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

Stem definitionDrug idCAS RN
MEK (MAPK kinase) tyrosine kinase inhibitors 4802 871700-17-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • GSK1120212B
  • trametinib dimethyl sulfoxide
  • trametinib
  • GSK1120212
  • mekinist
a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation
  • Molecular weight: 615.40
  • Formula: C26H23FIN5O4
  • CLOGP: 4.84
  • LIPINSKI: 1
  • HAC: 9
  • HDO: 2
  • TPSA: 102.06
  • ALOGS: -4.30
  • ROTB: 5

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 13.94 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.80 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.03 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 229 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
May 29, 2013 FDA NOVARTIS PHARMS CORP

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
Pyrexia 1106.00 21.11 810 10855 347992 46326405
Malignant neoplasm progression 642.43 21.11 316 11349 64610 46609787
Chills 277.62 21.11 213 11452 95819 46578578
Metastatic malignant melanoma 231.00 21.11 56 11609 1288 46673109
Uveitis 151.85 21.11 63 11602 8578 46665819
Death 144.38 21.11 281 11384 335267 46339130
Rash 138.38 21.11 286 11379 356226 46318171
Malignant melanoma 125.74 21.11 58 11607 10176 46664221
Product use in unapproved indication 124.29 21.11 132 11533 90141 46584256
Panniculitis 118.82 21.11 47 11618 5657 46668740
Metastases to central nervous system 117.62 21.11 57 11608 11164 46663233
Ejection fraction decreased 110.80 21.11 64 11601 17873 46656524
Malignant melanoma stage IV 102.60 21.11 17 11648 43 46674354
Dermatitis acneiform 97.06 21.11 37 11628 4033 46670364
Visual impairment 73.66 21.11 87 11578 66602 46607795
Blood creatine phosphokinase increased 70.17 21.11 57 11608 27667 46646730
Drug ineffective 65.39 21.11 45 11620 677793 45996604
Chorioretinopathy 60.03 21.11 17 11648 724 46673673
Paronychia 53.34 21.11 25 11640 4541 46669856
Erythema nodosum 48.19 21.11 22 11643 3764 46670633
Skin toxicity 45.78 21.11 21 11644 3633 46670764
Anaplastic thyroid cancer 45.30 21.11 8 11657 33 46674364
Metastases to meninges 37.08 21.11 15 11650 1912 46672485
Vogt-Koyanagi-Harada disease 35.85 21.11 8 11657 126 46674271
Hyperpyrexia 34.97 21.11 16 11649 2750 46671647
Drug hypersensitivity 34.83 21.11 9 11656 243816 46430581
Detachment of retinal pigment epithelium 32.67 21.11 9 11656 346 46674051
Metastasis 30.99 21.11 17 11648 4295 46670102
Serous retinal detachment 30.43 21.11 7 11658 127 46674270
Aspartate aminotransferase increased 30.10 21.11 63 11602 78637 46595760
Systemic inflammatory response syndrome 30.09 21.11 18 11647 5353 46669044
Fall 30.08 21.11 23 11642 329074 46345323
Pneumonitis 29.58 21.11 36 11629 28384 46646013
Blood lactate dehydrogenase increased 28.18 21.11 30 11635 20470 46653927
Vision blurred 27.27 21.11 61 11604 79647 46594750
Metastases to lung 27.07 21.11 22 11643 10674 46663723
Erythema multiforme 26.78 21.11 21 11644 9683 46664714
Lipase increased 26.77 21.11 20 11645 8583 46665814
Iridocyclitis 26.65 21.11 12 11653 1988 46672409
Dehydration 26.63 21.11 94 11571 159446 46514951
Retinal detachment 25.77 21.11 16 11649 5084 46669313
Diarrhoea 25.67 21.11 232 11433 559370 46115027
Metastases to spleen 25.58 21.11 6 11659 119 46674278
Vomiting 25.14 21.11 196 11469 452598 46221799
Disease progression 24.91 21.11 64 11601 91236 46583161
C-reactive protein increased 24.89 21.11 49 11616 58541 46615856
Drug interaction 24.57 21.11 10 11655 203084 46471313
BRAF V600E mutation positive 24.47 21.11 4 11661 9 46674388
Chest pain 24.24 21.11 7 11658 176317 46498080
Condition aggravated 23.84 21.11 16 11649 245036 46429361
Rash maculo-papular 23.79 21.11 32 11633 27842 46646555
Insomnia 23.70 21.11 6 11659 164918 46509479
Acute polyneuropathy 22.32 21.11 6 11659 210 46674187
Sinusitis 22.32 21.11 3 11662 129765 46544632
Second primary malignancy 22.05 21.11 16 11649 6568 46667829
Rhabdomyolysis 21.48 21.11 38 11627 41871 46632526

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
Pyrexia 1024.73 19.89 889 11494 293600 29646495
Malignant neoplasm progression 593.04 19.89 369 12014 71918 29868177
Metastatic malignant melanoma 353.63 19.89 95 12288 1975 29938120
Metastases to central nervous system 303.76 19.89 114 12269 7170 29932925
Chills 289.42 19.89 239 12144 72099 29867996
Malignant melanoma 177.78 19.89 78 12305 7333 29932762
Ejection fraction decreased 161.63 19.89 92 12291 15083 29925012
Death 153.94 19.89 405 11978 356878 29583217
Uveitis 97.89 19.89 47 12336 5430 29934665
Rash 92.94 19.89 228 12155 191661 29748434
Malignant melanoma stage IV 80.37 19.89 15 12368 48 29940047
Product use in unapproved indication 79.47 19.89 123 12260 73570 29866525
Metastases to liver 77.73 19.89 53 12330 11912 29928183
Metastases to stomach 70.37 19.89 14 12369 68 29940027
Blood creatine phosphokinase increased 67.78 19.89 87 12296 43761 29896334
Dermatitis acneiform 64.62 19.89 36 12347 5653 29934442
Metastases to lung 58.59 19.89 38 12345 7857 29932238
Visual impairment 56.08 19.89 66 12317 30372 29909723
Chorioretinopathy 54.27 19.89 21 12362 1431 29938664
Blood lactate dehydrogenase increased 50.67 19.89 52 12331 20549 29919546
C-reactive protein increased 50.25 19.89 75 12308 43398 29896697
Second primary malignancy 48.16 19.89 31 12352 6325 29933770
Metastases to peritoneum 45.97 19.89 19 12364 1538 29938557
Drug interaction 43.86 19.89 14 12369 199554 29740541
Metastases to meninges 43.60 19.89 17 12366 1182 29938913
Serous retinal detachment 42.84 19.89 12 12371 292 29939803
Procalcitonin increased 41.18 19.89 16 12367 1102 29938993
Malignant mesenteric neoplasm 39.38 19.89 8 12375 44 29940051
Panniculitis 37.84 19.89 14 12369 843 29939252
Acne 37.19 19.89 31 12352 9405 29930690
Metastases to bone 36.56 19.89 31 12352 9627 29930468
Jejunal ulcer perforation 36.15 19.89 8 12375 70 29940025
Metastases to skin 35.90 19.89 11 12372 369 29939726
Metastasis 35.09 19.89 20 12363 3278 29936817
Metastases to lymph nodes 34.15 19.89 21 12362 3956 29936139
Gastrointestinal wall thickening 33.28 19.89 13 12370 908 29939187
Toxicity to various agents 33.04 19.89 16 12367 177167 29762928
Squamous cell carcinoma 32.98 19.89 30 12353 10220 29929875
Haemophagocytic lymphohistiocytosis 32.18 19.89 29 12354 9762 29930333
Tissue infiltration 31.16 19.89 7 12376 66 29940029
Detachment of retinal pigment epithelium 31.02 19.89 10 12373 397 29939698
Metastases to heart 31.00 19.89 8 12375 141 29939954
Intestinal metastasis 30.38 19.89 8 12375 153 29939942
Eastern Cooperative Oncology Group performance status 30.01 19.89 6 12377 30 29940065
Omental necrosis 30.01 19.89 6 12377 30 29940065
Mesenteric neoplasm 29.69 19.89 6 12377 32 29940063
Ureteral disorder 29.37 19.89 8 12375 175 29939920
Paronychia 28.70 19.89 17 12366 2994 29937101
Melanoma recurrent 28.18 19.89 7 12376 105 29939990
Dehydration 27.97 19.89 113 12270 123426 29816669
Basal cell carcinoma 26.57 19.89 33 12350 16035 29924060
Drug ineffective 26.54 19.89 64 12319 340323 29599772
Disease progression 24.80 19.89 81 12302 79793 29860302
Brain neoplasm 24.71 19.89 15 12368 2762 29937333
Abdominal lymphadenopathy 24.51 19.89 9 12374 530 29939565
Hyperpyrexia 23.13 19.89 14 12369 2563 29937532
Anaplastic thyroid cancer 22.78 19.89 4 12379 8 29940087
Fat necrosis 22.75 19.89 7 12376 238 29939857
Small intestine carcinoma 22.19 19.89 8 12375 447 29939648
Anxiety 22.17 19.89 5 12378 89866 29850229
Inflammatory bowel disease 21.99 19.89 13 12370 2280 29937815
Histiocytic sarcoma 21.88 19.89 4 12379 11 29940084
Pneumonitis 21.77 19.89 40 12343 27414 29912681
Papilloedema 21.67 19.89 13 12370 2343 29937752
Leukoderma 21.39 19.89 5 12378 57 29940038
Influenza like illness 21.18 19.89 38 12345 25567 29914528
Myocardial infarction 20.99 19.89 13 12370 125612 29814483
Retinal detachment 20.72 19.89 17 12366 5043 29935052
Tumour invasion 20.44 19.89 7 12376 336 29939759
Vision blurred 20.43 19.89 50 12333 41766 29898329
Fatigue 20.36 19.89 212 12171 320461 29619634
Vomiting 19.89 19.89 157 12226 219661 29720434

Pharmacologic Action:

SourceCodeDescription
ATC L01EE01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
PROTEIN KINASE INHIBITORS
Mitogen-activated protein kinase (MEK) inhibitors
FDA MoA N0000175076 Protein Kinase Inhibitors
FDA EPC N0000175605 Kinase Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D047428 Protein Kinase Inhibitors
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:79091 mitogen-activated protein kinase inhibitors
CHEBI has role CHEBI:149553 anti-coronaviral agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Metastatic malignant melanoma indication 443493003
Malignant Melanoma with BRAF V600K Mutation indication
Malignant Melanoma with BRAF V600E Mutation indication

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 0.5MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL Jan. 8, 2021 TRAMETINIB IN COMBO WITH DABRAFENIB FOR TX. OF PTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST. THIS INDICATION IS BASED ON THE DEMONSTRATION OF DURABLE RESPONSE RATE
EQ 1MG MEKINIST NOVARTIS N204114 May 29, 2013 DISCN TABLET ORAL Jan. 8, 2021 TRAMETINIB IN COMBO WITH DABRAFENIB FOR TX. OF PTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST. THIS INDICATION IS BASED ON THE DEMONSTRATION OF DURABLE RESPONSE RATE
EQ 2MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL Jan. 8, 2021 TRAMETINIB IN COMBO WITH DABRAFENIB FOR TX. OF PTS WITH UNRESECTABLE OR METASTATIC MELANOMA WITH BRAF V600E OR V600K MUTATIONS AS DETECTED BY AN FDA-APPROVED TEST. THIS INDICATION IS BASED ON THE DEMONSTRATION OF DURABLE RESPONSE RATE
EQ 0.5MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL April 30, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 1MG MEKINIST NOVARTIS N204114 May 29, 2013 DISCN TABLET ORAL April 30, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 2MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL April 30, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 0.5MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL May 4, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 1MG MEKINIST NOVARTIS N204114 May 29, 2013 DISCN TABLET ORAL May 4, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 2MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL May 4, 2021 DABRAFENIB IN COMBINULLTION WITH TRAMETINIB FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 0.5MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL Oct. 6, 2022 ADDITION OF STUDY BRF117277, A NON-RANDOMIZED, OPEN-LABEL, MULTI-CENTER, MULTI-COHORT TRIAL OF DABRAFENIB PLUS TRAMETINIB IN SUBJECTS WITH BRAF MUTATION-POSITIVE MELANOMA THAT HAS METASTASIZED TO THE BRAIN
EQ 1MG MEKINIST NOVARTIS N204114 May 29, 2013 DISCN TABLET ORAL Oct. 6, 2022 ADDITION OF STUDY BRF117277, A NON-RANDOMIZED, OPEN-LABEL, MULTI-CENTER, MULTI-COHORT TRIAL OF DABRAFENIB PLUS TRAMETINIB IN SUBJECTS WITH BRAF MUTATION-POSITIVE MELANOMA THAT HAS METASTASIZED TO THE BRAIN
EQ 2MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL Oct. 6, 2022 ADDITION OF STUDY BRF117277, A NON-RANDOMIZED, OPEN-LABEL, MULTI-CENTER, MULTI-COHORT TRIAL OF DABRAFENIB PLUS TRAMETINIB IN SUBJECTS WITH BRAF MUTATION-POSITIVE MELANOMA THAT HAS METASTASIZED TO THE BRAIN
EQ 0.5MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL June 22, 2024 TRAMETINIB IN COMBINULLTION WITH DABRAFENIB, FOR THE TX. OF PTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 1MG MEKINIST NOVARTIS N204114 May 29, 2013 DISCN TABLET ORAL June 22, 2024 TRAMETINIB IN COMBINULLTION WITH DABRAFENIB, FOR THE TX. OF PTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 2MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL June 22, 2024 TRAMETINIB IN COMBINULLTION WITH DABRAFENIB, FOR THE TX. OF PTS WITH METASTATIC NON-SMALL CELL LUNG CANCER WITH BRAF V600E MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 0.5MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL April 30, 2025 TRAMETINIB IS INDICATED, IN COMBINULLTION WITH DABRAFENIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 1MG MEKINIST NOVARTIS N204114 May 29, 2013 DISCN TABLET ORAL April 30, 2025 TRAMETINIB IS INDICATED, IN COMBINULLTION WITH DABRAFENIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 2MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL April 30, 2025 TRAMETINIB IS INDICATED, IN COMBINULLTION WITH DABRAFENIB, FOR THE ADJUVANT TREATMENT OF PATIENTS WITH MELANOMA WITH BRAF V600E OR V600K MUTATIONS, AS DETECTED BY AN FDA-APPROVED TEST, AND INVOLVEMENT OF LYMPH NODE(S), FOLLOWING COMPLETE RESECTION
EQ 0.5MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL May 4, 2025 TRAMETINIB AND DABRAFENIB IN COMBINULLTION, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 1MG MEKINIST NOVARTIS N204114 May 29, 2013 DISCN TABLET ORAL May 4, 2025 TRAMETINIB AND DABRAFENIB IN COMBINULLTION, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS
EQ 2MG MEKINIST NOVARTIS N204114 May 29, 2013 RX TABLET ORAL May 4, 2025 TRAMETINIB AND DABRAFENIB IN COMBINULLTION, FOR THE TREATMENT OF PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ANULLPLASTIC THYROID CANCER (ATC) WITH BRAF V600E MUTATION AND WITH NO SATISFACTORY LOCOREGIONULLL TREATMENT OPTIONS

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dual specificity mitogen-activated protein kinase kinase 2 Kinase INHIBITOR IC50 9.04 WOMBAT-PK CHEMBL
Dual specificity mitogen-activated protein kinase kinase 1 Kinase INHIBITOR IC50 8.74 WOMBAT-PK CHEMBL

External reference:

IDSource
D10175 KEGG_DRUG
1187431-43-1 SECONDARY_CAS_RN
4032511 VANDF
C2703095 UMLSCUI
CHEBI:75991 CHEBI
QOM PDB_CHEM_ID
CHEMBL2103875 ChEMBL_ID
CHEMBL2105741 ChEMBL_ID
C560077 MESH_SUPPLEMENTAL_RECORD_UI
9421 INN_ID
DB08911 DRUGBANK_ID
33E86K87QN UNII
11707110 PUBCHEM_CID
6495 IUPHAR_LIGAND_ID
1425098 RXNORM
203115 MMSL
29478 MMSL
d08104 MMSL
015044 NDDF
015045 NDDF
708711009 SNOMEDCT_US
715545006 SNOMEDCT_US
734611008 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Mekinist HUMAN PRESCRIPTION DRUG LABEL 1 0078-0666 TABLET, FILM COATED 0.50 mg ORAL NDA 32 sections
Mekinist HUMAN PRESCRIPTION DRUG LABEL 1 0078-0668 TABLET, FILM COATED 2 mg ORAL NDA 32 sections