Your activity: 323 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

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)
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;
  • VAN-Levetiracetam [DSC]
Pharmacologic Category
  • Antiseizure Agent, Miscellaneous
Dosing: Adult

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

Craniotomy, seizure prophylaxis

Craniotomy, seizure prophylaxis (off-label use): IV, Oral: 1 g/day in 2 divided doses is commonly used; a dosage range of 500 mg to 3 g/day has been studied (Ref). After induction of anesthesia, administer first dose IV (eg, 500 mg to 1 g IV (Ref)); subsequently, 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 serum concentrations associated with seizure control (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. Use >4 days has not been studied.

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 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 dose: 4.5 g (Ref).

Subarachnoid hemorrhage

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

Loading dose: 20 mg/kg (rounded to the nearest 250 mg) (Ref) infused over 5 to 15 minutes (Ref).

Maintenance dose: 1 g over 15 minutes every 12 hours for 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): IV:

Loading dose: 20 mg/kg (rounded to the nearest 250 mg) (Ref) infused over 5 to 15 minutes (Ref).

Maintenance dose: 1 g over 15 minutes every 12 hours for 7 days; may be increased to a maximum dose of 1.5 g every 12 hours if necessary (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

No dosage adjustment necessary

Dosing: Pediatric

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

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

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

Dosing: Older Adult

Refer to adult dosing; consider lowering initial dose by 30% to 50% and increasing gradually (eg, ≤125 mg/week) due to reduced drug clearance (Ref).

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, 473 mL, 500 mL [DSC])

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: 500 mg [DSC] [scored; 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

Dosage Forms Considerations

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

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

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/2020/021035s104,021505s044lbl.pdf#page=31

Keppra XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/022285s029lbl.pdf#page=26

Spritam: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/207958s019lbl.pdf#page=36

Administration: Adult

IV: For IV use only; manufacturer recommends infusing over 15 minutes. Various rates of IV administration have been reported; doses ≤1 g (undiluted) have been administered over 2 to 5 minutes, doses ≤3 g (diluted) over 5 to 6 minutes, and doses ≤4.5 g (diluted) 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).

Use: Labeled Indications

Focal (partial) onset:

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:

Juvenile myoclonic epilepsy:

Immediate-release 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:

Immediate-release 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 lamoTRIgine, levOCARNitine, levoFLOXacin

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

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 problems (including aggressive behavior, agitation, 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: Behavioral problems (includes anger, anxiety, apathy, depersonalization, neurosis, personality disorder; children and adolescents: 7% to 38%; adults: 7% to 13%) (table 2), drowsiness (infants, children, adolescents, and adults: 8% to 15%) (table 3), fatigue (children and adolescents: 10% to 11%) (table 4), headache (14% to 19%), irritability (infants, children, and adolescents: 6% to 12%) (table 5), psychotic symptoms (infants, children, and adolescents: 2% to 17%; adults: 1%) (table 6)

Levetiracetam: Adverse Reaction: Behavioral Problems

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

Neuromuscular & skeletal: Asthenia (adults: 15%) (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

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%; includes abnormal gait, incoordination) (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%)

Miscellaneous: Head trauma (children and adolescents: 4%)

Frequency not defined: Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, leukopenia, lymphocytosis, neutropenia (Taberner Bonastre 2015)

Postmarketing:

Dermatologic: Acute generalized exanthematous pustulosis (Lee 2014), alopecia, eczema, erythema multiforme, maculopapular rash (Kim 2020), Stevens-Johnson syndrome (Park 2019), toxic epidermal necrolysis (Duong 2013)

Endocrine & metabolic: Hyponatremia, weight loss

Gastrointestinal: Pancreatitis

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

Hepatic: Hepatic failure (Jayashankar 2019), hepatitis

Hypersensitivity: Anaphylaxis (Koklu 2014), angioedema (Alkhotani 2012)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Bayram 2016)

Nervous system: Balance impairment, choreoathetosis, disturbance in attention, memory impairment, myasthenia, panic attack, suicidal ideation (rare: <1%) (Cramer 2003), suicidal tendencies (rare: <1%) (Cramer 2003)

Neuromuscular & skeletal: Dyskinesia (Yim 2019), myalgia

Ophthalmic: Blurred vision

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

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.

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 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: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. 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

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

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

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

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

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

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

CNS depression (impaired coordination, ataxia, abnormal gait, weakness, fatigue, dizziness, and somnolence); psychiatric and behavioral symptoms (aggression, agitation, anger, anxiety, apathy, confusion, depersonalization, depression, emotional lability, hostility, hyperkinesias, irritability, nervousness, neurosis, suicidal thoughts and personality disorder); diastolic BP in children 1 month to <4 years; CBC (in patients who experience significant weakness, pyrexia, recurrent infections or coagulation disorders); signs and symptoms of hypersensitivity reaction or rash.

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 therapeutic levels and efficacy or tolerability; base dosing on therapeutic response as opposed to serum concentrations. However, therapeutic drug levels may be useful in elderly patients, neonates, pregnant women, 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

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

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.

Pricing: US

Solution (Keppra Intravenous)

500 mg/5 mL (per mL): $14.44

Solution (Keppra Oral)

100 mg/mL (per mL): $2.06

Solution (levETIRAcetam in NaCl Intravenous)

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

500 mg/100 mL (per mL): $0.10 - $0.41

1000 mg/100 mL (per mL): $0.13 - $0.67

1500 mg/100 mL (per mL): $0.18 - $0.95

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): $9.71

750 mg (per each): $14.57

Tablet, 24-hour (levETIRAcetam ER Oral)

500 mg (per each): $4.41 - $4.47

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

Tablets (Keppra Oral)

250 mg (per each): $8.76

500 mg (per each): $10.71

750 mg (per each): $14.50

1000 mg (per each): $21.41

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.

Brand Names: International
  • Azacetam (EG);
  • Callexe (AR);
  • Callexe XR (AR);
  • Ceumid (CR, DO, EC, GT, HN, NI, PA, SV, UY);
  • Citazar (BD);
  • Desitrend (GB);
  • Dretacen (NL);
  • Dretacin (PH);
  • E Keppra (JP);
  • Eletam (BD);
  • Epictal (IN);
  • Epiletam (CZ, RO);
  • Epsytam (PH);
  • Erata (BD);
  • Focale (TH);
  • Iracet (BD, LK);
  • Ivetra (PH);
  • Julitam (PH);
  • Kelep (TH);
  • Kepcitam (LB);
  • Kepdin (PH);
  • Keplidon (VN);
  • Keppra (AE, AR, AT, AU, BB, BE, BG, BH, BM, BS, CH, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EC, EE, EG, ES, FI, FR, GB, GR, GT, HK, HN, HR, HU, ID, IE, IL, IN, IS, IT, JM, JO, KR, KW, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, NZ, PA, PH, PL, PR, PT, QA, RO, RU, SA, SE, SG, SI, SK, SV, TH, TR, TT, TW, UA, VN);
  • Keppra I.V. (AU);
  • Keppra XR (BB);
  • Kerron (AU);
  • Kevesy (NL, NO, SE);
  • Kevtam (AU);
  • Kineptia (VN);
  • Kopodex (CL, CO, EC, PE, PY);
  • Laurak (ES);
  • Lecetam (TH);
  • Lentira (PH);
  • Lethira (ID);
  • Letram (MY, TW, ZW);
  • Letta 500 (TH);
  • Levebon (AT);
  • Levepex (EG);
  • Levetacis (VN);
  • Levetam (UY);
  • Levetrim (IL);
  • Levicitam (UA);
  • Levim (TW);
  • Levipil (LK, PH);
  • Levit (PH);
  • Levitam (ID);
  • Levron (AR);
  • Lumark-500 (PH);
  • Malomibe (VN);
  • Matever (BE, DK, EE, HR, IE, MT, PT);
  • Millitam (TH);
  • Nirval (HR);
  • Nobelin (TW);
  • Normeg (EE);
  • Repitend (CZ, EE);
  • Rivoleve (CH);
  • Tietari (SG);
  • Torleva (IN, LK, VN, ZW);
  • Trund (NL);
  • Vexlev (PH);
  • Vitera (RO);
  • Zelta (PT);
  • Zitera (LB)


For country code abbreviations (show table)
  1. 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019;67(4):674-694. [PubMed 30693946]
  2. Alkhotani A, McLachlan RS. Levetiracetam induced angioedema in a patient with previous anticonvulsant hypersensitivity reaction to phenytoin and lamotrigine. Seizure. 2012;21(5):407-408. doi:10.1016/j.seizure.2012.03.007 [PubMed 22524985]
  3. Anderson PO, Sauberan JB. Modeling drug passage into human milk. Clin Pharmacol Ther. 2016;100(1):42-52. [PubMed 27060684]
  4. Andres E, Kerling F, Hamer H, Winterholler M. Behavioural changes in patients with intellectual disability treated with brivaracetam. Acta Neurol Scand. 2018;138(3):195-202. doi: 10.1111/ane.12943. [PubMed 29658982]
  5. Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. Philadelphia, PA: American College of Physicians; 2007.
  6. Bahte SK, Hiss M, Lichtinghagen R, Kielstein JT. A missed opportunity - consequences of unknown levetiracepam pharmacokinetics in a peritoneal dialysis patient. BMC Nephrol. 2014;15:49. doi:10.1186/1471-2369-15-49. [PubMed 24739070]
  7. Bansal AD, Hill CE, Berns JS. Use of antiepileptic drugs in patients with chronic kidney disease and end stage renal disease. Semin Dial. 2015;28(4):404-412. doi:10.1111/sdi.12385. [PubMed 25929593]
  8. Based on expert opinion.
  9. Bayram AK, Canpolat M, Çınar SL, et al. Drug reaction with eosinophilia and systemic symptoms syndrome induced by levetiracetam in a pediatric patient. J Emerg Med. 2016;50(2):e61-6. doi: 10.1016/j.jemermed.2015.10.004. [PubMed 26597350]
  10. Betts T, Waegemans T, Crawford P. A multicentre, double-blind, randomized, parallel group study to evaluate the tolerability and efficacy of two oral doses of levetiracetam, 2000 mg daily and 4000 mg daily, without titration in patients with refractory epilepsy. Seizure. 2000;9(2):80-87. [PubMed 10845730]
  11. Bhoi SK, Kalita J, Misra UK. Skin rash following levetiracetam. Seizure. 2016;37:45-47. doi: 10.1016/j.seizure.2016.02.014. [PubMed 26987035]
  12. Bilbao-Meseguer I, Rodríguez-Gascón A, Barrasa H, Isla A, Solinís MÁ. Augmented renal clearance in critically ill patients: a systematic review. Clin Pharmacokinet. 2018;57(9):1107-1121. doi:10.1007/s40262-018-0636-7. [PubMed 29441476]
  13. Brigo F, Bragazzi N, Nardone R, Trinka E. Direct and indirect comparison meta-analysis of levetiracetam versus phenytoin or valproate for convulsive status epilepticus. Epilepsy Behav. 2016;64(pt A):110-115. doi: 10.1016/j.yebeh.2016.09.030. [PubMed 27736657]
  14. Brockow K, Przybilla B, Aberer W, et al. Guideline for the diagnosis of drug hypersensitivity reactions: S2K-Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) and the German Dermatological Society (DDG) in collaboration with the Association of German Allergologists (AeDA), the German Society for Pediatric Allergology and Environmental Medicine (GPA), the German Contact Dermatitis Research Group (DKG), the Swiss Society for Allergy and Immunology (SGAI), the Austrian Society for Allergology and Immunology (ÖGAI), the German Academy of Allergology and Environmental Medicine (DAAU), the German Center for Documentation of Severe Skin Reactions and the German Federal Institute for Drugs and Medical Products (BfArM). Allergo J Int. 2015;24(3):94-105. doi: 10.1007/s40629-015-0052-6. [PubMed 26120552]
  15. Brodie MJ, Perucca E, Ryvlin P, Ben-Menachem E, Meencke HJ; Levetiracetam Monotherapy Study Group. Comparison of levetiracetam and controlled-release carbamazepine in newly diagnosed epilepsy. Neurology. 2007;68(6):402-408. [PubMed 17283312]
  16. Brodie MJ, Besag F, Ettinger AB, wt al. Epilepsy, antiepileptic drugs, and aggression: An evidence-based review. Pharmacol Rev. 2016;68(3):563-602. doi: 10.1124/pr.115.012021. [PubMed 27255267]
  17. Brophy GM, Bell R, Claassen J, et al; Neurocritical Care Society Status Epilepticus Guideline Writing Committee. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care. 2012;17(1):3-23. [PubMed 22528274]
  18. Cereghino JJ, Biton V, Abou-Khalil B, Dreifuss F, Gauer LJ, Leppik I. Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology. 2000;55(2):236-242. doi: 10.1212/wnl.55.2.236. [PubMed 10908898]
  19. Chau K, Yong J, Ismail K, Griffith N, Liu M, Makris A. Levetiracetam-induced severe acute granulomatous interstitial nephritis. Clin Kidney J. 2012;5(3):234-236. [PubMed 26069773]
  20. Chappell K, Kimmons LA, Haller JT, Canada RB, He H, Hudson JQ. Levetiracetam pharmacokinetics in critically ill patients undergoing renal replacement therapy. J Crit Care. 2021;61:216-220. doi:10.1016/j.jcrc.2020.10.032 [PubMed 33217623]
  21. Chen B, Detyniecki K, Choi H, et al. Psychiatric and behavioral side effects of anti-epileptic drugs in adolescents and children with epilepsy. Eur J Paediatr Neurol. 2017;21(3):441-449. doi: 10.1016/j.ejpn.2017.02.003. [PubMed 28238621]
  22. Chu SS, Wang HJ, Zhu LN, Xu D, Wang XP, Liu L. Therapeutic effect of intravenous levetiracetam in status epilepticus: a meta-analysis and systematic review. Seizure. 2019;74:49-55. doi: 10.1016/j.seizure.2019.11.007. [PubMed 31830677]
  23. Chung MG, O'Brien NF. Prevalence of early posttraumatic seizures in children with moderate to severe traumatic brain injury despite levetiracetam prophylaxis. Pediatr Crit Care Med. 2016;17(2):150-156. [PubMed 26669640]
  24. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, et al; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2012;43(6):1711-1737. [PubMed 22556195]
  25. Contin M, Mohamed S, Albani F, Riva R, Baruzzi A. Levetiracetam clinical pharmacokinetics in elderly and very elderly patients with epilepsy [published correction appears in Epilepsy Res. 2012;101(3):295]. Epilepsy Res. 2012;98(2-3):130-134. doi: 10.1016/j.eplepsyres.2011.08.020. [PubMed 21944894]
  26. Cramer JA, De Rue K, Devinsky O, Edrich P, Trimble MR. A systematic review of the behavioral effects of levetiracetam in adults with epilepsy, cognitive disorders, or an anxiety disorder during clinical trials. Epilepsy Behav. 2003;4(2):124-132. doi: 10.1016/s1525-5050(03)00005-2. [PubMed 12697136]
  27. De Luca F, Losappio LM, Mirone C, et al. Tolerated drugs in subjects with severe cutaneous adverse reactions (SCARs) induced by anticonvulsants and review of the literature. Clin Mol Allergy. 2017;15:16. doi: 10.1186/s12948-017-0072-5. [PubMed 29026345]
  28. Drislane F. Convulsive status epilepticus in adults: Treatment and prognosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 7, 2020.
  29. Duong TA, Haddad C, Valeyrie-Allanore L, Sbidian E, Chosidow O, Wolkenstein P. Levetiracetam: a possible new inducer of toxic epidermal necrolysis and Stevens-Johnson syndrome in 2 cases. JAMA Dermatol. 2013;149(1):113-115. doi: 10.1001/2013.jamadermatol.266. [PubMed 23324778]
  30. Eleni K. Dress syndrome induced by levetiracetam. J Eur Acad Dermatol Venereol. 2015;29(2):377-378. doi: 10.1111/jdv.12346. [PubMed 24397826]
  31. Elepsia XR (levetiracetam) [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries Inc; December 2020.
  32. Falsaperla R, Vitaliti G, Mauceri L, et al. Levetiracetam in neonatal seizures as first-line treatment: a prospective study. J Pediatr Neurosci. 2017;12(1):24-28. doi:10.4103/jpn.JPN_172_16 [PubMed 28553374]
  33. Fay MA, Sheth RD, Gidal BE. Oral absorption kinetics of levetiracetam: the effect of mixing with food or enteral nutrition formulas. Clin Ther. 2005;27(5):594-598. doi: 10.1016/j.clinthera.2005.05.010. [PubMed 15978308]
  34. Fuller KL, Wang YY, Cook MJ, Murphy MA, D'Souza WJ. Tolerability, safety, and side effects of levetiracetam versus phenytoin in intravenous and total prophylactic regimen among craniotomy patients: a prospective randomized study. Epilepsia. 2013;54(1):45-57. doi: 10.1111/j.1528-1167.2012.03563.x. [PubMed 22738092]
  35. Fürwentsches A, Bussmann C, Ramantani G, et al. Levetiracetam in the Treatment of Neonatal Seizures: A Pilot Study. Seizure. 2010;19(3):185-189. [PubMed 20133173]
  36. García Carretero R, Romero Brugera M, Olid-Velilla M, Salamanca-Ramirez I. Pancytopenia associated with levetiracetam in an epileptic woman. BMJ Case Rep. 2016;2016:bcr2016217407. doi:10.1136/bcr-2016-217407 [PubMed 27927707]
  37. Glauser TA, Mitchell WG, Weinstock A, et al. Pharmacokinetics of Levetiracetam in Infants and Young Children With Epilepsy. Epilepsia. 2007;48(6):1117-1122. [PubMed 17442002]
  38. Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults: report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48-61. doi:10.5698/1535-7597-16.1.48. [PubMed 26900382]
  39. Gohil JR, Agarwal TS. Levetiracetam adverse drug reaction: Pancytopenia. J Pediatr Neurosci. 2018;13(1):116-117. doi:10.4103/JPN.JPN_139_17 [PubMed 29899787]
  40. Gómez-Zorrilla S, Ferraz AV, Pedrós C, Lemus M, Peña C. Levetiracetam-induced drug reaction with eosinophilia and systemic symptoms syndrome. Ann Pharmacother. 2012;46(7-8):e20. doi: 10.1345/aph.1R084. [PubMed 22764327]
  41. Gowda VK, Romana A, Shivanna NH, Benakappa N, Benakappa A. Levetiracetam versus phenobarbitone in neonatal seizures - a randomized controlled trial. Indian Pediatr. 2019;56(8):643-646. [PubMed 31477643]
  42. Grosso S, Cordelli DM, Franzoni E, et al. Efficacy and Safety of Levetiracetam in Infants and Young Children With Refractory Epilepsy. Seizure. 2007;16(4):345-350. [PubMed 17368928]
  43. Guilfoyle SM, Follansbee-Junger K, Smith AW, et al. Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy. Epilepsia. 2018;59(1):146-154. doi: 10.1111/epi.13946. [PubMed 29114859]
  44. Han JY, Moon CJ, Youn YA, Sung IK, Lee IG. Efficacy of levetiracetam for neonatal seizures in preterm infants. BMC Pediatr. 2018;18(1):131. doi:10.1186/s12887-018-1103-1 [PubMed 29636029]
  45. Hansen CC, Ljung H, Brodtkorb E, Reimers A. Mechanisms underlying aggressive behavior induced by antiepileptic drugs: focus on topiramate, levetiracetam, and perampanel. Behav Neurol. 2018;2018:2064027. doi: 10.1155/2018/2064027. [PubMed 30581496]
  46. Harden CL, Meador KJ, Pennell PB, et al. Practice parameter update: management issues for women with epilepsy--focus on pregnancy (an evidence-based review): teratogenesis and perinatal outcomes: report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society. Neurology. 2009;73(2):133-141. [PubMed 19398681]
  47. Hernández-Díaz S, Smith CR, Shen A, et al. Comparative Safety of Antiepileptic Drugs During Pregnancy. Neurology. 2012;8(21):1692-1699. [PubMed 22551726]
  48. Hernández-Mitre MP, Medellín-Garibay SE, Rodríguez-Leyva I, et al. Population pharmacokinetics and dosing recommendations of levetiracetam in adult and elderly patients with epilepsy. J Pharm Sci. 2020;109(6):2070-2078. doi:10.1016/j.xphs.2020.02.018 [PubMed 32113977]
  49. Hiemke C, Bergemann N, Clement HW, et al. Consensus guidelines for therapeutic drug monitoring in neuropsychopharmacology: update 2017 [published correction appears in Pharmacopsychiatry. 2018;51(1-02):e1]. Pharmacopsychiatry. 2018;51(1-02):9-62. doi: 10.1055/s-0043-116492. [PubMed 28910830]
  50. Hnaini M, Darwich M, Koleilat N, et al. High-dose levetiracetam for neonatal seizures: a retrospective review. Seizure. 2020;82:7-11. doi:10.1016/j.seizure.2020.08.030 [PubMed 32950862]
  51. Ito S. Drug therapy for breast-feeding women. N Engl J Med. 2000;343(2):118-126. [PubMed 10891521]
  52. Iuchi T, Kuwabara K, Matsumoto M, Kawasaki K, Hasegawa Y, Sakaida T. Levetiracetam versus phenytoin for seizure prophylaxis during and early after craniotomy for brain tumours: a phase II prospective, randomised study. J Neurol Neurosurg Psychiatry. 2015;86(10):1158-1162. doi: 10.1136/jnnp-2014-308584. [PubMed 25511789]
  53. Jayashankar S, Munakomi S, Sayeerajan V, et al. Case report: Levetiracetam causing acute liver failure complicating post-operative management in a neurosurgical patient. F1000Res. 2019;8:187. doi:10.12688/f1000research.18198.1 [PubMed 30984385]
  54. Jirsch J, Hirsch LJ. Nonconvulsive status epilepticus: Classification, clinical features, and diagnosis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 18, 2020.
  55. Johannessen SI, Helde G, Brodtkorb E. Levetiracetam concentrations in serum and in breast milk at birth and during lactation. Epilepsia. 2005;46(5):775-777. [PubMed 15857447]
  56. Jones RT, Evans W, Mersfelder TL, Kavanaugh K. Rare red rashes: A case report of levetiracetam-induced cutaneous reaction and review of the literature. Am J Ther. 2016;23(3):e944-946. doi: 10.1097/MJT.0000000000000105. [PubMed 25259954]
  57. Josephson CB, Engbers JDT, Jette N, et al. Prescription trends and psychiatric symptoms following first receipt of one of seven common antiepileptic drugs in general practice. Epilepsy Behav. 2018;84:49-55. doi: 10.1016/j.yebeh.2018.04.012. [PubMed 29753294]
  58. Kalaria SN, Armahizer M, McCarthy P, Badjatia N, Gobburu JV, Gopalakrishnan M. A practice-based, clinical pharmacokinetic study to inform levetiracetam dosing in critically ill patients undergoing continuous venovenous hemofiltration (PADRE-01). Clin Transl Sci. 2020;13(5):950-959. doi:10.1111/cts.12782 [PubMed 32223067]
  59. Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2018;91(2):74-81. [PubMed 29898971]
  60. Kapur J, Elm J, Chamberlain JM, et al; NETT and PECARN Investigators. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med. 2019;381(22):2103-2113. doi: 10.1056/NEJMoa1905795. [PubMed 31774955]
  61. Keene JC, Morgan LA, Abend NS, et al. Treatment of neonatal seizures: comparison of treatment pathways from 11 neonatal intensive care units. Pediatr Neurol. 2022b;128:67-74. doi:10.1016/j.pediatrneurol.2021.10.004 [PubMed 34750046]
  62. Keene JC, Wainwright M, Morgan LA, et al. Retrospective evaluation of first-line levetiracetam use for neonatal seizures after congenital heart defect repair with or without extracorporeal membrane oxygenation. J Pediatr Pharmacol Ther. 2022a;27(3):254-262. doi:10.5863/1551-6776-27.3.254 [PubMed 35350164]
  63. Keppra (levetiracetam) injection [prescribing information]. Smyrna, GA: UCB Inc; October 2019.
  64. Keppra (levetiracetam) tablets and oral solution [prescribing information]. Smyrna, GA: UCB Inc; September 2022.
  65. Keppra XR (levetiracetam) [prescribing information]. Smyrna, GA: UCB Inc; October 2019.
  66. Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol. 2011;44(4):265-269. doi:10.1016/j.pediatrneurol.2010.11.005 [PubMed 21397167]
  67. Khan O, Cipriani C, Wright C, Crisp E, Kirmani B. Role of intravenous levetiracetam for acute seizure management in preterm neonates. Pediatr Neurol. 2013;49(5):340-343. doi:10.1016/j.pediatrneurol.2013.05.008 [PubMed 23921284]
  68. Kim HK, Kim DY, Bae EK, Kim DW. Adverse skin reactions with antiepileptic drugs using Korea adverse event reporting system database, 2008-2017. J Korean Med Sci. 2020;35(4):e17. doi: 10.3346/jkms.2020.35.e17. [PubMed 31997613]
  69. Kim J, Shin JW. Levetiracetam-induced thrombocytopenia in a patient with status epilepticus. Epileptic Disord. 2017;19(1):104-108. doi:10.1684/epd.2017.0889 [PubMed 28202425]
  70. Kochanek PM, Tasker RC, Carney N, et al. Guidelines for the management of pediatric severe traumatic brain injury, third edition: update of the Brain Trauma Foundation Guidelines [published correction appears in Pediatr Crit Care Med. 2019;20(4):404]. Pediatr Crit Care Med. 2019;20(3S)(suppl 1):S1-S82. [PubMed 30829890]
  71. Koklu E, Ariguloglu EA, Koklu S. Levetiracetam-induced anaphylaxis in a neonate. Pediatr Neurol. 2014;50(2):192-194. doi:10.1016/j.pediatrneurol.2013.09.006 [PubMed 24262344]
  72. Kossoff EH, Bergey GK, Freeman JM, et al. Levetiracetam Psychosis in Children With Epilepsy. Epilepsia. 2001;42(12):1611-1613. [PubMed 11879376]
  73. Koubeissi MZ, Amina S, Pita I, Bergey GK, Werz MA. Tolerability and efficacy of oral loading of levetiracetam. Neurology. 2008;70(22, pt 2):2166-2170. [PubMed 18505995]
  74. Kramer G, Hosli I, Glanzmann R et al. Levetiracetam accumulation in human breast milk. Epilepsia. 2002;43 (Suppl 7):105.
  75. Lee YY, Ko JH, Chung WH. Acute generalized exanthematous pustulosis induced by levetiracetam. Int J Dermatol. 2014;53(1):e5-6. doi: 10.1111/j.1365-4632.2012.05549.x. [PubMed 23451808]
  76. Levetiracetam in Sodium Chloride Injection [prescribing information]. Paramus, NJ: WG Critical Care, LLC; April 2021.
  77. Levetiracetam injection, for intravenous use [prescribing information]. Lake Forest, IL: Hospira; July 2021.
  78. Levetiracetam injection, for intravenous use [prescribing information]. Lake Forest, IL: Hospira; September 2015.
  79. Levy ZD, Slowey M, Schulder M. Acute generalized exanthematous pustulosis secondary to levetiracetam and valproic acid use. Am J Emerg Med. 2017;35(7):1036.e1-1036.e2. doi: 10.1016/j.ajem.2017.02.017. [PubMed 28189379]
  80. López-Fraile IP, Cid AO, Juste AO, Modrego PJ. Levetiracetam plasma level monitoring during pregnancy, delivery, and postpartum: clinical and outcome implications. Epilepsy Behav. 2009;15(3):372-375. [PubMed 19362602]
  81. Lyttle MD, Gamble C, Messahel S, et al. Emergency treatment with levetiracetam or phenytoin in status epilepticus in children-the EcLiPSE study: study protocol for a randomised controlled trial. Trials. 2017;18(1):283. doi:10.1186/s13063-017-2010-8 [PubMed 28629473]
  82. Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. J Perinatol. 2013;33(11):841-846. [PubMed 24051577]
  83. Mandelbaum DE, Bunch M, Kugler SL, et al. Efficacy of Levetiracetam at 12 Months in Children Classified By Seizure Type, Cognitive Status, and Previous Anticonvulsant Drug Use. J Child Neurol. 2005;20(7):590-594. [PubMed 16159526]
  84. Mawhinney E, Craig J, Morrow J, et al. Levetiracetam in pregnancy: results from the UK and Ireland epilepsy and pregnancy registers. Neurology. 2013;80(4):400-405. [PubMed 23303847]
  85. Miller GS. Pyridoxine Ameliorates Adverse Behavioral Effects of Levetiracetam in Children. Epilepsia. 2002;43(suppl 7):S62.
  86. Mølgaard-Nielsen D, Hviid A. Newer-generation antiepileptic drugs and the risk of major birth defects. JAMA. 2011;305(19):1996-2002. [PubMed 21586715]
  87. Morgan O, Medenwald B. Safety and tolerability of rapid administration undiluted levetiracetam. Neurocrit Care. 2020;32(1):131-134. doi:10.1007/s12028-019-00708-5 [PubMed 30919301]
  88. Mula M, Trimble MR, Sander JW. Psychiatric adverse events in patients with epilepsy and learning disabilities taking levetiracetam. Seizure. 2004;13(1):55-57. doi: 10.1016/s1059-1311(03)00111-0. [PubMed 14741183]
  89. Murphy-Human T, Welch E, Zipfel G, Diringer MN, Dhar R. Comparison of short-duration levetiracetam with extended-course phenytoin for seizure prophylaxis after subarachnoid hemorrhage. World Neurosurg. 2011;75(2):269-274. [PubMed 21492729]
  90. National Clinical Guideline Centre. Diagnoiss and management of drug allergy in adults, children and young people. Drug Allergy. 2014.
  91. Noachtar S, Andermann E, Meyvisch P, Andermann F, Gough WB, Schiemann-Delgado J; N166 Levetiracetam Study Group. Levetiracetam for the treatment of idiopathic generalized epilepsy with myoclonic seizures. Neurology. 2008;70(8):607-616. doi: 10.1212/01.wnl.0000297512.18364.40. [PubMed 18285535]
  92. Oh SJ, Kwon HI, Moon SH, Ro YS, Ko JY. Toxic epidermal necrolysis with isolated neutropenia related to the use of levetiracetam. J Dermatol. 2016;43(8):969-971. doi: 10.1111/1346-8138.13309. [PubMed 26893076]
  93. Opp J, Tuxhorn I, May T, et al. Levetiracetam in Children With Refractory Epilepsy: A Multicenter Open Label Study in Germany. Seizure. 2005;14(7):476-484. [PubMed 16182573]
  94. Paisansathan C, Ozcan MS. Anesthesia for craniotomy. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed January 16, 2020.
  95. Paret N, Gouraud A, Bernard N, et al. Long-term follow-up of infants exposed to levetiracetam during breastfeeding: Comparison to a control group. Birth Defects Res A Clin Mol Teratol. 2014;100:537-538. [PubMed 23911354]
  96. Park CS, Kang DY, Kang MG, et al; Korean Registry of Severe Cutaneous Adverse Reactions Consortium. Severe cutaneous adverse reactions to antiepileptic drugs: A nationwide registry-based study in Korea. Allergy Asthma Immunol Res. 2019;11(5):709-722. doi: 10.4168/aair.2019.11.5.709. [PubMed 31332981]
  97. Patsalos PN, Spencer EP, Berry DJ. Therapeutic drug monitoring of antiepileptic drugs in epilepsy: a 2018 update. Ther Drug Monit. 2018;40(5):526-548. doi: 10.1097/FTD.0000000000000546. [PubMed 29957667]
  98. Pearl PL, McCarter R, McGavin CL, et al. Results of phase II levetiracetam trial following acute head injury in children at risk for posttraumatic epilepsy. Epilepsia. 2013;54(9):e135-137. [PubMed 23876024]
  99. Pellock JM, Glauser TA, Bebin EM, et al. Pharmacokinetic Study of Levetiracetam in Children. Epilepsia, 2001;42(12):1574-1579. [PubMed 11879369]
  100. Perry MS, Benatar M. Efficacy and Tolerability of Levetiracetam in Children Younger Than 4 Years: A Retrospective Review. Epilepsia. 2007;48(6):1123-1127. [PubMed 17430408]
  101. Pourzitaki C, Tsaousi G, Apostolidou E, Karakoulas K, Kouvelas D, Amaniti E. Efficacy and safety of prophylactic levetiracetam in supratentorial brain tumour surgery: a systematic review and meta-analysis. Br J Clin Pharmacol. 2016;82(1):315-325. doi: 10.1111/bcp.12926. [PubMed 26945547]
  102. Ramael S, Daoust A, Otoul C, et al. Levetiracetam intravenous infusion: a randomized, placebo-controlled safety and pharmacokinetic study. Epilepsia. 2006a;47(7):1128-1135. doi: 10.1111/j.1528-1167.2006.00586.x. [PubMed 16886975]
  103. Ramael S, De Smedt F, Toublanc N, et al. Single-dose bioavailability of levetiracetam intravenous infusion relative to oral tablets and multiple-dose pharmacokinetics and tolerability of levetiracetam intravenous infusion compared with placebo in healthy subjects. Clin Ther. 2006b;28(5):734-744. doi: 10.1016/j.clinthera.2006.05.004. [PubMed 16861095]
  104. Ramantani G, Ikonomidou C, Walter B, et al. Levetiracetam: Safety and Efficacy in Neonatal Seizures. Eur J Paediatr Neurol. 2011;15(1):1-7. [PubMed 21094062]
  105. Rao LM, Hussain SA, Zaki T, et al. A comparison of levetiracetam and phenobarbital for the treatment of neonatal seizures associated with hypoxic-ischemic encephalopathy. Epilepsy Behav. 2018;88:212-217. doi:10.1016/j.yebeh.2018.09.015 [PubMed 30296665]
  106. Refer to manufacturer's labeling.
  107. Roweepra (levetiracetam) [prescribing information]. Naperville, IL: OWP Pharmaceuticals Inc; February 2022.
  108. Schrijvers R, Gilissen L, Chiriac AM, Demoly P. Pathogenesis and diagnosis of delayed-type drug hypersensitivity reactions, from bedside to bench and back. Clin Transl Allergy. 2015;5:31. doi: 10.1186/s13601-015-0073-8. [PubMed 26339470]
  109. Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012;72(1):43-49. doi:10.1038/pr.2012.51 [PubMed 22495532]
  110. Sharpe C, Reiner GE, Davis SL, et al. Levetiracetam versus phenobarbital for neonatal seizures: a randomized controlled trial. Pediatrics. 2020;145(6):e20193182. doi:10.1542/peds.2019-3182 [PubMed 32385134]
  111. Shoemaker MT, Rotenberg JS. Levetiracetam for the Treatment of Neonatal Seizures. J Child Neurol. 2007;22(1):95-98. [PubMed 17608315]
  112. Silverstein FS, Ferriero DM. Off-Label Use of Antiepileptic Drugs for the Treatment of Neonatal Seizures. Pediatr Neurol. 2008;39(2):77-79. [PubMed 18639748]
  113. Smetana KS, Cook AM, Bastin ML, Oyler DR. Antiepileptic dosing for critically ill adult patients receiving renal replacement therapy. J Crit Care. 2016;36:116-124. doi:10.1016/j.jcrc.2016.06.023. [PubMed 27546759]
  114. Sourbron J, Chan H, Wammes-van der Heijden EA, et al. Review on the relevance of therapeutic drug monitoring of levetiracetam. Seizure. 2018;62:131-135. doi: 10.1016/j.seizure.2018.09.004. [PubMed 30237016]
  115. Spencer DD, Jacobi J, Juenke JM, Fleck JD, Kays MB. Steady-state pharmacokinetics of intravenous levetiracetam in neurocritical care patients. Pharmacotherapy. 2011;31(10):934-941. doi:10.1592/phco.31.10.934. [PubMed 21950640]
  116. Spritam (levetiracetam) [prescribing information]. Blue Ash, OH: Aprecia Pharmaceuticals; January 2021.
  117. Striano P, Manganelli F, Boccella P, Perretti A, Striano S. Levetiracetam in patients with cortical myoclonus: a clinical and electrophysiological study. Mov Disord. 2005;20(12):1610-1614. [PubMed 16078205]
  118. Szaflarski JP, Sangha KS, Lindsell CJ, Shutter LA. Prospective, randomized, single-blinded comparative trial of intravenous levetiracetam versus phenytoin for seizure prophylaxis. Neurocrit Care. 2010;12(2):165-172. [PubMed 19898966]
  119. Taberner Bonastre MT, Peralta Muñoz S, Boza FM, Gumà I Padró J. Neutropenia secondary to exposure to levetiracetam. Tumori. 2015;101(5):e145-146. doi:10.5301/tj.5000312 [PubMed 26045109]
  120. Theitler J, Brik A, Shaniv D, Berkovitch M, Gandelman-Marton R. Antiepileptic drug treatment in community-dwelling older patients with epilepsy: a retrospective observational study of old- versus new-generation antiepileptic drugs. Drugs Aging. 2017;34(6):479-487. doi: 10.1007/s40266-017-0465-7. [PubMed 28478592]
  121. Thibault C, Naim MY, Abend NS, et al. A retrospective comparison of phenobarbital and levetiracetam for the treatment of seizures following cardiac surgery in neonates. Epilepsia. 2020;61(4):627-635. doi:10.1111/epi.16469 [PubMed 32162678]
  122. Tomson T, Palm R, Källén K, et al. Pharmacokinetics of Levetiracetam During Pregnancy, Delivery, in the Neonatal Period, and Lactation. Epilepsia. 2007;48(6):1111-1116. [PubMed 17381438]
  123. Trinka E, Marson AG, Van Paesschen W, et al; KOMET Study Group. KOMET: an unblinded, randomized, two parallel-group, stratified trial comparing the effectiveness of levetiracetam with controlled-release carbamazepine and extended-release sodium valproate as monotherapy in patients with newly diagnosed epilepsy. J Neurol Neurosurg Psychiatry. 2013;84(10):1138-1147. [PubMed 22933814]
  124. Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi:10.2165/11318140-000000000-00000. [PubMed 20000886]
  125. Vaisleib II, Neft RA. Rapid dosage titration of levetiracetam in children. Pharmacotherapy. 2008;28(3):393-396. [PubMed 18294118]
  126. Vajda FJ, Graham J, Roten A, et al. Teratogenicity of the newer antiepileptic drugs--the Australian experience. J Clin Neurosci. 2012;19(1):57-59. [PubMed 22104350]
  127. Van Matre ET, Mueller SW, Fish DN, et al. Levetiracetam pharmacokinetics in a patient with intracranial hemorrhage undergoing continuous veno-venous hemofiltration. Am J Case Rep. 2017;18:458-462. doi:10.12659/ajcr.902709. [PubMed 28446744]
  128. Venkatesan C, Young S, Schapiro M, Thomas C. Levetiracetam for the treatment of seizures in neonatal hypoxic ischemic encephalopathy. J Child Neurol. 2017;32(2):210-214. doi:10.1177/0883073816678102 [PubMed 27872177]
  129. Verwoerd C, Limjoco J, Rajamanickam V, Knox A. Efficacy of levetiracetam and phenobarbital as first-line treatment for neonatal seizures. J Child Neurol. 2022;37(5):401-409. doi:10.1177/08830738221086107 [PubMed 35311411]
  130. Walbert T, Harrison RA, Schiff D, et al. SNO and EANO practice guideline update: anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. Neuro Oncol. 2021;23(11):1835-1844. doi:10.1093/neuonc/noab152 [PubMed 34174071]
  131. Wheless JW, Clarke D, Hovinga CA, et al. Rapid Infusion of a Loading Dose of Intravenous Levetiracetam With Minimal Dilution: A Safety Study. J Child Neurol. 2009;24(8):946-951. [PubMed 19264738]
  132. White R, Bradnam V; British Pharmaceutical Nutrition Group. Handbook of Drug Administration via Enteral Feeding Tubes. 3rd ed. London, England: Pharmaceutical Press; 2015.
  133. Yamamoto J, Toublanc N, Kumagai Y, Stockis A. Levetiracetam pharmacokinetics in Japanese subjects with renal impairment. Clin Drug Investig. 2014;34(11):819–828. doi:10.1007/s40261-014-0237-7. [PubMed 25312351]
  134. Yang Y, Zheng F, Xu X, Wang X. Levetiracetam versus phenytoin for seizure prophylaxis following traumatic brain injury: a systematic review and meta-analysis. CNS Drugs. 2016;30(8):677-688. doi: 10.1007/s40263-016-0365-0. [PubMed 27395404]
  135. Yim SH, Choi YH, Heo K, Cho KH. A case of dyskinesia after levetiracetam administration. BMC Neurol. 2019;19(1):292. doi: 10.1186/s12883-019-1519-8. [PubMed 31739779]
Topic 9904 Version 697.0