Seizures

Drug / Indication

Formulations

Dosing

Pharmacokinetic Data

Carbamazepine (Tegretol®, Tegretol-XR®, Carbitrol®, )

Indicated for complex partial seizures, generalized tonic-clonic seizures, mixed seizure patterns or other partial or generalized seizures. Not indicated for Absence seizures.

Chewable tabs: 100 mg
Tablets: 200 mg
XR tabs: 100, 200, and 400 mg
Extended-release caps: 200 and 300 mg
Suspension: 100 mg/5ml

Peak plasma concentrations of carbamazepine epoxide are achieved in 2 hours or less for suspension, whereas enteric-coated tablets are slower on average 5–7 hours.

<6 yrs: Tablets, suspension: Start 5mg/kg PO daily divided BID-QID, increase every 5–7 days to a max of 35 mg/kg/day
6–12 yrs: Tablets, suspensions, XR tabs: Start 10mg/kg PO daily divided BID-QID, increasing by 100 mg every 7 days to a max of 1000 mg/day
Over 12 yrs: Tablets, suspensions XR tabs: Start at 200 mg PO BID, then increase by 200 mg every 7 days. Max: 1000 mg/24h (12–15 yrs), 1200 mg/24h (>15 yrs), 1600 mg/24h (adults, in rare instances)

Half-life: Initially range from 25–65 hrs, decreasing to 12–17 hrs on repeated doses

Bioavailability: 89%

Plasma Protein Binding: 70–80%

Clonazepam (Klonopin®)
Indicated for use alone or as an adjunct in the treatment of Lennox-Gastaut syndrome, akinetic and myoclonic seizures; also used in refractory absence seizures.

Tablets: 0.5, 1 and 2 mg

Peak plasma concentrations achieved usually in 1 to 4 hours.

Infants and Children: (<10 yrs of age or < 30 kg) Initial dose between 0.01 and 0.03 mg/kg/day divided BID-TID, then increase by 0.25–0.5 mg every 3 days. Maintenance dose range between 0.1 to 0.2 mg/kg.
Adults: (> 10 yrs or > 30 kg) Initial dose should not exceed 1.5 mg/day divided into 3 doses, increase by 0.5–1 mg every 3 days to a max dose of 20 mg/day.

Half-life: 30–40 hrs

Bioavailability: 90%

Plasma Protein Binding: 85%

Diazepam (Valium®)
Indicated as adjunct in convulsive disorders, such as status epilepticus.

Tablets: 2, 5, and 10 mg
Oral Solution: 5 mg/5ml and 10 mg/10ml
IV: 5 mg/ml Intensol (Concentrate solution): 5 mg/ml
Diastat® Rectal administration: 2.5, 5, 10, and 15 mg fixed unit-doses

Peak plasma concentrations are achieved in 30 to 90 minutes for tablets and rectal formulations.

Status epilepticus:
Infants to 5 yrs: IV: 0.05–0.3 mg/kg/dose given over 2–3 min every 15–30 min to a max of 5 mg; may repeat in 2–4 hrs as needed.
> 5 yrs: IV: 0.05–0.3 mg/kg/dose given over 2–3 min every 15–30 min to a max of 10 mg; may repeat in 2–4 hrs as needed.
Adults: IV: 5–10 mg Q10–20 min, up to 30 mg in 8-hr period, may repeat in 2–4 hrs as necessary
Intensol® (Intranasally): 2 mg doses have been used
Diastat® (Rectal administration): 2–5 yrs: 0.5 mg/kg
6–11 yrs: 0.3 mg/kg
12 yrs and adults: 0.2 mg/kg
A second dose may be required and given 4–12 hrs after the first
Other:
Children >6 months: PO: 1 to 2 1/2 mg, 1–2 times daily, increase as tolerated
Adults: PO: 2–10 mg, 2–4 times a day
Geriatrics: PO: 2–2 ½ mg QD-BID initially, increase gradually as needed

Half-life: 46–71 hrs
IV: 14.4 ± 7.0 hrs
Intranasal: 17.8 ± 15.5 hrs

Bioavailability: 90%

Plasma Protein Binding: 95–98%

Valproate/divalpro ex sodium (Depakote , Depakene )
Indicated for use as monotherapy and adjunctive therapy in the treatment of simple and complex absence seizures.
Adjunctive therapy in patients with multiple seizure types which includes absence seizures.

Delayed-release tablets: 125, 250, and 500 mg
Extended-release: 500 mg
Sprinkle capsules: 125 mg
Capsules: 250 mg
IV: 100 mg/ml
Syrup: 250 mg/5ml

Peak plasma concentration for syrup, capsule and tablet are achieved in less than 2 hrs, whereas for enteric- coated tablets is slower (3 to 8 hrs).

Children and adults: (IV) Total daily IV dose is equivalent to the total daily oral dose; IV dose should be divided every 6 hours; switch patients to oral as soon as clinically possible. IV has not been studied for >14 days.
Initial dose of 10–15 mg/kg/day in 1–3 divided doses, increase by 5–10 mg/kg/day every 7 days to maintenance dose of 30–60 mg/kg/day in 2–3 divided doses. Max dose is 60 mg/kg/day. (Divalproex can be given BID)

Depakene (valproic acid, capsules and syrup): Initial dose of 5–10 mg/kg/day until seizures are controlled. Max dose is 60 mg/kg/day. (If total daily dose exceeds 250 mg, should be given in divided doses).

Depakote (divalproex sodium) sprinkle capsules:
Monotherapy: Initial dose of 10–15 mg/kg/day. Max dose is 60 mg/kg
Adjunctive: May be added at a dosage of 10–15 mg/kg/day. Max daily dose is 60mg/kg. (Doses exceeding 250 mg must be in divided doses).

Depakote (divalproex sodium) delayed-release tablets:
Monotherapy and adjunctive therapy: 10–15 mg/kg/day. Max daily dose is 60 mg/kg

Half-life: Newborns (1st week of life): 30–60 hrs
Newborns <10 days: 10–67 hrs
Children > 2 months: 7–13 hrs
2–14 yrs: 3.5–20 hrs
Adults: 8–17 hrs

Bioavailability: Approximately 100% (oral and IV are equivalent)

Plasma Protein Binding:
80–90%

Phenytoin (Dilantin®)

Indicated for the control of generalized tonic clonic and complex partial seizures. Prevention and treatment of seizures occurring during or following neurosurgery.

Infatabs (chewable): 50 mg
Suspension: 125 mg/5ml
Extended-release capsule:30 and 100 mg
IV: 50 mg/ml

Peak plasma concentra Tion achieved for extended-release capsule is between 4–12 hours and for chewable table and suspension ranges between 2–3 hours.

**Kapseals and IV are formulated with the sodium salt of phenytoin. Suspension and infatabs are formulated with the free acid form. There is approximately an 8% increase in the drug content with the free acid form over the sodium salt. Dosage adjustments and serum level monitoring may be necessary.

Pediatrics:
Seizure disorder:
Neonates: Start 15–20 mg/kg IV X 1 or 3 divided oral doses given 2–4 hrs apart. Maintenance 5–8 mg/kg/day IV/PO divided BID-TID. Begin maintenance dose 12 hrs after loading dose.
Infants and children: Start 10–20 mg/kg IV X 1 or 3 divided oral doses given 2–4 hrs apart. Decrease by 1–2 mg/kg/day for every 2–3 yrs of age. Begin maintenance dose 12 hr after loading dose. Maintenance dose is 5–10 mg/kg/day IV/PO divided BID- TID.
>6 yrs and adolescents: For all formulations: May require the minimum adult dose of 300 mg/day
Adults: Infatabs: Maintenance is usually 300 – 400 mg/day divided BID-TID. Max is 600 mg/day.
Extended-release: See dose above
Suspension: See dose above
Status Epilepticus (IV):
Neonates: Loading dose 15–20 mg/kg in single or divided dose. Begin maintenance dose 12 hrs after: 5 mg/kg/day in 2 divided doses, usual 5– 8 mg/kg/day in 2 divided doses, some patients may require dosing Q8hrs
Infants and children: Loading dose 15–18 mg/kg in a single or divided dose, maintenance dose of 5 mg/kg/day in 2–3 divided doses
Usual doses: 0.5–3 yrs: 8–10 mg/kg/day
4–6 yrs: 7.5–9 mg/kg/day
7–9 yrs: 7–8 mg/kg/day
10–16 yrs: 6–7 mg/kg/day
Adults: Loading dose 15–18 mg/kg in a single or divided doses, maintenance dose of 300 mg/day or 4–6 mg/kg/day in 2–3 divided doses

Half-life:
Oral: 7–42 hrs (average 22 hrs)
Infatabs: 7–29 hrs (average 14 hrs)

Bioavailability: 100%

Plasma Protein Binding: 90–95%

Gabapentin (Neurontin®)

Indicated as adjunctive therapy in adults for the treatment of partial seizures with and without secondary generalization

Capsules: 100, 300, and 400 mg
Tablets: 600 and 800 mg

Peak plasma concentrations achieved within 2 to 3 hours.

Pediatric dosing: Start 10–20 mg/kg/day, increase by 10 mg/kg/day to a maintenance does of 30 mg/kg/day. Max is 50–100 mg/kg/day in refractory patients.
> 12 yrs and adults: Start 300 mg PO X 1 day 1, increase by 300 mg PO BID on day 2 and increase by 300 mg PO TID on day 3.
Effective dose is 900 to 1800 mg/day given in divided doses TID to a maximum of 3600 mg/day.
The maximum time between doses in the TID schedule should not exceed 12 hours.
Benign Rolandic Epilepsy: 23–35 mg/kg/day
Geriatrics and Renal patients: Reduction of dose maybe required in patients with age-related compromised renal function
CrCl (ml/min) Dose
> 60 400 mg TID
30–60 300 mg BID
15–30 300 mg QD
<15 300 mg QOD

Half-life: 5–7 hrs

Bioavailability: 60%

Plasma Protein Binding: < 3%

*Saturable absorption

Lamotrigine (Lamictal®)

Indicated as adjunctive therapy in adults with partial seizures as well as generalized seizures of Lennox-Gastaut Syndrome

Dispersible Tablets: 5 and 25 mg
Tablets: 25, 100, 150, and 200 mg

**Both formulations are found to be equivalent whether administered dispersed in water, chewed and swallowed, or swallowed as whole.

Peak plasma concentration achieved within 2 to 3 hours.

Adding to a regimen containing VPA in 2–12 yrs: Start 0.15 mg/kg/day in divided QD-BID X 2 wks, then increase to 0.3 mg/kg daily divided QD-BID x 2 wks, then increase every 1–2 wks by 0.3 mg/kg/day to a usual maintenance dose of 1–5 mg/kg/day. Max is 200 mg/day divided QD-BID.

Adding to an enzyme-inducing regimen without VPA in 2–12 yrs: Start 0.6 mg/kg PO daily divided QD-BID in 2 divided doses X 2 wks, then increase to 1.2 mg/kg PO daily divided QD-BID X 2 wks, then increase every 1–2 weeks to maintenance of 5–15 mg/kg/day. Max is 400 mg/day in 2 divided doses

Adding to a regimen containing VPA in >12 yrs: Start 25 mg QOD X 2 wks, then increase to 25 mg QD X 2 wks. Increase by 25–50 mg/day every 1–2 weeks until usual maintenance dose of 100–400 mg/day in 1–2 divided doses.

Adding to an enzyme-inducing regimen without VPA in >12 yrs: Start 50 mg/day X 2 wks, then increase to 100 mg/day in 2 divided doses X 2 wks. Increase by 100 mg/day every 1–2 wks until usual maintenance dose of 300–500 mg/day BID. Doses as high as 700 mg/day divided BID have been used.

Half-life: Ages 10 mo-5.3 yrs: 7.7–44.9 hrs
Ages 5–11 yrs: 7.0–65.8 hrs
Adults: 14.4–70.3 hrs
**Depends if patient is on an inducing or inhibiting anticonvulsant

Bioavailability: 98%

Plasma Protein Binding: 55%

Levetiracetam Keppra®

Tablets: 250, 500 and 750 mg

Peak plasma concentration within by 1.5 hrs.

Children: One study used 13–30 mg/kg in 5–12 yo. Data suggested children metabolized drug more quickly than adults.

Adults: Start 500 mg PO every 12h, increase by 1000 mg/day every 2 wks to a maintenance dose between 500–1500 mg PO Q12H. Max dose is 3000 mg/day.
Renal dosing:
Adults: CrCl 30–50: 250–750 mg Q12H
10–30: 250–500 mg Q12H
<10: 50–100 mg Q24H

Half-life: 6–8 hrs

Bioavailability: 100%

Plasma Protein Binding: <10%

Lorazepam (Ativan®)

Indicated as adjunctive therapy for convulsive disorders, specifically Status Epilepticus.

Tablets : 0.5, 1, and 2 mg
IV: 2 mg/ml
Tubex Blunt Pointe (sterile cartridge units): 1 mg/0.5ml, 2 mg/ml, and 4 mg/ml
Intensol (concentrate solution): 2 mg/ml and 4 mg/ml

Peak plasma concentration achieved 1.5 to 2 hours.

Status Epilepticus:
Neonates: 0.05 mg/kg IV over 2–5 minutes; may repeat in 10–15 min
Infants and children: 0.1 mg/kg slow IV over 2–5 min, do not exceed 4 mg/single dose; may repeat second dose of 0.05 mg/kg slow IV in 10–15 min if needed
Adolescents: 0.07 mg/kg slow IV over 2–5 min; max dose of 4 mg/dose; may repeat in 10–15 min
Adults: 4 mg/dose given slowly over 2–5 min; may repeat in 10–15 min; max dose per 12-hour period is 8 mg
Geriatrics: (PO) Initial dose of 1–2 mg/day in divided doses, adjust as needed and as tolerated

Half-life: 12 hrs

Bioavailability: 90%

Plasma Protein Binding: 85%

Midazolam (Versed®)

Indicated for use in infants with status epilepticus refractory to other treatments.

IV: 1 mg/ml and 5 mg/ml
Oral solution: 2 mg/ml

6 months to <6 yrs: Syrup:

• May require higher than usual dose up to 1.0 mg/kg, max dose of 20 mg

6 yrs to <16 yrs: Syrup:

• single dose of 0.25 to 0.5 mg/kg, max dose of 20 mg
  

Status Epilepticus refractory to standard therapy:

• (IV) Infants >2 months and children: Loading dose of 0.15 mg/kg followed by a continuous infusion of 1 mcg/kg/min, range of 1–18 mcg/kg/min

Half-life: PO: 2.2–6.8 hrs
IV: 2.9–4.5 hrs

Bioavailability: >90%

Plasma Protein Binding: 97%

Oxcarbazepine (Trileptal®)

Tablet: 150, 300, 600 mg

Peak plasma concentration within 4 hours

Children: Doses Start 8–10 mg/kg, do not exceed 600 mg/day in divided doses. Target dose should be achieved over a 2 week period and is dependent on patient weight.

20–29 kg: 900 mg/day
29.1–39 kg: 1200 mg/day
>39 kg: 1800 mg/day
Ranging from 20–75 mg/kg/day have been used
Adults: 600–3000 mg/day divided BID

Half-life: 3 to 13 hrs

Bioavailability: 96%

Plasma Protein Binding: 33%

Phenobarbital (Luminal®)

Indicated for generalized and partial seizures.

Tablets: 15, 16, 30, 32, 60, 65, and 100 mg
Oral Powder Capsules: 16 mg
Elixir: 15 mg/5ml and 20 mg/5ml
IV: 30 mg/ml, 60 mg/ml, 65 mg/ml, 130 mg/ml

Peak plasma concentration is about 2 hours after an oral dose.

Status Epilepticus: (IV)
Pediatric dose: Start 10–20 mg/kg IV X 1. Then 5–10 mg/kg IV Q 15–30 min. Max 40 mg/kg.
Neonates: Loading dose of 15–20 mg/kg in a single or divided dose Infants, children, and adults: 15–18 mg/kg in a single or divided doses; usual max loading dose is 20 mg/kg
Maintenance dose: (IV or PO)
(usually starts 12 hrs after the loading dose)
Neonates: 3–4 mg/kg/day QD, may increase to 5 mg/kg/day if needed
Infants: 5–6 mg/kg/day in 1–2 divided doses
Children and adults: 1–5 yrs: 6–8 mg/kg/day in 1–2 divided doses
5–12 yrs: 4–6 mg/kg/day in 1–2 divided doses
>12 yrs and adults: 1–3 mg/kg/day in 1–2 divided doses
Seizure disorder:
2 months: 3–5 mg/kg PO/IV daily divided QD-BID
2 mo- 2 yrs: 5–8 mg/kg PO/IV daily divided QD-BID
> 2 yrs: 3–5 mg/kg PO/IV daily divided QD-BID
**Dose should also be reduced with renal impairment or hepatic disease.

Half-life:
Adults: 53–118 hrs (mean 79 hrs)
Children and newborns (<48 hrs old): 60–180 hrs (mean 110 hrs)

Bioavailability: 70–90%

Plasma Protein Binding:20–45%

Tiagabine (Gabatril®)

Indicated as adjunctive therapy in adults and children 12 years and older in the treatment of partial seizures.

Tablets: 2, 4, 12, 16, and 20 mg

Peak plasma concentration obtained in 30 minutes.

12–18 yrs: Start 1–3 mg/kg/day PO QHS X 1 wk, increase to 8 mg PO QD on wk 2, then increase by 4–8 mg/wk to a max of 32 mg/day. Total daily dose should be given in divided doses of 2–4 times/day
Adults: Initiate at 4 mg QD, increase PRN to max of 56 mg/day divided 2–4 times/day
Geriatrics: See above adult dosing

Half-life:7–9 hrs

Bioavailability:90%

Plasma Protein Binding:95%

Topiramate (Topamax )

Indicated as adjunctive therapy for adults and pediatric patients ages 2–16 years with partial onset seizures or primary generalized tonic-clonic seizures.

Tablets: 25, 100, and 200 mg
Sprinkle capsules: 15 and 25 mg

Peak plasma concentration achieved between 2 to 4 hours.

2–16 yrs: Start 1–3 mg/kg/day PO QHS X 1 wk. Titrate by 1–3 mg/kg/day divided bid at 1–2 wk intervals.
Recommended total daily dose as adjunctive is 5–9 mg/kg/day in 2 divided doses, titrate up to optimal clinical response. Max 60 mg/kg/d Primary generalized tonic-clonic seizures: slower initial titration rate, dose of 6 mg/kg/day to be reached at 8 weeks
Infantile Spasms: Up to 24 mg/kg/day has been used
17 yrs and adults: Initiate at 50 mg/day, daily maintenance dose as adjunctive therapy is 400 mg/day in 2 divided doses. Daily doses above 1600 mg have not been studied
**Primary generalized tonic-clonic seizures: slower initial titration rate, maintenance dose should be reached at the end of 8 weeks

Geriatrics: Reduce the usual adult dose by half if CrCl < 70 ml/min

Half-life: 21 hrs
Bioavailability: 80%
Plasma Protein Binding: 13–17%