Antiepileptic Drugs Flashcards
cannabidiol indications
seizures within the spectrum of Lennox-Gastaut, which includes all seizure types, even a small percentage of typical absence seizures
approved for seizures associated with DS
cannabidiol initial dose
5mg/kg/day bid x1 wk
cannabidiol maintenance dose
10mg/kg/day bid
cannabidiol maximum dose
20mg/kg/day bid
cannabidiol considerations
serum transaminases and bilirubin levels recommended before starting
cannabidiol adverse effects
somnolence, decreased appetite, diarrhea, elevation in transaminases, fatigue, and insomnia
cannabidiol drug interacitons
reduces metabolism of clobazam (reduce dose)
w/ valproate increases transaminase elevation
brivaracetam (briviact) mechanism
similar to levetiracetam
binds the presynaptic vesicle glycoprotein A2
no calcium channel or AMPA receptor effect
brivaracetam (briviact) indications
localization related epilepsies, but may have wide spectrum of efficacy
brivaracetam (brivact) doses available
10, 25, 50, 75, and 100mg tablets, IV solution of 50mg/5mL and oral 10mg/mL
brivaracetam (brivact) half life
9hrs
brivaracetam (brivact) initial dose
adolescents >16 years old: 50mg bid x1 wk
may be raised to 100mg bid
brivaracetam (brivact) adverse effects
overall greater tolerability with fewer behavioral or mood side effects
carbamazepine (tegretol) indications
partial seizures, primary or secondary generalized tonic-clonic seizures
carbamazepine (tegretol) considerations
increases the frequency of absence and myoclonic seizures and is therefore contraindicated
carbamazepine (tegretol) pharmacokinetics
85% protein-bound
induces its own metabolism
initial dose should be 25% of maintenance dose to prevent toxicity
carbamazepine (tegretol) usual maintenance dose
15-20mg/kg/day to provide blood concentration of 4-12 microg/mL
carbamazepine (tegretol) maintenance dose infants
often require 30mg/kg/day
carbamazepine (tegretol) half life
5-27hrs
carbamazepine (tegretol) dose frequency
children usually require 3x/day
carbamazepine (tegretol) drug interactions
concurrent use of cimetidine, erythromycin, grapefruit, fluoxetine, and propoxyphene interferes with carbamazepine metabolism and causes toxicity
carbamazepine (tegretol) adverse effects
depression of peripheral leukocytes is expected
screen for HLA-B*1502 in Asian ancestry to decrease risk of Stevens-Johnson syndrome and toxic epidermal necrosis
cognitive disturbances
sedation, ataxia, and nystagmus at toxic blood concentrations
clobazam (onfi) indications
seizures within the spectrum of Lennox-Gastaut, which includes all seizure types, even a small percentage of typical absence seizures
clobazam (onfi) initial dose
if <30kg: 5mg daily, titrating up to 20mg/day (divided bid)
if >30kg: 10mg daily, titrating up to 40mg/day (divided bid)
clobazam (onfi) adverse effects
sedation
clonazepam (klonopin) indications
infantile spasms, myoclonic seizures, absence, and partial seizures
clonazepam (klonopin) initial dose
0.025 mg/kg/day divided into 2 doses
increase 0.025 mg/kg q3-5 days
clonazepam (klonopin) usual maintenance dose
0.1 mg/kg/day in 3 divided doses
clonazepam (klonopin) therapeutic blood concentration
0.02-0.07 microg/mL
clonazepam (klonopin) pharmacokinetics
47% protein-bound
half life 20-40hrs
clonazepam (klonopin) adverse effects
toxic effects within therapeutic range include sedation, cognitive impairment, hyperactivity, and excessive salivation
ethosuximide indications
drug of choice for treating absence epilepsy
also useful for myoclonic absence
ethosuximide pharmacokinetics
absorbed rapidly
peak blood concentrations within 4 hours
half life 30hrs in children
ethosuximide initial dose
20mg/kg/day in 3 divided doses after meals
ethosuximide dose increments
10mg/kg/day as needed and tolerated
ethosuximide therapeutic levels
between 50 and 120 microg/mL
ethosuximide adverse effects
nausea and abdominal pain from gastric irritation
felbamate indications
wide spectrum of anti epileptic activity
primary use for refractory partial and generalized seizures, the LGS, atypical absence, and atonic seizures
felbamate pharmacokinetics
rapidly absorbed after oral intake
max plasma occurs in 2-6hrs
felbamate initial dose
15mg/kg/day in three divided doses
felbamate considerations
avoid nighttime doses if the drug causes insomnia
felbamate dose increments
weekly increments of 15mg/kg as needed
felbamate total dose
45mg/kg/day
felbamate therapeutic levels
between 50 and 100 microg/mL
felbamate adverse effects
mild and dose related - nausea, anorexia, insomnia, weight loss except in combination with other antiepileptic drugs
fatal liver damage and aplastic anemia in about 1 in 10,000 exposures
felbamate drug interactions
increases plasma concentrations of phenytoin and valproate by as much as 30%
carbamazepine concentration falls, but concentration of active epoxide metabolite increases almost 50%
gabapentin indications
partial seizures with and without secondary generalization and neuropathic pain
gabapentin titration dose
10-60mg/kg/day over 2 weeks
gabapentin adverse effects
sedation, edema, and increased weight
lacosamide (vimpat) indications
partial seizures with and without secondary generalization
lacosamide (vimpat) titration dose
from 2-10mg/kg/day over 2-4 weeks
lacosamide (vimpat) mechanism of action
on sodium channel, but different than traditional sodium channel anticonvulsants
lacosamide (vimpat) adverse effects
sedation, ataxia, and dizziness
lamotrigine (lamictal) indications
useful in absence epilepsy, absence seizures, JME, and LGS, partial epilepsies, and primary generalized tonic-clonic seizures
spectrum of activity similar to valproate
lamotrigine (lamictal) initial doses
monotherapy: 0.3mg/kg/day
liver enzyme inducing drugs: 0.6mg/kg/day
with valproate: 0.15mg/kg/day for the first 2 weeks then increase by same amount daily
lamotrigine (lamictal) maintenance doses
monotherapy: 5-7mg/kg/day
with valproate: 1-3mg/kg/day
liver enzyme inducers: 5-15mg/kg/day
lamotrigine (lamictal) adverse effects
rash, which is more likely with titrations faster than recommended
dizziness, ataxia, diplopia, insomnia, and headache
levetiracetam (keppra) indications
broad spectrum of activity and useful in most seizure types
especially effective in JME
excellent first line for most epilepsies
levetiracetam (keppra) initial dose
20mg/kg/day divided bid
levetiracetam (keppra) target dose
20-80mg/kg/day video BID
levetiracetam (keppra) status epilepticus
bolus of 60mg/kg/day
levetiracetam (keppra) adverse effects
minimally liver metabolized
excreted in urine
makes some children cranky
small dose of pyridoxine 50mg relieves irritability
levetiracetam (keppra) mechanism of action
probably an effect on GABA as its cofactor
oxcarbazepine (trileptal) indications
partial seizures, primary or secondary GTCS
oxcarbazepine (trileptal) initial dose
10mg/kg in 2 divided doses
oxcarbazepine (trileptal) maintenance
increased to 20-60mg/kg in two divided doses
oxcarbazepine (trileptal) adverse effects
drowsiness
hyponatremia is a potential problem in older populations or patients taking diuretics and SSRIs
perampanel (fycompa) indications
partial seizures with and without secondary generalization and primary generalized tonic-clonic seizures
perampanel (fycompa) titration dose
2-12mg/day over 5-15 weeks
perampanel (fycompa) mechanism of action
noncompetitive inhibition of glutaminergic AMPA receptors
perampanel (fycompa) pharmacokinetics
half life 105hrs
perampanel (fycompa) incremental dosing
increased from 2mg daily by 2mg every 2-3 weeks to desired target
perampanel (fycompa) adverse effects
sedation, ataxia, and irritability
phenobarbital indications
partial and generalized tonic-clonic-seizures
especially useful to treat status epilepticus
phenobarbital initial and maintenance dosage
3-5mg/kg/day
phenobarbital pharmacokinetics
half life 50-200hrs in term newborns
once daily dosing satisfactory
phenobarbital steady state
after 2 weeks
phenobarbital therapeutic blood concentrations
15-40 microg/mL
phenobarbital adverse effects
dose related:
- hyperactivity
- adverse behavioral changes occur in half of children between ages 2 and 10
- cognitive impairment
stevens-johnson syndrome
drowsiness and cognitive dysfunction after 10 years
allergic rash
phenytoin (dilantin) indications
tonic-clonic and partial seizures
phenytoin (dilantin) pharmacokinetics
oral absorption is slow and unpredictable in newborns, erratic in infants, and probably not reliable until 3-5 years of age
70-95% protein-bound
half life up to 60hrs in term newborns; up to 140 in premature infants; 5-14hrs in children; 10-34hrs in adults
phenytoin (dilantin) maintenance dose
7mg/kg/day in children in 2 or 3 divided doses
phenytoin (dilantin) rapid oral loading
3x maintenance dose
phenytoin (dilantin) adverse effects
hypersensitivity, gum hypertrophy, and hirsutism
hypersensitiviy within 6wks : rash, fever, and lymphadenopathy characteristic
pregabalin (Lyrica) indications
partial seizures with and without secondary generalization and neuropathic pain
pregabalin (Lyrica) titration dose
from 2-10mg/kg/day over 2 weeks
pregabalin (Lyrica) mechanism of action
similar to gabapentin, but efficacy significantly higher
pregabalin (Lyrica) adverse effects
sedation, edema, and increased weight
primidone (mysoline) indications
tonic-clonic and partial seizures
primidone (mysoline) pharmacokinetics
metabolizes to at least 2 active metabolites: phenobarbital and phenylethylmalonamide (PEMA)
half life 6-12 hrs; PEMA is 20hrs
primidone (mysoline) maintenance dosage
10-25mg/kg/day
primidone (mysoline) initial dose
25% of maintenance dosage or intolerable sedation occurs
primidone (mysoline) therapeutic blood concentrations
8-12 microg/mL
primidone (mysoline) adverse effects
same as phenobarbital except risk of intolerable sedation from first tablet is greater
rufinamide (banzel) indications
seizures within the spectrum of Lennox-Gastaut, which includes all seizure types other than typical absence seizures (present in a small percent of LGS)
rufinamide (banzel) initial dose
15mg/kg/day
rufinamide (banzel) titrating dose
up to 45mg/kg/day divided into 2 doses over 2 weeks
rufinamide (banzel) drug interactions
valproic acid may decrease the metabolism by 15-70%
rufinamide (banzel) adverse effects
sedation, emesis, and GI symptoms
stiripentol (diatomite) indications
approved for the treatment of seizures in DS as an adjunctive therapy to clobazam
inhibition of CYP3A4 and 2C19 results in increasing levels of clobazam and norclobazam
stiripentol (diatomite) recommended dose
50mg/kg/day divided into 2 or 3 doses
stiripentol (diatomite) max dose
3g divided into 2 or 3 doses
stiripentol (diatomite) possible mechanisms of action
GABA-A receptors and inhibitor of cytochrome P450, resulting in increased levels of clobazam
stiripentol (diatomite) pharmacokinetics
half life 4.5-13hrs
increases with dosage between 500 and 2000mg/day
stiripentol (diatomite) adverse effects
decreased appetite and weight, drowsiness, ataxia, low muscle tone, dystonia, neutropenia, aggressiveness, irritability, insomnia, elevation of gamma-glutamyltransferase
tiagabine (gabitril) indications
adjunctive therapy for partial-onset and generalized seizures
tiagabine (gabitril) initial dose
single day dose of 0.2mg/kg/day
tiagabine (gabitril) titration
increase every 2 weeks by 0.2 mg/kg until achieving optimal benefit or adverse reactions
tiagabine (gabitril) adverse effects
somnolence and difficulty concentrating
topiramate (topamax) indications
partial-onset and generalized epilepsies, especially the LGS. migraine prophylaxis and reasonable in children with both disorders
topiramate (topamax) initial dose
1-2mg/kg/day
topiramate (topamax) incremental increas
up to 10-15mg/kg/day divided into two doses
topiramate (topamax) adverse effects
weight loss at therapeutic dosages
cognitive impairment
fatigue and altered mental status at toxic dosages
glaucoma rare indosyncratic reaction
oligohydrosis - advise patient to avoid overheating
valproate (depakote) indications
mainly for generalized seizures
especially useful for mixed seizure disorders including myoclonic seizures, simple absence, myoclonic absence, myoclonus, and tonic-clonic seizures
valproate (depakote) pharmacokinetics
oral absorption is rapid
half life 6-15hrs
3x daily dosing in oral suspension; enteric-coated capsule slows absorption so bid dosing
95% protein bound at 50microg/mL; 80% protein bound at 100microg/mL
valproate (depakote) initial
20mg/kg/day
valproate (depakote) increments
10mg/kg/day to dose of 60mg/kg/day provide a blood concentration of 50-100microg/mL
valproate (depakote) IV
dose of 25mg/kg leads to serum level of 100microg/mL
maintenance start 1-3hrs after loading at 20mg/kg/day divided into 2 doses
valproate (depakote) adverse effects
dose-related and idiosyncratic hepatotoxicity
dose-related reduction in platelet count, pancreatitis, and hyperammonemia (cognitive disturbance and nausea)
thrombocytopenia
carnitine supplement may help relieve cognitive impairment
idiosyncratic fatal liver necrosis d/t production of an aberrant and toxic metabolite - present similar to Reye syndrome
vigabatrin (sabril) indications
effective treating infantile spasms and partial seizures
vigabatrin (sabril) pharmacokinetics
long acting, so single day dosing
twice daily dosing preferable to reduce adverse effects
vigabatrin (sabril) initial
50mg/kg/day
vigabatrin (sabril) increases
incrementally as needed to 200-250mg/kg/day
vigabatrin (sabril) adverse effects
peripheral loss of vision
consists of circumferential field constriction with nasal sparing
behavioral problems, fatigue, confusion, and GI upset mild and dose-related
zonisamide (zonegran) indications
like levetiracetam, zonisamide is a broad spectrum of activity
effective against both primary generalized and partial onset epilepsies
one of the most effective drugs in myoclonic epilepsies
zonisamide (zonegran) pharmacokinetics
long-acting drug given at bedtime
zonisamide (zonegran) initial dose
2mg/kg/day
zonisamide (zonegran) max dose
around 15mg/kg/day
zonisamide (zonegran) adverse effects
drowsiness and anorexia
oligohydrosis and hyperthermia - monitor for decreased sweating and hyperthermia is required
