Usual Adult Dose for Epilepsy

Immediate-Release:
Initial dose: 500 mg orally or IV twice a day

• Increase in increments of 500 mg twice a day every 2 weeks based on efficacy and tolerability

Maintenance dose: 500 to 1500 mg orally or IV twice a day
Maximum dose: 3000 mg/day

Extended-Release (Partial Onset Seizures Only):
Initial dose: 1000 mg orally once a day

• Increase in increments of 1000 mg every 2 weeks based on efficacy and tolerability

Maintenance dose: 1000 to 3000 mg orally once a day
Maximum dose: 3000 mg/day

Comments:

• This drug may be initiated either IV or orally; administer IV via IV infusion over at least 15 minutes.
• For adjunctive therapy in patients with partial onset seizures, there is no evidence that doses greater than 3000 mg/day confer additional benefit.
• For adjunctive therapy in patients with myoclonic seizures or primary generalized tonic-clonic seizures, the effectiveness of doses lower than 3000 mg/day has not been studied.
• The extended-release tablets are only indicated as adjunctive therapy in the treatment of partial onset seizures.

Uses:

• Adjunct therapy in the treatment of partial onset seizures in patients with epilepsy
• Adjunctive therapy for myoclonic seizures in patients with juvenile myoclonic epilepsy
• Adjunctive therapy for primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy

Usual Adult Dose for Seizures

Immediate-Release:
Initial dose: 500 mg orally or IV twice a day

• Increase in increments of 500 mg twice a day every 2 weeks based on efficacy and tolerability

Maintenance dose: 500 to 1500 mg orally or IV twice a day
Maximum dose: 3000 mg/day

Extended-Release (Partial Onset Seizures Only):
Initial dose: 1000 mg orally once a day

• Increase in increments of 1000 mg every 2 weeks based on efficacy and tolerability

Maintenance dose: 1000 to 3000 mg orally once a day
Maximum dose: 3000 mg/day

Comments:

• This drug may be initiated either IV or orally; administer IV via IV infusion over at least 15 minutes.
• For adjunctive therapy in patients with partial onset seizures, there is no evidence that doses greater than 3000 mg/day confer additional benefit.
• For adjunctive therapy in patients with myoclonic seizures or primary generalized tonic-clonic seizures, the effectiveness of doses lower than 3000 mg/day has not been studied.
• The extended-release tablets are only indicated as adjunctive therapy in the treatment of partial onset seizures.

Uses:

• Adjunct therapy in the treatment of partial onset seizures in patients with epilepsy
• Adjunctive therapy for myoclonic seizures in patients with juvenile myoclonic epilepsy
• Adjunctive therapy for primary generalized tonic-clonic seizures in patients with idiopathic generalized epilepsy

Usual Pediatric Dose for Epilepsy

PARTIAL ONSET SEIZURES:
Immediate-Release:
1 month to less than 6 months:
Initial dose: 7 mg/kg oral/IV twice a day; increase in increments of 7 mg/kg twice a day in 2-week intervals
Maximum dose: 21 mg/kg twice a day (clinical trials mean daily dose=35 mg/kg/day)

6 months to less than 4 years:
Initial dose: 10 mg/kg oral/IV twice a day; increase in increments of 10 mg/kg twice a day in 2-week intervals
Maximum dose: 25 mg/kg twice a day; (clinical trials mean daily dose=47 mg/kg/day)

4 years to less than 16 years:
Initial dose: 10 mg/kg twice a day; increase in increments of 10 mg/kg twice a day in 2-week intervals
Maximum dose: 30 mg/kg twice a day (clinical trials mean daily dose=44 mg/kg/day)

Alternatively,
4 years to less than 16 years: weight 20 to 40 kg: 250 mg oral/IV twice a day, increase in increments of 250 mg twice a day in 2-week intervals; Maximum dose: 750 mg twice a day
4 years to less than 16 years: weight greater than 40 kg: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals; Maximum dose: 1500 mg twice a day
16 years and older: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals; Maximum dose: 1500 mg twice a day

Extended-Release:
12 years or older:
Initial dose: 1000 mg orally once a day

• Increase in increments of 1000 mg every 2 weeks to the maximum daily dose

Maintenance dose: 1000 to 3000 mg orally once a day
Maximum dose: 3000 mg/day

MYOCLONIC SEIZURES:
12 years and older:
Initial dose: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals
Maintenance dose: 500 to 1500 mg twice a day
Maximum dose of 3000 mg/day

PRIMARY GENERALIZED TONIC-CLONIC SEIZURES:
6 years to less than 16 years:
Initial dose: 10 mg/kg oral/IV twice a day, increase in increments of 10 mg/kg twice a day in 2-week intervals
Maximum dose: 30 mg/kg twice a day

16 years and older:
Initial dose: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals
Maximum dose: 1500 mg twice a day

Comments:

• This drug may be initiated either IV or orally; IV may be used when oral administration is temporarily not feasible; only whole tablets should be given; for patients with body weight of 20 kg or less, the oral solution should be prescribed.
• For adjunctive therapy in patients with partial onset seizures, there is no evidence that doses greater than 3000 mg/day confer additional benefit; the effectiveness of doses lower than the daily mg/kg dose in pediatric patients 1 month to less than 16 years has not been studied. If a patient is unable to tolerate prescribed dose, the dose should be reduced; mean daily doses in clinical trials are included for reference.
• For adjunctive therapy in patients with myoclonic seizures or primary generalized tonic-clonic seizures, the effectiveness of doses lower than 3000 mg/day has not been studied.
• The extended-release tablets are only indicated as adjunctive therapy in the treatment of partial onset seizures.

Uses:

• Adjunct therapy in the treatment of partial onset seizures in patients 1 month or older with epilepsy
• Adjunctive therapy for myoclonic seizures in patients 12 years or older with juvenile myoclonic epilepsy
• Adjunctive therapy for primary generalized tonic-clonic seizures in patients 6 years or older with idiopathic generalized epilepsy

Usual Pediatric Dose for Seizures

PARTIAL ONSET SEIZURES:
Immediate-Release:
1 month to less than 6 months:
Initial dose: 7 mg/kg oral/IV twice a day; increase in increments of 7 mg/kg twice a day in 2-week intervals
Maximum dose: 21 mg/kg twice a day (clinical trials mean daily dose=35 mg/kg/day)

6 months to less than 4 years:
Initial dose: 10 mg/kg oral/IV twice a day; increase in increments of 10 mg/kg twice a day in 2-week intervals
Maximum dose: 25 mg/kg twice a day; (clinical trials mean daily dose=47 mg/kg/day)

4 years to less than 16 years:
Initial dose: 10 mg/kg twice a day; increase in increments of 10 mg/kg twice a day in 2-week intervals
Maximum dose: 30 mg/kg twice a day (clinical trials mean daily dose=44 mg/kg/day)

Alternatively,
4 years to less than 16 years: weight 20 to 40 kg: 250 mg oral/IV twice a day, increase in increments of 250 mg twice a day in 2-week intervals; Maximum dose: 750 mg twice a day
4 years to less than 16 years: weight greater than 40 kg: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals; Maximum dose: 1500 mg twice a day
16 years and older: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals; Maximum dose: 1500 mg twice a day

Extended-Release:
12 years or older:
Initial dose: 1000 mg orally once a day

• Increase in increments of 1000 mg every 2 weeks to the maximum daily dose

Maintenance dose: 1000 to 3000 mg orally once a day
Maximum dose: 3000 mg/day

MYOCLONIC SEIZURES:
12 years and older:
Initial dose: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals
Maintenance dose: 500 to 1500 mg twice a day
Maximum dose of 3000 mg/day

PRIMARY GENERALIZED TONIC-CLONIC SEIZURES:
6 years to less than 16 years:
Initial dose: 10 mg/kg oral/IV twice a day, increase in increments of 10 mg/kg twice a day in 2-week intervals
Maximum dose: 30 mg/kg twice a day

16 years and older:
Initial dose: 500 mg oral/IV twice a day, increase in increments of 500 mg twice a day in 2-week intervals
Maximum dose: 1500 mg twice a day

Comments:

• This drug may be initiated either IV or orally; IV may be used when oral administration is temporarily not feasible; only whole tablets should be given; for patients with body weight of 20 kg or less, the oral solution should be prescribed.
• For adjunctive therapy in patients with partial onset seizures, there is no evidence that doses greater than 3000 mg/day confer additional benefit; the effectiveness of doses lower than the daily mg/kg dose in pediatric patients 1 month to less than 16 years has not been studied. If a patient is unable to tolerate prescribed dose, the dose should be reduced; mean daily doses in clinical trials are included for reference.
• For adjunctive therapy in patients with myoclonic seizures or primary generalized tonic-clonic seizures, the effectiveness of doses lower than 3000 mg/day has not been studied.
• The extended-release tablets are only indicated as adjunctive therapy in the treatment of partial onset seizures.

Uses:

• Adjunct therapy in the treatment of partial onset seizures in patients 1 month or older with epilepsy
• Adjunctive therapy for myoclonic seizures in patients 12 years or older with juvenile myoclonic epilepsy
• Adjunctive therapy for primary generalized tonic-clonic seizures in patients 6 years or older with idiopathic generalized epilepsy

Renal Dose Adjustments

ADULTS:
Immediate-release:

• Mild renal impairment (CrCl 50 to 80 mL/min): 500 to 1000 mg mg oral/IV every 12 hours
• Moderate renal impairment (CrCl 30 to 50 mL/min): 250 to 750 mg oral/IV every 12 hours
• Severe renal impairment (CrCl less than 30 mL/min): 250 to 500 mg oral/IV every 12 hours

Extended-release:

• Mild renal impairment (CrCl 50 to 80 mL/min): 1000 to 2000 mg oral/IV every 24 hours
• Moderate renal impairment (CrCl 30 to 50 mL/min): 500 to 1500 mg oral/IV every 24 hours
• Severe renal impairment (CrCl less than 30 mL/min): 500 to 1000 mg oral/IV every 24 hours

PEDIATRIC PATIENTS: The dosage should be adjusted according to renal function; however, no specific dose adjustment guidelines have been suggested.

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Elderly: Use care in dose selection; renal function monitoring is recommended

Upon Discontinuation:

• Dose should be gradually decreased to minimize the potential for withdrawal seizures

Precautions

CONTRAINDICATIONS:

• Hypersensitivity to levetiracetam; angioedema and anaphylaxis have occurred

Safety and efficacy have not been established in patients younger than 1 month.

• Safety and efficacy for the extended-release tablet have not been established in patients younger than 12 years.
• Safety and efficacy for the tablet for oral suspension have not been established in patients younger than 4 years.

Consult WARNINGS section for additional precautions.

Dialysis

Adult patients:
Immediate-release:

• Maintenance dose: 500 to 1000 mg orally or IV once a day
• Following dialysis: A single 250 to 500 mg supplemental dose is recommended

Extended-release: Not recommended

Specific guidance for children has not been provided

Other Comments

Administration advice:

• Take twice a day in equally divided doses; may take with or without food

ORAL:
Tablets: Swallow whole; do not crush or chew
Oral solution: Use a calibrated measuring device to measure (not a household teaspoon)
Tablets for oral suspension: Intended to disintegrate in the mouth when taken with a sip of liquid

• Peel foil from blister by bending up and lifting the peel tab around the blister seal
• Place tablet on tongue with a dry hand; follow with a sip of water and swallow once the tablet has disintegrated; do not swallow tablet intact; partial tablets should not be used
• Alternatively, place tablet in small volume of liquid in a cup; allow tablet to disperse, then consume entire contents immediately; rinse residue in cup with additional liquid and swallow

Extended-release Tablets: Swallow whole; do not chew, break, or crush

IV: Administer via IV infusion over at least 15 minutes twice a day

Preparation:

• Available as single-use dual port bags or single-use vials that require dilution
• Dose should be administered/diluted to 100 mL prior to administration unless a smaller volume is needed; for patients requiring a smaller volume do not exceed a concentration of 15 mg/mL

Storage Requirements:
IV: Mixed in PVC infusion bags with Sodium chloride 0.9%, Lactated Ringer's, or Dextrose 5%, chemically stable at 59F to 86F (15C to 30C) for up to 4 hours

Compatibility/incompatibility:

• The IV solution is incompatible with phenytoin sodium in a polyvinyl chloride bag
• The following antiepileptic drugs have demonstrated chemical stability for up to 24 hours at 59F to 86F (15C to 30C): Lorazepam, diazepam, sodium valproate

Monitoring:

• Assess renal function prior to therapy; renal function monitoring is recommended in elderly patients
• Monitor diastolic blood pressure in patients less than 4 years
• Monitor plasma levels carefully during pregnancy and postpartum, especially if dose adjustments were made during pregnancy
• Monitor for emergence or worsening of depression, suicidal thoughts, or any unusual changes in mood or behavior

Patient Advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Patients should understand that this drug may cause changes in behavior, suicidal thoughts or thoughts about self-harm; patients/caregivers should report these changes promptly to a healthcare provider.
• Patients should understand that this drug may cause dizziness, somnolence, and incoordination; patients should not engage in hazardous activities requiring mental alertness until the effects of this drug are known.
• Patients should understand that anaphylaxis and serious dermatological reactions have been reported; patients should seek immediate medical care if they develop signs and symptoms of anaphylaxis or angioedema and notify their healthcare provider promptly if they develop a rash.