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Levetiracetam: Drug information

Levetiracetam: Drug information
(For additional information see "Levetiracetam: Patient drug information" and see "Levetiracetam: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
Levetiracetam Safety Alert November 2023

The FDA has issued a drug safety communication warning that levetiracetam (Keppra, Keppra XR, Elepsia XR, Spritam) can cause Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), a rare but serious hypersensitivity reaction that can be life-threatening if not diagnosed and treated quickly. The onset of DRESS typically occurs 2 to 8 weeks after starting levetiracetam; symptoms may include rash, fever, or swollen lymph nodes but can quickly progress, resulting in injury to organs including the liver, kidney, lungs, heart, or pancreas, the need for hospitalization, and death. The FDA is requiring warnings about this risk to be added to the prescribing information and Medication Guide. Health care providers should advise patients of the signs and symptoms of DRESS and to stop taking their medication and seek immediate medical attention if DRESS is suspected during treatment with levetiracetam.

Further information may be found at https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-rare-serious-drug-reaction-antiseizure-medicines-levetiracetam-keppra-keppra-xr-elepsia-xr

Brand Names: US
  • Elepsia XR;
  • Keppra;
  • Keppra XR;
  • Roweepra;
  • Roweepra XR [DSC];
  • Spritam
Brand Names: Canada
  • ACH-Levetiracetam;
  • AG-Levetiracetam;
  • APO-Levetiracetam;
  • Auro-Levetiracetam;
  • BIO-Levetiracetam [DSC];
  • JAMP-Levetiracetam;
  • Keppra;
  • M-Levetiracetam;
  • MINT-Levetiracetam;
  • NAT-Levetiracetam;
  • NRA-Levetiracetam;
  • PDP-Levetiracetam;
  • PMS-Levetiracetam;
  • Priva-Levetiracetam [DSC];
  • PRO-Levetiracetam-250;
  • PRO-Levetiracetam-500;
  • PRO-Levetiracetam-750;
  • RAN-Levetiracetam [DSC];
  • RIVA-Levetiracetam;
  • SANDOZ Levetiracetam;
  • TEVA-Levetiracetam
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous
Dosing: Adult

Dosage guidance:

Dosing: When switching between oral and IV formulations, the total daily dose should be the same.

Craniotomy, seizure prophylaxis

Craniotomy, seizure prophylaxis (off-label use):

Initial: IV: 500 mg to 1 g intraoperatively prior to incision (Ref).

Maintenance: IV, Oral: 1 g/day in 2 divided doses; usual dosage range: 500 mg to 3 g/day (Ref); adjust dose based on response and tolerability (Ref).

Focal onset seizures and generalized onset seizures

Focal (partial) onset seizures and generalized onset seizures:

Note: FDA approved for mono- and adjunctive therapy of focal (partial) onset seizures, and adjunctive therapy of juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures; used off label for other seizure types (Ref).

Oral:

Immediate release (tablets, oral solution, tablets for oral suspension): Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose based on response and tolerability to the maximum recommended dose of 1.5 g twice daily.

Extended release (FDA approved only for focal [partial] onset seizures): Initial: 1 g once daily; increase every 2 weeks by 1 g/day based on response and tolerability to a maximum of 3 g once daily.

Note: In patients with epilepsy, oral loading doses of 1.5 to 2 g (immediate release) have been well tolerated and may be useful for more rapidly achieving steady-state serum concentrations (Ref); however, the necessity of an oral loading dose has not been established.

IV: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose based on response and tolerability to a maximum of 1.5 g twice daily.

Note: Additional benefit of oral or IV doses >3 g/day has not been established; however, oral doses of 4 g/day have been studied in patients with refractory epilepsy but may be associated with a greater incidence of somnolence (Ref).

Status epilepticus

Status epilepticus (off-label use): IV: 1 to 3 g as a single dose administered at a rate of 2 to 5 mg/kg/minute (Ref) or 40 to 60 mg/kg as a single dose infused over 5 to 15 minutes in combination with a parenteral benzodiazepine. Maximum single dose: 4.5 g (Ref).

Subarachnoid hemorrhage

Subarachnoid hemorrhage (short-term seizure prophylaxis) (off-label use):

Note: Consider use in patients with seizure at presentation (onset seizure) or patients at high risk for seizures (eg, those with ruptured middle cerebral artery aneurysm, high-grade aneurysmal subarachnoid hemorrhage, intracranial hemorrhage, hydrocephalus, cortical infarction) (Ref).

Loading dose: IV: 20 mg/kg (rounded to the nearest 250 mg) as a one-time dose (Ref).

Maintenance dose: IV: 1 g every 12 hours for up to 7 days; may be increased to a maximum dose of 1.5 g every 12 hours if necessary (Ref).

Traumatic brain injury

Traumatic brain injury (severe acute ) (short-term seizure prophylaxis) (off-label use):

Loading dose: IV: 20 mg/kg (rounded to the nearest 250 mg) as a one-time dose (Ref).

Maintenance dose: IV: 1 g every 12 hours for 7 days; may be increased to a maximum dose of 1.5 g every 12 hours if necessary (Ref).

Conversion between oral levetiracetam IR and ER dosage forms: When switching between ER and IR formulations of levetiracetam, the same total daily dose should be used (Ref).

Discontinuation of therapy: In chronic therapy, withdraw gradually to minimize the potential of increased seizure frequency and status epilepticus, unless safety concerns require a more rapid withdrawal.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Loading doses should be utilized when indicated (see adult dosing) and administered unadjusted for renal function or dialytic therapy. For maintenance doses, the risks/benefits favor dosing on the higher side of the recommended dosing range when initiating treatment, particularly in patients with acute seizures (Ref).

Altered kidney function:

Note: The manufacturer's labeling recommends estimating CrCl using the Cockcroft-Gault formula adjusted for BSA as follows: CrCl (mL/minute/1.73 m2) = CrCl (mL/minute)/BSA (m2) x 1.73.

IR and IV formulations (Ref):

CrCl 80 to 130 mL/minute/1.73 m2: 500 mg to 1.5 g every 12 hours.

CrCl 50 to <80 mL/minute/1.73 m2: 500 mg to 1 g every 12 hours.

CrCl 30 to <50 mL/minute/1.73 m2: 250 to 750 mg every 12 hours.

CrCl 15 to <30 mL/minute/1.73 m2: 250 to 500 mg every 12 hours.

CrCl <15 mL/minute/1.73 m2: 250 to 500 mg every 24 hours (Ref).

ER tablet:

CrCl >80 mL/minute/1.73 m2: 1 to 3 g every 24 hours.

CrCl 50 to 80 mL/minute/1.73 m2: 1 to 2 g every 24 hours.

CrCl 30 to 50 mL/minute/1.73 m2: 500 mg to 1.5 g every 24 hours.

CrCl <30 mL/minute/1.73 m2: 500 mg to 1 g every 24 hours.

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma (eg, traumatic brain injury) or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to confirm presence of ARC in these patients (Ref).

Note: Doses derived from pharmacokinetic simulations (Ref) and expert opinion.

IR and IV formulations: CrCl >130 mL/minute/1.73 m2: 1.5 to 2 g every 12 hours.

ER tablet: CrCl >130 mL/minute/1.73 m2: 3 to 4 g every 24 hours.

Hemodialysis, intermittent (thrice weekly): Dialyzable (50%):

IR and IV formulations: 500 mg to 1 g every 24 hours; a supplemental dose of 250 to 500 mg is recommended post each hemodialysis session (Ref).

ER tablet: Use not recommended.

Peritoneal dialysis: Note: Limited data available; dosing based on a case report demonstrating toxicity at a higher dose (Ref) and expert opinion.

IR and IV formulations: 250 to 500 mg every 24 hours.

ER tablet: Use not recommended.

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of ~1,500 to 3,000 mL/hour, unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: Note: Dose based on limited data (Ref) and expert opinion. Higher effluent rates (eg, 4,000 to 5,000 mL/hour) may require higher total daily doses (eg, up to 4 g/day), although the safety of these higher doses has not been evaluated (Ref).

IR and IV formulations: 750 mg to 1.25 g every 12 hours.

PIRRT (eg, sustained low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations and initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

Note: Dose based on limited data (Ref) and expert opinion.

IR and IV formulations: 500 mg to 1 g every 12 hours.

Dosing: Hepatic Impairment: Adult

The hepatic dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD

Note: Levetiracetam is not extensively metabolized by the liver. In a single-dose pharmacokinetic study, there were no differences in the parameters of patients with Child-Turcotte-Pugh class A and B cirrhosis, but clearance was reduced and half-life was prolonged in patients with Child-Turcotte-Pugh class C cirrhosis compared to healthy volunteers. These changes were attributed to reduced kidney function seen in the Child-Turcotte-Pugh class C patients and not due to altered hepatic function (Ref).

Hepatic impairment prior to treatment initiation:

Initial or dose titration in patients with preexisting liver cirrhosis:

Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref).

Dosage adjustment in patients with chronic, worsening hepatic function during treatment (eg, progression from Child-Turcotte-Pugh class A to B):

Progression from baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref).

Acute worsening of hepatic function (eg, requiring hospitalization):

Child-Turcotte-Pugh class A to C: No dosage adjustment necessary; however, consider discontinuation of levetiracetam therapy in patients with suspected levetiracetam-induced liver injury (Ref).

Dosing: Older Adult

Refer to adult dosing; lower doses (eg, administration of 50% to 70% of the usual dose) and gradual dose increases (eg, ≤125 mg/week) may be required due to reduced drug clearance (Ref).

Dosing: Pediatric

(For additional information see "Levetiracetam: Pediatric drug information")

Dosage guidance:

Safety: Avoid abrupt discontinuation of therapy to reduce risk of increased seizure frequency or status epilepticus.

Dosing: Use oral solution in infants and children ≤20 kg. Parenteral IV therapy should be temporary and transitioned to oral when able; when switching from oral to IV formulation, the total daily dose (individual dose and frequency) should be the same.

Myoclonic seizures with juvenile myoclonic epilepsy; adjunct

Myoclonic seizures with juvenile myoclonic epilepsy; adjunct: Children ≥12 years and Adolescents: IV, Oral (immediate release: Tablets, oral solution [eg, Keppra], or tablets for oral suspension [Spritam]): Initial 500 mg twice daily; increase dosage every 2 weeks by 500 mg/dose twice daily based on response and tolerability to the recommended dose of 1,500 mg twice daily.

Partial-onset seizures

Partial-onset (focal) seizures: Note: Dosing for monotherapy or adjunct therapy is the same for indicated oral preparations.

Infants 1 to <6 months: IV, Oral (immediate release: Oral solution [monotherapy or adjunct]): Initial: 7 mg/kg/dose twice daily; increase dosage every 2 weeks by 7 mg/kg/dose twice daily based on response and tolerability to the recommended dose of 21 mg/kg/dose twice daily.

Infants ≥6 months and Children <4 years: IV, Oral (immediate release: Oral solution or tablets [monotherapy or adjunct]): Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily based on response and tolerability to the recommended dose of 25 mg/kg/dose twice daily.

Children ≥4 years and Adolescents <16 years:

IV: Monotherapy or adjunct: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily based on response and tolerability to the recommended dose of 30 mg/kg/dose twice daily; the maximum daily dose was 3,000 mg/day in clinical trials.

Oral:

Immediate release: Monotherapy or adjunct:

Weight-directed dosing: Oral solution: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily based on response and tolerability to the recommended dose of 30 mg/kg/dose twice daily; the maximum daily dose was 3,000 mg/day in clinical trials.

Fixed dosing: Tablet (immediate release [eg, Keppra] or for oral suspension [Spritam]):

20 to 40 kg: Initial: 250 mg twice daily; increase dosage every 2 weeks by 250 mg twice daily based on response and tolerability to the maximum recommended dose of 750 mg twice daily.

>40 kg: Initial: 500 mg twice daily; increase dosage every 2 weeks by 500 mg twice daily based on response and tolerability to the maximum recommended dose of 1,500 mg twice daily.

Extended release (eg, Elepsia XR [adjunct]; Keppra XR [monotherapy or adjunct]): Children ≥12 years and Adolescents: Initial: 1,000 mg once daily; may increase dosage every 2 weeks by 1,000 mg/day based on response and tolerability to a maximum recommended dose of 3,000 mg once daily.

Adolescents ≥16 years:

IV: Monotherapy or adjunct: Initial: 500 mg twice daily; increase dosage every 2 weeks by 500 mg/dose twice daily based on response and tolerability to a maximum recommended dose of 1,500 mg twice daily.

Oral:

Immediate release (tablets, oral solution [eg, Keppra], tablets for oral suspension [Spritam]; monotherapy or adjunct): Initial: 500 mg twice daily; increase dosage every 2 weeks by 500 mg twice daily based on response and tolerability to the maximum recommended dose of 1,500 mg twice daily.

Extended release (eg, Elepsia XR [adjunct], Keppra XR [monotherapy or adjunct]): Initial: 1,000 mg once daily; increase dosage every 2 weeks by 1,000 mg/day based on response and tolerability to a maximum recommended dose of 3,000 mg once daily.

Seizure prophylaxis, traumatic brain injury

Seizure prophylaxis, traumatic brain injury: Note: Current guidelines state that there is not sufficient evidence to recommend levetiracetam over phenytoin (Ref).

Infants, Children, and Adolescents: Limited data available, optimal dose not defined: IV, Oral (tablets, oral solution [eg, Keppra]): 20 to 55 mg/kg/day in divided doses twice daily; reported range: 5 to 55 mg/kg/day (Ref). In one prospective observational study, patients with moderate to severe traumatic brain injury (TBI) (n=34, ages 5 days to 16 years) received a median dose of 20 mg/kg/day in divided doses twice daily (range: 5 to 40 mg/kg/day). 17.6% patients experienced seizure despite therapy, with the highest percentage in younger patients and those with a history of abuse (Ref). Another prospective observational study of patients with TBI at risk for seizures used a dose of 55 mg/kg/day in divided doses (n=20, ages 6 to 17 years); one patient developed seizures 7 days after initial trauma (Ref).

Status epilepticus, urgent therapy/second-phase therapy or refractory

Status epilepticus, urgent therapy/second-phase therapy or refractory:

American epilepsy society guidelines (Ref): Limited data available: Infants, Children, and Adolescents: IV: 60 mg/kg as a single dose; maximum dose: 4,500 mg/dose; initiate maintenance therapy based upon clinical response and type of seizure disorder.

Neurocritical care guidelines (Ref): Limited data available: Infants, Children, and Adolescents: IV: 20 to 60 mg/kg as a single dose; initiate maintenance therapy based upon clinical response and type of seizure disorder; Note: Maximum dose in adults is 3,000 mg/dose.

Tonic-clonic seizures; primary generalized; adjunct

Tonic-clonic seizures; primary generalized; adjunct:

Children ≥6 years and Adolescents <16 years:

IV: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily based on response and tolerability to the recommended dose of 30 mg/kg/dose twice daily.

Oral: Immediate release:

Weight-directed: Oral solution or tablets: Initial: 10 mg/kg/dose twice daily; increase dosage every 2 weeks by 10 mg/kg/dose twice daily based on response and tolerability to the recommended dose of 30 mg/kg/dose twice daily.

Fixed-dosing: Orally disintegrating tablets [Spritam]:

20 to 40 kg: Initial: 250 mg twice daily; increase dosage every 2 weeks by 250 mg twice daily based on response and tolerability to the maximum recommended dose of 750 mg twice daily.

>40 kg: Initial: 500 mg twice daily; increase dosage every 2 weeks by 500 mg twice daily based on response and tolerability to the maximum recommended dose of 1,500 mg twice daily.

Adolescents ≥16 years: IV, Oral (immediate release: Oral solution or tablets [eg, Keppra], tablets for oral suspension [Spritam]): Initial: 500 mg twice daily; increase dosage every 2 weeks by 500 mg/dose twice daily based on response and tolerability to the recommended dose of 1,500 mg twice daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Altered kidney function:

IV, Oral (immediate-release formulations [tablets, oral solution] and tablets for oral suspension): Infants, Children, and Adolescents: GFR <50 mL/minute/1.73 m2: Administer 50% of the dose (Ref).

Oral extended-release formulations (Elepsia XR, Keppra XR): Children ≥12 years and Adolescents: There are no pediatric-specific recommendations provided in the manufacturer's labeling; based on experience in adult patients, dosage adjustment may be necessary.

Augmented renal clearance (CrCl >130 mL/minute/1.73 m2): There are no pediatric-specific recommendations for dosing in patients with augmented renal clearance; based on adult pharmacokinetic studies, dosage adjustment may be necessary.

Hemodialysis, intermittent: Dialyzable (50%):

IV, Oral (immediate-release formulations [tablets, oral solution] and tablets for oral suspension): Infants, Children, and Adolescents: Administer 50% of normal dose every 24 hours; a supplemental dose after hemodialysis is recommended (Ref).

Oral extended-release formulations (Elepsia XR, Keppra XR): Children ≥12 years and Adolescents: There are no pediatric-specific recommendations provided in the manufacturer's labeling; based on experience in adult patients, use not recommended.

Peritoneal dialysis:

IV, Oral (immediate-release formulations [tablets, oral solution] and tablets for oral suspension): Infants, Children, and Adolescents: Administer 50% of the dose (Ref).

Oral extended-release formulations (Elepsia XR, Keppra XR): Children ≥12 years and Adolescents: There are no pediatric-specific recommendations provided in the manufacturer's labeling; based on experience in adult patients, use not recommended.

Continuous renal replacement therapy (CRRT):

IV, Oral (immediate-release formulations [tablets, oral solution] and tablets for oral suspension): Infants, Children, and Adolescents: Administer 50% of the dose; monitor closely (Ref). Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Close monitoring of patient response and adverse reactions is recommended.

PIRRT (eg, sustained low-efficiency diafiltration): There are no pediatric-specific recommendations provided in the manufacturer's labeling. Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Based on adult experience, dose adjustment may be necessary, and close monitoring of patient response and adverse reactions is recommended.

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment necessary

Adverse Reactions (Significant): Considerations
CNS depression

Levetiracetam may cause CNS depression (asthenia, ataxia [includes abnormal gait, incoordination], fatigue, dizziness, and somnolence [drowsiness]), which may impair physical or mental abilities. Of note, somnolence was the most common reason for levetiracetam discontinuation in the US pivotal partial seizure trial (Ref).

Mechanism: Dose-related; most likely related to activity at the synaptic vesicle protein 2a.

Onset: Varied; generally, appear within the first month of treatment and during the up-titration period (Ref).

Risk factors:

Somnolence:

• Doses ≥4 g/day (potential risk factor) (Ref)

• Initiation and up-titration (Ref)

• IV formulation (Ref)

Hypersensitivity reactions (delayed)

Levetiracetam is associated with a variety of delayed hypersensitivity reactions, ranging from mild maculopapular rash (Ref) to severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref), drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref), and acute generalized exanthematous pustulosis (Ref).

Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions, including maculopapular eruptions and SCARs, are T-cell-mediated (Ref).

Onset: Delayed hypersensitivity reactions: Varied; maculopapular rash usually develops within 7 to 14 days (Ref). SCARs usually occur 1 to 8 weeks after initiation (Ref); re-exposure may lead to more rapid onset (usually within 1 to 4 days) (Ref).

Risk factors:

• Cross-reactivity: Not adequately described. In patients with a history of DRESS from an aromatic antiseizure medication (eg, phenytoin, carbamazepine), levetiracetam (a non-aromatic antiseizure medication) has been well tolerated (Ref).

Psychiatric and behavioral abnormalities

Psychotic symptoms, paranoid ideation, hallucinations, and behavioral changes (including aggressive behavior, agitation, outbursts of anger, anxiety, apathy, confusion, depersonalization, depression, emotional lability, hostility, dyskinesia, irritability, nervousness, neurosis, and personality disorder) may occur in adult and pediatric patients; dose reduction or discontinuation may be required. Suicidal ideation and suicidal tendencies have also been reported (Ref).

Mechanism: Exact mechanism unknown; some evidence suggests that a negative modulating effect on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors contributes to increased aggressive behavior (Ref).

Onset: Varied; may occur as early as 1 week after initiation.

Risk factors:

• Developmental delays or intellectual disability (Ref)

• Females (Ref)

• Type of epilepsy, (especially frontal lobe epilepsy [including brain tumor-related], absence epilepsy, and difficult-to-treat [“treatment-resistant”] epilepsy) (Ref)

• History of psychiatric disorders (eg, ADHD, depression, anxiety, personality disorder, suicidality, or psychotropic or recreational drug use) (Ref)

• History of social deprivation (Ref)

• Pediatric patients (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences are for all indications and populations (infants, children, adolescents, and adults) unless otherwise specified.

>10%:

Cardiovascular: Increased blood pressure (diastolic; infants and children <4 years: 17%) (table 1)

Levetiracetam: Adverse Reaction: Increased Blood Pressure

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

17%

2%

Infants and children

N/A

N/A

N/A

Gastrointestinal: Vomiting (children and adolescents: 15%)

Infection: Infection (adults: 13%)

Nervous system: Asthenia (adults: 15%) (table 2), behavioral changes (including outbursts of anger, apathy, depersonalization, neurosis, personality disorder; children and adolescents: 7% to 38%; adults: 7% to 13%) (table 3), drowsiness (infants, children, adolescents, and adults: 8% to 15%) (table 4), fatigue (children and adolescents: 10% to 11%) (table 5), headache (14% to 19%), irritability (infants, children, and adolescents: 6% to 12%) (table 6), psychotic symptoms (infants, children, and adolescents: 2% to 17%; adults: 1%) (table 7)

Levetiracetam: Adverse Reaction: Asthenia

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

15%

9%

Adults

Partial-onset seizures

769

439

Levetiracetam: Adverse Reaction: Behavioral Changes

Drug (Levetiracetam)

Placebo

Population

Dosage Form

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

7%

4%

Children and adolescents

N/A

Partial-onset seizures

165

131

38%

19%

Children and adolescents

N/A

N/A

N/A

N/A

7%

0%

Adults

XR tablets

Partial-onset seizures

N/A

N/A

13%

6%

Adults

N/A

N/A

N/A

N/A

Levetiracetam: Adverse Reaction: Drowsiness

Drug (Levetiracetam)

Placebo

Population

Dosage Form

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

13%

2%

Infants and children

N/A

Partial-onset seizures

60

56

13%

9%

Children and adolescents

N/A

Partial-onset seizures

165

131

12%

2%

Adolescents and adults

N/A

Myoclonic seizures

60

60

15%

8%

Adults

N/A

Partial-onset seizures

769

439

8%

3%

N/A

XR tablets

Partial-onset seizure

77

79

Levetiracetam: Adverse Reaction: Fatigue

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

11%

5%

Children and adolescents

Partial-onset seizures

165

131

10%

8%

Children and adolescents

PGTC seizures

79

84

Levetiracetam: Adverse Reaction: Irritability

Drug (Levetiracetam)

Placebo

Population

Dosage Form

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

12%

0%

Infants and children

N/A

Partial-onset seizures

60

56

7%

1%

Children and adolescents

N/A

Partial-onset seizures

165

131

6%

2%

Children and adolescents

N/A

PGTC seizures

79

84

7%

0%

N/A

XR tablets

Partial-onset seizures

77

79

Levetiracetam: Adverse Reaction: Psychotic Symptoms

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

17%

5%

Infants and children

N/A

N/A

N/A

2%

2%

Children and adolescents

N/A

N/A

N/A

1%

0.2%

Adults

N/A

N/A

N/A

Respiratory: Nasopharyngitis (7% to 15%)

1% to 10%:

Gastrointestinal: Anorexia (3% to 4%), constipation (children and adolescents: 3%), decreased appetite (children and adolescents: 8%), diarrhea (children and adolescents: 6% to 8%), gastroenteritis (children and adolescents: 2%), nausea (5%), upper abdominal pain (children and adolescents: 9%)

Hematologic & oncologic: Bruise (children and adolescents: 3%), eosinophilia (children and adolescents: 9%)

Infection: Influenza (3% to 8%)

Nervous system: Aggressive behavior (children and adolescents: 10%; adults: 1%) (table 8), agitation (children and adolescents: 4%) (table 9), amnesia (adults: 2%), anxiety (2%) (table 10), ataxia (adult partial-onset seizures: 3%) (table 11), confusion (children and adolescents: 2% to 3%) (table 12), depression (3% to 5%) (table 13), dizziness (5% to 9%) (table 14), emotional lability (2% to 5%) (table 15), falling (children and adolescents: 3%),hostility (adults: 2%) (table 16), insomnia (children and adolescents: 5%), lethargy (children and adolescents: 6%), mood changes (children and adolescents: 3%), nervousness (adults: 4%) (table 17), pain (adults: 7%), paranoid ideation (children and adolescents: 2%; adults: <1%) (table 18), paresthesia (adults: 2%), sedated state (children and adolescents: 2%), vertigo (3% to 5%)

Levetiracetam: Adverse Reaction: Aggressive Behavior

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

10%

5%

Children and adolescents

Partial-onset seizures

165

131

Levetiracetam: Adverse Reaction: Agitation

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

4%

1%

Children and adolescents

Partial-onset seizures

165

131

Levetiracetam: Adverse Reaction: Anxiety

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

2%

1%

Adults

Partial-onset seizures

769

439

Levetiracetam: Adverse Reaction: Ataxia

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

3%

1%

Adults

Partial-onset seizures

769

439

3%

2%

Adults

Partial-onset seizures

N/A

N/A

Levetiracetam: Adverse Reaction: Confusion

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

2%

0%

Children and adolescents

Partial-onset seizures

165

131

3%

0%

Children and adolescents

N/A

N/A

N/A

Levetiracetam: Adverse Reaction: Depression

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

3%

1%

Children and adolescents

Partial-onset seizures

165

131

5%

2%

Adolescents and adults

Myoclonic Seizures

60

60

4%

2%

Adults

Partial-onset seizures

769

439

Levetiracetam: Adverse Reaction: Dizziness

Drug (Levetiracetam)

Placebo

Population

Dosage Form

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

7%

5%

Children and adolescents

N/A

Partial-onset seizures

165

131

9%

4%

Adults

N/A

Partial-onset seizures

769

439

5%

3%

N/A

XR tablets

Partial-Onset Seizure

77

79

Levetiracetam: Adverse Reaction: Emotional Lability

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

2%

1%

Children and adolescents

Partial-onset seizures

165

131

5%

1%

Children and adolescents

PGTC seizures

79

84

2%

0%

Adults

Partial-onset seizures

769

439

Levetiracetam: Adverse Reaction: Hostility

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

2%

1%

Adults

Partial-onset seizures

769

439

Levetiracetam: Adverse Reaction: Nervousness

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

4%

2%

Adults

Partial-onset seizures

769

439

Levetiracetam: Adverse Reaction: Paranoid Ideation

Drug (Levetiracetam)

Placebo

Population

Indication

Number of Patients (Levetiracetam)

Number of Patients (Placebo)

2%

0%

Children and adolescents

N/A

N/A

N/A

Neuromuscular & skeletal: Arthralgia (children and adolescents: 2%), joint sprain (children and adolescents: 2%), neck pain (children and adolescents: 2% to 8%)

Ophthalmic: Conjunctivitis (children and adolescents: 2%), diplopia (adults: 2%)

Otic: Otalgia (children and adolescents: 2%)

Respiratory: Cough (2% to 9%), nasal congestion (children and adolescents: 9%), pharyngitis (6% to 7%), pharyngolaryngeal pain (children and adolescents: 7%), rhinitis (2% to 4%), sinusitis (adults: 2%)

Frequency not defined: Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, leukopenia, lymphocytosis

Postmarketing:

Cardiovascular: Prolonged QT interval on ECG (Mann 2023), torsades de pointes (Mann 2023)

Dermatologic: Acute generalized exanthematous pustulosis (Lee 2014), alopecia (Pitton Rissardo 2023), bullous pemphigoid (Santaliz-Ruiz 2022), eczema, erythema multiforme, maculopapular rash (Kim 2020), psoriasiform eruption (Gencler 2015), skin hyperpigmentation (Algahtani 2017), Stevens-Johnson syndrome (Park 2019), toxic epidermal necrolysis (Duong 2013)

Endocrine & metabolic: Hypokalemia (Coughlin 2022), hyponatremia (Nasrallah 2005), weight loss (Gelisse 2008)

Gastrointestinal: Gingival hyperplasia (James 2022), pancreatitis (including acute pancreatitis [Almeida 2013])

Genitourinary: Sexual disorder (Calabrò 2013)

Hematologic & oncologic: Agranulocytosis, hypogammaglobulinemia (Ozdemir 2018), neutropenia (Taberner Bonastre 2015), pancytopenia (with bone marrow suppression in some cases) (Gohil 2018, Garcia Carretero 2016), thrombocytopenia (Kim 2017)

Hepatic: Hepatic failure (Jayashankar 2019), hepatitis (including autoimmune hepatitis [Hegazy 2023]), hepatotoxicity (Rogalewski 2021)

Hypersensitivity: Anaphylaxis (Koklu 2014), angioedema (Alkhotani 2012), drug reaction with eosinophilia and systemic symptoms (Bayram 2016), hypersensitivity angiitis (Gupta 2017)

Nervous system: Aseptic meningitis (Vickery 2022), choreoathetosis, disturbance in attention, encephalopathy (Verma 2013), exacerbation of epilepsy (SCN8A-related epilepsy), hallucination (including auditory hallucination and visual hallucination) (Tahir 2022), hypomania (Altınöz 2019), manic reaction (Stoppa 2022), memory impairment, myasthenia, myoclonus (Nonaka 2022), obsessive compulsive disorder, panic attack, parkinsonism (Gatto 2006), polyneuropathy (Kapoor 2005), suicidal ideation (Cramer 2003), suicidal tendencies (Cramer 2003)

Neuromuscular & skeletal: Dyskinesia (Yim 2019), myalgia (Akiyama 2014), rhabdomyolysis (Boucher 2022; Saito 2023), systemic lupus erythematosus (Jadhav 2021)

Ophthalmic: Blurred vision

Renal: Acute kidney injury (Hurwitz 2009), granulomatous interstitial nephritis (Chau 2012), interstitial nephritis (Hurwitz 2009)

Respiratory: Eosinophilic pneumonitis (Fagan 2017), interstitial lung disease (Newsome 2007)

Contraindications

Hypersensitivity (eg, anaphylaxis, angioedema) to levetiracetam or any component of the formulation.

Warnings/Precautions

Disease-related concerns:

• Renal impairment: Use caution with renal impairment; dosage adjustment may be necessary.

Other warnings/precautions:

• Withdrawal: Antiseizure medications should not be discontinued abruptly because of the possibility of increasing seizure frequency and status epilepticus; therapy should be withdrawn gradually to minimize the potential of increased seizure frequency, unless safety concerns require a more rapid withdrawal.

Dosage Forms Considerations

Note: Tablets for oral suspension and soluble disintegrating tablet both refer to Spritam.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Keppra: 500 mg/5 mL (5 mL)

Generic: 500 mg/100 mL (100 mL); 1000 mg/100 mL (100 mL); 1500 mg/100 mL (100 mL); 500 mg/5 mL (5 mL)

Solution, Intravenous [preservative free]:

Generic: 500 mg/100 mL (100 mL); 1000 mg/100 mL (100 mL); 1500 mg/100 mL (100 mL); 500 mg/5 mL (5 mL); 250 mg/50 mL in NaCl 410 mg/50 mL (50 mL)

Solution, Oral:

Keppra: 100 mg/mL (473 mL) [gluten free, lactose free; contains methylparaben, propylparaben; grape flavor]

Generic: 100 mg/mL (5 mL, 10 mL, 473 mL)

Tablet, Oral:

Keppra: 250 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake]

Keppra: 500 mg [scored]

Keppra: 750 mg [scored; contains fd&c yellow #6(sunset yellow)alumin lake]

Keppra: 1000 mg [scored]

Roweepra: 500 mg [DSC]

Roweepra: 500 mg [contains corn starch]

Roweepra: 750 mg [DSC] [contains corn starch, fd&c yellow #6(sunset yellow)alumin lake]

Roweepra: 1000 mg [DSC] [contains corn starch]

Generic: 250 mg, 500 mg, 750 mg, 1000 mg

Tablet Disintegrating Soluble, Oral:

Spritam: 250 mg, 500 mg, 750 mg, 1000 mg [spearmint flavor]

Tablet Extended Release 24 Hour, Oral:

Elepsia XR: 1000 mg, 1500 mg [contains fd&c blue #1 (brill blue) aluminum lake]

Keppra XR: 500 mg, 750 mg

Roweepra XR: 500 mg [DSC], 750 mg [DSC]

Generic: 500 mg, 750 mg

Generic Equivalent Available: US

May be product dependent

Pricing: US

Solution (Keppra Intravenous)

500 mg/5 mL (per mL): $15.97

Solution (Keppra Oral)

100 mg/mL (per mL): $2.28

Solution (levETIRAcetam in NaCl Intravenous)

250 mg/50 mL (per mL): $0.19

500 mg/100 mL (per mL): $0.07 - $0.33

1000 mg/100 mL (per mL): $0.13 - $0.54

1500 mg/100 mL (per mL): $0.18 - $0.72

Solution (levETIRAcetam Intravenous)

500 mg/5 mL (per mL): $0.29 - $3.00

Solution (levETIRAcetam Oral)

100 mg/mL (per mL): $0.10 - $1.01

Tablet Disintegrating Soluble (Spritam Oral)

250 mg (per each): $12.02

500 mg (per each): $12.02

750 mg (per each): $12.02

1000 mg (per each): $12.02

Tablet, 24-hour (Elepsia XR Oral)

1000 mg (per each): $33.28

1500 mg (per each): $41.68

Tablet, 24-hour (Keppra XR Oral)

500 mg (per each): $10.74

750 mg (per each): $16.13

Tablet, 24-hour (levETIRAcetam ER Oral)

500 mg (per each): $4.45 - $4.47

750 mg (per each): $6.67 - $6.68

Tablets (Keppra Oral)

250 mg (per each): $9.69

500 mg (per each): $11.85

750 mg (per each): $16.05

1000 mg (per each): $23.70

Tablets (levETIRAcetam Oral)

250 mg (per each): $0.05 - $3.26

500 mg (per each): $0.08 - $3.52

750 mg (per each): $0.12 - $4.77

1000 mg (per each): $0.17 - $11.50

Tablets (Roweepra Oral)

500 mg (per each): $3.51

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 500 mg/5 mL (5 mL)

Solution, Oral:

Generic: 100 mg/mL (300 mL)

Tablet, Oral:

Keppra: 250 mg, 500 mg, 750 mg

Generic: 250 mg, 500 mg, 750 mg, 1000 mg

Administration: Adult

IV: For IV use only; manufacturer recommends infusing over 15 minutes. However, undiluted doses ≤2 g have been administered over 2 to 5 minutes (Ref) and undiluted doses ≤4.5 g have been administered over 5 minutes (Ref). Alternatively, a 1:1 dilution with compatible diluent (eg, 1 g levetiracetam per 10 mL diluted in 10 mL of NS; total volume administered: 20 mL) has been administered over 5 minutes with doses up to 4 g (Ref) and doses up to 4.5 g over 10 minutes (Ref).

Oral: Administer without regard to meals.

Oral solution: Administer with a calibrated measuring device (not a household teaspoon or tablespoon).

Tablet:

Disintegrating soluble tablet for oral suspension: Remove from blister by peeling back the foil (do not push tablet through the foil). Place whole tablet on the tongue with dry hand, follow with a sip of liquid and swallow only after tablet disintegrates. Do not swallow tablets intact. Partial tablets should not be administered. Tablet disintegrates in a mean time of 11 seconds (ranging from 2 to 27 seconds) in the mouth when taken with a sip of liquid.

Alternatively, allow whole tablet to disperse in a small volume of liquid (one tablespoon or enough to cover the tablet) in a cup; consume entire contents immediately; resuspend any residue by adding an additional small volume of liquid and swallow the full amount.

Immediate release: Manufacturer labeling recommends that tablets should be swallowed whole, not chewed or crushed; however, some studies support crushing and mixing with applesauce (Note: Levetiracetam has a bitter taste) or administering via enteral feeding tube. Mix with 120 mL of enteral nutrition formula or disperse crushed tablets (500 mg tablet strength studied) in 10 mL of water, shake for 5 minutes to dissolve, and administer immediately via enteral feeding tube (Ref).

Extended release: Only administer as whole tablet; do not crush, break, or chew.

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR tablet, orally disintegrating tablet, or oral solution.

Administration: Pediatric

Oral: May be administered without regard to meals.

Immediate release:

Oral solution: Administer with calibrated measuring device (not household teaspoon or tablespoon).

Tablets: Manufacturer labeling recommends that tablets should be swallowed whole, not chewed or crushed; however, some studies support crushing and mixing with applesauce, or sprinkling on food; it should be noted that levetiracetam has a bitter taste which may need masked; it has also been administered via enteral feeding tube (Ref). In adults, levetiracetam 500 mg tablets were studied crushed and mixed in 120 mL of enteral nutrition formula, 4 oz of applesauce (Ref), or 10 mL of water and shaken for 5 minutes to disperse (Ref).

Tablets, disintegrating for oral suspension (Spritam): Remove from blister by peeling back the foil (do not push tablet through the foil). Place whole tablet on the tongue with dry hand; follow with a sip of liquid and swallow only after tablet disintegrates; do not swallow intact tablet. Partial/split tablets should not be administered. Tablet disintegrates in a mean time of 11 seconds (ranging from 2 to 27 seconds) in the mouth when taken with a sip of liquid.

Alternatively, allow whole tablet to disperse in a small volume of liquid (eg, 15 mL or enough to cover the tablet[s]) in a cup; consume entire contents immediately; resuspend any residue in cup by adding an additional small volume of liquid and swallow the full amount.

Extended-release tablets: Swallow tablets whole; do not break, crush, or chew.

Parenteral: IV: Vials must be diluted prior to use. Do not use if solution contains particulate matter or is discolored. Discard unused portions; does not contain preservative.

Neonates:

Concentrations ≤15 mg/mL: Infuse over 10 to 15 minutes (Ref).

Concentrations of 20 mg/mL: Infuse at a rate of 1 mg/kg/minute (Ref).

Infants, Children, and Adolescents:

Concentrations ≤15 mg/mL: Infuse over 15 minutes per the manufacturer; in status epilepticus a rate of 2 to 5 mg/kg/minute has been recommended (Ref).

Concentration 50 mg/mL: A 1:1 dilution (50 mg/mL) infused over 5 to 10 minutes (with doses up to 60 mg/kg or 4,500 mg) through a peripheral line has been reported in patients ≥6 months (Ref).

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Elepsia XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/204417s004lbl.pdf#page=25

Keppra: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021035s113,021505s052lbl.pdf#page=32

Keppra XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022285s034lbl.pdf#page=26

Spritam: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/207958s023lbl.pdf#page=36

Use: Labeled Indications

Focal (partial) onset seizures:

IR tablets/oral solution: Treatment of focal (partial) onset seizures in adults, adolescents, children, and infants ≥1 month of age with epilepsy.

Tablets for oral suspension: Treatment of focal (partial) onset seizures in adults and children ≥4 years of age and >20 kg.

ER tablets: Treatment of focal (partial) onset seizures in adults and adolescents ≥12 years of age with epilepsy.

IV: Treatment of focal (partial) onset seizures in adults and children ≥1 month of age with epilepsy.

Limitation of use: IV use is only as an alternative when oral administration is temporarily not feasible.

Generalized onset seizures:

Juvenile myoclonic epilepsy:

IR tablets/oral solution/tablets for oral suspension: Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years and older with juvenile myoclonic epilepsy.

IV: Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years and older with juvenile myoclonic epilepsy.

Primary generalized tonic-clonic seizures:

IR tablets/oral solution/tablets for oral suspension: Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years and older with idiopathic generalized epilepsy.

IV: Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years and older with idiopathic generalized epilepsy.

Use: Off-Label: Adult

Craniotomy, seizure prophylaxis; Status epilepticus; Subarachnoid hemorrhage (short-term seizure prophylaxis); Traumatic brain injury, severe acute (short-term seizure prophylaxis)

Medication Safety Issues
Sound-alike/look-alike issues:

Keppra may be confused with Keflex, Keppra XR

LevETIRAcetam may be confused with brivaracetam, lamoTRIgine, levOCARNitine, levoFLOXacin

Potential for dispensing errors between Keppra and Kaletra (lopinavir/ritonavir)

Metabolism/Transport Effects

Substrate of OAT1/3

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Apixaban: LevETIRAcetam may diminish the therapeutic effect of Apixaban. Risk C: Monitor therapy

Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Brivaracetam: LevETIRAcetam may diminish the therapeutic effect of Brivaracetam. Specifically, the therapeutic effect of brivaracetam may be diminished and/or negligible when given to patients already receiving levetiracetam. Management: Consider alternatives to the combined use of levetiracetam and brivaracetam due to an apparent lack of brivaracetam effectiveness in patients receiving levetiracetam. Risk D: Consider therapy modification

Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

CarBAMazepine: LevETIRAcetam may enhance the adverse/toxic effect of CarBAMazepine. CarBAMazepine may decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Dabigatran Etexilate: LevETIRAcetam may enhance the anticoagulant effect of Dabigatran Etexilate. LevETIRAcetam may diminish the therapeutic effect of Dabigatran Etexilate. Risk C: Monitor therapy

Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy

DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification

Edoxaban: LevETIRAcetam may diminish the therapeutic effect of Edoxaban. Risk C: Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification

Fosphenytoin-Phenytoin: May decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Gabapentin: LevETIRAcetam may enhance the CNS depressant effect of Gabapentin. Risk C: Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification

Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

LamoTRIgine: LevETIRAcetam may enhance the CNS depressant effect of LamoTRIgine. Risk C: Monitor therapy

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mefloquine: May diminish the therapeutic effect of Antiseizure Agents. Mefloquine may decrease the serum concentration of Antiseizure Agents. Management: Mefloquine is contraindicated for malaria prophylaxis in persons with a history of seizures. If antiseizure drugs are being used for another indication, monitor antiseizure drug concentrations and treatment response closely with concurrent use. Risk D: Consider therapy modification

Methotrexate: LevETIRAcetam may increase the serum concentration of Methotrexate. Risk C: Monitor therapy

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

MetyraPONE: Antiseizure Agents may diminish the diagnostic effect of MetyraPONE. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

Mianserin: May diminish the therapeutic effect of Antiseizure Agents. Risk C: Monitor therapy

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orlistat: May decrease the serum concentration of Antiseizure Agents. Risk C: Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

OXcarbazepine: May decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

PHENobarbital: LevETIRAcetam may enhance the CNS depressant effect of PHENobarbital. PHENobarbital may decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy

Primidone: LevETIRAcetam may enhance the CNS depressant effect of Primidone. Primidone may decrease the serum concentration of LevETIRAcetam. Risk C: Monitor therapy

Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Rivaroxaban: LevETIRAcetam may decrease the serum concentration of Rivaroxaban. Risk C: Monitor therapy

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Valproate Products: LevETIRAcetam may enhance the CNS depressant effect of Valproate Products. Risk C: Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification

Food Interactions

Food may delay, but does not affect the extent of absorption. Management: Administer without regard to meals.

Pregnancy Considerations

Levetiracetam crosses the placenta and can be detected in the newborn following delivery (Johannessen 2005; López-Fraile 2009; Tomson 2007).

An increase in the overall rate of major congenital malformations has not been observed following maternal use of levetiracetam. Available studies have not been large enough to determine if there is an increased risk of specific birth defects (Hernández-Díaz 2012; Mawhinney 2013; Mølgaard-Nielsen 2011; Vajda 2012). In general, maternal polytherapy with antiseizure drugs may increase the risk of congenital malformations; monotherapy with the lowest effective dose is recommended. Newborns of women taking antiseizure medications may be at an increased risk of SGA and a 1 minute APGAR score <7 (Harden 2009).

Due to pregnancy-induced physiologic changes, plasma concentrations of levetiracetam gradually decrease during pregnancy, especially during the third trimester; patients should be closely monitored during pregnancy and postpartum.

A registry is available for women exposed to levetiracetam during pregnancy: Pregnant women may enroll themselves into the North American Antiepileptic Drug (AED) Pregnancy Registry (888-233-2334 or http://www.aedpregnancyregistry.org/).

Breastfeeding Considerations

Levetiracetam is present in breast milk.

The relative infant dose (RID) of levetiracetam is 7.9% when calculated using data derived from the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 1 to 3 g/day.

In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).

The RID of levetiracetam was calculated using an average milk:maternal plasma ratio of 1.05, providing an estimated daily infant dose via breast milk of ~2.4 mg/kg/day. This average milk:maternal plasma ratio was calculated using samples collected from 11 mother-infant pairs 4 to 23 days postpartum following maternal administration of oral levetiracetam 1 to 3 g/day. Concomitant maternal medications included lamotrigine, carbamazepine, tiagabine, clobazam, and/or oxcarbazepine which may have impacted maternal plasma concentrations. Levetiracetam was detected in the plasma of the breastfed infants (Tomson 2007).

Adverse effects, including hypotonia, sedation, vomiting, weight loss, and poor suckling have been reported in breastfed infants (Kramer 2002; Paret 2014). Insufficient lactation and subsequent discontinuation of breastfeeding has also been reported (Paret 2014).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Maternal plasma concentrations should be monitored postpartum.

Monitoring Parameters

Diastolic BP in children 1 month to <4 years; CBC (in patients who experience significant weakness, pyrexia, recurrent infections or coagulation disorders); suicidality (eg, suicidal thoughts, depression, behavioral changes).

Reference Range

Timing of serum samples: Draw trough just before next dose.

Laboratory alert level: 50 mcg/mL (SI: 294 mcmol/L) (AGNP [Hiemke 2018])

Therapeutic reference range: Note: There is no clear correlation with serum concentrations and efficacy or tolerability; base dosing on therapeutic response as opposed to serum concentrations; however, serum concentration monitoring may be useful in older adult patients, neonates, pregnant patients, and patients on enzyme-inducing drugs or with renal insufficiency due to the wide range of alterations in clearance (Sourbron 2018).

Epilepsy: 12 to 46 mcg/mL (SI: 70 to 270 mcmol/L) (AGNP [Hiemke 2018]; Patsalos 2018)

Mechanism of Action

The precise mechanism by which levetiracetam exerts its antiseizure effect is unknown. However, several studies have suggested the mechanism may involve one or more of the following central pharmacologic effects: inhibition of voltage-dependent N-type calcium channels; facilitation of GABA-ergic inhibitory transmission through displacement of negative modulators; reduction of delayed rectifier potassium current; and/or binding to synaptic proteins which modulate neurotransmitter release.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Oral: Rapid and almost complete.

Immediate release: Food decreases Cmax by 20% and delays time to Cmax (Tmax) by 1.5 hours.

Extended release: Intake of a high-fat, high-calorie breakfast before the administration results in a higher Cmax and longer median Tmax; the median Tmax is 2 hours longer in the fed state.

Distribution: Vd: Similar to total body water.

Term neonates: 1.01 ± 0.13 L/kg (range: 0.81 to 1.24 L/kg) (Sharpe 2012).

Infants and Children <4 years of age: 0.63 ± 0.08 L/kg (Glauser 2007).

Children 6 to 12 years of age: 0.72 ± 0.12 L/kg (Pellock 2001).

Adults: 0.5 to 0.7 L/kg.

Protein binding: <10%.

Metabolism: Not extensive; 24% of dose is metabolized by enzymatic hydrolysis of acetamide group (major metabolic pathway; hydrolysis occurs primarily in the blood; not cytochrome P450 dependent); two minor metabolites (one via hydroxylation of 2-oxo-pyrrolidine ring and one via opening of the 2-oxo-pyrrolidine ring in position 5) are also formed; metabolites are inactive and renally excreted.

Bioavailability: 100%; bioavailability of ER tablets is similar to IR tablets; tablets, oral solution, and injection are bioequivalent.

Half-life elimination: Increased in patients with renal impairment:

Term neonates (PNA ≤5 days at therapy initiation) (Sharpe 2012):

Day 1 of therapy : 18.5 ± 7.1 hours (range: 8.8 to 32.7 hours).

Day 7 of therapy: 9.1 ± 2 hours (range: 5.3 to 12.7 hours).

Infants and Children <4 years of age: 5.3 ± 1.3 hours (Glauser 2007).

Children 4 to 12 years of age: 6 ± 1.1 hours (Pellock 2001).

Adults: ~6 to 8 hours; ER tablet: ~7 hours.

Time to peak, plasma:

IV: 5 to 30 minutes (Ramael 2006a).

Oral solution: Fasting infants and children <4 years of age: 1.4 ± 0.9 hours.

Oral: Immediate release: Fasting adults and children: ~1 hour.

Oral: Extended release: ~4 hours; median time to peak is 2 hours longer in the fed state.

Excretion: Urine (66% as unchanged drug and 27% as inactive metabolites); undergoes glomerular filtration and subsequent partial tubular reabsorption.

Clearance: Correlated with CrCl; clearance is decreased in patients with renal dysfunction.

Term neonates (PNA ≤5 days at therapy initiation) (Sharpe 2012):

Day 1 of therapy : 0.71 ± 0.27 mL/minute/kg (range: 0.38 to 1.42 mL/minute/kg).

Day 7 of therapy: 1.31 ± 0.35 mL/minute/kg (range: 0.88 to 2.37 mL/minute/kg).

Infants <6 months: 1.23 mL/minute/kg (Glauser 2007).

Infants and Children 6 months to 4 years of age: 1.57 mL/minute/kg (Glauser 2007).

Children 6 to 12 years of age: 1.43 mL/minute/kg; 30% to 40% higher than adults on a per kg basis (Pellock 2001).

Adults: 0.96 mL/minute/kg.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Clearance is decreased and half-life is increased.

Hepatic function impairment: Clearance is decreased in patients with severe (Child-Pugh class C) impairment.

Older adult: Half-life is increased and clearance is decreased.

Sex: Cmax and AUC are higher in women.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Adcitan | Anolet | Convolt | Epicitam | Kepetam | Keppra | Lepsenal | Letram | Levekepp | Levetiracetam sandoz | Tiraptic;
  • (AR) Argentina: Callexe | Callexe xr | Equilea | Keppra | Lafonten | Leptam | Levaxon | Levecom | Levenova | Levetiracetam richet | Levital | Levron | Molival | Racetam | Vecetam;
  • (AT) Austria: Eprilexan | Keppra | Levebon | Levelept | Levetiracetam 1a pharma | Levetiracetam accord | Levetiracetam actavis | Levetiracetam aristo | Levetiracetam Bluefish | Levetiracetam easypharm | Levetiracetam G.L | Levetiracetam genericon | Levetiracetam hikma | Levetiracetam krka | Levetiracetam medicamentum | Levetiracetam ratiopharm | Levetiracetam sandoz | Levetiracetam stada | Levetiracetam sun | Levetiracetam ucb | Prepalepan;
  • (AU) Australia: Apo levetiracetam | Chemmart Levetiracetam | Hospira Levetiracetam | Kepcet | Keppra | Kerron | Kevtam | Levactam | Levetiracetam aft | Levetiracetam an | Levetiracetam Generic Health | Levetiracetam juno | Levetiracetam mylan | Levetiracetam pfizer | Levetiracetam sandoz | Levetiracetam sun | Levi | Levitaccord | Levitam | Noumed levetiracetam | Terry White Chemists Levetiracetam;
  • (BD) Bangladesh: Citazar | Eletam | Epicet | Iracet | Levefix | Levetira | Leviceta | Levipil | Neurocet;
  • (BE) Belgium: Keppra | Levetiracetam actavis | Levetiracetam apotex | Levetiracetam aspen | Levetiracetam eg | Levetiracetam kela | Levetiracetam sandoz | Levetiracetam teva;
  • (BG) Bulgaria: Alvotiracetam | Epiletam | Keppra | Lepsitam | Levebon | Levetiracetam accord | Levetiracon | Noepix | Normeg | Repitend;
  • (BR) Brazil: Antara | Etira | Iludral | Keppra | Keppra xr | Spark | Tam;
  • (CH) Switzerland: Keppra | Lev desitin | Levetiracetam actavis | Levetiracetam desitin | Levetiracetam helvepharm | Levetiracetam mepha | Levetiracetam sandoz | Levetiracetam Spirig | Levetiracetam spirig hc | Levetiracetam teva;
  • (CL) Chile: Ceumid | Convultam | Keppra | Kopodex | Kopodex xr | Kredit | Leoval | Levepsy | Levevitae | Prebb;
  • (CN) China: Keppra;
  • (CO) Colombia: Acizan | Ceumid | Convulam | Etitam | Ictafin | Kepertan | Keppra | Kopodex | Kopodex xr | Levevitae | Levipil | Levore | Levtec | Monavri xr | Pegra | Ubinona | Vecetam | Xitucira;
  • (CZ) Czech Republic: Dretacen | Epiletam | Kapidokor | Keppra | Letiramyl | Levelanz | Levetiracetam accord | Levetiracetam actavis | Levetiracetam apotex | Levetiracetam aurovitas | Levetiracetam desitin | Levetiracetam G.L. pharma | Levetiracetam mylan | Levetiracetam orion | Levetiracetam pmcs | Levetiracetam stada | Levetiracetam teva | Levetiracetam ucb | Matever | Normeg | Prepalepan | Pterocyn | Repitend | Trund;
  • (DE) Germany: Kepcet | Keppra | Kevesy | Levepil | Levetiracetam 1a pharma | Levetiracetam aaa | Levetiracetam accord | Levetiracetam Acis | Levetiracetam actavis | Levetiracetam al | Levetiracetam Aliud pharma | Levetiracetam Altan | Levetiracetam amarox | Levetiracetam ametas | Levetiracetam amneal | Levetiracetam aristo | Levetiracetam aurobindo | Levetiracetam axcount | Levetiracetam basics | Levetiracetam Betapharm | Levetiracetam biomo | Levetiracetam Bluefish | Levetiracetam bristol Lab | Levetiracetam ct | Levetiracetam desitin | Levetiracetam ever | Levetiracetam Fair Med Healthcare | Levetiracetam glenmark | Levetiracetam Heumann | Levetiracetam Hexal | Levetiracetam hikma | Levetiracetam holsten | Levetiracetam Hormosan | Levetiracetam hospira | Levetiracetam Juta | Levetiracetam micro labs | Levetiracetam mylan | Levetiracetam neuraxpharm | Levetiracetam normon | Levetiracetam pfizer | Levetiracetam puren | Levetiracetam ratiopharm | Levetiracetam stada | Levetiracetam sun | Levetiracetam TAD | Levetiracetam tillomed | Levetiracetam ucb | Levetiracetam Winthrop | Levetiracetam zentiva | Levetiragamma | Matever;
  • (DO) Dominican Republic: Callexe | Callexe xr | Ceumid | Convultin | Derinoe | Eurolevetir | Evetiram | Felcetam | Ipnopan | Keppra | Kopodex | Leoval | Lepcetam | Letracem | Levesam | Lortam | Meldiban | Tamlet t;
  • (EC) Ecuador: Antara | Callexe | Callexe 1000 | Callexe 500 | Callexe xr 500 | Callexe xr 750 | Ceumid | Contepil | Derinoe xr | Etabyx | Keppra | Kopodex | Leoval | Levecom | Levetirox | Levipil | Moditen | Tamlet t | Xitucira;
  • (EE) Estonia: Epilem | Keppra | Kevesy | Levetam | Levetiracetam accord | Levetiracetam gsk | Levetiracetam pharmaswiss | Matever | Normeg;
  • (EG) Egypt: Futatreat | Kalopratam | Kepilepsy | Keppra | Kepradil | Levectam | Levepex | Levepsy | Liptitam | Matrilive | Olmedersa | Seizurless | Sycocetam | Tiralepsy | Tiratam | Trinovume;
  • (ES) Spain: Keppra | Laurak | Levetiracetam actavis | Levetiracetam almus | Levetiracetam alter | Levetiracetam amneal | Levetiracetam apotex | Levetiracetam aristo | Levetiracetam aurobindo | Levetiracetam aurovitas | Levetiracetam Bluefish | Levetiracetam brill pharma | Levetiracetam cinfa | Levetiracetam Combino | Levetiracetam combino pharm | Levetiracetam combix | Levetiracetam farmalider | Levetiracetam g.e.s | Levetiracetam hospira | Levetiracetam kern pharma | Levetiracetam krka | Levetiracetam Mabo | Levetiracetam mylan | Levetiracetam Norm | Levetiracetam normon | Levetiracetam pensa | Levetiracetam Qualigen | Levetiracetam ranbaxy | Levetiracetam ratiopharm | Levetiracetam Sandos | Levetiracetam sandoz | Levetiracetam sanovel | Levetiracetam stada | Levetiracetam sun | Levetiracetam tarbis | Levetiracetam Tecnimede | Levetiracetam teva | Levetiracetam ucb | Levetiracetam zentiva | Tirbas;
  • (FI) Finland: Keppra | Kevesy | Levetiracetam 1a farma | Levetiracetam accord | Levetiracetam actavis | Levetiracetam aspen | Levetiracetam Avansor | Levetiracetam hospira | Levetiracetam orion | Levetiracetam sandoz | Levetiracetam stada | Levetiracetam sun | Matever;
  • (FR) France: Keppra | Leptax | Levetiracetam accord | Levetiracetam actavis | Levetiracetam aguettant | Levetiracetam alter | Levetiracetam arrow | Levetiracetam biogaran | Levetiracetam cristers | Levetiracetam eg | Levetiracetam Evolugen | Levetiracetam hikma | Levetiracetam hospira | Levetiracetam krka | Levetiracetam mylan | Levetiracetam ranbaxy | Levetiracetam sandoz | Levetiracetam sun | Levetiracetam teva | Levetiracetam zentiva | Levetiracetam zydus;
  • (GB) United Kingdom: Desitrend | Genlev | Keppra | Kevesy | Levetiracetam accord | Levetiracetam amarox | Levetiracetam bristol Lab | Levetiracetam brown | Levetiracetam hikma | Levetiracetam hospira | Levetiracetam teva | Levetiracetam wockhardt;
  • (GR) Greece: Keppra | Kepricet | Letira | Levetiracetam pharmaswiss | Levetiracetam teva | Levetiracetam ucb | Levetiracetam/actavis | Levetiracetam/galenica | Levetiracetam/hospira | Levetiracetam/mylan | Levetiracetam/sandoz | Lyberen | Matever | Newlev | Vetiracem;
  • (HK) Hong Kong: Apo levetiracetam | Keppra | Levetiracetam teva;
  • (HR) Croatia: Keppra | Levetiracetam Belupo | Lyvam | Nirval;
  • (HU) Hungary: Kapidokor | Keppra | Levedia | Levelan | Levetiracetam accord | Levetiracetam actavis | Levetiracetam pharmaswiss | Levetiracetam ratiopharm | Levetiracetam sandoz | Levetiracetam stada | Levetiracetam teva | Levetiracetam ucb | Levetiragamma | Levil | Matever;
  • (ID) Indonesia: Antilep actavis | Kepra | Lethira | Levexa | Levitam;
  • (IE) Ireland: Keppra | Levetiracetam ratiopharm | Levetiracetam thame | Mevluxa;
  • (IL) Israel: Keppra;
  • (IN) India: Amendo | Confilev | Emlevo | Epibrus | Epictal | Epifast | Epikey | Epiletra | Epilive | Epinext | Episeize | Epitra | Epitra er | Epiwel | Eplepmax | Fritolev | Fritolev xr | Ictacetam | Keppra | L tam | Lecetam | Lenerve | Lev | Levacetam | Levapie | Levecad | Levecon | Levecon sr | Levefree | Levemex | Levemex od | Levenue | Levepsy | Levera | Levesam | Levesol | Levetee | Leveteo | Levetor | Levetrix | Levexx | Levialfa | Levicent | Levictus | Levigress | Levihop | Levilex | Levinxt | Levipil | Levisign | Levitam | Levitra 250 | Levitram | Levitune | Levitune 500 xr | Levoraka | Levroxa | Levtam | Livatira | Livrich | Lysiprin | Neolet | Qlexin | Tiramax | Torleva | Trinix xr | Uleev | Verocet | Vetira;
  • (IQ) Iraq: Kepracetam | Levemax;
  • (IT) Italy: Epitiram | Exitelev | Grifoxina | Italept | Keppra | Levetiracetam accord | Levetiracetam actavis | Levetiracetam almus | Levetiracetam aristo | Levetiracetam aurobindo | Levetiracetam Aurobindo Italia | Levetiracetam Bluefish | Levetiracetam doc | Levetiracetam DOCgen | Levetiracetam eg | Levetiracetam hikma | Levetiracetam hospira | Levetiracetam krka | Levetiracetam mylan | Levetiracetam pensa | Levetiracetam ratiopharm | Levetiracetam sandoz | Levetiracetam sun | Levetiracetam tecnigen | Levetiracetam teva | Levetiracetam tillomed | Levetiracetam zentiva | Matever | Unipitiram;
  • (JO) Jordan: Antagra | Epitam | Epixx | Keppra | Kotral | Seizam | Tiraptic;
  • (JP) Japan: E keppra | Levetiracetam jg | Levetiracetam meiji | Levetiracetam nissin | Levetiracetam sandoz | Levetiracetam towa | Levetiracetam vtrs;
  • (KE) Kenya: Keppra | Lerace | Levigress | Levipil | Torleva;
  • (KR) Korea, Republic of: Dongkoo levetiracetam | Epilatam | Epild | Episk | Kepiram | Keppabear | Keppra | Keppra xr | Kepreptol | Kepreptol er | Keratam | Leppil | Letiram | Levecetam | Levecure | Levetiqual | Levetiram | Levewon | Levira | Levirotin | Levitam | Levpil | Pfizer levetiracetam | Q pam | Q pam xr | Staretam | Tinacetam;
  • (KW) Kuwait: Keppra;
  • (LB) Lebanon: Epitam | Kepam | Kepcitam | Keppra | Levetiracetam arrow | Levetiracetam biogaran | Levetiracetam TAD | Levipram | Zitera;
  • (LT) Lithuania: Dretacen | Keppra | Levetiracetam accord | Matever;
  • (LU) Luxembourg: Keppra | Levetiracetam eg;
  • (LV) Latvia: Keppra | Levetiracetam accord | Levetiracetam desitin | Levetiracetam pharmaswiss | Levetiracetam teva | Levetiracetam ucb | Levetrim | Matever;
  • (MA) Morocco: Keppra;
  • (MX) Mexico: 6 ur | Alemap | Autevazen | Biocet | Branche | Ellcetar | Ellekta | Endoestat | Evicovac | Exitelev | Genamar | Ivetra | Keppra | Keppra xr | Korcetav | Lecer | Lepicet | Leprezil | Leprezil sl | Levetiracetam accord | Levexx | Leviflex | Levipil | Loraxtan | Lpsyrid | Movuren | Pisarpek | Tamlet s | Tamlet t | Tayix | Tirapil | Tiraprob | Urcadiol | Vetrilep | Vexager | Vulsoran | Zeletvann;
  • (MY) Malaysia: Epitech | Keppra | Letram | Levera | Levet | Torleva;
  • (NG) Nigeria: Keppra;
  • (NL) Netherlands: Keppra | Kevesy | Levetiracetam accord | Levetiracetam actavis | Levetiracetam amarox | Levetiracetam aurobindo | Levetiracetam cf | Levetiracetam hospira | Levetiracetam pharmacin | Levetiracetam ratiopharm | Levetiracetam sandoz | Levetiracetam sun | Levetiracetam teva | Matever;
  • (NO) Norway: Keppra | Kevesy | Levetiracetam accord | Levetiracetam amneal | Levetiracetam aspen | Levetiracetam hospira;
  • (NZ) New Zealand: Everet | Keppra | Levetiracetam aft | Noumed levetiracetam;
  • (PE) Peru: Ceumid | Keppra | Kopodex | Leoval | Letivce | Levevitae | Levexyl | Levipil;
  • (PH) Philippines: Akucetam | Devetam | Dretacen | Epira | Epsytam | Focale | Ivetra | Julitam | Kepdin | Keppra | Lentira | Letram | Levipil | Levit | Levtrawell | Vexlev;
  • (PK) Pakistan: Antilep | Barlev | Cetratame | Devenda | Elicia | Elicia er | Emscot | Epian | Epicetam | Episaf | Eplipsa | Eppra | Evic | Fitzloc | Hevetam | Keppet | Keppra | Keptiron | Klevra | Le tact | Lecetam | Leepra | Lefaz | Lekra | Lepsi | Lerace | Levectam | Levenue | Levepsy | Levetec | Levetfold | Leveticam | Levetram | Levezine | Levic | Levital | Levixa | Levotam | Levra | Lumark | Lumark xr | LVT | Recetam | Seizoram | Speppra | Speppra xr | Tamel | Tamlev | Tiracit | Tiram | Tirasynth | Tiratam | Vetrawin | Vicet | Xeticam;
  • (PL) Poland: Cezarius | Eliptus | Eprilexan | Keppra | Levebon | Levetiracetam accord | Levetiracetam actavis | Levetiracetam apotex | Levetiracetam aurovitas | Levetiracetam Bluefish | Levetiracetam generics | Levetiracetam mylan | Levetiracetam NeuroPharma | Levetiracetam orion | Levetiracetam pharmaswiss | Levetiracetam ranbaxy | Levetiracetam stada | Levetiracetam teva | Levetiracetam Zdrovit | Levetiragamma | Normeg | Polkepral | Prepalepan | Symetra | Trund | Vetira | Zelta;
  • (PR) Puerto Rico: Elepsia xr | Keppra | Keppra xr | Levetiracetam ER | Roweepra | Spritam;
  • (PT) Portugal: Keppra | Laurak | Levetiracetam accord | Levetiracetam actavis | Levetiracetam actavis group | Levetiracetam alter | Levetiracetam aristo | Levetiracetam aurobindo | Levetiracetam aurovitas | Levetiracetam Bluefish | Levetiracetam bluepharma | Levetiracetam Ciclum | Levetiracetam ciclum farma | Levetiracetam Cinaz | Levetiracetam cinfa | Levetiracetam Combino | Levetiracetam Farmoz | Levetiracetam generis | Levetiracetam gp | Levetiracetam hikma | Levetiracetam jaba | Levetiracetam Labesfal | Levetiracetam medirex | Levetiracetam mepha | Levetiracetam normon | Levetiracetam pensa | Levetiracetam ratiopharm | Levetiracetam sandoz | Levetiracetam tecnigen | Levetiracetam teva | Levetiracetam tirbas | Levetiracetam Tolife | Levetiracetam ucb | Levetiracetam vitoria | Levetiracetam wynn | Levetiracetam zentiva;
  • (PY) Paraguay: Ceumid | Ceumid xr | Kopodex | Kopodex xr | Levaxon | Levecom | Levetam | Levetiracetam bauel top | Levetiracetam dallas | Levetiracetam heisecke | Levetiracetam imedic | Levetiracetam libra | Levetiracetam prosalud | Levetiracetam seven | Molival | Vecetam;
  • (QA) Qatar: Antagra XR | Epitam | Epixx | Kepam | Kepcitam | Keppra | Tiraptic;
  • (RO) Romania: Epiletam | Keppra | Levelanz | Levetiracetam accord | Levetiracetam sun | Levetiracetam teva | Trund | Vetira;
  • (RU) Russian Federation: Elsetor | Epikepran | Epiterra | Epiterra long | Epitropil | Kepayra vero | Keppra | Komviron | Konvilept | Letiram | Levetinol | Levetiracetam alium | Levetiracetam canon | Tirapol | Zenicetam;
  • (SA) Saudi Arabia: Arpek | Efram XR | Epitam | Kepam | Keppra | Lavie | Letirem | Levetam | Vales | Vitram;
  • (SE) Sweden: Keppra | Keppra Ebb | Kevesy | Levetira Accord | Levetira actavis group | Levetiracetam 1a farma | Levetiracetam 2care4 | Levetiracetam accord | Levetiracetam actavis | Levetiracetam amneal | Levetiracetam aspen | Levetiracetam Bluefish | Levetiracetam ebb | Levetiracetam hospira | Levetiracetam medartuum | Levetiracetam orion | Levetiracetam ratiopharm | Levetiracetam sandoz | Levetiracetam stada | Levetiracetam sun | Levetiracetam teva | Matever;
  • (SG) Singapore: Keppra | Levetiracetam aft | Tietari;
  • (SI) Slovenia: Keppra | Levetiracetam accord | Levetiracetam actavis | Levetiracetam pharmaswiss | Levetiracetam sandoz | Levetiracetam sun | Levetiracetam teva | Lyvam | Matever;
  • (SK) Slovakia: Epiletam | Keppra | Levemed | Levetiracetam accord | Levetiracetam actavis | Levetiracetam pharmaswiss | Levetiracetam ratiopharm | Levetiracetam sandoz | Levetiracetam stada | Levetiracetam teva | Levetiracetam ucb | Matever | Pterocyn | Repitend | Trund;
  • (TH) Thailand: Focale | Keppra | Lecetam | Levacore | Levetiracetam hainan poly | Torleva;
  • (TN) Tunisia: Antiomal | Epitam | Epixx | Keppra | Levet | Vetira;
  • (TR) Turkey: Anlev | Epi No | Epilecure | Epilem | Epileptal | Epitam | Epixx | Keppra | L Cetam | Leptica | Lesitam | Lev-End | Levebrain | Levemax | Levesto | Levetam | Netrolex | Odyparx | Tirgen | Vetria;
  • (TW) Taiwan: Epilen | Keppra | Letampin | Levetir | Levim | Levotam | Nobelin | Pharacetam | Ufree;
  • (UA) Ukraine: Deseiz | Keppra | Levenium | Levetiracetam teva | Levicitam | Logufen | Normeg;
  • (UG) Uganda: Quetra | Torleva;
  • (UY) Uruguay: Ceumid | Keppra | Kodex | Levecom | Levetam | Levetiracetam libra;
  • (VE) Venezuela, Bolivarian Republic of: Ancitam | Ceumid | Keppra | Kopodex | Lepcetam | Levedalt | Levetiracetam bluepharma | Levetuni;
  • (VN) Viet Nam: Intalevi | Meyerlecetam | Sunlevira | Zokicetam;
  • (ZA) South Africa: Citara | Dyna Levetiracetam | Epikepp | Kelev | Keppra | Levetiracetam biotech | Levetiracetam unicorn | Redilev | Torcetam;
  • (ZW) Zimbabwe: Letram | Torleva
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