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Systematic (IUPAC) name
Clinical data
Trade names Keppra
AHFS/Drugs.com monograph
MedlinePlus a699059
Pregnancy cat. B3 (AU) C (US)
Legal status Prescription Only (S4) (AU) Prescription only
Routes Oral, intravenous
Pharmacokinetic data
Bioavailability ~100%
Protein binding <10%
Metabolism Enzymatic hydrolysis of acetamide group
Half-life 6 - 8 hr
Excretion Urinary
CAS number 102767-28-2 YesY
ATC code N03AX14
PubChem CID 5284583
DrugBank DB01202
ChemSpider 4447633 YesY
UNII 44YRR34555 YesY
KEGG D00709 YesY
Chemical data
Formula C8H14N2O2 
Mol. mass 170.209 g/mol
 N (what is this?)  (verify)

Levetiracetam (INN) /lɛvɨtɪˈræsɨtæm/ is an anticonvulsant medication used to treat epilepsy.[1] It is the S-enantiomer of etiracetam, structurally similar to the prototypical nootropic drug piracetam.

Levetiracetam is marketed under the trade name Keppra. Keppra is manufactured by UCB Pharmaceuticals Inc. Since November 2008 the drug has been available as a generic brand in the United States.

Medical uses[edit]

Levetiracetam has been approved in the European Union as a monotherapy treatment for epilepsy in the case of partial seizures, or as an adjunctive therapy for partial, myoclonic and tonic-clonic seizures.[2] It is also used in veterinary medicine for similar purposes.

Levetiracetam has potential benefits for other psychiatric and neurologic conditions such as Tourette syndrome, autism, bipolar disorder and anxiety disorder,[3] as well as Alzheimer's disease.[4] However, its most serious adverse effects are behavioral, and its benefit-risk ratio in these conditions is not well understood.[3]

Along with other anticonvulsants like gabapentin, it is also sometimes used to treat neuropathic pain. It has not been found to be useful for essential tremors.[5]

Adverse effects[edit]

Levetiracetam is generally well tolerated,[6] but may cause drowsiness, weakness, unsteady gait, fatigue, coordination problems, headache, pain, forgetfulness, anxiety, irritability or agitation, dizziness, mood changes, nervousness, loss of appetite, vomiting, diarrhea, throat pain, constipation, and changes in skin pigmentation.

Serious side effects may include depression, hallucinations, suicidal thoughts, seizures that are worse or different, fever, sore throat, signs of infection, double vision, itching, rash, swelling of the face. A study published in 2005 suggests that the addition of pyridoxine (vitamin B6) may curtail some of the psychiatric symptoms.[7]

A rare side effect of levetiracitam is a pins and needles sensation in the patient's legs, similar to neuropathy.

Levetiracetam was also found to have a variety of adverse effects on 2% of patients (particularly those predisposed to psychological symptoms); ranging from psychotic depression to fully realised psychosis, requiring hospitalisation.

Measurement in bodily fluids[edit]

Assay of Levetiracetam[8][edit]

There are only a few papers published reporting therapeutic drug monitoring methods of levetiracetam. Three of them employed HPLC with UV-detection,[9][10][11] and two methods were using GC with NPD-detection,.[10][12] Microemulsion electrokinetic chromatography with UV-detection was utilized in one method.[13] Two methods facilitating chiral separation of the S- and R- enantiomer of levetiracetam, one utilizing GC–MS and the other HPLC–UV, were published,.[14][15] These methods were designed to investigate in dogs the pharmacokinetic and pharmacodynamic properties of the two enantiomers separately. For routine therapeutic drug monitoring in men, these methods were not appropriate. In all but one of the methods,[11] sample preparation with SPE or liquid–liquid extraction is necessary. Pucci et al.[11] evaluated the feasibility of protein precipitation as the only sample preparation step in comparison to SPE. They concluded, that protein precipitation is a suitable and fast sample preparation for measuring routine patient samples. Mecarelli et al. [16] studied the concentration of levetiracetam in both serum and saliva of patients with epilepsy.

Various HPLC,[17][18][19][20][21][22][23] and LC-MS,[24][25][26] methods have been reported for the determination of levetiracetam in pure and pharmaceutical dosage forms.

Mechanism of action[edit]

The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. However, the drug binds to a synaptic vesicle glycoprotein, SV2A,[27] and inhibits presynaptic calcium channels [28] reducing neurotransmitter release and acting as a neuromodulator. This is believed to impede impulse conduction across synapses. [29]

Available forms[edit]

  • Ready-to-administer bags of Sodium Chloride Injection, at concentrations of 500 mg/100 mL, 1000 mg/100 mL and 1500 mg/100 mL[30]
  • 250 mg tablets
  • 500 mg tablets
  • 750 mg tablets
  • 1000 mg tablets

See also[edit]


  1. ^ Abou-Khalil B (June 2008). "Levetiracetam in the treatment of epilepsy". Neuropsychiatr Dis Treat 4 (3): 507–23. doi:10.2147/NDT.S2937. PMC 2526377. PMID 18830435. 
  2. ^ BNF 59. BMA & RPSGB. 2010. 
  3. ^ a b Farooq MU, Bhatt A, Majid A, Gupta R, Khasnis A, Kassab MY (2009). "Levetiracetam for managing neurologic and psychiatric disorders". Am J Health Syst Pharm 66 (6): 541–61. doi:10.2146/ajhp070607. PMID 19265183. 
  4. ^ Sanchez, Pascal; Zhu, Verret, Vossel, Orr, Cirrito, Devidze, Ho, Yu, Palop (August 6, 2012). "Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer's disease model". PNAS 109 (42): E2895–903. doi:10.1073/pnas.1121081109. PMC 3479491. PMID 22869752. 
  5. ^ http://www.neurology.org/content/early/2011/10/18/WNL.0b013e318236f0fd.abstract
  6. ^ Gambardella A, Labate A, Colosimo E, Ambrosio R, Quattrone A (February 2008). "Monotherapy for partial epilepsy: focus on levetiracetam". Neuropsychiatr Dis Treat 4 (1): 33–8. doi:10.2147/NDT.S1655. PMC 2515905. PMID 18728811. 
  7. ^ "Clinical Epilepsy: Pediatrics". Epilepsia 46 (s8): 142–67. 2005. doi:10.1111/j.1528-1167.2005.460801_16.x. 
  8. ^ Prafulla Kumar Sahu, M. Mathrusri Annapurna; Analytical Method development by Liquid Chromatography, LAP LAMBERT Academic Publishing GmbH & Co. KG, Germany, ISBN 978-3-8443-2869-1.
  9. ^ N. Ratnaraj, H.C. Doheny, P.N. Patsalos, Ther. Drug Monit. 18 (1996) 154.
  10. ^ a b T.A. Vermeij, P.M. Edelbroek, J. Chromatogr. B Biomed. Appl. 662 (1994) 134.
  11. ^ a b c V. Pucci, F. Bugamelli, R. Mandrioli, A. Ferranti, E. Kenndler, M.A. Raggi, Biomed. Chromatogr. 18 (2004) 37.
  12. ^ R. Coupez, R. Straetemans, G. Sehgal, A. Stockis, Z.S. Lu, J. Clin. Pharmacol. 43 (2003) 1370.
  13. ^ M. Ivanova, A. Piunti, E. Marziali, N. Komarova, M.A. Raggi, E. Kenndler, Electrophoresis 24 (2003) 992.
  14. ^ N. Isoherranen, M. Roeder, S. Soback, B. Yagen, V. Schurig, M. Bialer, J. Chromatogr. B Biomed. Sci. Appl. 745 (2000) 325.
  15. ^ N. Isoherranen, B. Yagen, S. Soback, M. Roeder, V. Schurig, M. Bialer, Epilepsia 42 (2001) 825.
  16. ^ O. Mecarelli, P. Li Voti, S. Pro, F.S. Romolo, M. Rotolo, P. Pulitano, N. Accornero, N. Vanacore, Saliva and serum levetiracetam concentrations in patients with epilepsy. Therapeutic Drug Monitoring (2007), 29(3), 313-318.
  17. ^ Prafulla Kumar Sahu*, Dillip Kumar Sahoo, M.M.Annapurna, M.E.Bhanoji Rao, Development and validation of an RP-HPLC method for determination of Levetiracetam in Bulk and Pharmaceutical Dosage Forms, Analytical Chemistry: An Indian Journal, 2009, 8(1).
  18. ^ C. Manuela, M. Susan, A. Fiorenzo, R. Roberto and B. Agostino, J chromatogr B., 2008, 873(1), 129.
  19. ^ N. Appala Raja, J. Venkateswara Rao, K. Vanitha Prakash, K. Mukkanti and K. Srinivasu, E Journal of Chemistry, 2008, 5(S2), 1098.
  20. ^ J. Valarmathy, L. Samueljoshua, G. Rathinavel, C. Selvin Thanija and T. Sivakumar,Research J Pharm and Tech., 2008, 1(3), 395.
  21. ^ J. Marten Lobenhoffer and S.M. Bode Boger, J Chromatogr B., 2005, 815, 197.
  22. ^ N. Ratnaraj, C. Doheny Helen and N. Patsalos Philip, Ther Drug Monit, 1996, 18(2), 154.
  23. ^ A.C. Vermeij and P.M. Edelbroek, J Chromatogr B., 1994, 662,134.
  24. ^ M. Kamal Matar, J Pharm Biomed Anal., 2008, 48(3), 822.
  25. ^ G. Saravanan, G. Jhothy, Y. Suresh, A. Annerao, M. Ramakrishna, M. Yogeshwar Reddy and B. Ravibabu, Chromatographia, 2008, 67, 173.
  26. ^ Tiedong Guo, M. Lisa Oswald, M. Damodara Rao and J. Steven Soldin, Clinica Chimica Acta, 2007, 375, 115.
  27. ^ Lynch BA, Lambeng N, Nocka K, et al. (June 2004). "The synaptic vesicle protein SV2A is the binding site for the antiepileptic drug levetiracetam". Proc Natl Acad Sci USA. 101 (26): 9861–6. doi:10.1073/pnas.0308208101. PMC 470764. PMID 15210974. 
  28. ^ Vogl C, Mochida S, Wolff C et al. (August 2012). "The Synaptic Vesicle Glycoprotein 2A Ligand Levetiracetam Inhibits Presynaptic Ca2+ Channels through an Intracellular Pathway". Mol Pharmacol. 82 (2): 199–208. doi:10.1124/mol.111.076687. PMID 22554805. 
  29. ^ Rogawski, MA (June 2006). "Diverse mechanisms of antiepileptic drugs in the development pipeline". Epilepsy Research 69 (3): 273–94. doi:10.1016/j.eplepsyres.2006.02.004. PMC 1562526. PMID 16621450. 
  30. ^ "Mylan Inc. (MYL) Launches Innovative Version of Antiepileptic Drug Levetiracetam". ClinicaSpace (press release) (Mylan). 20 Jan 2012. Retrieved 22 Jan 2012. 

External links[edit]