Levetiracetam is effective as single-drug treatment for newly diagnosedfocal epilepsy in adults.[15][16] It reduces focal seizures by 50% or more as an add-on medication.[17]
Levetiracetam is effective for treatment of generalized tonic-clonic epilepsy.[16] It has been approved in the United States as add-on treatment formyoclonic, andtonic-clonic seizures.[4] Levetiracetam has been approved in the European Union as amonotherapy treatment for epilepsy in the case of partial seizures or as anadjunctive therapy for partial, myoclonic, and tonic-clonic seizures.[19]
Based on low-quality evidence, levetiracetam is about as effective as phenytoin for prevention of early seizures after traumatic brain injury.[22] It may be effective for prevention of seizures associated withsubarachnoid hemorrhages.[23]
Levetiracetam has not been found to be useful for treatment ofneuropathic pain,[24] nor for treatment ofessential tremors.[25] Levetiracetam has not been found to be useful for treating all developmental disorders within theautism spectrum;[26][27] studies have only proven to be an effective treatment for partial, myoclonic, or tonic-clonic seizures associated with autism spectrum disorder.[28]
Levetiracetam's efficacy and tolerability in individuals withintellectual disability is comparable to those without.[29]
Studies in female pregnant rats have shown minor fetal skeletal abnormalities when given maximum recommended human doses of levetiracetam orally throughout pregnancy and lactation.[medical citation needed]
Studies were conducted to look for increased adverse effects in the elderly population as compared to younger patients. One such study published in Epilepsy Research showed no significant increase in incidence of adverse symptoms experienced by young or elderly patients with disorders of the central nervous system.[medical citation needed]
Levetiracetam is the most commonly prescribed initial antiepileptic in infants who are between the ages of 1-36 months old. One study found 66% of participants to be seizure free after an average of 12 months on levetiracetam, a relatively high percentage compared to other antiepileptics.[30]
The most common adverse effects of levetiracetam treatment include effects on the central nervous system such as somnolence, decreased energy, headache, dizziness, mood swings and coordination difficulties. These adverse effects are most pronounced in the first month of therapy. About 4% of patients dropped out of pre-approval clinical trials due to these side effects.[4]
About 13% of people taking levetiracetam experience adverse neuropsychiatric symptoms, which are usually mild. These include agitation, hostility, apathy, anxiety, emotional lability, and depression. Serious psychiatric adverse side effects that are reversed by drug discontinuation occur in about 1%. These include hallucinations, suicidal thoughts, or psychosis. These occur mostly within the first month of therapy, but can rarely develop at any time during treatment.[31]
Although rare,Stevens–Johnson syndrome (SJS) andtoxic epidermal necrolysis (TEN), which appears as a painful spreading rash with redness and blistering and/or peeling skin, have been reported in patients treated with levetiracetam.[32] The incidence of SJS following exposure to anti-epileptics such as levetiracetam is about 1 in 3,000.[33]
Levetiracetam should not be used in people who have previously shown hypersensitivity to levetiracetam or any of the inactive ingredients in the tablet or oral solution. Such hypersensitivity reactions include, but are not limited to, unexplained rash with redness or blistered skin, difficulty breathing, and tightness in the chest or airways.[4]
In a study, the incidence of decreased bone mineral density of patients on levetiracetam was significantly higher than for those on different epileptic medications.[34]
Levetiracetam, along with other anti-epileptic drugs, can increase the risk of suicidal behavior or thoughts. Patients taking levetiracetam should be monitored closely for signs of worsening depression, suicidal thoughts or tendencies, or any altered emotional or behavioral states.[4]
Kidney impairment decreases the rate of elimination of levetiracetam from the body. Individuals with reduced kidney function may require dose adjustments, guided by monitoring ofkidney function.[4]
Dose adjustment of levetiracetam is not necessary in liver impairment.[4]
The exact mechanism by which levetiracetam acts to treat epilepsy is unknown. Levetiracetam does not exhibit pharmacologic actions similar to that of classical anticonvulsants. It does not inhibit voltage-dependent Na+ channels, does not affect GABAergic transmission, and does not bind to GABAergic or glutamatergic receptors.[37] However, the drug binds toSV2A,[38] asynaptic vesicleglycoprotein, and inhibitspresynapticcalcium channels,[39] reducingneurotransmitter release and acting as aneuromodulator. This is believed to impede impulse conduction across synapses.[40] As of 2024, this is widely accepted to be its mechanism of action.[10] However, the molecular basis of this action remains unknown.[10]
The absorption of levetiracetam tablets and oral solution is rapid and essentially complete. The bioavailability of levetiracetam is close to 100 percent, and the effect of food on absorption is minor.[4]
Levetiracetam does not undergo extensive metabolism, and the metabolites formed are not active and do not exert pharmacological activity. Metabolism of levetiracetam is not by liver cytochrome P450 enzymes, but through other metabolic pathways such as hydrolysis and hydroxylation.[4]
In persons with normal kidney function, levetiracetam is eliminated from the body primarily by the kidneys with about 66 percent of the original drug passed unchanged into urine. The plasma half-life of levetiracetam in adults is about 6 to 8 hours,[4] although the mean CSF half life of approx. 24 hours better reflects levels at site of action.[42]
Levetiracetam is available as regular and extended release oral formulations and as intravenous formulations.[43]
The immediate release tablet has been available as ageneric in the United States since 2008, and in the UK since 2011.[44][17] The patent for the extended release tablet will expire in 2028.[45]
In 2015, Aprecia'sorally disintegrating tablet form of the drug manufactured usingpharmaceutical 3D printing techniques was approved by theFDA, under the trade name Spritam.[46] Some have said that the drug has been improved by 3D printing, as the formula used now has improved disintegration properties.[47]
Levetiracetam is a Schedule 4 substance in Australia under thePoisons Standard (February 2020).[48] A Schedule 4 substance is classified as "Prescription Only Medicine, or Prescription Animal Remedy – Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription."[48]
Under Japanese law, levetiracetam and other racetams cannot be brought into the country except for personal use by a traveler for whom it has been prescribed.[49] Travelers who plan to bring more than a month's worth must apply for an import certificate, known as a Yakkan Shoumei (薬監証明,yakkan shōmei).[50]
Levetiracetam has been studied in the past for treating symptoms of neurobiological conditions such asTourette syndrome,[51] andanxiety disorder.[52] However, its most serious adverse effects are behavioral, and its benefit-risk ratio in these conditions is not well understood.[52]
Levetiracetam is being tested as a drug to reduce hyperactivity in the hippocampus inAlzheimer's disease.[53]
Many antiepileptic drugs cause changes in basicEEG activity. These include, in particular, carbamazepine, benzodiazepines, and phenobarbital. However, the effect of levetiracetam on basic EEG activity is minimal; no measurable increase in drug-induced beta activity was observed. At the same time, a significant reduction in seizure-like EEG abnormalities was observed.[55]
Of the ten medications evaluated in a 2023 systematic review of the literature, levetiracetam was found to be the only medication with sufficient evidence showing that it may cause seizure freedom in some infants.[30] Further, adverse effects from levetiracetam were rarely severe enough for the medication to be discontinued in this age group. Because available research included only two published studies reporting seizure freedom rates, however, the strength of the evidence was judged to be low.[30]
^abKumar A, Maini K, Kadian R (December 2023)."Levetiracetam.".StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.PMID29763065 – via U.S. National Library of Medicine, National Institute of Health.
^World Health Organization (2023).The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization.hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
^Brophy GM, Bell R, Claassen J, Alldredge B, Bleck TP, Glauser T, et al. (Neurocritical Care Society Status Epilepticus Guideline Writing Committee) (August 2012). "Guidelines for the evaluation and management of status epilepticus".Neurocritical Care.17 (1):3–23.doi:10.1007/s12028-012-9695-z.PMID22528274.S2CID4675838.
^Meierkord H, Boon P, Engelsen B, Göcke K, Shorvon S, Tinuper P, et al. (March 2010). "EFNS guideline on the management of status epilepticus in adults".European Journal of Neurology.17 (3):348–355.doi:10.1111/j.1468-1331.2009.02917.x.PMID20050893.S2CID1032139.
^Khan NR, VanLandingham MA, Fierst TM, Hymel C, Hoes K, Evans LT, et al. (December 2016). "Should Levetiracetam or Phenytoin Be Used for Posttraumatic Seizure Prophylaxis? A Systematic Review of the Literature and Meta-analysis".Neurosurgery.79 (6):775–782.doi:10.1227/NEU.0000000000001445.PMID27749510.
^Hirota T, Veenstra-Vanderweele J, Hollander E, Kishi T (April 2014). "Antiepileptic medications in autism spectrum disorder: a systematic review and meta-analysis".Journal of Autism and Developmental Disorders.44 (4):948–957.doi:10.1007/s10803-013-1952-2.PMID24077782.S2CID36509998.
^Browne TR, Szabo GK, Leppik IE, Josephs E, Paz J, Baltes E, et al. (June 2000). "Absence of pharmacokinetic drug interaction of levetiracetam with phenytoin in patients with epilepsy determined by new technique".Journal of Clinical Pharmacology.40 (6):590–595.doi:10.1002/j.1552-4604.2000.tb05984.x.PMID10868309.S2CID35576679.
^Gidal BE, Baltès E, Otoul C, Perucca E (2005). "Effect of levetiracetam on the pharmacokinetics of adjunctive antiepileptic drugs: a pooled analysis of data from randomized clinical trials".Epilepsy Research.64 (1–2):1–11.doi:10.1016/j.eplepsyres.2005.01.005.PMID15823510.S2CID13555324.
^Dimova H, Wang X, Men A, Krudys K (3 October 2013).Clinical Pharmacology/Biopharmaceutics Review (Report). US Food & Drug Administration (FDA). Archived fromthe original on 14 December 2019.Keppra injection and Keppra XR (Levetiracetam) Labeling Supplements to fulfill PREA PMR
^Webber K (12 September 2011)."FDA Access Data"(PDF).ANDA 091291. Department of Health and Human Services.Archived(PDF) from the original on 4 March 2016. Retrieved4 November 2015.
^abFarooq MU, Bhatt A, Majid A, Gupta R, Khasnis A, Kassab MY (March 2009). "Levetiracetam for managing neurologic and psychiatric disorders".American Journal of Health-System Pharmacy.66 (6):541–561.doi:10.2146/ajhp070607.PMID19265183.
^Derkowski W, Kedzia A (2008). "Computer analysis of EEG activity in patients with epilepsy treated with levetiracetam.". In Zarzycki J (ed.).The computer-aided scientific research = Komputerowe wspomaganie badań naukowych. The Works of Wrocław Scientific Society = Prace Wrocławskiego Towarzystwa Naukowego. Seria B. Wrocław: Wrocław Scientific Society. pp. 233–238.ISBN978-83-7374-056-3.
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