levetiracetam indications/contra

Stem definitionDrug idCAS RN
amide type nootrope agents, piracetam derivatives 1563 102767-28-2

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • keppra
  • levetiracetam
  • matever
  • (-)-Levetiracetam
  • levroxa
  • UCB-6474
  • UCB 6474
The precise mechanism(s) by which levetiracetam exerts its antiepileptic effect is unknown. The antiepileptic activity of levetiracetam was assessed in a number of animal models of epileptic seizures. Levetiracetam did not inhibit single seizures induced by maximal stimulation with electrical current or different chemoconvulsants and showed only minimal activity in submaximal stimulation and in threshold tests. Protection was observed, however, against secondarily generalized activity from focal seizures induced by pilocarpine and kainic acid, two chemoconvulsants that induce seizures that mimic some features of human complex partial seizures with secondary generalization. Levetiracetam also displayed inhibitory properties in the kindling model in rats, another model of human complex partial seizures, both during kindling development and in the fully kindled state. In vitro and in vivo recordings of epileptiform activity from the hippocampus have shown that levetiracetam inhibits burst firing without affecting normal neuronal excitability, suggesting that levetiracetam may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity. Levetiracetam at concentrations of up to 10 uM did not demonstrate binding affinity for a variety of known receptors, such as those associated with benzodiazepines, GABA (gamma-aminobutyric acid), glycine, NMDA (N-methyl-D-aspartate), re-uptake sites, and second messenger systems. Furthermore, in vitro studies have failed to find an effect of levetiracetam on neuronal voltage-gated sodium or T-type calcium currents and levetiracetam does not appear to directly facilitate GABAergic neurotransmission. However, in vitro studies have demonstrated that levetiracetam opposes the activity of negative modulators of GABA- and glycine-gated currents and partially inhibits N-type calcium currents in neuronal cells. A saturable and stereoselective neuronal binding site in rat brain tissue has been described for levetiracetam. Experimental data indicate that this binding site is the synaptic vesicle protein SV2A, thought to be involved in the regulation of vesicle exocytosis. Although the molecular significance of levetiracetam binding to synaptic vesicle protein SV2A is not understood, levetiracetam and related analogs showed a rank order of affinity for SV2A which correlated with the potency of their antiseizure activity in audiogenic seizure-prone mice. These findings suggest that the interaction of levetiracetam with the SV2A protein may contribute to the antiepileptic mechanism of action of the drug.
  • Molecular weight: 170.21
  • Formula: C8H14N2O2
  • CLOGP: -0.34
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 1
  • TPSA: 63.40
  • ALOGS: 0.24
  • ROTB: 3

Drug dosage:

DoseUnitRoute
1.50 g O
1.50 g P

Approvals:

DateAgencyCompanyOrphan
Sept. 29, 2000 EMA
Nov. 30, 1999 FDA UCB INC

FDA Adverse Event Reporting System

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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
Seizure 7066.59 35.51 2050 12643 38350 3332816
Pregnancy 3114.30 35.51 769 13924 7111 3364055
Status epilepticus 2379.38 35.51 532 14161 3003 3368163
Abortion spontaneous 2096.55 35.51 601 14092 10184 3360982
Foetal exposure during pregnancy 2092.47 35.51 652 14041 14899 3356267
Exposure during pregnancy 1910.88 35.51 702 13991 26861 3344305
Epilepsy 1437.37 35.51 407 14286 6538 3364628
Generalised tonic-clonic seizure 1431.21 35.51 419 14274 7623 3363543
Product substitution issue 1238.44 35.51 370 14323 7230 3363936
Drug ineffective 1128.80 35.51 776 13917 115314 3255852
Somnolence 1076.48 35.51 487 14206 31717 3339449
Aggression 1005.24 35.51 348 14345 11037 3360129
Off label use 900.49 35.51 510 14183 53467 3317699
Thrombocytopenia 894.15 35.51 441 14252 34827 3336339
Maternal drugs affecting foetus 884.29 35.51 244 14449 3527 3367639
Drug reaction with eosinophilia and systemic symptoms 861.09 35.51 283 14410 7612 3363554
Condition aggravated 772.64 35.51 414 14279 38819 3332347
Overdose 619.58 35.51 341 14352 33637 3337529
Abnormal behaviour 531.74 35.51 211 14482 9817 3361349
Premature baby 530.36 35.51 193 14500 7060 3364106
Maternal exposure during pregnancy 523.38 35.51 210 14483 10061 3361105
Partial seizures 481.64 35.51 120 14573 1127 3370039
Drug interaction 472.57 35.51 322 14371 46490 3324676
Agitation 464.41 35.51 235 14458 19471 3351695
Abortion induced 445.37 35.51 143 14550 3548 3367618
Caesarean section 440.26 35.51 149 14544 4377 3366789
Stillbirth 439.53 35.51 117 14576 1458 3369708
Psychotic disorder 432.52 35.51 175 14518 8559 3362607
Confusional state 428.15 35.51 280 14413 37718 3333448
Toxicity to various agents 414.89 35.51 298 14395 46756 3324410

Pharmacologic Action:

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SourceCodeDescription
ATC N03AX14 NERVOUS SYSTEM
ANTIEPILEPTICS
ANTIEPILEPTICS
Other antiepileptics
CHEBI has role CHEBI:35623 anticonvulsant
FDA PE N0000008486 Decreased Central Nervous System Disorganized Electrical Activity

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Epilepsy characterized by intractable complex partial seizures indication 442481002
Simple partial seizure indication 117891000119100
Partial Epilepsy Treatment Adjunct indication
Tonic-Clonic Epilepsy Treatment Adjunct indication
Myoclonic Epilepsy Adjunct Treatment indication
Suicidal thoughts contraindication 6471006
Hallucinations contraindication 7011001
Mood swings contraindication 18963009
Ataxia contraindication 20262006
Indifference contraindication 20602000
Abnormal gait contraindication 22325002
Feeling agitated contraindication 24199005
Depressive disorder contraindication 35489007 DOID:2848
Anxiety contraindication 48694002
Feeling irritable contraindication 55929007
Aggressive behavior contraindication 61372001
Psychotic disorder contraindication 69322001
Hostile behavior contraindication 79351003
Depersonalization contraindication 79499004
Fatigue contraindication 84229001
Leukopenia contraindication 84828003 DOID:615
Kidney disease contraindication 90708001 DOID:2527
Pancytopenia contraindication 127034005 DOID:12450
Disease of liver contraindication 235856003 DOID:409
Drowsy contraindication 271782001
Neutropenic disorder contraindication 303011007 DOID:1227
Behavioral Disorders contraindication

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.66 acidic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
1GM SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9339489 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
1GM SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
1GM SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FASTED CONDITIONS
1GM SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FED CONDITIONS
250MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9339489 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
250MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
250MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FASTED CONDITIONS
250MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FED CONDITIONS
500MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9339489 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
500MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
500MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FASTED CONDITIONS
500MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FED CONDITIONS
750MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9339489 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
750MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM
750MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FASTED CONDITIONS
750MG SPRITAM APRECIA PHARMS N207958 July 31, 2015 RX TABLET, FOR SUSPENSION ORAL 9669009 March 14, 2034 METHOD OF ADMINISTERING LEVETIRACETAM UNDER FED CONDITIONS

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Synaptic vesicle glycoprotein 2A Transporter MODULATOR Ki 6.10 CHEMBL CHEMBL
Carbonic anhydrase 1 Enzyme WOMBAT-PK
Voltage-dependent T-type calcium channel subunit alpha-1G Ion channel WOMBAT-PK
Sodium channel protein type 1 subunit alpha Ion channel WOMBAT-PK
Synaptic vesicle glycoprotein 2A Unclassified INHIBITOR IC50 6.10 IUPHAR

External reference:

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IDSource
CHEBI:6437 CHEBI
C0876060 UMLSCUI
6826 IUPHAR_LIGAND_ID
D00709 KEGG_DRUG
44YRR34555 UNII
6450 INN_ID
N0000148644 NDFRT
114477 RXNORM
66397 MMSL
d04499 MMSL
008058 NDDF
116076009 SNOMEDCT_US
387000003 SNOMEDCT_US
8574 MMSL
4021198 VANDF
CHEMBL1286 ChEMBL_ID
C026098 MESH_SUPPLEMENTAL_RECORD_UI
DB01202 DRUGBANK_ID
5284583 PUBCHEM_CID

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0054-0224 SOLUTION 100 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0121-0799 SOLUTION 100 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0121-1598 SOLUTION 1000 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0121-2397 SOLUTION 1500 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0121-4799 SOLUTION 500 mg ORAL ANDA 18 sections
LEVETIRACETAM HUMAN PRESCRIPTION DRUG LABEL 1 0121-4802 SOLUTION 100 mg ORAL ANDA 15 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0143-9574 INJECTION 100 mg INTRAVENOUS ANDA 16 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0143-9673 INJECTION 100 mg INTRAVENOUS ANDA 16 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0378-5613 TABLET, FILM COATED 250 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0378-5615 TABLET, FILM COATED 500 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0378-5617 TABLET, FILM COATED 750 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0378-5619 TABLET, FILM COATED 1000 mg ORAL ANDA 17 sections
LEVETIRACETAM HUMAN PRESCRIPTION DRUG LABEL 1 0409-1886 INJECTION, SOLUTION 100 mg INTRAVENOUS ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0472-0235 SOLUTION 100 mg ORAL ANDA 17 sections
levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0517-3605 INJECTION, SOLUTION, CONCENTRATE 100 mg INTRAVENOUS ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0591-3635 TABLET, FILM COATED, EXTENDED RELEASE 500 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0591-3699 TABLET, FILM COATED, EXTENDED RELEASE 750 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0603-1384 SOLUTION 100 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7550 TABLET, FILM COATED 250 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7551 TABLET, FILM COATED 500 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7552 TABLET, FILM COATED 750 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7553 TABLET 1000 mg ORAL ANDA 13 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7684 TABLET 1000 mg ORAL ANDA 15 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7976 TABLET, FILM COATED 250 mg ORAL ANDA 13 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7977 TABLET, FILM COATED 500 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7978 TABLET, FILM COATED 750 mg ORAL ANDA 13 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0615-7979 TABLET, FILM COATED 1000 mg ORAL ANDA 17 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0904-6051 TABLET 250 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0904-6052 TABLET 500 mg ORAL ANDA 18 sections
Levetiracetam HUMAN PRESCRIPTION DRUG LABEL 1 0904-6053 TABLET 750 mg ORAL ANDA 18 sections