagocytic lymphohistiocytosis 91.72 61.09 23 1942 1360 2354760
Bacteraemia 91.39 61.09 24 1941 1706 2354414
Human bocavirus infection 90.77 61.09 12 1953 8 2356112
Human herpesvirus 6 infection 90.52 61.09 18 1947 362 2355758
Bacterial infection 90.03 61.09 25 1940 2196 2353924
Hepatic failure 89.52 61.09 31 1934 5658 2350462
Left ventricular dysfunction 89.14 61.09 22 1943 1218 2354902
Hepatocellular injury 87.35 61.09 28 1937 4027 2352093
Platelet count decreased 85.86 61.09 40 1925 15773 2340347
Device related infection 84.79 61.09 26 1939 3233 2352887
Ejection fraction decreased 84.29 61.09 25 1940 2776 2353344
Pneumatosis intestinalis 82.70 61.09 17 1948 406 2355714
Neutropenic colitis 82.13 61.09 16 1949 288 2355832
Venous thrombosis 81.99 61.09 19 1946 802 2355318
Osteonecrosis 81.80 61.09 31 1934 7311 2348809
Diarrhoea 79.61 61.09 70 1895 83494 2272626
Coagulopathy 79.05 61.09 24 1941 2885 2353235
Unresponsive to stimuli 78.37 61.09 27 1938 4849 2351271
Hypertension 78.35 61.09 45 1920 27316 2328804
Hypokalaemia 77.19 61.09 33 1932 10621 2345499
Seizure 74.78 61.09 42 1923 24424 2331696
Venoocclusive disease 71.75 61.09 14 1951 254 2355866
Disseminated intravascular coagulation 71.59 61.09 23 1942 3327 2352793
Enterobacter infection 71.44 61.09 14 1951 260 2355860
Fluid overload 71.35 61.09 22 1943 2784 2353336
Aplasia 68.98 61.09 15 1950 472 2355648
Acute lymphocytic leukaemia recurrent 67.82 61.09 13 1952 214 2355906
Enterococcal infection 67.71 61.09 16 1949 735 2355385
Staphylococcal sepsis 67.07 61.09 17 1948 1048 2355072
Hyponatraemia 67.04 61.09 32 1933 13293 2342827
Herpes simplex 67.04 61.09 17 1948 1050 2355070
Hepatotoxicity 66.68 61.09 22 1943 3459 2352661
Differentiation syndrome 65.83 61.09 12 1953 148 2355972
Pancreatitis acute 64.49 61.09 22 1943 3831 2352289
Cerebral haemorrhage 64.04 61.09 24 1941 5480 2350640
Anaemia 63.54 61.09 43 1922 34749 2321371
Pulse waveform abnormal 62.04 61.09 8 1957 3 2356117
Ankle brachial index decreased 62.04 61.09 8 1957 3 2356117
Enteritis 61.85 61.09 16 1949 1070 2355050

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
Febrile neutropenia 1198.29 60.42 309 2055 10791 1733626
Neutropenia 539.38 60.42 188 2176 18072 1726345
Haematotoxicity 459.69 60.42 91 2273 867 1743550
Hypofibrinogenaemia 423.91 60.42 68 2296 150 1744267
Sepsis 415.83 60.42 158 2206 19280 1725137
Pyrexia 314.95 60.42 169 2195 46231 1698186
Aspergillus infection 251.00 60.42 59 2305 1314 1743103
Multiple organ dysfunction syndrome 243.90 60.42 88 2276 9154 1735263
Septic shock 239.66 60.42 84 2280 8025 1736392
Hypertriglyceridaemia 237.06 60.42 55 2309 1154 1743263
Posterior reversible encephalopathy syndrome 231.31 60.42 56 2308 1419 1742998
Acute myeloid leukaemia 227.00 60.42 64 2300 2977 1741440
Pancytopenia 219.13 60.42 86 2278 11271 1733146
Tumour lysis syndrome 216.81 60.42 55 2309 1696 1742721
Hyperbilirubinaemia 206.93 60.42 56 2308 2231 1742186
Colitis 198.47 60.42 62 2302 4118 1740299
Respiratory failure 188.97 60.42 83 2281 14422 1729995
Pneumonia 172.57 60.42 115 2249 46067 1698350
Hypotension 166.96 60.42 96 2268 29558 1714859
Hypoxia 154.08 60.42 56 2308 5907 1738510
Bone marrow failure 153.87 60.42 54 2310 5146 1739271
Osteonecrosis 151.98 60.42 50 2314 3912 1740505
Thrombocytopenia 150.20 60.42 80 2284 21169 1723248
Bacteraemia 142.11 60.42 40 2324 1840 1742577
Bronchopulmonary aspergillosis 139.93 60.42 38 2326 1528 1742889
Fungal infection 130.44 60.42 39 2325 2223 1742194
Multiple-drug resistance 121.85 60.42 25 2339 285 1744132
Acute kidney injury 118.14 60.42 82 2282 34862 1709555
Neutropenic colitis 118.09 60.42 24 2340 260 1744157
Stomatitis 111.26 60.42 43 2321 5361 1739056
Acute lymphocytic leukaemia recurrent 110.78 60.42 23 2341 279 1744138
Mucosal inflammation 110.77 60.42 40 2324 4129 1740288
Blood bilirubin increased 108.90 60.42 44 2320 6166 1738251
Abdominal pain 105.97 60.42 64 2300 21426 1722991
Alanine aminotransferase increased 100.20 60.42 51 2313 12227 1732190
Leukopenia 98.86 60.42 45 2319 8435 1735982
Seizure 98.49 60.42 60 2304 20381 1724036
Glioma 97.27 60.42 17 2347 73 1744344
Respiratory distress 95.45 60.42 38 2326 5119 1739298
Acute respiratory distress syndrome 94.04 60.42 34 2330 3517 1740900
Hypoalbuminaemia 92.11 60.42 27 2337 1433 1742984
Blood fibrinogen decreased 90.89 60.42 18 2346 169 1744248
Device related infection 88.17 60.42 29 2335 2257 1742160
Hepatotoxicity 87.20 60.42 31 2333 3053 1741364
Coagulopathy 86.45 60.42 30 2334 2751 1741666
Oesophageal stenosis 86.09 60.42 19 2345 313 1744104
Neutropenic sepsis 82.84 60.42 25 2339 1467 1742950
Product use in unapproved indication 82.28 60.42 41 2323 9381 1735036
Febrile bone marrow aplasia 76.96 60.42 21 2343 857 1743560
Leukaemia recurrent 76.91 60.42 17 2347 282 1744135
Pulmonary oedema 76.87 60.42 35 2329 6551 1737866
Mucormycosis 75.52 60.42 20 2344 727 1743690
Aplasia 74.75 60.42 18 2346 442 1743975
Venoocclusive disease 73.67 60.42 17 2347 345 1744072
Infection 71.81 60.42 41 2323 12319 1732098
Pleural effusion 70.36 60.42 39 2325 11071 1733346
Clostridium difficile colitis 68.55 60.42 22 2342 1582 1742835
Hyponatraemia 66.48 60.42 35 2329 8965 1735452
Sinus tachycardia 66.10 60.42 24 2340 2508 1741909
Gamma-glutamyltransferase increased 65.55 60.42 29 2335 5069 1739348
Neutrophil count decreased 63.72 60.42 30 2334 6051 1738366
Differentiation syndrome 62.64 60.42 13 2351 157 1744260
Cerebral venous thrombosis 61.97 60.42 13 2351 166 1744251
Ejection fraction decreased 61.29 60.42 22 2342 2223 1742194
Platelet count decreased 60.85 60.42 41 2323 16482 1727935

Pharmacologic Action:

SourceCodeDescription
ATC L01DB02 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
CYTOTOXIC ANTIBIOTICS AND RELATED SUBSTANCES
Anthracyclines and related substances
ATC L01XY01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Combinations of antineoplastic agents
FDA EPC N0000175414 Anthracycline Topoisomerase Inhibitor
FDA CS M0028312 Anthracyclines
FDA MoA N0000000176 Topoisomerase Inhibitors
MeSH PA D000903 Antibiotics, Antineoplastic
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
CHEBI has role CHEBI:35610 antineoplastic agent
MeSH PA D059005 Topoisomerase II Inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Acute lymphoid leukemia indication 91857003 DOID:9952
Acute myeloid leukemia, disease indication 91861009
Erythroleukemia, FAB M6 indication 93451002
Kaposi's sarcoma indication 109385007
Acute promyelocytic leukemia, FAB M3 indication 110004001
Acute monocytic/monoblastic leukemia indication 413442004
Nephroblastoma off-label use 302849000 DOID:2154
Neuroblastoma off-label use 432328008 DOID:769
Mycosis contraindication 3218000 DOID:1564
Pericarditis contraindication 3238004 DOID:1787
Ventricular tachycardia contraindication 25569003
Viral disease contraindication 34014006 DOID:934
Hyperuricemia contraindication 35885006 DOID:1920
Conduction disorder of the heart contraindication 44808001
Chronic heart failure contraindication 48447003
Myocarditis contraindication 50920009 DOID:820
Epilepsy contraindication 84757009 DOID:1826
Cardiomyopathy contraindication 85898001 DOID:0050700
Bacterial infectious disease contraindication 87628006
Kidney disease contraindication 90708001 DOID:557
Disease of liver contraindication 235856003 DOID:409
Pregnancy, function contraindication 289908002
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001
Granulocytopenic disorder contraindication 417672002
Protozoal Infection contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 7.85 acidic
pKa2 9.79 acidic
pKa3 11.6 acidic
pKa4 8.6 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS 8431806 April 22, 2025 FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS 7850990 Jan. 23, 2027 FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS 8022279 Sept. 14, 2027 FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS 8092828 April 1, 2029 FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS 10166184 Oct. 15, 2032 METHOD OF RECONSTITUTING A LYOPHILIZED LIPOSOMAL COMPOSITION FOR ADMINISTERING CYTARABINE AND DAUNORUBICIN TO TREAT ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS 10028912 Sept. 29, 2034 METHOD OF ADMINISTERING A RECONSTITUTED LIPOSOMAL COMPOSITION CONTAINING CYTARABINE AND DAUNORUBICIN TO TREAT ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS 10028912 Sept. 29, 2034 METHOD OF RECONSTITUTING A LYOPHILIZED LIPOSOMAL COMPOSITION FOR ADMINISTERING CYTARABINE AND DAUNORUBICIN TO TREAT ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
44MG VYXEOS CELATOR PHARMS N209401 Aug. 3, 2017 RX POWDER INTRAVENOUS Aug. 3, 2020 NEW PRODUCT

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
DNA topoisomerase 2-alpha Enzyme INHIBITOR WOMBAT-PK CHEMBL
Multidrug resistance-associated protein 6 Transporter WOMBAT-PK
ATP-binding cassette sub-family G member 2 Transporter WOMBAT-PK
Multidrug resistance-associated protein 1 Transporter WOMBAT-PK
Multidrug resistance protein 1 Transporter WOMBAT-PK
72 kDa type IV collagenase Enzyme IC50 5.72 CHEMBL
ORF 73 Unclassified AC50 5.63 CHEMBL

External reference:

IDSource
D003630 MESH_DESCRIPTOR_UI
4019704 VUID
N0000147796 NUI
C0011015 UMLSCUI
D01264 KEGG_DRUG
5L84T2Z6NP UNII
371770-68-2 SECONDARY_CAS_RN
35300007 SNOMEDCT_US
4019704 VANDF
3109 RXNORM
004821 NDDF
372715008 SNOMEDCT_US
d00205 MMSL
CHEMBL178 ChEMBL_ID
DB00694 DRUGBANK_ID
CHEMBL1563 ChEMBL_ID
CHEMBL1200475 ChEMBL_ID
DM1 PDB_CHEM_ID
CHEBI:41977 CHEBI
2257 INN_ID
7063 IUPHAR_LIGAND_ID
30323 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Daunorubicin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0143-9550 INJECTION 5 mg INTRAVENOUS NDA 12 sections
Daunorubicin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0143-9551 INJECTION 5 mg INTRAVENOUS NDA 12 sections
daunorubicin hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 0703-5233 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 14 sections
Daunorubicin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42658-019 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 11 sections
Daunorubicin Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 42658-021 INJECTION, SOLUTION 5 mg INTRAVENOUS ANDA 11 sections
VYXEOS HUMAN PRESCRIPTION DRUG LABEL 2 68727-745 INJECTION, POWDER, LYOPHILIZED, FOR SUSPENSION 44 mg INTRAVENOUS NDA 17 sections