Trade Names:Keppra- Tablets 250 mg- Tablets 500 mg- Tablets 750 mg- Tablets 1,000 mg- Solution, oral 100 mg/mL- Injection, solution (concentrate) 100 mg/mL
Trade Names:Keppra XR- Tablets, extended-release 500 mg- Tablets, extended-release 750 mgApo-Levetiracetam (Canada)CO Levetiracetam (Canada)
Mechanism unknown; may selectively prevent hypersynchronization of epileptiform burst firing and propagation of seizure activity.
T max is 1 h. Oral bioavailability is 100%. Food does not affect the extent of absorption, but it can decrease C max 20% and delay T max 1.5 h. Steady state is achieved after 2 days of multiple, twice-daily dosing.Extended-Release
C max is about 4 h. T max is about 3 h longer with extended-release (ER) than with immediate-release tablets.
Kinetics are linear over dose range of 500 to 5,000 mg. Less than 10% is protein bound.
Not extensively metabolized. Major metabolic pathway is the enzymatic hydrolysis of the acetamide group, which produces the carboxylic acid metabolite ucb L057.
Plasma half-life is approximately 7 h. It is eliminated from the systemic circulation by renal excretion as unchanged drug, which represents 66% of dose.
Total body Cl decreases 40% in patients with CrCl 50 to 80 mL/min, 50% in patients with CrCl 30 to 50 mL/min, and 60% in patients with CrCl less than 30 mL/min. Dosage reduction is recommended.Hepatic Function ImpairmentSevere (Child-Pugh Class C)
Total body Cl decreases 50%. No dosage adjustment is needed.Elderly
Total body Cl decreased 38%; half-life was 2.5 h longer.ChildrenImmediate-release tablets/solution
Cl was approximately 40% higher (children 6 to 12 yr of age).GenderImmediate-release tablets/solution/IV
C max and AUC are 20% higher in women.Extended-release
C max 21% to 30% higher and AUC 8% to 18% higher in women compared with men.RaceExtended-release
Pharmacokinetic studies have not been conducted.Immediate-release
Pharmacokinetics comparable between white and Asian patients.
Adjunctive therapy in partial-onset seizures in adults and children 4 yr of age and older with epilepsy; adjunctive therapy in myoclonic seizures in adults and adolescents 12 yr of age and older with juvenile myoclonic epilepsy; adjunctive treatment of primary generalized tonic-clonic seizures in adults and children 6 yr of age and older with idiopathic generalized epilepsy.Extended-release
Adjunctive therapy in the treatment of partial-onset seizures in patients 16 yr of age and older with epilepsy.IV
Adjunctive therapy in the treatment of partial-onset seizures in adults with epilepsy; alternative route for patients when oral administration is not feasible. Adjunctive therapy in the treatment of myoclonic seizures in adults with juvenile myoclonic epilepsy; adjunctive therapy in the treatment of primary generalized tonic-clonic seizures in adults with idiopathic generalized epilepsy.
Adjunctive therapy for bipolar disorder; monotherapy in new-onset pediatric epilepsy; prevention of migraine; tardive dyskinesia.
Immediate-release tablets/solution/IV Initiate therapy with 500 mg twice daily; dosage may be increased by 1,000 mg/day every 2 wk (max, 3,000 mg/day).Partial-Onset SeizuresAdults and adolescents 16 yr of age and older Immediate-release tablets/solution/IV (as 15-min infusion)
Initiate therapy with 500 mg twice daily; dosage may be increased by 1,000 mg/day every 2 wk (max, 3,000 mg/day).Extended-release
Start with 1,000 mg once daily. The dosage may be increased in increments of 1,000 mg/day at 2 wk intervals (max, 3,000 mg/day).Children 4 to 16 yr of age
PO Initiate therapy with 10 mg/kg twice daily; dose may be increased by 20 mg/kg daily every 2 wk (max, 30 mg/kg twice daily).Primary Generalized Tonic-Clonic SeizuresAdults
IV Start with 500 mg twice daily. Dosage should be increased by 1,000 mg/day every 2 wk to the recommended dosage of 3,000 mg/day.Adults and adolescents 16 yr of age and older
Immediate-release tablets/solution Start with 500 mg twice daily. Dosage should be increased by 1,000 mg/day every 2 wk to the recommended dosage of 3,000 mg/day.Children 6 to 15 yr of age
Immediate-release tablets/solution Start with 10 mg/kg twice daily. Dose should be increased every 2 wk by increments of 20 mg/kg to the recommended dosage of 30 mg/kg twice daily.Dosage Adjustment for Renal Function ImpairmentImmediate-release tablets/solution/IV
For mild renal function impairment (CrCl 50 to 80 mL/min), give 500 to 1,000 mg every 12 h. For moderate impairment (CrCl 30 to 50 mL/min), give 250 to 750 mg every 12 h. For severe impairment (CrCl less than 30 mL/min), give 250 to 500 mg every 12 h. For patients on dialysis, give 500 to 1,000 mg every 24 h. Following dialysis, a 250 to 500 mg supplemental dose is recommended.Extended-release
For mild renal impairment (CrCl 50 to 80 mL/min), give 1,000 to 2,000 mg every 24 h. For moderate impairment (CrCl 30 to 50 mL/min), give 500 to 1,500 mg every 24 h. For severe impairment (CrCl less than 30), give 500 to 1,000 mg every 24 h.
Store tablets, oral solution, and undiluted IV injection at 59° to 86°F. Following dilution, IV solution is stable for at least 24 h when stored in polyvinyl chloride bags at 59° to 86°F.
Increased risk of carbamazepine toxicity, unrelated to elevated plasma concentrations, has been reported.Enzyme-inducing antiepileptic drugs
Although total body Cl of levetiracetam is increased about 22%, dosage adjustment is not recommended.Probenecid
The C max of the inactive metabolite of levetiracetam is approximately doubled.
None well documented.
Somnolence (23%); asthenia (15%); headache (14%); hostility (12%); fatigue, nervousness (10%); dizziness (9%); personality disorder (8%); irritability (7%); agitation, emotional lability (6%); depression, mood swings, vertigo (5%); anxiety, ataxia, seizures (3%); amnesia, confusion, depressed mood, hypersomnia, increased reflexes, insomnia, paresthesia (2%); aggression (1%); suicidal behavior (postmarketing).
Pruritus, skin discoloration, vesiculobullous rash (2%); alopecia (postmarketing).
Nasopharyngitis (14%); rhinitis (13%); pharyngitis (10%); conjunctivitis (3%); amblyopia, diplopia, ear pain (2%).
Vomiting (15%); anorexia (13%); diarrhea (8%); nausea (5%); gastroenteritis (4%); anorexia, constipation (3%); pancreatitis (postmarketing).
Albuminuria (4%); urine abnormality (2%).
Ecchymosis (4%); leukopenia, neutropenia, pancytopenia (with bone marrow suppression in some cases), thrombocytopenia (postmarketing).
Abnormal LFTs, hepatic failure, hepatitis (postmarketing).
Dehydration (2%); weight loss (postmarketing).
Neck pain (8%).
Increased cough (11%); asthma, sinusitis (2%).
Accidental injury (17%); infection (13%); influenza (8%); pain (7%); flu syndrome (3%); face edema, viral infection (2%).
Category C .
Excreted in breast milk.
Safety and efficacy not established in children younger than 4 yr of age.IV/Extended-release
Safety and efficacy not established in children younger than 16 yr of age.
There were insufficient numbers of elderly subjects in clinical studies to adequately assess efficacy in elderly patients. No overall difference in safety was observed between subjects who were 65 yr of age and older compared with younger subjects.
Use reduced doses. Administer supplemental doses to dialysis patients because the drug is removed during treatment.
Infrequent abnormalities in hematologic parameters and liver function tests have been reported.
Treatment of partial-onset seizures was associated with behavioral abnormalities, coordination difficulties, and somnolence and fatigue.
Decreases in RBC, hemoglobin, and hematocrit were seen.
Do not discontinue abruptly because of possible increased seizure frequency.
Aggression, agitation, coma, depressed level of consciousness, drowsiness, respiratory depression, somnolence.
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