pemetrexed ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
antineoplastics; thymidylate synthetase inhibitors 2073 137281-23-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • LY231514
  • pemetrexed diacid monohydrate
  • pemetrexed sodium
  • pemetrexed sodium hydrate
  • pemetrexed
  • pemetrexed disodium
  • alimta
  • pemetrexed disodium heptahydrate
Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT.
  • Molecular weight: 427.42
  • Formula: C20H21N5O6
  • CLOGP: -0.12
  • LIPINSKI: 2
  • HAC: 11
  • HDO: 6
  • TPSA: 186.97
  • ALOGS: -3.97
  • ROTB: 9

  • Status: OFP

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

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 3 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 90 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 80 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 1.38 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution) 0.15 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.30 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.19 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.85 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 20, 2004 EMA ELI LILLY NEDERLAND B.V.
Feb. 4, 2004 FDA LILLY

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
Malignant neoplasm progression 862.83 18.54 423 15588 67701 50521412
Disease progression 288.14 18.54 240 15771 95626 50493487
Pancytopenia 217.04 18.54 193 15818 83837 50505276
Anaemia 198.83 18.54 315 15696 252141 50336972
Neutropenia 166.64 18.54 219 15792 147746 50441367
Drug resistance 165.28 18.54 92 15919 18897 50570216
Thrombocytopenia 139.09 18.54 186 15825 127487 50461626
Febrile neutropenia 123.12 18.54 153 15858 97514 50491599
Bone marrow failure 121.86 18.54 87 15924 27537 50561576
Metastases to central nervous system 118.67 18.54 62 15949 11220 50577893
Neoplasm progression 117.64 18.54 87 15924 29070 50560043
Acquired gene mutation 112.40 18.54 30 15981 801 50588312
Tubulointerstitial nephritis 88.79 18.54 57 15954 15154 50573959
Pneumonitis 82.50 18.54 71 15940 29439 50559674
Nephropathy toxic 78.42 18.54 42 15969 7987 50581126
Mucosal inflammation 78.23 18.54 79 15932 40063 50549050
Therapy partial responder 71.54 18.54 37 15974 6554 50582559
Metastases to adrenals 70.47 18.54 20 15991 674 50588439
Dehydration 69.89 18.54 151 15860 152298 50436815
EGFR gene mutation 68.73 18.54 16 15995 239 50588874
Non-small cell lung cancer 64.92 18.54 27 15984 2910 50586203
Arthralgia 64.77 18.54 29 15982 438673 50150440
Renal tubular necrosis 64.08 18.54 40 15971 10128 50578985
Pleural effusion 62.90 18.54 101 15910 81353 50507760
Hepatocellular injury 61.74 18.54 57 15954 25890 50563223
Metastases to meninges 60.27 18.54 23 15988 1979 50587134
Death 59.98 18.54 232 15779 325147 50263966
Immune-mediated lung disease 57.25 18.54 15 15996 372 50588741
Haemoptysis 56.66 18.54 54 15957 25519 50563594
Joint swelling 56.41 18.54 6 16005 245280 50343833
Myelosuppression 56.00 18.54 41 15970 13476 50575637
Pulmonary embolism 53.92 18.54 107 15904 101597 50487516
Pain 53.38 18.54 63 15948 578840 50010273
Haematotoxicity 52.13 18.54 32 15979 7863 50581250
Drug ineffective 51.42 18.54 115 15896 819218 49769895
Acute kidney injury 50.76 18.54 173 15838 227885 50361228
Neutrophil count decreased 49.91 18.54 67 15944 45959 50543154
Colitis 49.49 18.54 61 15950 38468 50550645
Osteonecrosis of jaw 49.23 18.54 56 15955 32470 50556643
Renal tubular disorder 49.18 18.54 21 15990 2416 50586697
Hepatitis 49.04 18.54 55 15956 31398 50557715
General physical health deterioration 48.82 18.54 126 15885 142308 50446805
Posterior reversible encephalopathy syndrome 48.09 18.54 39 15972 14889 50574224
Melanoderma 47.78 18.54 11 16000 156 50588957
Malignant pleural effusion 46.76 18.54 20 15991 2310 50586803
Fall 46.54 18.54 24 15987 334908 50254205
Product dose omission issue 46.37 18.54 3 16008 183835 50405278
Blood creatinine increased 46.36 18.54 85 15926 76075 50513038
Interstitial lung disease 45.29 18.54 69 15942 53107 50536006
Lung cancer metastatic 43.76 18.54 19 15992 2276 50586837
Drug hypersensitivity 43.03 18.54 13 15998 250997 50338116
Vomiting 42.68 18.54 270 15741 460488 50128625
Myocarditis 42.02 18.54 28 15983 7919 50581194
Abdominal discomfort 41.55 18.54 11 16000 231630 50357483
Nausea 41.42 18.54 371 15640 705027 49884086
Lung adenocarcinoma 41.42 18.54 22 15989 4112 50585001
Immune-mediated pancreatitis 40.24 18.54 8 16003 53 50589060
Rheumatoid arthritis 39.54 18.54 8 16003 202542 50386571
Malignant transformation 39.51 18.54 11 16000 345 50588768
Renal failure 39.30 18.54 97 15914 106536 50482577
Maternal exposure during pregnancy 39.15 18.54 3 16008 159775 50429338
Jaw operation 38.79 18.54 13 15998 767 50588346
Immune-mediated hepatic disorder 38.14 18.54 9 16002 143 50588970
Hepatotoxicity 38.05 18.54 45 15966 27181 50561932
Subacute cutaneous lupus erythematosus 37.92 18.54 17 15994 2198 50586915
White blood cell count decreased 37.68 18.54 101 15910 116621 50472492
Sinusitis 37.14 18.54 5 16006 170553 50418560
Metastases to bone 36.11 18.54 36 15975 17959 50571154
Contraindicated product administered 35.93 18.54 3 16008 148955 50440158
Nephritis 35.86 18.54 16 15995 2046 50587067
Off label use 35.57 18.54 264 15747 474162 50114951
Non-small cell lung cancer metastatic 35.19 18.54 11 16000 519 50588594
Gamma-glutamyltransferase increased 35.01 18.54 45 15966 29578 50559535
Performance status decreased 34.85 18.54 18 15993 3177 50585936
Secondary hypertension 34.84 18.54 8 16003 112 50589001
Platelet count decreased 33.35 18.54 88 15923 100638 50488475
Nasopharyngitis 33.03 18.54 10 16001 192917 50396196
Peripheral swelling 32.94 18.54 12 15999 205924 50383189
Hypertransaminasaemia 32.78 18.54 18 15993 3593 50585520
Radiation pneumonitis 31.98 18.54 13 15998 1322 50587791
Decreased appetite 31.93 18.54 137 15874 200786 50388327
Weight increased 31.90 18.54 12 15999 201879 50387234
BRAF V600E mutation positive 31.61 18.54 6 16005 30 50589083
Lung neoplasm malignant 31.11 18.54 31 15980 15453 50573660
Systemic lupus erythematosus 30.91 18.54 4 16007 140618 50448495
Insomnia 30.05 18.54 9 16002 174856 50414257
Lymphangiosis carcinomatosa 29.86 18.54 12 15999 1184 50587929
Metastases to lung 29.74 18.54 26 15985 10994 50578119
Transaminases increased 29.38 18.54 40 15971 27784 50561329
Metastases to liver 29.38 18.54 34 15977 20070 50569043
Rash maculo-papular 29.20 18.54 39 15972 26602 50562511
Gene mutation 29.16 18.54 12 15999 1259 50587854
Pericardial effusion 28.88 18.54 38 15973 25551 50563562
Skin toxicity 28.78 18.54 17 15994 3896 50585217
Multiple-drug resistance 28.66 18.54 16 15995 3298 50585815
Hepatitis toxic 28.25 18.54 15 15996 2801 50586312
Neonatal respiratory depression 27.90 18.54 6 16005 61 50589052
Anaphylactic shock 27.65 18.54 33 15978 20122 50568991
Hepatic function abnormal 27.24 18.54 42 15969 32639 50556474
Glossodynia 26.10 18.54 3 16008 115566 50473547
Sarcomatoid carcinoma 26.02 18.54 5 16006 27 50589086
Swelling 25.56 18.54 16 15995 200856 50388257
Oesophagitis 25.44 18.54 26 15985 13357 50575756
Therapeutic product effect decreased 25.27 18.54 6 16005 136044 50453069
Asthenia 24.67 18.54 179 15832 318863 50270250
Tracheal fistula 24.55 18.54 5 16006 38 50589075
Immune-mediated enterocolitis 24.29 18.54 10 16001 1050 50588063
Adenocarcinoma 24.28 18.54 13 15998 2468 50586645
Paronychia 23.93 18.54 16 15995 4548 50584565
Non-small cell lung cancer stage IV 23.89 18.54 6 16005 125 50588988
Leukoencephalopathy 23.77 18.54 15 15996 3868 50585245
Sepsis 23.74 18.54 94 15917 132831 50456282
Febrile bone marrow aplasia 23.58 18.54 18 15993 6293 50582820
Leukopenia 23.37 18.54 60 15951 67468 50521645
Hypokalaemia 22.44 18.54 70 15941 87922 50501191
Focal segmental glomerulosclerosis 22.03 18.54 10 16001 1331 50587782
Skin hyperpigmentation 21.84 18.54 16 15995 5260 50583853
Dermatitis bullous 21.55 18.54 18 15993 7155 50581958
Diverticular perforation 21.32 18.54 13 15998 3155 50585958
Gastrointestinal toxicity 21.23 18.54 15 15996 4662 50584451
Meningitis herpes 21.14 18.54 6 16005 202 50588911
Carcinoembryonic antigen increased 21.12 18.54 10 16001 1464 50587649
Wound 21.00 18.54 4 16007 105790 50483323
Immune-mediated myocarditis 20.87 18.54 5 16006 85 50589028
Feeling abnormal 20.59 18.54 7 16004 125485 50463628
Peripheral ischaemia 20.07 18.54 14 15997 4262 50584851
Renal salt-wasting syndrome 19.80 18.54 6 16005 255 50588858
Metastasis 19.78 18.54 14 15997 4361 50584752
Arthropathy 19.50 18.54 13 15998 157893 50431220
Exposure during pregnancy 19.42 18.54 7 16004 121008 50468105
Epistaxis 19.28 18.54 54 15957 63900 50525213
Proteinuria 19.27 18.54 25 15986 16572 50572541
Cholangitis 19.21 18.54 14 15997 4565 50584548
Nephrogenic diabetes insipidus 19.14 18.54 8 16003 873 50588240
Immune-mediated hepatitis 18.94 18.54 8 16003 896 50588217
Muscle spasms 18.94 18.54 8 16003 125545 50463568
Somnolence 18.82 18.54 13 15998 154972 50434141

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
Malignant neoplasm progression 792.31 16.73 597 25675 73262 29474993
Pancytopenia 360.06 16.73 405 25867 82763 29465492
Interstitial lung disease 252.75 16.73 283 25989 57435 29490820
Neutropenia 229.13 16.73 415 25857 131296 29416959
Thrombocytopenia 224.68 16.73 417 25855 134406 29413849
Anaemia 218.90 16.73 522 25750 200429 29347826
Bone marrow failure 156.38 16.73 155 26117 27294 29520961
Mucosal inflammation 155.70 16.73 165 26107 31430 29516825
Disease progression 154.89 16.73 268 26004 81648 29466607
Febrile neutropenia 122.18 16.73 292 25980 111948 29436307
General physical health deterioration 120.02 16.73 275 25997 102582 29445673
Myelosuppression 117.70 16.73 93 26179 12134 29536121
Pneumonitis 109.91 16.73 130 26142 27914 29520341
Neoplasm progression 107.64 16.73 106 26166 18506 29529749
Febrile bone marrow aplasia 102.65 16.73 70 26202 7281 29540974
Pleural effusion 97.13 16.73 204 26068 71704 29476551
Leukopenia 82.07 16.73 163 26109 55040 29493215
Decreased appetite 79.23 16.73 296 25976 145046 29403209
Immune-mediated lung disease 76.71 16.73 28 26244 740 29547515
Neutrophil count decreased 76.34 16.73 138 26134 43429 29504826
Metastases to central nervous system 70.25 16.73 55 26217 7076 29541179
Enteritis 68.25 16.73 53 26219 6738 29541517
Drug ineffective 65.54 16.73 141 26131 363029 29185226
Completed suicide 64.29 16.73 4 26268 90242 29458013
Aplasia 62.27 16.73 41 26231 4022 29544233
Platelet count decreased 59.33 16.73 216 26056 104456 29443799
Dehydration 55.37 16.73 225 26047 114523 29433732
Drug interaction 54.56 16.73 57 26215 197328 29350927
Product dose omission issue 52.15 16.73 11 26261 96372 29451883
Immune-mediated adverse reaction 51.06 16.73 18 26254 429 29547826
Skin toxicity 50.49 16.73 35 26237 3736 29544519
Haematotoxicity 50.01 16.73 44 26228 6655 29541600
Diarrhoea 49.48 16.73 481 25791 332217 29216038
Immune-mediated enterocolitis 47.35 16.73 25 26247 1628 29546627
Immune-mediated hepatic disorder 47.32 16.73 16 26256 335 29547920
Neutropenic sepsis 46.97 16.73 55 26217 11672 29536583
Fall 45.83 16.73 54 26218 177124 29371131
Pneumothorax 44.06 16.73 62 26210 15780 29532475
Colitis 43.70 16.73 90 26182 31158 29517097
Vomiting 43.08 16.73 329 25943 211931 29336324
Large intestine perforation 42.70 16.73 42 26230 7314 29540941
Pulmonary embolism 42.54 16.73 157 26115 76377 29471878
Headache 41.90 16.73 56 26216 173951 29374304
Septic shock 41.41 16.73 136 26136 62424 29485831
Overdose 41.39 16.73 10 26262 79809 29468446
Nausea 41.38 16.73 415 25857 288840 29259415
Radiation pneumonitis 40.38 16.73 25 26247 2204 29546051
Haemoptysis 39.25 16.73 85 26187 30465 29517790
Bradycardia 38.71 16.73 6 26266 65623 29482632
Lung disorder 38.46 16.73 84 26188 30278 29517977
Lung adenocarcinoma 38.41 16.73 30 26242 3845 29544410
Tubulointerstitial nephritis 37.61 16.73 61 26211 17582 29530673
Superior vena cava syndrome 37.10 16.73 15 26257 526 29547729
Hepatocellular injury 36.81 16.73 67 26205 21176 29527079
White blood cell count decreased 36.69 16.73 159 26113 83203 29465052
EGFR gene mutation 35.86 16.73 10 26262 106 29548149
Toxicity to various agents 35.01 16.73 63 26209 173598 29374657
Respiratory failure 34.48 16.73 174 26098 96957 29451298
Peritonitis 34.00 16.73 53 26219 14771 29533484
Small intestinal perforation 33.94 16.73 20 26252 1612 29546643
Pain in extremity 32.65 16.73 30 26242 110403 29437852
Muscle spasms 32.12 16.73 9 26263 65073 29483182
Rash 31.89 16.73 282 25990 189537 29358718
Non-small cell lung cancer 31.56 16.73 24 26248 2957 29545298
Hiccups 31.33 16.73 39 26233 8814 29539441
Pneumonia 30.91 16.73 426 25846 319746 29228509
Metastases to bone 29.41 16.73 40 26232 9858 29538397
Therapy partial responder 28.91 16.73 29 26243 5170 29543085
Sepsis 28.79 16.73 221 26051 142461 29405794
Epistaxis 28.65 16.73 106 26166 51598 29496657
Tremor 28.30 16.73 15 26257 73523 29474732
Peripheral swelling 27.64 16.73 11 26261 63728 29484527
Blood pressure increased 27.04 16.73 16 26256 73787 29474468
Purpura 26.96 16.73 37 26235 9195 29539060
Lung cancer metastatic 26.71 16.73 20 26252 2407 29545848
Pulmonary toxicity 26.68 16.73 27 26245 4863 29543392
Extremity necrosis 26.58 16.73 17 26255 1586 29546669
Disseminated intravascular coagulation 26.12 16.73 56 26216 19924 29528331
Performance status decreased 24.90 16.73 23 26249 3704 29544551
Nasopharyngitis 24.74 16.73 11 26261 59654 29488601
Pseudocellulitis 24.66 16.73 6 26266 35 29548220
Dyspnoea 24.66 16.73 417 25855 326315 29221940
Nephritis 24.40 16.73 18 26254 2118 29546137
Drug resistance 24.38 16.73 57 26215 21483 29526772
Feeling abnormal 24.26 16.73 9 26263 54436 29493819
Eastern Cooperative Oncology Group performance status worsened 23.67 16.73 12 26260 718 29547537
Hyperpyrexia 23.14 16.73 18 26254 2292 29545963
Musculoskeletal stiffness 23.07 16.73 3 26269 37455 29510800
Metastases to meninges 23.07 16.73 14 26258 1191 29547064
Hypopituitarism 23.03 16.73 16 26256 1714 29546541
Renal failure 22.96 16.73 182 26090 118417 29429838
Rhabdomyolysis 22.53 16.73 13 26259 60795 29487460
Rheumatoid nodule 22.28 16.73 17 26255 2105 29546150
Myalgia 21.99 16.73 20 26252 73999 29474256
Malignant pleural effusion 21.91 16.73 14 26258 1304 29546951
Pericarditis malignant 21.72 16.73 5 26267 22 29548233
Aphthous ulcer 21.36 16.73 22 26250 4046 29544209
Opsoclonus myoclonus 21.23 16.73 6 26266 67 29548188
Dysphagia 20.60 16.73 100 26172 54826 29493429
Arthralgia 20.54 16.73 60 26212 139557 29408698
Vasculitis 20.53 16.73 30 26242 7898 29540357
Acute kidney injury 20.51 16.73 340 25932 264927 29283328
Occipital neuralgia 20.43 16.73 5 26267 30 29548225
Gastrointestinal perforation 20.42 16.73 20 26252 3463 29544792
Cardiac failure congestive 20.13 16.73 23 26249 76558 29471697
Acquired gene mutation 20.02 16.73 13 26259 1245 29547010
Depression 19.86 16.73 28 26244 85119 29463136
Adrenocorticotropic hormone deficiency 19.82 16.73 10 26262 592 29547663
Lichenoid keratosis 19.79 16.73 16 26256 2154 29546101
Lymphangiosis carcinomatosa 19.69 16.73 11 26261 801 29547454
Pericardial effusion 19.66 16.73 52 26220 21156 29527099
Myocarditis 19.54 16.73 35 26237 10921 29537334
Injection site pain 19.05 16.73 3 26269 32443 29515812
Rash maculo-papular 19.01 16.73 56 26216 24233 29524022
Agitation 18.96 16.73 11 26261 51293 29496962
Hallucination 18.92 16.73 8 26264 44704 29503551
Immune-mediated renal disorder 18.87 16.73 5 26267 43 29548212
Tumour necrosis 18.71 16.73 12 26260 1125 29547130
Cardiac disorder 18.67 16.73 5 26267 37258 29510997
Pericarditis 18.28 16.73 30 26242 8727 29539528
Pyrexia 18.12 16.73 357 25915 287265 29260990
Weight increased 18.09 16.73 25 26247 76642 29471613
Anxiety 18.05 16.73 30 26242 85335 29462920
Insomnia 18.03 16.73 32 26240 88729 29459526
Cachexia 17.87 16.73 25 26247 6324 29541931
Electrocardiogram QT prolonged 17.82 16.73 5 26267 36132 29512123
Bicytopenia 17.79 16.73 14 26258 1813 29546442
Laryngeal leukoplakia 17.76 16.73 5 26267 55 29548200
Tumour pseudoprogression 17.74 16.73 8 26264 368 29547887
Nephropathy toxic 17.47 16.73 33 26239 10723 29537532
Vision blurred 17.30 16.73 7 26265 40169 29508086
Radiation oesophagitis 17.16 16.73 8 26264 398 29547857
Diaphragmatic rupture 17.13 16.73 4 26268 19 29548236
Hypersensitivity pneumonitis 17.09 16.73 12 26260 1307 29546948
Hypoglycaemia 16.98 16.73 11 26261 48335 29499920
Epidermolysis 16.81 16.73 7 26265 265 29547990
Human chorionic gonadotropin increased 16.80 16.73 4 26268 21 29548234

FDA Adverse Event Reporting System (Geriatric)

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
Malignant neoplasm progression 1288.81 15.86 776 33001 112095 64352860
Pancytopenia 501.33 15.86 487 33290 142822 64322133
Disease progression 363.32 15.86 408 33369 141272 64323683
Anaemia 336.31 15.86 661 33116 378019 64086936
Neutropenia 327.18 15.86 506 33271 239118 64225837
Thrombocytopenia 318.76 15.86 482 33295 223319 64241636
Interstitial lung disease 266.78 15.86 291 33486 97441 64367514
Bone marrow failure 259.48 15.86 209 33568 47743 64417212
Febrile neutropenia 200.21 15.86 355 33422 187302 64277653
Pneumonitis 182.87 15.86 175 33602 50190 64414765
Myelosuppression 178.01 15.86 126 33651 23704 64441251
Metastases to central nervous system 174.61 15.86 102 33675 13810 64451145
Drug resistance 173.10 15.86 145 33632 34957 64429998
Neoplasm progression 161.47 15.86 149 33628 40815 64424140
Mucosal inflammation 161.40 15.86 181 33596 62403 64402552
Immune-mediated lung disease 135.08 15.86 42 33735 1160 64463795
General physical health deterioration 118.82 15.86 302 33475 204123 64260832
Acquired gene mutation 118.11 15.86 43 33734 1943 64463012
Tubulointerstitial nephritis 117.11 15.86 110 33667 30799 64434156
EGFR gene mutation 116.92 15.86 29 33748 335 64464620
Pleural effusion 111.79 15.86 221 33556 126338 64338617
Febrile bone marrow aplasia 109.17 15.86 70 33707 11185 64453770
Completed suicide 103.71 15.86 3 33774 224411 64240544
Neutrophil count decreased 103.52 15.86 162 33615 77034 64387921
Therapy partial responder 100.05 15.86 64 33713 10184 64454771
Decreased appetite 97.35 15.86 346 33431 280943 64184012
Hepatocellular injury 96.90 15.86 119 33658 45116 64419839
Skin toxicity 92.45 15.86 52 33725 6550 64458405
Fall 92.10 15.86 52 33725 416774 64048181
Leukopenia 92.05 15.86 179 33598 101063 64363892
Haematotoxicity 91.26 15.86 66 33711 12830 64452125
Immune-mediated hepatic disorder 87.34 15.86 25 33752 515 64464440
Colitis 86.94 15.86 129 33648 58545 64406410
Acute kidney injury 84.46 15.86 460 33317 448780 64016175
Non-small cell lung cancer 80.88 15.86 43 33734 4847 64460108
Arthralgia 80.67 15.86 68 33709 442192 64022763
Aplasia 76.89 15.86 47 33730 6906 64458049
Platelet count decreased 74.77 15.86 225 33552 167486 64297469
Pain 74.74 15.86 109 33668 553402 63911553
Lung cancer metastatic 73.69 15.86 35 33742 3105 64461850
Product dose omission issue 71.27 15.86 9 33768 194738 64270217
Metastases to meninges 71.07 15.86 33 33744 2782 64462173
Immune-mediated enterocolitis 69.75 15.86 32 33745 2624 64462331
Radiation pneumonitis 68.77 15.86 34 33743 3294 64461661
Haemoptysis 68.62 15.86 105 33672 48943 64416012
Lung adenocarcinoma 67.51 15.86 43 33734 6790 64458165
Nephropathy toxic 65.70 15.86 62 33715 17452 64447503
Headache 65.07 15.86 111 33666 529356 63935599
Joint swelling 63.76 15.86 17 33760 215365 64249590
Enteritis 61.81 15.86 51 33726 12026 64452929
Drug ineffective 61.47 15.86 230 33547 840017 63624938
Peripheral swelling 59.15 15.86 18 33759 209135 64255820
Immune-mediated adverse reaction 58.57 15.86 20 33757 747 64464208
Diarrhoea 58.04 15.86 605 33172 722099 63742856
Pulmonary embolism 56.62 15.86 187 33590 146169 64318786
Myocarditis 55.80 15.86 56 33721 16987 64447968
Osteonecrosis of jaw 55.34 15.86 85 33692 39740 64425215
Melanoderma 55.08 15.86 16 33761 348 64464607
Nasopharyngitis 53.44 15.86 18 33759 196055 64268900
Dehydration 52.69 15.86 239 33538 216524 64248431
Musculoskeletal stiffness 52.37 15.86 3 33774 123203 64341752
Pain in extremity 52.31 15.86 49 33728 303036 64161919
Rash maculo-papular 51.33 15.86 90 33687 46936 64418019
Metastases to adrenals 50.02 15.86 20 33757 1169 64463786
White blood cell count decreased 48.49 15.86 187 33590 157650 64307305
Abdominal discomfort 47.54 15.86 18 33759 182304 64282651
Blood creatinine increased 46.83 15.86 167 33610 135615 64329340
Drug hypersensitivity 46.52 15.86 34 33743 237781 64227174
Septic shock 46.51 15.86 141 33636 105296 64359659
Metastases to liver 46.51 15.86 60 33717 23881 64441074
Sinusitis 46.15 15.86 10 33767 145918 64319037
Vomiting 45.86 15.86 465 33312 550652 63914303
Weight increased 45.08 15.86 28 33749 213320 64251635
Contraindicated product administered 44.71 15.86 3 33774 107826 64357129
Hypertransaminasaemia 44.59 15.86 34 33743 7157 64457798
Pneumothorax 44.26 15.86 59 33718 24239 64440716
Injection site pain 43.67 15.86 4 33773 111404 64353551
Malignant pleural effusion 43.26 15.86 24 33753 2943 64462012
Rheumatoid arthritis 43.20 15.86 16 33761 164278 64300677
Skin hyperpigmentation 42.90 15.86 32 33745 6519 64458436
Subacute cutaneous lupus erythematosus 42.82 15.86 24 33753 3001 64461954
Renal failure 42.41 15.86 198 33579 181490 64283465
Tumour pseudoprogression 41.78 15.86 14 33763 493 64464462
Overdose 41.18 15.86 16 33761 159550 64305405
Renal tubular necrosis 40.76 15.86 54 33723 22056 64442899
Nausea 40.24 15.86 605 33172 785195 63679760
Sepsis 39.24 15.86 230 33547 230111 64234844
Performance status decreased 39.20 15.86 28 33749 5336 64459619
Lymphangiosis carcinomatosa 38.81 15.86 19 33758 1802 64463153
Maternal exposure during pregnancy 38.79 15.86 3 33774 95881 64369074
Lichenoid keratosis 38.05 15.86 23 33754 3311 64461644
Small intestinal perforation 37.97 15.86 21 33756 2559 64462396
Hepatotoxicity 37.93 15.86 72 33705 39890 64425065
Respiratory failure 37.86 15.86 176 33601 161007 64303948
Malignant transformation 37.20 15.86 16 33761 1125 64463830
Neutropenic sepsis 37.12 15.86 53 33724 23219 64441736
Transaminases increased 37.07 15.86 76 33701 44518 64420437
Immune-mediated pancreatitis 36.94 15.86 9 33768 96 64464859
Muscle spasms 36.62 15.86 14 33763 141009 64323946
Pericardial effusion 36.36 15.86 70 33707 39184 64425771
Therapeutic product effect decreased 36.28 15.86 8 33769 115343 64349612
Tracheal fistula 35.74 15.86 9 33768 111 64464844
Bradycardia 35.60 15.86 9 33768 118210 64346745
Off label use 35.42 15.86 495 33282 632311 63832644
Toxicity to various agents 35.40 15.86 87 33690 363426 64101529
Feeling abnormal 35.13 15.86 13 33764 133589 64331366
Depression 34.81 15.86 27 33750 183264 64281691
Non-small cell lung cancer metastatic 34.58 15.86 14 33763 845 64464110
Peritonitis 34.19 15.86 53 33724 24970 64439985
Hepatic function abnormal 34.18 15.86 92 33685 64221 64400734
Drug intolerance 34.08 15.86 29 33748 187963 64276992
Hiccups 34.02 15.86 31 33746 8345 64456610
Nephritis 33.69 15.86 22 33755 3624 64461331
Gene mutation 33.57 15.86 18 33759 2064 64462891
Blood pressure increased 33.30 15.86 25 33752 172527 64292428
Lung neoplasm malignant 32.97 15.86 48 33729 21400 64443555
Jaw operation 32.74 15.86 13 33764 746 64464209
Epistaxis 32.38 15.86 119 33658 98012 64366943
Insomnia 31.79 15.86 34 33743 197802 64267153
Large intestine perforation 31.68 15.86 36 33741 12568 64452387
Purpura 31.60 15.86 42 33735 17204 64447751
Extremity necrosis 31.56 15.86 19 33758 2715 64462240
Thrombophlebitis migrans 31.53 15.86 10 33767 295 64464660
Lung disorder 31.42 15.86 86 33691 60614 64404341
Bicytopenia 31.39 15.86 21 33756 3601 64461354
Asthma 31.19 15.86 6 33771 95219 64369736
Dizziness 31.14 15.86 118 33659 430045 64034910
Pseudocellulitis 30.65 15.86 7 33770 55 64464900
Swelling 29.92 15.86 24 33753 160194 64304761
Arthropathy 29.80 15.86 13 33764 120954 64344001
Pulmonary toxicity 29.63 15.86 29 33748 8532 64456423
Metastases to pleura 29.39 15.86 14 33763 1250 64463705
Pyrexia 29.23 15.86 432 33345 558212 63906743
Tremor 29.22 15.86 21 33756 148209 64316746
Hepatitis 29.21 15.86 70 33707 45512 64419443
Pericarditis malignant 28.77 15.86 6 33771 29 64464926
Sarcomatoid carcinoma 28.77 15.86 6 33771 29 64464926
Contusion 28.47 15.86 12 33765 113953 64351002
Gamma-glutamyltransferase increased 28.44 15.86 72 33705 48438 64416517
Superior vena cava syndrome 28.38 15.86 13 33764 1062 64463893
Renal tubular disorder 27.99 15.86 24 33753 5963 64458992
Immune-mediated hepatitis 27.97 15.86 17 33760 2472 64462483
Drug interaction 27.73 15.86 97 33680 361986 64102969
Immune-mediated myocarditis 27.57 15.86 10 33767 447 64464508
Metastases to bone 27.52 15.86 43 33734 20392 64444563
BRAF V600E mutation positive 27.13 15.86 6 33771 40 64464915
Wound 26.85 15.86 4 33773 76473 64388482
Hypopituitarism 26.85 15.86 17 33760 2656 64462299
Suicide attempt 26.65 15.86 3 33774 71004 64393951
Radiation neuropathy 26.22 15.86 4 33773 0 64464955
Asthenia 26.00 15.86 340 33437 427704 64037251
Oesophagobronchial fistula 25.97 15.86 8 33769 214 64464741
Secondary hypertension 25.83 15.86 8 33769 218 64464737
Immune-mediated renal disorder 25.75 15.86 6 33771 52 64464903
Oesophagitis 25.70 15.86 43 33734 21587 64443368
Exposure during pregnancy 25.22 15.86 5 33772 77670 64387285
Mobility decreased 24.96 15.86 7 33770 85833 64379122
Hypothyroidism 24.72 15.86 61 33716 40396 64424559
Adrenocorticotropic hormone deficiency 24.60 15.86 11 33766 849 64464106
Suicidal ideation 24.51 15.86 3 33774 66539 64398416
Gastrointestinal toxicity 24.20 15.86 21 33756 5301 64459654
Carcinoembryonic antigen increased 24.20 15.86 14 33763 1859 64463096
Gastrointestinal perforation 23.86 15.86 21 33756 5403 64459552
Toxic epidermal necrolysis 23.73 15.86 57 33720 37109 64427846
Glossodynia 23.62 15.86 3 33774 64693 64400262
Anxiety 23.44 15.86 44 33733 202605 64262350
Disseminated intravascular coagulation 23.28 15.86 52 33725 32296 64432659
Renal impairment 23.08 15.86 135 33642 134882 64330073
Diverticular perforation 22.56 15.86 20 33757 5193 64459762
Cholangitis 22.45 15.86 28 33749 10774 64454181
Pneumonia 22.32 15.86 414 33363 559162 63905793
Immune-mediated cholangitis 21.83 15.86 6 33771 106 64464849
Nasal congestion 21.22 15.86 3 33774 59655 64405300
Hypoaesthesia 21.15 15.86 25 33752 139083 64325872
Influenza 21.11 15.86 15 33762 106516 64358439
Loss of personal independence in daily activities 20.89 15.86 6 33771 72448 64392507
Osteoarthritis 20.72 15.86 4 33773 63332 64401623
Hypersensitivity 20.72 15.86 45 33732 196407 64268548
Infusion related reaction 20.57 15.86 34 33743 164433 64300522
Proteinuria 20.44 15.86 45 33732 27678 64437277
Autoimmune myocarditis 20.41 15.86 7 33770 265 64464690
Laryngeal leukoplakia 20.30 15.86 5 33772 56 64464899
Hypophysitis 20.27 15.86 16 33761 3543 64461412
Memory impairment 19.88 15.86 10 33767 85672 64379283
Systemic lupus erythematosus 19.66 15.86 8 33769 77604 64387351
Somnolence 19.59 15.86 49 33728 203596 64261359
Immune-mediated dermatitis 19.53 15.86 6 33771 159 64464796
Lung adenocarcinoma recurrent 19.41 15.86 4 33773 18 64464937
Pericardial effusion malignant 19.39 15.86 6 33771 163 64464792
Immune-mediated hypothyroidism 19.28 15.86 6 33771 166 64464789
Hepatitis toxic 19.28 15.86 17 33760 4383 64460572
Hallucination 19.27 15.86 7 33770 72781 64392174
Death 19.18 15.86 357 33420 482348 63982607
Urinary tract infection 19.11 15.86 60 33717 231536 64233419
Intestinal perforation 18.94 15.86 31 33746 15282 64449673
Adenocarcinoma 18.94 15.86 15 33762 3336 64461619
Posterior reversible encephalopathy syndrome 18.94 15.86 39 33738 22907 64442048
Secondary adrenocortical insufficiency 18.90 15.86 13 33764 2332 64462623
Rash 18.87 15.86 341 33436 458208 64006747
Myalgia 18.73 15.86 34 33743 158583 64306372
Hypoglycaemia 18.69 15.86 12 33765 89880 64375075
Hospitalisation 18.65 15.86 8 33769 75199 64389756
Enterocolitis 18.62 15.86 27 33750 11991 64452964
Toxic skin eruption 18.61 15.86 35 33742 19249 64445706
Opsoclonus myoclonus 18.57 15.86 6 33771 188 64464767
Pulmonary artery thrombosis 18.25 15.86 10 33767 1196 64463759
Blister 17.97 15.86 10 33767 80957 64383998
Meningitis herpes 17.86 15.86 6 33771 213 64464742
Leukoencephalopathy 17.68 15.86 20 33757 6947 64458008
Maximal voluntary ventilation abnormal 17.59 15.86 3 33774 3 64464952
Tumour necrosis 17.49 15.86 11 33766 1698 64463257
Lymphangitis 17.47 15.86 10 33767 1301 64463654
Metastasis 17.34 15.86 18 33759 5677 64459278
Cardiac failure congestive 17.27 15.86 26 33751 130554 64334401
Metastatic neoplasm 17.18 15.86 16 33761 4426 64460529
Multiple-drug resistance 17.07 15.86 19 33758 6483 64458472
Hepatic enzyme increased 17.06 15.86 26 33751 129917 64335038
Heart rate decreased 16.95 15.86 4 33773 55063 64409892
Scleroderma-like reaction 16.86 15.86 5 33772 117 64464838
Metastases to kidney 16.78 15.86 7 33770 456 64464499
Renal salt-wasting syndrome 16.77 15.86 7 33770 457 64464498
Product use issue 16.62 15.86 34 33743 151681 64313274
Coma 16.50 15.86 13 33764 87602 64377353
Nephrogenic diabetes insipidus 16.50 15.86 11 33766 1876 64463079
Hyperhidrosis 16.40 15.86 25 33752 124895 64340060
Malaise 16.34 15.86 131 33646 396116 64068839
Stasis dermatitis 16.23 15.86 9 33768 1102 64463853

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01BA04 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Folic acid analogues
FDA MoA N0000000111 Folic Acid Metabolism Inhibitors
FDA EPC N0000175584 Folate Analog Metabolic Inhibitor
MeSH PA D000970 Antineoplastic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D005493 Folic Acid Antagonists
MeSH PA D019384 Nucleic Acid Synthesis Inhibitors
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:50683 dihydrofolic acid reductase inhibitors
CHEBI has role CHEBI:63720 dTMP synthase inhibitors
CHEBI has role CHEBI:63721 glycinamide ribonucleotide formyltransferase inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Non-small cell lung cancer indication 254637007 DOID:3908
Malignant mesothelioma of pleura indication 254645002 DOID:7474
Kidney disease contraindication 90708001 DOID:557
Impaired renal function disorder contraindication 197663003
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Breastfeeding (mother) contraindication 413712001




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.34 acidic
pKa2 5.15 acidic
pKa3 9.45 acidic
pKa4 13.09 acidic
pKa5 3.95 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
500MG/20ML (25MG/ML) PEMFEXY EAGLE PHARMS N209472 Feb. 8, 2020 RX SOLUTION INTRAVENOUS 7772209 May 24, 2022 USE OF PEMETREXED WITH PRIOR AND/OR REPEATED VITAMIN B12 AND FOLIC ACID ADMINISTRATION IN PATIENTS WITH MESOTHELIOMA
500MG/20ML (25MG/ML) PEMFEXY EAGLE PHARMS N209472 Feb. 8, 2020 RX SOLUTION INTRAVENOUS 7772209 May 24, 2022 USE OF PEMETREXED WITH PRIOR AND/OR REPEATED VITAMIN B12 AND FOLIC ACID ADMINISTRATION IN PATIENTS WITH NON-SQUAMOUS NON-SMALL CELL LUNG CANCER

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Thymidylate synthase Enzyme INHIBITOR IC50 6.47 WOMBAT-PK CHEMBL
Dihydrofolate reductase Enzyme INHIBITOR IC50 5.18 WOMBAT-PK CHEMBL
Trifunctional purine biosynthetic protein adenosine-3 Enzyme INHIBITOR Ki 6.42 CHEMBL DRUG LABEL
Serine hydroxymethyltransferase, cytosolic Enzyme Kd 4.77 CHEMBL
Folate receptor beta Membrane receptor IC50 7.22 CHEMBL
Proton-coupled folate transporter Transporter Ki 7.03 CHEMBL
Folate transporter 1 Transporter IC50 6.86 CHEMBL
Folate receptor alpha Membrane receptor IC50 7.38 CHEMBL
Folylpolyglutamate synthase, mitochondrial Enzyme WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme IC50 6.37 CHEMBL
Dihydrofolate reductase Enzyme Ki 6.25 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.64 CHEMBL
Thymidylate synthase Enzyme IC50 4.82 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.64 CHEMBL
Thymidylate synthase Enzyme Ki 6.47 CHEMBL
Thymidylate synthase Enzyme IC50 4.70 CHEMBL
Thymidylate synthase Enzyme Ki 6.26 CHEMBL
Dihydrofolate reductase Enzyme IC50 5.64 CHEMBL
Thymidylate synthase Enzyme IC50 5.96 CHEMBL
Thymidylate synthase (EC 2.1.1.45) (TS) (TSase) Enzyme IC50 4.12 CHEMBL
Trifunctional purine biosynthetic protein adenosine-3 Enzyme INHIBITOR Ki 5.03 IUPHAR

External reference:

IDSource
4021417 VUID
N0000148831 NUI
D03828 KEGG_DRUG
150399-23-8 SECONDARY_CAS_RN
4021417 VANDF
C0210657 UMLSCUI
CHEBI:63724 CHEBI
4DW PDB_CHEM_ID
CHEMBL225072 ChEMBL_ID
CHEMBL2360464 ChEMBL_ID
D000068437 MESH_DESCRIPTOR_UI
DB00642 DRUGBANK_ID
135410875 PUBCHEM_CID
6837 IUPHAR_LIGAND_ID
7675 INN_ID
357166-29-1 SECONDARY_CAS_RN
04Q9AIZ7NO UNII
1666923 RXNORM
17856 MMSL
32871 MMSL
48646 MMSL
d05047 MMSL
008494 NDDF
008495 NDDF
409159000 SNOMEDCT_US
411089001 SNOMEDCT_US
735172002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Alimta HUMAN PRESCRIPTION DRUG LABEL 1 0002-7623 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS NDA 33 sections
Alimta HUMAN PRESCRIPTION DRUG LABEL 1 0002-7640 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS NDA 33 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 0781-3518 INJECTION, SOLUTION 100 mg INTRAVENOUS NDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 0781-3519 INJECTION, SOLUTION 500 mg INTRAVENOUS NDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 0781-3520 INJECTION, SOLUTION 1000 mg INTRAVENOUS NDA 27 sections
Pemetrexed disodium HUMAN PRESCRIPTION DRUG LABEL 1 43598-370 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1 g INTRAVENOUS ANDA 28 sections
Pemetrexed disodium HUMAN PRESCRIPTION DRUG LABEL 1 43598-386 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 28 sections
Pemetrexed disodium HUMAN PRESCRIPTION DRUG LABEL 1 43598-387 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 28 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 60505-6065 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 60505-6066 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 60505-6067 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1000 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 60505-6068 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 750 mg INTRAVENOUS ANDA 27 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-134 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 28 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-450 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 28 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-621 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 750 mg INTRAVENOUS ANDA 28 sections
Pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 63323-622 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1 g INTRAVENOUS ANDA 28 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70710-1654 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 24 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70710-1655 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 24 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70710-1674 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1000 mg INTRAVENOUS ANDA 24 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70771-1691 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 100 mg INTRAVENOUS ANDA 1 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70771-1692 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 500 mg INTRAVENOUS ANDA 1 sections
pemetrexed HUMAN PRESCRIPTION DRUG LABEL 1 70771-1693 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 1000 mg INTRAVENOUS ANDA 1 sections