EpilepsyRx

Levetiracetam

Keppra · Keppra XR

DailyMed-verified antiseizure indications

Indication / use

Label / evidence summary
Keppra immediate-release: focal-onset seizures from age 1 month; adjunctive myoclonic-seizure treatment in juvenile myoclonic epilepsy from age 12 years, and treatment of primary generalized tonic-clonic seizures in idiopathic generalized epilepsy from age 6 years. Keppra XR and Elepsia XR: focal-onset seizures from age 12 years (Elepsia XR is adjunctive). Spritam has separate age and weight requirements.
Role
Maintenance
Class
SV2A binding; modulation of synaptic vesicle function

Indications checked 26 September 2026. Product, route, age, and treatment-role limits apply. A DailyMed listing alone does not establish FDA approval.

Formulations & strengths

U.S. products unless another country is named. Strengths are per unit or stated volume.

Brand & formulation labels

Each link names the product and formulation it covers. Archived labels do not establish current availability.

Dosing & administration

Adult / product-specific schedule
Immediate release: typically 500 mg twice daily initially; titrate by indication to a usual maximum of 3,000 mg/day.
Pediatric
Focal seizures: 1–<6 months start 7 mg/kg twice daily → 21 mg/kg twice daily, increasing every 2 weeks. 6 months–<4 years start 10 → 25 mg/kg twice daily; 4–<16 years start 10 → 30 mg/kg twice daily (max 3,000 mg/day), in 2-week steps. Tablets have separate weight-band schedules; use oral solution for ≤20 kg. Myoclonic/PGTC schedules differ; see label.
Titration / repeat dosing
Adults: 500 mg twice daily; increase by 500 mg twice daily every 2 weeks to 1,500 mg twice daily. Pediatric focal seizures: begin 7–10 mg/kg twice daily by age and increase every 2 weeks to 21–30 mg/kg twice daily.

Dose adjustment & concentrations

Renal impairment
Dose adjustment required by creatinine clearance; supplemental dose after dialysis.
Hepatic impairment
Usually no adjustment; severe impairment may warrant renal-function assessment.
Serum reference information
Mayo trough reference interval 10–40 mcg/mL. Concentrations can assist with adherence, renal changes or pregnancy; response and tolerability take precedence over reaching this interval.

Safety

Boxed warning
No boxed warning.
Contraindications
Hypersensitivity to levetiracetam; anaphylaxis and angioedema have occurred.
Serious precautions & monitoring
Monitor irritability, aggression, psychosis, mood and sedation. Serious rash, DRESS, anaphylaxis/angioedema and hematologic abnormalities require assessment. Monitor blood pressure in children under 4; reassess seizure control during pregnancy. Avoid abrupt withdrawal.

Common / selected adverse effects

  • Somnolence, asthenia and dizziness.
  • Irritability, aggression and other behavioral symptoms; pediatric and adult trial rates differ.

Drug interactions: toxicity & clinical action

Partner / combinationClinical effectClinical action
Other ASMs / sedativesLow pharmacokinetic interaction potential in label studies, but additive somnolence/behavioral burden remains possible.Monitor clinical tolerability; renal function is a major determinant of levetiracetam exposure.
ProbenecidReduces clearance of the inactive metabolite, without changing parent-drug pharmacokinetics in the study.Do not infer a routine parent-drug dose change from this metabolite effect.
BrivaracetamNo added therapeutic benefit demonstrated from concomitant treatment.Review the need for two SV2A ligands.

Pregnancy & contraception

Fetal / neonatal risk
More than two decades of human levetiracetam pregnancy experience have not identified increased major-malformation or miscarriage risk. AAN/AES/SMFM recommends considering it when appropriate for the epilepsy syndrome and seizure-control needs.
Contraception
At 500 mg twice daily, levetiracetam did not alter ethinylestradiol/levonorgestrel exposure or ovulation markers in the label study.
Pregnancy / postpartum monitoring
Levetiracetam concentrations may decrease during pregnancy, especially in the third trimester. Monitor through pregnancy and reassess postpartum, particularly after pregnancy-related dose increases.

Clinical evidence

Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.

Direct pivotal trial Guideline-supported off-label use

Trial summary

Study design / duration
Multiple randomized, double-blind, placebo-controlled adjunctive trials; 12–18-week treatment periods after prospective baselines, with seizure-frequency reduction and ≥50% responder rate endpoints.
Primary endpoint
No single pivotal endpoint is identified in the cited source.
Results
Adjunctive focal-seizure trials: ≥50% responder rates were approximately 23–41% with levetiracetam versus 10–18% with placebo, varying by dose and study. Trial in generalized tonic-clonic seizures: median weekly seizure reduction was 77% versus 45% with placebo.

Trial publications

Comparative evidence

Findings
SANAD II: open-label randomized initial treatment of newly diagnosed focal epilepsy, age ≥5. For time to 12-month remission, levetiracetam did not meet noninferiority versus lamotrigine; zonisamide did in the intention-to-treat analysis. In generalized/unclassified epilepsy, SANAD II failed to establish levetiracetam non-inferiority to valproate for 12-month remission; per-protocol results favored valproate.

Mechanism of action

  • Binds SV2A, a synaptic vesicle protein involved in vesicle exocytosis. Experimental correlations support a contribution of this interaction to antiseizure activity.
  • The precise human mechanism is incompletely established. It is not a direct GABA-A agonist or a conventional sodium-channel blocker, and its action is not simply selective suppression of one transmitter.

Pharmacology

Adult values unless specified. Vd/F denotes apparent oral distribution volume.

Pharmacokinetics

Bioavailability
Approximately 100% oral bioavailability; tablets and oral solution are bioequivalent.
Elimination half-life
Adults: 7 ± 1 hour. Young children (1 month to <4 years): approximately 5.3 hours in the label study.
Volume of distribution
Approximately 0.5–0.7 L/kg (Keppra UK SmPC).
Active metabolite(s)
None: the principal hydrolysis product ucb L057 is pharmacologically inactive.
Active-metabolite half-life
Not applicable — no clinically established active metabolite.
Protein binding
<10%
Metabolism / elimination
Limited enzymatic hydrolysis; not CYP-dependent

Renal impairment and older age can prolong elimination.

Molecular structure

Molecular structure of Levetiracetam
Principal compound; salt and product forms may differ.
NIH PubChem structure and record ↗

Product history

Initial U.S. approval
1999
Brands
Keppra · Keppra XR
Manufacturer / marketer
UCB (Keppra/Keppra XR)
Generic availability
Yes
Related drugs
Brivaracetam—also an SV2A ligand, with higher SV2A affinity.

Sources & review status

Representative sources are selected product labels, not an exhaustive list of generic manufacturers. Consult the exact product and formulation prescribed. Brand-name package inserts are linked separately.

Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 5/2026. This is a draft reference; final review is pending.