Version July 2025
Dosage guidance:
Dosing: When switching between oral and IV formulations, the total daily dose should be the same.
Focal (partial) onset seizures and generalized onset seizures:
Note: FDA approved for mono- and adjunctive therapy of focal (partial) onset seizures, and adjunctive therapy of juvenile myoclonic epilepsy and primary generalized tonic-clonic seizures; used off label for other seizure types (Ref).
Oral:
Immediate release (tablets, oral solution, tablets for oral suspension): Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose based on response and tolerability to the maximum recommended dose of 1.5 g twice daily.
Extended release (FDA approved only for focal [partial] onset seizures): Initial: 1 g once daily; increase every 2 weeks by 1 g/day based on response and tolerability to a maximum of 3 g once daily.
Note: In patients with epilepsy, oral loading doses of 1.5 to 2 g (immediate release) have been well tolerated and may be useful for more rapidly achieving steady-state serum concentrations (Ref); however, the necessity of an oral loading dose has not been established.
IV: Initial: 500 mg twice daily; increase every 2 weeks by 500 mg/dose based on response and tolerability to a maximum of 1.5 g twice daily.
Note: Additional benefit of oral or IV doses >3 g/day has not been established; however, oral doses of 4 g/day have been studied in patients with refractory epilepsy but may be associated with a greater incidence of somnolence (Ref).
Subarachnoid hemorrhage (short-term seizure prophylaxis) (off-label use):
Note: Consider use in patients with seizure at presentation (onset seizure) or patients at high risk for seizures (eg, those with ruptured middle cerebral artery aneurysm, high-grade aneurysmal subarachnoid hemorrhage, intracranial hemorrhage, hydrocephalus, cortical infarction) (Ref).
Loading dose: IV: 20 mg/kg (rounded to the nearest 250 mg) as a one-time dose (Ref).
Maintenance dose: IV: 1 g every 12 hours for up to 7 days; may be increased to a maximum dose of 1.5 g every 12 hours if necessary (Ref).
Traumatic brain injury (severe acute ) (short-term seizure prophylaxis) (off-label use):
Loading dose: IV: 20 mg/kg (rounded to the nearest 250 mg) as a one-time dose (Ref).
Maintenance dose: IV: 1 g every 12 hours for 7 days; may be increased to a maximum dose of 1.5 g every 12 hours if necessary (Ref).
Conversion between oral levetiracetam IR and ER dosage forms: When switching between ER and IR formulations of levetiracetam, the same total daily dose should be used (Ref).
Discontinuation of therapy: In chronic therapy, withdraw gradually to minimize the potential of increased seizure frequency and status epilepticus, unless safety concerns require a more rapid withdrawal.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Levetiracetam is not extensively metabolized by the liver. In a single-dose pharmacokinetic study, there were no differences in the parameters of patients with Child-Turcotte-Pugh class A and B cirrhosis, but clearance was reduced and half-life was prolonged in patients with Child-Turcotte-Pugh class C cirrhosis compared to healthy volunteers. These changes were attributed to reduced kidney function seen in the Child-Turcotte-Pugh class C patients and not due to altered liver function (Ref).
Liver impairment prior to treatment initiation:
Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref).
Liver impairment developing in patient already receiving levetiracetam:
Chronic disease progression (eg, outpatient):
Baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref).
Acute worsening of liver function (eg, requiring hospitalization):
Baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary; however, consider discontinuation of levetiracetam therapy in patients with suspected levetiracetam-induced liver injury (Ref).
Refer to adult dosing; lower doses (eg, administration of 50% to 70% of the usual dose) and gradual dose increases (eg, ≤125 mg/week) may be required due to reduced drug clearance (Ref).
(For additional information see "Levetiracetam: Pediatric drug information")
Dosage guidance:
Safety: Avoid abrupt discontinuation of therapy to reduce risk of increased seizure frequency or status epilepticus.
Dosing: Use oral solution in infants and children ≤20 kg. Parenteral IV therapy should be temporary and transitioned to oral when able; when switching from oral to IV formulation, the total daily dose (individual dose and frequency) should be the same.
Myoclonic seizures with juvenile myoclonic epilepsy; adjunct: 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 (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: 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:
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:
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.
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.
No dosage adjustment necessary
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)
Levetiracetam-induced hepatotoxicity, including asymptomatic elevated transaminases, was reported in ~3% of levetiracetam adverse events reported between July 2018 and March 2020 to the US Food and Drug Administration Adverse Event Reporting System (Ref). Severe levetiracetam-induced hepatotoxicity requiring intervention is limited to case reports (Ref). Presentation of hepatotoxicity is broad and includes hepatocellular (eg, elevations in liver transaminases); cholestatic (eg, elevated bilirubin accompanied by symptomatic jaundice); or mixed with or without immunologic features (eg, fever, eosinophil infiltrate) (Ref). Most cases resolved upon discontinuation; however, there are reports of liver transplantation and death (Ref).
Mechanism: Non–dose-related; idiosyncratic, non–dose-related (Ref).
Onset: Varied; 1 day to 5 months (Ref).
Risk factors:
• Preexisting liver steatosis (Ref)
• Concurrent use of temozolomide (Ref)
• Presence of 6-methylguanine-DNA methyltransferase (MGMT) mutation (Ref)
• Female sex (Ref)
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).
Psychotic symptoms, paranoid ideation, hallucinations, and behavioral changes (including aggressive behavior, agitation, outbursts of anger, anxiety, apathy, confusion, depersonalization, depression, emotional lability, hostility, dyskinesia, irritability, nervousness, neurosis, and personality disorder) may occur in adult and pediatric patients; dose reduction or discontinuation may be required. Suicidal ideation and suicidal tendencies have also been reported (Ref).
Mechanism: Exact mechanism unknown; some evidence suggests that a negative modulating effect on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors contributes to increased aggressive behavior (Ref).
Onset: Varied; may occur as early as 1 week after initiation.
Risk factors:
• Developmental delays or intellectual disability (Ref)
• Females (Ref)
• Type of epilepsy, (especially frontal lobe epilepsy [including brain tumor-related], absence epilepsy, and difficult-to-treat [“treatment-resistant”] epilepsy) (Ref)
• History of psychiatric disorders (eg, ADHD, depression, anxiety, personality disorder, suicidality, or psychotropic or recreational drug use) (Ref)
• History of social deprivation (Ref)
• Pediatric patients (Ref)
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)
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
17% |
2% |
Infants and children |
N/A |
N/A |
N/A |
Gastrointestinal: Vomiting (children and adolescents: 15%)
Infection: Infection (adults: 13%)
Nervous system: Asthenia (adults: 15%) (table 2), behavioral changes (including outbursts of anger, apathy, depersonalization, neurosis, personality disorder; children and adolescents: 7% to 38%; adults: 7% to 13%) (table 3), drowsiness (infants, children, adolescents, and adults: 8% to 15%) (table 4), fatigue (children and adolescents: 10% to 11%) (table 5), headache (14% to 19%), irritability (infants, children, and adolescents: 6% to 12%) (table 6), psychotic symptoms (infants, children, and adolescents: 2% to 17%; adults: 1%) (table 7)
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
15% |
9% |
Adults |
Partial-onset seizures |
769 |
439 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
17% |
5% |
Infants and children |
N/A |
N/A |
N/A |
|
2% |
2% |
Children and adolescents |
N/A |
N/A |
N/A |
|
1% |
0.2% |
Adults |
N/A |
N/A |
N/A |
Respiratory: Nasopharyngitis (7% to 15%)
1% to 10%:
Gastrointestinal: Anorexia (3% to 4%), constipation (children and adolescents: 3%), decreased appetite (children and adolescents: 8%), diarrhea (children and adolescents: 6% to 8%), gastroenteritis (children and adolescents: 2%), nausea (5%), upper abdominal pain (children and adolescents: 9%)
Hematologic & oncologic: Bruise (children and adolescents: 3%), eosinophilia (children and adolescents: 9%)
Infection: Influenza (3% to 8%)
Nervous system: Aggressive behavior (children and adolescents: 10%; adults: 1%) (table 8), agitation (children and adolescents: 4%) (table 9), amnesia (adults: 2%), anxiety (2%) (table 10), ataxia (adult partial-onset seizures: 3%) (table 11), confusion (children and adolescents: 2% to 3%) (table 12), depression (3% to 5%) (table 13), dizziness (5% to 9%) (table 14), emotional lability (2% to 5%) (table 15), falling (children and adolescents: 3%),hostility (adults: 2%) (table 16), insomnia (children and adolescents: 5%), lethargy (children and adolescents: 6%), mood changes (children and adolescents: 3%), nervousness (adults: 4%) (table 17), pain (adults: 7%), paranoid ideation (children and adolescents: 2%; adults: <1%) (table 18), paresthesia (adults: 2%), sedated state (children and adolescents: 2%), vertigo (3% to 5%)
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
10% |
5% |
Children and adolescents |
Partial-onset seizures |
165 |
131 |
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
4% |
1% |
Children and adolescents |
Partial-onset seizures |
165 |
131 |
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% |
1% |
Adults |
Partial-onset seizures |
769 |
439 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% |
1% |
Adults |
Partial-onset seizures |
769 |
439 |
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
4% |
2% |
Adults |
Partial-onset seizures |
769 |
439 |
|
Drug (Levetiracetam) |
Placebo |
Population |
Indication |
Number of Patients (Levetiracetam) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|
|
2% |
0% |
Children and adolescents |
N/A |
N/A |
N/A |
Neuromuscular & skeletal: Arthralgia (children and adolescents: 2%), joint sprain (children and adolescents: 2%), neck pain (children and adolescents: 2% to 8%)
Ophthalmic: Conjunctivitis (children and adolescents: 2%), diplopia (adults: 2%)
Otic: Otalgia (children and adolescents: 2%)
Respiratory: Cough (2% to 9%), nasal congestion (children and adolescents: 9%), pharyngitis (6% to 7%), pharyngolaryngeal pain (children and adolescents: 7%), rhinitis (2% to 4%), sinusitis (adults: 2%)
Frequency not defined: Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, leukopenia, lymphocytosis
Postmarketing:
Cardiovascular: Prolonged QT interval on ECG (Ref), torsades de pointes (Ref)
Dermatologic: Acute generalized exanthematous pustulosis (Ref), alopecia (Ref), bullous pemphigoid (Ref), eczema, erythema multiforme, maculopapular rash (Ref), psoriasiform eruption (Ref), skin hyperpigmentation (Ref), Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref)
Endocrine & metabolic: Hypokalemia (Ref), hyponatremia (Ref), weight loss (Ref)
Gastrointestinal: Gingival hyperplasia (Ref), pancreatitis (including acute pancreatitis (Ref))
Genitourinary: Sexual disorder (Ref)
Hematologic & oncologic: Agranulocytosis, hypogammaglobulinemia (Ref), neutropenia (Ref), pancytopenia (with bone marrow suppression in some cases) (Ref), thrombocytopenia (Ref)
Hepatic: Hepatic failure (Ref), hepatitis (including autoimmune hepatitis (Ref)), hepatotoxicity (Ref)
Hypersensitivity: Anaphylaxis (Ref), angioedema (Ref), drug reaction with eosinophilia and systemic symptoms (Ref), hypersensitivity angiitis (Ref)
Nervous system: Aseptic meningitis (Ref), choreoathetosis, disturbance in attention, encephalopathy (Ref), exacerbation of epilepsy (SCN8A-related epilepsy), hallucination (including auditory hallucination and visual hallucination) (Ref), hypomania (Ref), manic reaction (Ref), memory impairment, myasthenia, myoclonus (Ref), obsessive compulsive disorder, panic attack, parkinsonism (Ref), polyneuropathy (Ref), suicidal ideation (Ref), suicidal tendencies (Ref)
Neuromuscular & skeletal: Dyskinesia (Ref), myalgia (Ref), rhabdomyolysis (Ref), systemic lupus erythematosus (Ref)
Ophthalmic: Blurred vision
Renal: Acute kidney injury (Ref), granulomatous interstitial nephritis (Ref), interstitial nephritis (Ref)
Respiratory: Eosinophilic pneumonitis (Ref), interstitial lung disease (Ref)
Hypersensitivity (eg, anaphylaxis, angioedema) to levetiracetam or any component of the formulation.
Disease-related concerns:
• Bariatric surgery: Presurgical assessment of the indication for use, symptoms, and goals of therapy should be documented to enable postsurgical assessment. Case series demonstrated altered levetiracetam exposure after bariatric surgery (Margolin 2022; Triplett 2021). May consider pre- and postsurgical therapeutic drug monitoring to evaluate exposure (AGNP [Hiemke 2018]). Monitor for continued efficacy after bariatric surgery and consider switching to an alternate medication if symptoms worsen.
• 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.
Note: Tablets for oral suspension and soluble disintegrating tablet both refer to Spritam.
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 [DSC])
Solution, Oral:
Keppra: 100 mg/mL (473 mL) [gluten free, lactose free; contains methylparaben, propylparaben; grape flavor]
Generic: 100 mg/mL (5 mL, 10 mL, 473 mL); 500 mg/5 mL (5 mL)
Tablet, Oral:
Keppra: 250 mg [scored; contains fd&c blue #2 (indigo carm) aluminum lake]
Keppra: 500 mg [scored]
Keppra: 750 mg [scored; contains fd&c yellow #6(sunset yellow)alumin lake]
Keppra: 1000 mg [scored]
Roweepra: 500 mg [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]
Generic: 250 mg
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
Generic: 500 mg, 750 mg
Yes
Solution (Keppra Intravenous)
500 mg/5 mL (per mL): $16.37
Solution (Keppra Oral)
100 mg/mL (per mL): $2.34
Solution (levETIRAcetam in NaCl Intravenous)
500 mg/100 mL (per mL): $0.07 - $0.33
1000 mg/100 mL (per mL): $0.10 - $0.54
1500 mg/100 mL (per mL): $0.13 - $0.72
Solution (levETIRAcetam Intravenous)
500 mg/5 mL (per mL): $0.29 - $2.52
Solution (levETIRAcetam Oral)
100 mg/mL (per mL): $0.04 - $1.01
Tablet Disintegrating Soluble (levETIRAcetam Oral)
250 mg (per each): $22.50
Tablet Disintegrating Soluble (Spritam Oral)
250 mg (per each): $12.92
500 mg (per each): $12.92
750 mg (per each): $12.92
1000 mg (per each): $12.92
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): $11.01
750 mg (per each): $16.53
Tablet, 24-hour (levETIRAcetam ER Oral)
500 mg (per each): $4.45 - $4.47
750 mg (per each): $6.67 - $6.68
Tablets (Keppra Oral)
250 mg (per each): $9.94
500 mg (per each): $12.14
750 mg (per each): $16.45
1000 mg (per each): $24.29
Tablets (levETIRAcetam Oral)
250 mg (per each): $0.05 - $2.88
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.
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
IV: For IV use only; manufacturer recommends infusing over 15 minutes. However, undiluted doses ≤2 g have been administered over 2 to 5 minutes (Ref) and undiluted doses ≤4.5 g have been administered over 5 minutes (Ref). Alternatively, a 1:1 dilution with compatible diluent (eg, 1 g levetiracetam per 10 mL diluted in 10 mL of NS; total volume administered: 20 mL) has been administered over 5 minutes with doses up to 4 g (Ref) and doses up to 4.5 g over 10 minutes (Ref).
Oral: Administer without regard to meals.
Oral solution: Administer with a calibrated measuring device (not a household teaspoon or tablespoon).
Tablet:
Disintegrating soluble tablet for oral suspension: Remove from blister by peeling back the foil (do not push tablet through the foil). Place whole tablet on the tongue with dry hand, follow with a sip of liquid and swallow only after tablet disintegrates. Do not swallow tablets intact. Partial tablets should not be administered. Tablet disintegrates in a mean time of 11 seconds (ranging from 2 to 27 seconds) in the mouth when taken with a sip of liquid.
Alternatively, allow whole tablet to disperse in a small volume of liquid (one tablespoon or enough to cover the tablet) in a cup; consume entire contents immediately; resuspend any residue by adding an additional small volume of liquid and swallow the full amount.
Immediate release: Manufacturer labeling recommends that tablets should be swallowed whole, not chewed or crushed; however, some studies support crushing and mixing with applesauce (Note: Levetiracetam has a bitter taste) (Ref).
Extended release: Only administer as whole tablet; do not crush, break, or chew.
Bariatric surgery: Levetiracetam is available in an ER formulation and the release characteristics may be significantly altered in an unknown manner in patients who have undergone bariatric surgery; providers should determine if the condition being treated can be safely monitored or if a switch to an alternative is necessary (Ref). Levetiracetam is also available in an IR formulation. Oral solutions may contain nonabsorbable sugars (eg, mannitol, sorbitol, xylitol) that can cause dumping syndrome after bariatric surgery; refer to manufacturer's labeling and monitor for tolerability with use.(Ref)
Enteral feeding tube
The following recommendations are based upon the best available evidence and clinical expertise. Senior editorial team: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Oral solution:
Gastric tubes (eg, NG, PEG) or post-pyloric tubes (eg, jejunal) (≥8 French): To reduce osmolality, dilute in a volume of purified water that is 3 times the levetiracetam solution volume (eg, 10 mL levetiracetam solution diluted in 30 mL purified water); draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some undiluted formulations have been reported to have an osmolality of 4,000 to 5,000 mOsm/kg (Ref); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates, infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during levetiracetam administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Oral tablets, disintegrating:
Enteral feeding tube administration utilizing levetiracetam disintegrating tablets has not been evaluated.
Oral tablets, extended release:
Enteral feeding tube administration utilizing levetiracetam ER tablets has not been evaluated; the manufacturer recommends ER tablets should not be broken, crushed, or chewed.
Oral tablets, immediate release:
Gastric tubes (eg, NG, PEG) or post-pyloric tubes (eg, jejunal) (≥8 French): Crush tablets into a fine powder and mix with 10 mL purified water prior to administration; shake well for 5 minutes to disperse (Ref). Draw up mixture into enteral dosing syringe and administer via feeding tube.
Dosage form information: Some formulations may be film-coated; administration of film-coated levetiracetam tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are dispersed sufficiently with an adequate amount of purified water prior to administration (Ref).
General guidance: Hold enteral nutrition during levetiracetam administration (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) before administration (Ref). Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water (eg, 15 mL) and restart enteral nutrition (Ref).
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties among manufacturers.
The following feeding tube recommendations are based upon the best available evidence and clinical expertise. Senior editor panel: Joseph I. Boullata, PharmD, RPh, CNS-S, FASPEN, FACN; Peggi A. Guenter, PhD, RN, FASPEN; Kathleen Gura, PharmD, BCNSP, FASHP, FASPEN, FPPA, FMSHP; Mark G. Klang, MS, RPh, BCNSP, PhD, FASPEN; Linda Lord, NP, ACNP-BC, CNSC, FASPEN.
Note: Recommendations may not account for differences in inactive ingredients, osmolality, or other formulation properties among manufacturers.
Oral: May be administered without regard to meals.
Immediate release:
Oral solution (commercially available): Administer with calibrated measuring device (not household teaspoon or tablespoon).
Administration via feeding tube:
Gastric tubes (eg, NG, PEG) or post-pyloric tubes (eg, jejunal) (≥8 French): Dilute in a volume of purified water that is 3 times the levetiracetam solution volume (eg, 10 mL levetiracetam solution diluted in 30 mL purified water) to reduce the osmolality; draw up diluted solution into enteral dosing syringe and administer via feeding tube (Ref).
Dosage form information: Some commercially available oral solutions have been reported to have an osmolality of ~4,000 to 5,000 mOsm/kg when undiluted (Ref); oral solutions with an osmolality >600 mOsm/kg may increase the probability of adverse GI effects (eg, diarrhea, cramping, abdominal distention, slowed gastric emptying), particularly if administered post-pylorically, inadequately diluted, and/or used in at-risk patients (eg, neonates and infants, patients with short bowel syndrome) (Ref).
General guidance: Hold enteral nutrition during levetiracetam administration (Ref). Flush feeding tube with an appropriate volume of purified water before administration (Ref); see ASPEN recommendations (Ref) or institution-specific protocols for appropriate flush volume. Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (Ref).
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. In adults, levetiracetam 500 mg tablets were studied crushed and mixed in 4 oz of applesauce (Ref).
Administration via feeding tube:
Gastric tubes (eg, NG, PEG) or post-pyloric tubes (eg, jejunal) (≥8 French): Crush tablets into a fine powder and mix with 10 mL of purified water prior to administration; shake well for 5 minutes to disperse (Ref). Draw up mixture into enteral dosing syringe and administer via feeding tube.
Dosage form information: Some tablets may be film-coated; administration of film-coated tablets via feeding tube may increase the risk of clogging the tube; if used, ensure tablets are sufficiently dispersed in purified water prior to administration (Ref).
General guidance: Hold enteral nutrition during levetiracetam administration (Ref). Flush feeding tube with an appropriate volume of purified water before administration (Ref); see ASPEN recommendations (Ref) or institution-specific protocols for appropriate flush volume. Following administration, rinse container used for preparation with purified water; draw up rinse and administer contents to ensure delivery of entire dose (Ref). Flush feeding tube with an appropriate volume of purified water and restart enteral nutrition (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.
Administration via feeding tube: Enteral feeding tube administration utilizing levetiracetam disintegrating tablets has not been evaluated.
Extended-release tablets: Swallow tablets whole; do not break, crush, or chew.
Administration via feeding tube: Enteral feeding tube administration utilizing levetiracetam extended-release tablets has not been evaluated; the manufacturer recommends that extended-release tablets should not be broken, crushed, or chewed.
Parenteral: IV: Vials may be diluted prior to use. Do not use if solution contains particulate matter or is discolored. Discard unused portions; does not contain preservative. Alternatively, may administer undiluted for high-dose treatment (Ref).
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).
Concentration of 100 mg/mL (undiluted): Infuse over 5 minutes (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 of 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).
Concentration of 100 mg/mL (undiluted): Infuse over 5 minutes or at a rate of 500 mg/minute (Ref); Note: Safety shown for doses up to 4,500 mg/dose (Ref).
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
Keppra: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021035s113,021505s052lbl.pdf
Keppra XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022285s034lbl.pdf
Spritam: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/207958s025lbl.pdf#page=38
Focal (partial) onset seizures:
IR tablets/oral solution: Treatment of focal (partial) onset seizures in adults, adolescents, children, and infants ≥1 month of age with epilepsy.
Tablets for oral suspension: Treatment of focal (partial) onset seizures in adults and children ≥4 years of age and >20 kg.
ER tablets: Treatment of focal (partial) onset seizures in adults and adolescents ≥12 years of age with epilepsy.
IV: Treatment of focal (partial) onset seizures in adults and children ≥1 month of age with epilepsy.
Limitation of use: IV use is only as an alternative when oral administration is temporarily not feasible.
Generalized onset seizures:
Juvenile myoclonic epilepsy:
IR tablets/oral solution/tablets for oral suspension: Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years and older with juvenile myoclonic epilepsy.
IV: Adjunctive therapy in the treatment of myoclonic seizures in adults and adolescents 12 years and older with juvenile myoclonic epilepsy.
Primary generalized tonic-clonic seizures:
IR tablets/oral solution/tablets for oral suspension: Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years and older with idiopathic generalized epilepsy.
IV: Adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults and children 6 years and older with idiopathic generalized epilepsy.
Craniotomy, seizure prophylaxis; Status epilepticus; Subarachnoid hemorrhage (short-term seizure prophylaxis); Traumatic brain injury, severe acute (short-term seizure prophylaxis)
Keppra may be confused with Keflex, Keppra XR
LevETIRAcetam may be confused with brivaracetam, lamoTRIgine, levOCARNitine, levoFLOXacin
Potential for dispensing errors between Keppra and Kaletra (lopinavir/ritonavir)
Levetiracetam is identified in the Screening Tool of Older Person's Prescriptions (STOPP) criteria as a potentially inappropriate medication in older adults (≥65 years of age) with a history of recurrent falls due to an increased risk of falls (O’Mahony 2023).
Substrate of OAT1/3;
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
Acrivastine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Alcohol (Ethyl): CNS Depressants may increase CNS depressant effects of Alcohol (Ethyl). Risk C: Monitor
Alizapride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Amisulpride (Oral): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Apixaban: LevETIRAcetam may decrease therapeutic effects of Apixaban. Risk C: Monitor
Articaine: May increase CNS depressant effects of CNS Depressants. Management: Consider reducing the dose of articaine if possible when used in patients who are also receiving CNS depressants. Monitor for excessive CNS depressant effects with any combined use. Risk D: Consider Therapy Modification
Azelastine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Benperidol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Blonanserin: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Brexanolone. Risk C: Monitor
Brimonidine (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Brivaracetam: LevETIRAcetam may decrease therapeutic effects 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 increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Bromperidol: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Buclizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Buprenorphine: CNS Depressants may increase CNS depressant effects 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
BusPIRone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Cannabinoid-Containing Products: CNS Depressants may increase CNS depressant effects of Cannabinoid-Containing Products. Risk C: Monitor
CarBAMazepine: LevETIRAcetam may increase adverse/toxic effects of CarBAMazepine. CarBAMazepine may decrease serum concentration of LevETIRAcetam. Risk C: Monitor
Cetirizine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk D: Consider Therapy Modification
Chloral Hydrate/Chloral Betaine: CNS Depressants may increase CNS depressant effects of Chloral Hydrate/Chloral Betaine. Management: Consider alternatives to the use of chloral hydrate or chloral betaine and additional CNS depressants. If combined, consider a dose reduction of either agent and monitor closely for enhanced CNS depressive effects. Risk D: Consider Therapy Modification
Chlormethiazole: May increase CNS depressant effects 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 increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
CNS Depressants: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Dabigatran Etexilate: LevETIRAcetam may decrease therapeutic effects of Dabigatran Etexilate. LevETIRAcetam may increase anticoagulant effects of Dabigatran Etexilate. Risk C: Monitor
Dantrolene: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Daridorexant: May increase CNS depressant effects 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 increase hyponatremic effects of Desmopressin. Risk C: Monitor
DexmedeTOMIDine: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Difenoxin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dihydralazine: CNS Depressants may increase hypotensive effects of Dihydralazine. Risk C: Monitor
Dimethindene (Topical): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Dothiepin: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Doxylamine: CNS Depressants may increase CNS depressant effects of Doxylamine. Risk C: Monitor
DroPERidol: May increase CNS depressant effects of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider Therapy Modification
Edoxaban: LevETIRAcetam may decrease therapeutic effects of Edoxaban. Risk C: Monitor
Emedastine (Systemic): May increase CNS depressant effects of CNS Depressants. Management: Consider avoiding this combination if possible. If required, monitor for excessive sedation or CNS depression, limit the dose and duration of combination therapy, and consider CNS depressant dose reductions. Risk C: Monitor
Entacapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Esketamine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Flunarizine: CNS Depressants may increase CNS depressant effects of Flunarizine. Risk X: Avoid
Flunitrazepam: CNS Depressants may increase CNS depressant effects 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 serum concentration of LevETIRAcetam. Risk C: Monitor
Gabapentin: LevETIRAcetam may increase CNS depressant effects of Gabapentin. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
HydrOXYzine: May increase CNS depressant effects of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider Therapy Modification
Ixabepilone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kava Kava: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Ketotifen (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Kratom: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
LamoTRIgine: LevETIRAcetam may increase CNS depressant effects of LamoTRIgine. Risk C: Monitor
Lemborexant: May increase CNS depressant effects 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
Levocetirizine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lisuride: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofepramine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Lofexidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Loxapine: CNS Depressants may increase CNS depressant effects of Loxapine. Management: Consider reducing the dose of CNS depressants administered concomitantly with loxapine due to an increased risk of respiratory depression, sedation, hypotension, and syncope. Risk D: Consider Therapy Modification
Magnesium Sulfate: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mefloquine: May decrease therapeutic effects of Antiseizure Agents. Mefloquine may decrease 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
Melitracen [INT]: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Mequitazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metergoline: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Methotrexate: LevETIRAcetam may increase serum concentration of Methotrexate. Risk C: Monitor
Methotrimeprazine: CNS Depressants may increase CNS depressant effects of Methotrimeprazine. Methotrimeprazine may increase CNS depressant effects 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
Methoxyflurane: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Metoclopramide: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
MetyraPONE: Coadministration of Antiseizure Agents and MetyraPONE may alter diagnostic results. Management: Consider alternatives to the use of the metyrapone test in patients taking antiseizure agents. Risk D: Consider Therapy Modification
MetyroSINE: CNS Depressants may increase sedative effects of MetyroSINE. Risk C: Monitor
Mianserin: May decrease therapeutic effects of Antiseizure Agents. Risk C: Monitor
Minocycline (Systemic): May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Moxonidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Nabilone: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Nalfurafine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Noscapine: CNS Depressants may increase adverse/toxic effects of Noscapine. Risk X: Avoid
Olopatadine (Nasal): May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Opicapone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Opioid Agonists: CNS Depressants may increase CNS depressant effects 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
Opipramol: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Orlistat: May decrease serum concentration of Antiseizure Agents. Risk C: Monitor
Orphenadrine: CNS Depressants may increase CNS depressant effects of Orphenadrine. Risk X: Avoid
OXcarbazepine: May decrease serum concentration of LevETIRAcetam. Risk C: Monitor
Oxomemazine: May increase CNS depressant effects of CNS Depressants. Risk X: Avoid
Oxybate Salt Products: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects 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
Paliperidone: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Paraldehyde: CNS Depressants may increase CNS depressant effects of Paraldehyde. Risk X: Avoid
Perampanel: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Periciazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
PHENobarbital: LevETIRAcetam may increase CNS depressant effects of PHENobarbital. PHENobarbital may decrease serum concentration of LevETIRAcetam. Risk C: Monitor
Pipamperone: May increase adverse/toxic effects of CNS Depressants. Risk C: Monitor
Piribedil: CNS Depressants may increase CNS depressant effects of Piribedil. Risk C: Monitor
Pizotifen: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Pramipexole: CNS Depressants may increase sedative effects of Pramipexole. Risk C: Monitor
Primidone: LevETIRAcetam may increase CNS depressant effects of Primidone. Primidone may decrease serum concentration of LevETIRAcetam. Risk C: Monitor
Procarbazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Rilmenidine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Rivaroxaban: LevETIRAcetam may decrease serum concentration of Rivaroxaban. Risk C: Monitor
Ropeginterferon Alfa-2b: CNS Depressants may increase adverse/toxic effects 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 increase sedative effects of ROPINIRole. Risk C: Monitor
Rotigotine: CNS Depressants may increase sedative effects of Rotigotine. Risk C: Monitor
Suvorexant: CNS Depressants may increase CNS depressant effects 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 increase CNS depressant effects of Thalidomide. Risk X: Avoid
Trimeprazine: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valerian: May increase CNS depressant effects of CNS Depressants. Risk C: Monitor
Valproic Acid and Derivatives: LevETIRAcetam may increase CNS depressant effects of Valproic Acid and Derivatives. Risk C: Monitor
Zolpidem: CNS Depressants may increase CNS depressant effects of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider Therapy Modification
Zuranolone: May increase CNS depressant effects of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider Therapy Modification
Food may delay, but does not affect the extent of absorption. Management: Administer without regard to meals.
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/).
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.
Diastolic BP in children 1 month to <4 years; CBC (in patients who experience significant weakness, pyrexia, recurrent infections or coagulation disorders); suicidality (eg, suicidal thoughts, depression, behavioral changes).
Timing of serum samples: Draw trough just before next dose.
Laboratory alert level: 50 mcg/mL (SI: 294 micromole/L) (AGNP [Hiemke 2018]).
Therapeutic reference range: Note: There is no clear correlation with serum concentrations and efficacy or tolerability; base dosing on therapeutic response as opposed to serum concentrations; however, serum concentration monitoring may be useful in older adult patients, neonates, pregnant patients, and patients on enzyme-inducing drugs or with renal insufficiency due to the wide range of alterations in clearance (Sourbron 2018).
Epilepsy: 12 to 46 mcg/mL (SI: 70 to 270 micromole/L) (AGNP [Hiemke 2018]; Patsalos 2018).
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.
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.
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.
