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Levetiracetam

AEMPS

Antiepileptics (other)

ATC code: N03AX14

Brand names: Keppra, Keppra XR

Updated · Methodology

Indications

A

Focal epilepsy

First line

First-line for focal epilepsy in adults and children per NG217 2022 and /AES 2018 (a free choice alongside lamotrigine). Start 250–500 mg twice daily; target 1000–3000 mg daily. In the head-to-head SANAD II trial (2021), levetiracetam was worse than lamotrigine for seizure control, so lamotrigine is often preferred, including on cost-effectiveness. Levetiracetam is pharmacologically convenient (minimal drug interactions, no hepatic enzyme induction, no weight gain), but in some patients it causes irritability, mood swings, and behavioral changes, with a risk of suicidal ideation, so mood should be monitored.

Sources

  1. AEMPS: Ficha técnica de Levetiracetam (2024)
  2. NICE: Epilepsies in children, young people and adults (NG217) (2022)
  3. Neurology: Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy (2018)
  4. The Lancet: The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial (2021)
  5. Cochrane Database of Systematic Reviews: Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data (2022)

ICD-10: G40.2 · ICD-11: 8A60

B

Post-stroke recovery

Second line

In post-stroke seizures, levetiracetam is preferred over phenytoin – fewer cognitive side effects and interactions. Per Stroke Guidelines, long-term secondary antiepileptic prophylaxis after a single seizure is not indicated – used only for recurrent seizures or status epilepticus.

For post-stroke seizures. Not for general «recovery enhancement».

Sources

  1. AEMPS: Ficha técnica de Levetiracetam (2024)
  2. ESO: European Stroke Organisation guidelines on post-stroke care (2021)

ICD-10: I69 · ICD-11: 8B25

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

F

Memory and concentration enhancement

Not recommended

Levetiracetam is an antiepileptic drug promoted in biohacker circles as a mild attention stabilizer or anti-anxiety agent for people without epilepsy. The rationale rests on two small studies in patients with mild cognitive impairment due to Alzheimer's disease (Bakker 2012, Vossel 2021) and on its sedative side effect. International guidelines for anxiety disorders ( NG87, , WFSBP) and for mild cognitive impairment ( 2018) do not mention levetiracetam. There are no clinical studies in healthy adults for concentration improvement or anxiety reduction. The side-effect profile (irritability, depression, behavioral disturbances up to suicidal risk, boxed warning) is not justified in people without epilepsy. If levetiracetam was prescribed for concentration or anxiety, consider seeking a second opinion.

Sources

  1. AEMPS: Ficha técnica de Levetiracetam (2024)
  2. Cochrane: Ginkgo biloba for cognitive impairment and dementia (2009)
How to read tiers A–F
  • AStrong evidence – first or second line in international guidelines
  • BRecommended in selected cases
  • CStudy data contradict each other
  • DBenefit not proven, no documented harm
  • FDocumented harm, or risk without benefit

Mechanism of action

Binds the presynaptic synaptic vesicle protein 2A (SV2A) in CNS neurons. Reduces release of excitatory neurotransmitters (glutamate) during pathological high-frequency neuronal activity. Does not affect normal neurotransmission. Minimal hepatic metabolism, renally excreted unchanged — few drug interactions, making levetiracetam convenient in polypharmacy and pregnancy.

Safety

Boxed warning

FDA class warning for antiepileptics: increased risk of suicidal ideation and behavior. Special monitoring in the first weeks of therapy and at dose changes.

Contraindications

  • Hypersensitivity

Serious adverse effects

  • Severe psychiatric effects — depression, psychosis, suicidal ideation (5–10 % of patients)
  • Severe cutaneous reactions — Stevens-Johnson syndrome (rare)
  • Thrombocytopenia, leukopenia (rare)
  • Acute kidney injury (very rare)

Common adverse effects

  • Somnolence, fatigue
  • Irritability, agitation
  • Dizziness
  • Headache
  • Nasopharyngitis

Pregnancy: can you take Levetiracetam?

AEMPS summary of product characteristics (section 4.6): a large body of post-marketing data on pregnant women exposed to levetiracetam monotherapy (more than 1,800, including more than 1,500 first-trimester exposures) does not suggest an increased risk of major congenital malformations. Evidence on neurodevelopment is limited: two Nordic population-based registry studies of more than 1,000 children of women with epilepsy exposed to levetiracetam monotherapy in utero do not suggest a higher risk of autism spectrum disorders or intellectual disability compared with children of women with epilepsy not exposed to antiepileptics, although follow-up was shorter in the levetiracetam group (for example, 4.4 versus 6.8 years in one study). Levetiracetam can be used in pregnancy if, after careful evaluation, it is considered clinically necessary, at the lowest effective dose; treatment is reviewed when a pregnancy is planned, monotherapy is preferred, and abrupt withdrawal is avoided because seizures can have serious consequences for the woman and the fetus. Plasma levetiracetam concentrations fall during pregnancy, most markedly in the third trimester (up to 60% of the pre-pregnancy baseline), so adequate clinical management of the pregnant woman must be ensured.

Breastfeeding: can you take Levetiracetam?

Transfers into milk in small amounts. Compatible with breastfeeding per LactMed, with infant monitoring.

Peak milk concentration
55.0 mg/L
Calculate RIDFull profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Twice daily with or without food. Extended-release Keppra XR — once daily. In eGFR below 80 — dose adjustment. During surgery and NPO status, switch to IV form at equivalent dose. Taper over 2–4 weeks on discontinuation — abrupt withdrawal may provoke seizures, including in patients in long remission.

Monitoring

Therapeutic drug monitoring (TDM) for levetiracetam is usually unnecessary — pharmacokinetics are predictable. Monitor: CBC, creatinine, liver enzymes at baseline and as indicated. Special attention to neuropsychiatric effects (irritability, aggression, depression), especially in children and adolescents. In patients with prior depression, discuss alternatives before initiation.

Drug–drug interactions

2 pairs found. Sorted from critical to minor.

MajorAlprazolamBenzodiazepines. Short-to-medium-acting anxiolytics

Mechanism

Additive CNS depression and sedation. No direct pharmacokinetic interaction – levetiracetam is not CYP-metabolised.

Symptoms

Drowsiness, slowed thinking and reactions, impaired coordination. With marked depression: slow, shallow breathing and confusion, up to coma (alprazolam SmPC). In older patients, sedation and muscle weakness increase the risk of falls (alprazolam SmPC).

Management

The alprazolam SmPC requires limiting the dose and duration of co-administration with antiepileptics, which include levetiracetam (alprazolam SmPC; alprazolam label of the US Food and Drug Administration, ). Use alprazolam at the lowest effective dose for the shortest time, no longer than 2–4 weeks; in older patients, start with 0.25 mg two or three times a day and use caution because of sedation, muscle weakness and the risk of falls (alprazolam SmPC). Advise the patient not to drive or operate machinery while taking alprazolam (alprazolam FDA label).

Sources

Pair details →Alprazolam →

MinorAmitriptylineTricyclic antidepressants (TCA)

Mechanism

Levetiracetam is not metabolised by the CYP system; no pharmacokinetic interaction with amitriptyline. Mild additive CNS depression is possible.

Symptoms

Possible mild sedation and fatigue at the start; usually resolve within 1–2 weeks.

Management

No dose adjustment needed. In epilepsy with depression or neuropathic pain, the combination is reasonable. Amitriptyline lowers seizure threshold at high doses, so begin with minimal doses (10 mg at bedtime) and monitor seizure frequency.

Sources

Pair details →Amitriptyline →

Label mentions15 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

  • ModerateMethotrexate
    «Metotrexato: Se ha notificado que la administración concomitante de levetiracetam y metotrexato disminuye el aclaramiento de metotrexato, lo que conduce a un aumento/prolongación de la concentración…»

    AEMPS, section 4.5 · Open on CIMA

  • anticonceptivos hormonalesclass named in the label
    «Anticonceptivos orales y otras interacciones farmacocinéticas: Dosis diarias de 1.000 mg de levetiracetam no influenciaron la farmacocinética de los anticonceptivos orales (etinilestradiol y…»

    AEMPS, section 4.5 · Open on CIMA

  • Digoxin
    «Anticonceptivos orales y otras interacciones farmacocinéticas: Dosis diarias de 1.000 mg de levetiracetam no influenciaron la farmacocinética de los anticonceptivos orales (etinilestradiol y…»

    AEMPS, section 4.5 · Open on CIMA

  • Ethinylestradiol
    «Anticonceptivos orales y otras interacciones farmacocinéticas: Dosis diarias de 1.000 mg de levetiracetam no influenciaron la farmacocinética de los anticonceptivos orales (etinilestradiol y…»

    AEMPS, section 4.5 · Open on CIMA

  • Gabapentin
    «Medicamentos antiepilépticos: Los datos de los estudios clínicos, realizados en adultos antes de la comercialización, indican que levetiracetam no influye en las concentraciones séricas de los…»

    AEMPS, section 4.5 · Open on CIMA

  • Lamotrigine
    «Medicamentos antiepilépticos: Los datos de los estudios clínicos, realizados en adultos antes de la comercialización, indican que levetiracetam no influye en las concentraciones séricas de los…»

    AEMPS, section 4.5 · Open on CIMA

  • laxantesclass named in the label
    «Laxantes: Al administrar de forma concomitante el laxante osmótico macrogol con levetiracetam por vía oral, se han notificado casos aislados de disminución de la eficacia de levetiracetam. Por ello…»

    AEMPS, section 4.5 · Open on CIMA

  • Levonorgestrel
    «Anticonceptivos orales y otras interacciones farmacocinéticas: Dosis diarias de 1.000 mg de levetiracetam no influenciaron la farmacocinética de los anticonceptivos orales (etinilestradiol y…»

    AEMPS, section 4.5 · Open on CIMA

  • Phenobarbital
    «Medicamentos antiepilépticos: Los datos de los estudios clínicos, realizados en adultos antes de la comercialización, indican que levetiracetam no influye en las concentraciones séricas de los…»

    AEMPS, section 4.5 · Open on CIMA

  • Phenytoin
    «Medicamentos antiepilépticos: Los datos de los estudios clínicos, realizados en adultos antes de la comercialización, indican que levetiracetam no influye en las concentraciones séricas de los…»

    AEMPS, section 4.5 · Open on CIMA

  • Valproic acid
    «Medicamentos antiepilépticos: Los datos de los estudios clínicos, realizados en adultos antes de la comercialización, indican que levetiracetam no influye en las concentraciones séricas de los…»

    AEMPS, section 4.5 · Open on CIMA

  • Warfarin
    «Anticonceptivos orales y otras interacciones farmacocinéticas: Dosis diarias de 1.000 mg de levetiracetam no influenciaron la farmacocinética de los anticonceptivos orales (etinilestradiol y…»

    AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

  • Carbamazepine
    «Combinaciones que requieren una consideración específica: Se ha notificado que el uso concomitante de carbamazepina y levetiracetam incrementa la toxicidad inducida por la carbamazepina.»

    AEMPS, section 4.5 · Open on CIMA

  • Eslicarbazepine acetate
    «Valproato y levetiracetam: Un análisis farmacocinético de la población en estudios de fase III con pacientes epilépticos adultos indicó que la administración concomitante de valproato o levetiracetam…»

    AEMPS, section 4.5 · Open on CIMA

  • Lamotrigine
    «Fármacos que tienen poco o ningún efecto en la concentración de lamotrigina: Levetiracetam»

    AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Levetiracetam used for?

Levetiracetam is evaluated for the following indications with varying evidence strength: Focal epilepsy (evidence tier A), Post-stroke recovery (evidence tier B), Memory and concentration enhancement (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Levetiracetam?

Common side effects of Levetiracetam (≥ 1 in 100): Somnolence, fatigue, Irritability, agitation, Dizziness, Headache, Nasopharyngitis. See the Safety section for uncommon and serious reactions.

Is Levetiracetam safe during pregnancy?

AEMPS summary of product characteristics (section 4.6): a large body of post-marketing data on pregnant women exposed to levetiracetam monotherapy (more than 1,800, including more than 1,500 first-trimester exposures) does not suggest an increased risk of major congenital malformations. Evidence on neurodevelopment is limited: two Nordic population-based registry studies of more than 1,000 children of women with epilepsy exposed to levetiracetam monotherapy in utero do not suggest a higher risk of autism spectrum disorders or intellectual disability compared with children of women with epilepsy not exposed to antiepileptics, although follow-up was shorter in the levetiracetam group (for example, 4.4 versus 6.8 years in one study). Levetiracetam can be used in pregnancy if, after careful evaluation, it is considered clinically necessary, at the lowest effective dose; treatment is reviewed when a pregnancy is planned, monotherapy is preferred, and abrupt withdrawal is avoided because seizures can have serious consequences for the woman and the fetus. Plasma levetiracetam concentrations fall during pregnancy, most markedly in the third trimester (up to 60% of the pre-pregnancy baseline), so adequate clinical management of the pregnant woman must be ensured.

Is Levetiracetam compatible with breastfeeding?

Transfers into milk in small amounts. Compatible with breastfeeding per LactMed, with infant monitoring.

Who should not take Levetiracetam?

Levetiracetam is contraindicated in: Hypersensitivity. Full list in the Safety section.

Does Levetiracetam carry an FDA boxed warning?

FDA class warning for antiepileptics: increased risk of suicidal ideation and behavior. Special monitoring in the first weeks of therapy and at dose changes.

Official sources

Direct links to regulator labels. Open in a new tab.

Other drugs in this group

Phenobarbital, Phenytoin, Pregabalin, Topiramate, Carbamazepine, Gabapentin, Valproic acid, Zonisamide