Dosing and uses of Keppra, Keppra XR (levetiracetam)
Adult dosage forms and strengths
tablet, immediate-release (Keppra, Generic)
- 250mg
- 500mg
- 750mg
- 1g
3-D tablet, immediate-release (Spritam)
- 250mg
- 500mg
- 750mg
- 1g
tablet, extended-release (Keppra XR)
- 500mg
- 750mg
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
Used as adjunctive therapy
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): 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
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
- 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
Pediatric dosage forms and strengths
tablet, immediate-release (Keppra, Generic)
- 250mg
- 500mg
- 750mg
- 1g
3-D tablet, immediate-release (Spritam)
- 250mg
- 500mg
- 750mg
- 1g
tablet, extended-release (Keppra XR)
- 500mg
- 750mg
oral solution (Keppra, Generic)
- 100mg/mL
injectable solution
- 5mg/mL
- 10mg/mL
- 15mg/mL
- 100mg/mL
Partial Onset Seizures
Used as adjunctive therapy
Immediate-release tablets (Keppra)
- <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)
- <4 years: Safety and efficacy not established
- ≥4 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 (750 mg BID)
- ≥4 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 mg BID)
Extended-release tablets (Keppra XR)
- <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
Keppra, Keppra XR (levetiracetam) adverse (side) 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
Hematology: Leukopenia, neutropenia, pancytopenia, thrombocytopenia
Skeletomuscular: Muscle weakness
Psychological: Panic attack
General: Weight loss
Hyponatremia
Warnings
Contraindications
Hypersensitivity
Cautions
Risk of somnolence, asthenia and behavioral abnormalities in peds
Withdraw gradually
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
Drug rash with eosinophilia and systemic syndrome (DRESS) reported
May impair ability to operate heavy machinery
Decreases in red blood cell count, hematocrit, hemoglobin, neutrophils, and white blood cell counts reported
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
Pregnancy and lactation
Pregnancy category: C; As with all antiepileptic drugs, physiological changes (ie, intravascular volume expansion) during pregnancy may affect therapeutic levels and result in decreased serum concentrations
Lactation: Excreted in breast milk; not recommended
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 of Keppra, Keppra XR (levetiracetam)
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
May store diluted IV solution in PVC bags at 15-30°C (59-86°F) for up to 24 hr
