Dosing & Uses
Dosage Forms & Strengths
tablet, immediate-release (Keppra, generic)
- 250mg
- 500mg
- 750mg
- 1000mg
3-D tablet, immediate-release (Spritam)
- 250mg
- 500mg
- 750mg
- 1000mg
tablet, extended-release
- 500mg (Keppra XR)
- 750mg (Keppra XR)
- 1000mg (Elepsia XR)
- 1500mg (Elepsia XR)
oral solution (Keppra, generic)
- 100mg/mL
injectable solution
- 5mg/mL
- 10mg/mL
- 15mg/mL
- 100mg/mL
Myoclonic Seizures
Immediate-release (Keppra, Spritam): 500 mg IV/PO q12hr; may increase q2week by 500 mg/dose to recommended dose of 1500 mg q12hr
Effectiveness of doses >3000 mg/day has not been adequately studied
Partial Onset Seizure
Indicated for treatment of partial onset seizures
Immediate-release (Keppra, Spritam): 500 mg PO q12hr; may increase q2week by 500 mg/dose; not to exceed 3000 mg/day
Extended-release (Keppra XR or Elepsia XR): 1000 mg PO qDay; may increase q2week by 1000 mg/day; not to exceed 3000 mg/day
IV: 500 mg q12hr; may increase q2week by 500 mg/dose; not to exceed 3000 mg/day
Primary Generalized Tonic Clonic Seizures
Immediate-release (Keppra, Spritam): 500 mg IV/PO q12hr; may increase q2week by 500 mg/dose to recommended dose of 1500 mg q12hr
Effectiveness of doses >3000 mg/day has not been adequately studied
Dosage Modifications
Renal impairment
-
Immediate release and IV formulations
- CrCl >80 mL/min/1.73 m²: Dose adjustment not required
- CrCl 50-80 mL/min/1.73 m²: 500-1000 mg PO q12hr
- CrCl 30-50 mL/min/1.73 m²: 250-750 mg PO q12hr
- CrCl <30 mL/min/1.73 m²: 250-500 mg PO q12hr
- Dialysis (conventional): 500-1000 mg PO qDay, THEN 250-500 mg supplemental dose after dialysis
-
Extended release tablets (Keppra XR)
- CrCl >80 mL/min/1.73 m²: Dose adjustment not required
- CrCl 50-80 mL/min/1.73 m²: 1000-2000 mg PO q24hr
- CrCl 30-50 mL/min/1.73 m²: 500-1500 mg PO q24hr
- CrCl <30 mL/min/1.73 m²: 500-1000 mg PO q24hr
- End-stage renal disease requiring hemodialysis: Immediate release formulation recommended
-
Extended release tablets (Elepsia XR)
- CrCl >80 mL/min/1.73 m²: Dose adjustment not required
- CrCl 50-80 mL/min/1.73 m²: 1000-2000 mg PO q24hr
- CrCl <50 mL/min/1.73 m²: Not recommended
- End-stage renal disease requiring hemodialysis: Immediate release formulation recommended
Dosing Considerations
Avoid abrupt withdrawal to reduce the risk of increased seizure frequency and status epilepticus
Dosage Forms & Strengths
tablet, immediate-release (Keppra, generic)
- 250mg
- 500mg
- 750mg
- 1000mg
disintegrating tablet, immediate-release (Spritam)
- 250mg
- 500mg
- 750mg
- 1000mg
tablet, extended-release
- 500mg (Keppra XR)
- 750mg (Keppra XR)
- 1000mg (Elepsia XR)
- 1500mg (Elepsia XR)
oral solution (Keppra, generic)
- 100mg/mL
injectable solution
- 5mg/mL
- 10mg/mL
- 15mg/mL
- 100mg/mL
Partial Onset Seizures
Immediate-release tablets (Keppra)
- Indicated for monotherapy or adjunctive treatment of partial-onset seizures in patients aged ≥1 month
- <1 month: Safety and efficacy not established
- 1-6 months: 7 mg/kg PO q12hr; increase by increments of 7 mg/kg q12hr q2weeks to recommended dose of 21 mg/kg q12hr
- 6 months-4 years: 10 mg/kg PO q12hr, increase in increments of 10 mg/kg q12hr q2weeks to recommended dose of 25 mg/kg q12hr
- 4-16 years: 10 mg/kg PO q12hr; increase q2week by 10 mg/kg/dose to 30 mg/kg q12hr
- >16 years: 500 mg PO q12hr, increase by 500 mg q12hr q2weeks to recommended dose of 1500 mg q12hr
Immediate-release 3-D tablets (Spritam)
- Indicated for treatment of partial-onset seizures in patients aged >4 years
- <4 years: Safety and efficacy not established
- ≥4 years weighing 20-40 kg: 250 mg PO BID initially; increase daily dose q2wk by increments of 500 mg (250 mg BID) to a maximum daily dose of 1500 mg (750 mg BID)
- ≥4 years weighing >40 kg: 500 mg PO BID initially; increase daily dose q2wk by increments of 1000 mg (500 mg BID) to a maximum daily dose of 3000 mg (1500 mg BID)
Extended-release tablets (Keppra XR or Elepsia XR)
- Indicated as adjunctive therapy for treatment of partial-onset seizures in patients ≥12 years
- <12 years: Safety and efficacy not established
- &12 years: 1000 mg PO qDay initially; may adjust dose by 1000 mg increments q2wk to a maximum of 3000 mg/day
Primary Generalized Tonic-Clonic Seizures
<6 years: Safety and efficacy not established
Keppra
- 6-16 years: 10 mg/kg PO q12hr; increase q2week by 10 mg/kg/dose to recommended dose of 30 mg/kg q12hr; efficacy of doses <60 mg/kg/day not established
- >16 years: 500 mg PO q12hr, increase by 500 mg q12hr q2weeks to recommended dose of 1500 mg q12hr
Spritam
- ≥6 years weighing 20-40 kg: 250 mg PO BID initially; increase the daily dose q2wk by increments of 500 mg (250 mg BID) to a maximum recommended daily dose of 1500 mg/day (750 mg BID) ≥6 years weighing
- >40 kg: 500 mg PO BID initially; increase the daily dose q2wk by increments of 1000 mg (500 mg BID) to a maximum recommended daily dose of 3000 mg (1500 BID)
- Effectiveness of doses >3000 mg/day has not been adequately studied
Myoclonic Seizures
Keppra, Spritam
<12 years: Safety and efficacy not established
≥12 years: 500 mg PO q12hr; increase by 500 mg q12hr q2week to recommended dose of 1500 mg q12hr
Effectiveness of doses >3000 mg/day has not been studied
Neonatal Seizures (Orphan)
Orphan indication sponsor
- University of California; UCSD Medical Center 0935; La Jolla, CA 92093-0935
Dosing Considerations
Avoid abrupt withdrawal to reduce the risk of increased seizure frequency and status epilepticus
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
Asthenia (11-15%)
Headache (14-19%)
Infection (11-15%)
Increased blood pressure (17% in children < 4 years)
Somnolence (11-15%)
Drowsiness (2-23%)
Fatigue (10-11%)
Anorexia (3-13%)
Weakness (9-15%)
Nasopharyngitis (7-15%)
Cough (2-11%)
1-10%
Viral infection (2%)
Asthma (2%)
Dizziness (5-9%)
Nervousness (2-10%)
Amnesia (2%)
Anxiety (2-3%)
Ataxia (3%)
Depression (2-5%)
Hostility (10%)
Paresthesia (2%)
Sinusitis (2%)
Diplopia (2%)
Amblyopia (2%)
Conjunctivitis (2-3%)
Albuminuria (4%)
<1%
Abnormal hepatic function tests
Dyskinesia
Eczema
Neutropenia
Decreased hematocrit
Leukopenia
Suicidal tendencies
Hepatitis
Pancreatitis
Bone marrow suppression
Epidermal necrolysis
Postmarketing Reports
Hepatic: Abnormal liver function tests, hepatic failure, hepatitis, pancreatitis
Skin: Alopecia, erythema multiforme; drug rash with eosinophilia and systemic syndrome (DRESS)
Neurologic: Choreoathetosis, dyskinesia, worsening of seizures
Hematology: Leukopenia, neutropenia, pancytopenia, thrombocytopenia, agranulocytosis
Skeletomuscular: Muscle weakness
Psychological: Panic attack
General: Weight loss
Hyponatremia
Acute kidney injury
Anaphylaxis and angioedema
Warnings
Contraindications
Hypersensitivity
Cautions
Somnolence and asthenia occurred most frequently within first 4 weeks of treatment; patients should be monitored for signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on levetiracetam to gauge whether it adversely affects ability to drive or operate machinery
As with most antiepileptic drugs, drug should generally be withdrawn gradually because of risk of increased seizure frequency and status epilepticus; if withdrawal needed because of serious adverse reaction, rapid discontinuation can be considered
Psychiatric reactions: 13.3% of adults and 37.6% of children treated with levetiracetam reported nonpsychotic behavioral symptoms (eg, aggression, agitation, anger, anxiety, apathy, depersonalization, lability, hostility, hyperkinesis, irritability, nervousness, neurosis, and personality disorder) compared to 6.2% and 18.6% of adult and pediatric placebo patients respectively; dose reduction or discontinuation may be required
Monitor patients for behavioral abnormalities including psychotic symptoms, suicidal ideation, irritability, aggressive behavior, and for new or worsening depression, suicidal thoughts/behavior, and/or unusual changes in mood or behavior
Serious dermatological reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) reported; median time of onset is reported to be 14-17 days; if signs or symptoms suggest SJS/TEN, use of this drug should not be resumed and alternative therapy should be considered
Drug rash with eosinophilia and systemic syndrome (DRESS) reported
May impair ability to operate heavy machinery
Therapy can cause hematologic abnormalities, including decreases in white blood cell (WBC), neutrophil, and red blood cell (RBC) counts; decreases in hemoglobin and hematocrit; and increases in eosinophil counts; cases of agranulocytosis, pancytopenia, and thrombocytopenia reported in postmarketing setting; a complete blood count is recommended in patients experiencing significant weakness, pyrexia, recurrent infections, or coagulation disorders
Increases in eosinophil counts observed
Monitor patients 1 month to <4 years of age for increases in diastolic blood pressure
Seizure control during pregnancy: Physiological changes during pregnancy may gradually decrease therapeutic plasma concentrations, this is particularly pronounced during the 3rd trimester; closely monitor serum levels during pregnancy and through the postpartum period
Agranulocytosis reported; in pediatric patients (4 to <16 years of age), statistically significant decreases in WBC and neutrophil counts were seen in patients treated with immediate-release levetiracetam; no patient was discontinued secondary to low WBC or neutrophil counts
One percent of adult patients and 2% of pediatric patients (4 to 16 years of age) treated with immediate-release levetiracetam experienced psychotic symptoms (paranoia)
Use caution in renal impairment; adjust dose; use immediate release formulation, instead of the extended release formulation, in patients with ESRD requiring hemodialysis
Can cause anaphylaxis or angioedema after the first dose or at any time during treatment; if patient develops signs or symptoms of anaphylaxis or angioedema, therapy should be discontinued and patient should seek immediate medical attention; therapy should be discontinued permanently if clear alternative etiology for reaction cannot be established
Pregnancy & Lactation
Pregnancy
There are no adequate and well-controlled studies in pregnant women; prolonged experience in pregnant women has not identified a drug-associated risk of major birth defects or miscarriage, based on published literature, which includes data from pregnancy registries, and reflects experience over two decades
In animal studies, levetiracetam produced evidence of developmental toxicity, including teratogenic effects, at doses similar to or greater than human therapeutic doses
Use during pregnancy only if the potential benefit justifies the potential risk to the fetus
Drug blood levels may decrease during pregnancy; physiological changes during pregnancy may affect drug concentration; decrease in drug plasma concentrations has been observed during pregnancy; this decrease is more pronounced during third trimester; dose adjustments may be necessary to maintain clinical response
Enroll patients in the North American Antiepileptic Drug pregnancy registry; 1-888-233-2334 or visit http://www.aedpregnancyregistry.org
Lactation
Drug is excreted in human milk; there are no data on effects of drug on breastfed infant, or on milk production
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal conditio
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Antiepileptic mechanism unknown; may inhibit voltage-depedent N-type calcium channels; may bind to synaptic proteins that modulate neurotransmitter release; through displacement of negative modulators may facilitate GABA-ergic inhibitory transmission
Pyrrolidone derivative
Absorption
Bioavailability: 100%
Peak plasma time: 1 hr (immediate release); 4 hr (extended release)
Distribution
Protein bound: <10%
Metabolism
Metabolism: Hepatic enzymatic hydrolysis
Metabolites: Inactive
Elimination
Half-life: 6-8 hr (increased in elderly or renal disease)
Total body clearance: 0.96 mL/min/kg
Renal clearance: 0.6 mL/min/kg; 4 mL/min/kg (metabolite)
Clearance ~40% higher in children
Dialyzable: Yes
Excretion: Urine (66%)
Administration
IV Use
IV preparation: Dilute IV solution in 100 mL compatible solution
IV administration: Infuse IV over 15 minutes
Compatabilities
- Solutions: NS, LR, D5W
- Additive/syringe: lorazepam, diazepam, valproate sodium
Oral Administration
May take with or without food
Use oral solution for children who weigh ≤20 kg
Elepsia XR, Keppra XR: Swallow tablet whole; do not chew, split, crush, or cut tablets
Spritam
- Developed with ZipDose technology, which uses 3-dimensional printing to create a porous formulation of the antiepileptic that disintegrates rapidly with a sip of liquid, even at a high dose of up to 1000 mg
- May take with or without food
- Place the whole tablet on the tongue with a dry hand and follow with a sip of liquid
- Swallow only after tablet disintegrates in mouth (mean disintegration time 11 seconds [range 2-27 seconds])
- Tablet should not be swallowed intact
- Instruct patients not to push the tablet through the foil; the foil should be peeled from the blister by bending and lifting the peel tab around the blister seal so the table does not break
Storage
Unused vials: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
May store diluted IV solution in PVC bags at 15-30°C (59-86°F) for up to 24 hr
Extended-release or immediate release tablets: Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Solution: Store at 20-25°C (68-77°F)
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Formulary
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