Seizure Drugs Flashcards
What is the dosing schedule for Lamotrigine?
No Concomitant therapy: 25mg QD for 14 days 50mg QD for 14 days 100mg QD for 7 days then 200mg QD Concomitant Inducer(carbamazepine, phenytoin): 50mg daily for 14 days 100mg daily for 14 days 200mg daily for 7 days 400mg daily With UGT inhibiter (Valproate) 25mg every other day for 14 days 25mg daily for 14 days 50mg daily for 7 days 100mg once daily
What are the adverse effects of Lamotragine?
Serious rash (Steven Johnsons syndrome BLACK BOX, toxic epidermal necrolysis), blurred double vision,
What is the pregnancy category for Lamotragine and how does it impact oral contraception?
Category C, OC’s may decrease serum concentrations of OC’s and vise versa
What is the initial dosing for Levetiracetam (Keppra) for non SE patients
IR or/IV: 500mg BID x 14 days, increase by 1000 mg every 14 days. MAX: 3000mg/day
XR: 1000 mg daily, increase by 1000mg every 14 days
How is Keppra dosed for decreased renal function?
CrCl 30-50mL/min: 250-750 mg PO BID
CrCl
How is Keppra dosed for SE?
1000 - 3000mg IV or 2-5mg/kg/min IV
What are the adverse effects of Keppra?
Behavioral abnormalities: psychosis, suicidal thoughts or behaviors, unusual mood changes or worsening depression, somnolence, asthenia, dizziness, fatigue, aggression, irritability, decreased appetite, SJS/TEN, leukopenia
PREG CATEGORY C
What is the initial dosing for Valproate (Depakote, depakene, Depacon)?
IV and all dosage forms except ER: 10-15mg/kg/day in divided doses, increase weekly by 5-10mg/kg/day
Usual initial dose: 250mg BID or 500mg QD
ER: 10-15 mg/kg/day (once a day dosing) increasing weekly by 5-10mg/kg/day. Usual initial dose: 500mg daily.
MAX: 60mg/kg/day
What is the target serum concentration for Valproate?
50-125 mcg/ml
What is the dose for Valproate for SE?
Initial: 20-40mg/kg IV, may give additional 20mg/kg; may use alternative dosing of 3-6mg/kg/min, may give additional dose 10 minutes after loading dose. IV is dosed Q 6 hours after load; IV to PO conversion is 1:1.
What are the warnings associated with Valproate?
Contraindicated in severe hepatic dysfunction
BOX WARNING: hepatic failure/pancreatitis
Warnings: CNS depression, HYPERAMMONEMIA, thrombocytopenia, increased risk of suicidal thoughts/behaviors
Adverse Effects: tremor, somnolence, nausea/vomiting, weight gain, alopecia, PCOS
Preg Category D (X for migraines)
Use with caution in traumatic head injury; preferred for glioblastoma multiforme,: CBC with platelets, LFTs, serum concentration
What is the dosing for Zonisamide (Zonegran)**
100mg once daily, increase by 100mg/day every 14 days.
Max: 3000mg/day
Zonisamide is contraindicated in what conditions?
Sulfa hypersensitivity; caution in hepatic disease
Warnings: Metabolic acidosis, renal caliculi, sulfonamide reactions
What are the adverse effects of Zonisamide (Zonegran)? **
Drowsiness, dizziness, confusion, tremor, nausea/vomiting, weight loss, paresthesias
How is Zonisamide metabolized and what percent is renally cleared?
Metablolized via glucuronidation (UDP-GT)
35% renally cleared
What are the monitoring paramaters for Zonisamide?
CBC, LFT’s, SCr, FDA evaluating risk of DRESS syndrome for possible inclusion in prescribing information
What is the dose for Clobazam (Onfi)C-IV? **
5mg BID daily, increase to 10mg BID daily at wk 1, increase to 20mg once daily at week 2.
Max: 40mg/day
What warnings and Adverse Effects are associated with Clobazam (Onfi)?
Somnolence/sedation, withdrawal symptoms, SJS, TEN, drug dependence, suicidal thoughts/behaviors
Adverse Effects: constipation, somnolence, sedation, increased body temperature, lethargy, drooling
True or False: Clobazam may decrease the effectiveness of oral contraceptives.
True
Pregnancy Category C
What is the dose for Clonazepam (Klonopin)?**
1.5mg/day in 3 divided doses, increase by 0.5-1mg every 3 days. Max of 20mg/day
What conditions are contraindicated for the use of Clonazepam? What warnings are associated with this med?
Severe hepatic Disease
CNS depression, respiratory depression, anterograde amnesia, paradoxical reactions, withdrawal symptoms
What Adverse Effects are associated with Clonazepam?
Ataxia, confusion, drowsiness, slurred speech
What are P450 interactions of Clonazepam, Preg category and monitoring parameters?
P4503A4 substrate Major
Preg Category D
Monitoring Parameters: CBC and LFTs
What is the dosing for Carbamazepine ***(Tegretol, Tegretol XR, Carbatrol, Epitol)
IR or ER
200mg BID, increase by 200mg/day once weekly
Suspension: 100mg (5mL) four times daily, increase by 200mg/day once weekly
Max: 1600mg/day
Monitor serum concentrations: 4-12mcg/ml (>12 = toxicity)
Usually just for kids, a lot of dosing challenges with this.
What are the contraindications of Carbamazepine?
Concurrent use with TCA, carbamazepine sensitivity
What are the boxed warnings of Carbamazepine?
SJS/TEN (most likely in patients of Asian descent who are + for HLA-B1502; Drug reactionwith Eosinophilia and Systemic Symptoms (DRESS) hypersensitivity reaction if positive for HLA-A3101 (Northern European descent); aplastic anemia, agranulocytosis
What are the Adverse effects of Carbamazepine?
drowsiness, dizziness, HA, fatigue, nausea/vomiting Vitamin D/ Calcium deficiency, double vision, sedation, leukopenia, syndrome of inappropriate antidiuretic hormone (SIADH), hyponatremia
What is the P450 influence and Pregnancy category for Carbamazepine?
P450 3A4 Substrate major, P450 2C8 minor
Preg Category D
What is the UGT substrate influence of Carbamazepine?
UGT strong inducer: 1A3, 2B6, 2C8, 2C9, 2C19, 3A4
What are the monitoring parameters for Carbamazepine?
LFTs, CBC with platelets, electrolytes, BUN/SCr
May autoinduce own metabolism for several weeks after initiation and dose increase.
Eslicarbazepine Acetate (Aptiom) dosing?**
400mg once daily for 1 week, increase to 800 mg once daily.
MAX: 1200mg once daily (after a min of 800mg once daily)
Moderate to severe renal impairment: 600mg once daily
What warning is associated with Eslicarbazepine Acetate>
Dermatologic reaction (SJS/TEN), hyponatremia, Same Box warning as Carbamazepine
What active metabolite comes from Eslicarbazepine and what is it’s impact on P450?
Eslicarbazepine, active metabolite of oxcarbzepine P450 2C19 inhibitor Moderate
Same HLA effects as Carbamazepine
MONITOR electrolytes!!
What is the dose of Exobagine (Potiga) C-V?
Include renal dosing and max dosing.
100mg three imes daily, increase by up to 50mg TID once a wk.
Max: 1200mg
Renal Dosing: CrCl
What is the Box warning and other warnings for Exobagine?
Boxed: Retinal abnormalities - may progress to vision loss
Warnings: urinary retention, grey-blue/brown skin discoloration (sign of toxicity) QTc prolongation, memory impairment, hallucinations, double vision
What are the important monitoring parameters for Ezobagine (Potiga)?
Baseline ophthalmic exam, repeat every 6 months
Extensive metabolism via UGT
Felmbamate (Felbatol) dosing?
1200mg/day in 3 to 4 didvided doses, increase every 2 wks by 600mg/day. Max: 3600mg/day
RENAL: CrCl
What is the Box warning for Felbamate?
Aplastic Anemia, hepatic failure
What are Important monitoring parameters for Felbamate?
LFTs at baselihne and frequently thereafter; discontinue if evidence of bone marrow suppression. Monitor CBC with differential/platelets, LFTs at least every 3 months
Gabapentin Dosing? Renal adjustment?
300mg TID, increase every 1-3 days by 300-800mg/day
Max: 3600mg/day
Renal: CrCl 30-60ml/min: 600 - 1800mg/day
Not rec for CrCl
Gabapentin adverse effects?
Somnolence, Peripheral edema,
100% renal clearance, monitor baseline then routinely!
What unique dosage form does Gabapentin come in?
Compounding powder for oral suspension: 2500mg/420ml
What is Lacosamide (Vimpar) dosing?
Comes in IR and Oral solt.
50mg BID daily, increase by 100mg/day each week.
Max: 400mg/day
What is Lacosamide dosing for SE?
200-400mg IV, infuse 200mg IV over 5 minutes
What warnings are associated with Lacosamide?
Caution in patients with cardiac conduction abnormalities, prolongs PR interval, Dermatological reactions, visual disturbances
What major adverse effects are associated with Lacosamide?
Idiosyncratic reactions: hepatic impairment, 1st degree AV block
What is the P450 reaction of Lacosamide?
p450 2C19 substrate and inhibitor: MAJOR
What is the dose conversion of Oxcarbazepine when switching from Carbamazepine?
Oxcarbazepine is 1.5X the dose of carbamazepine
What are the major Warnings associated with Oxcarbazepine?
Derm reactions (HLA-B1502 and HLA - A3101 - SJS/TEN/DRESS), hyponatremia (
What P450 interaction does Oxcarbazepine have?
Major/Strong P450 3A4/5 substrate/inducer
P450 2C19 inhibitor: Moderate
MONITOR ELECTROLYTES
What is the major boxed warning for Perampanel (Fycompa) C-III
Dose related serious and /or life threatening neuropsychiatric events!!
NOT for psych patients!!
What are adverse affects of Perampanel?
gait disturbances and somnolence
What is the SE dose for Phenobarbital?
Loading dose: 15-18 mg/kg IV (ventilated)
10mg/kg IV (non-ventilated) Increased by 5mg/kg IV infused over 30-60minutes
What is the SE max dose and goal serum concentration for phenobarbital?
25-30mg/kg IV (SE), 50-100mg/min IV
Serum concentration: 15-40mcg/ml
What are the adverse effects of Phenobarbital?
Somnolence, confusion, cognitive impairment, impaired calcium metabolism
What is the pregnancy category and P450 metabolism of phenobarb?
Category D
P450 2C9 substrate major
P450 1A2,2C,3A and UGT inducer: strong
What is phenytoin dose for SE?
15-20mg/kg IV, may give additional 5-10mg/kg
Max 50mg/minute loading dose
May give additional dose 10mins after load.
What is loading dose of Fosphenytoin for SE?
20mg phenytoin equivalent/kg IV or IM
May give an additional 5mg/kg; may give an additional dose 10mins after load.
Max: 150mg PE/minute loading dose
What is the goal for serum concentrations of phenytoin?
10-20 mcg/ml
Fosphenytoin to phenytoin conversion occurs in 0.5-1 hour post dose.
What are the adverse effects of fosphenytoin (IV)?
hypotension, arrhythmias
What are the adverse effects of phenytoin (IV)?
Arrythmias, hypotension, purple glove syndrome (local reaction)
What are the contraindications of phenytoin?
sinus bradycardia or 2cnd/3rd degree heart block
What is the pregnancy category and P450 metabolizer?
Preg category D, P450 2C9/2C19 substrate: major
P450 1A2, 2C19, 3A4 and UGT inducer strong
What are the monitoring parameters for Phenytoin?
Serum concentration and serum albumin
What are the phenytoin warnings?
Decreased bone mineral density, dermatological reactions, blood dyscarias
What are the Adverse effects of Phenytoin?
Nystagmus, ataxia, double vision, hepatotoxicity, hisuitism, gingival hyperplasia, cardiac arrhythmias, SJS, alteration of vitamin D metabolism, osteoporosis
What is the renal dosing for Pregabalin (Lyrica)
Renal Dosing: CrCl 30-60mL/min: 300mg
CrCl 15-30 mL/min: 150mg
CrCl
What are the warnings with Pregabalin?
Angioedema and Peripheral edema
Primidone (mysoline) is metabolized to what drug?
Phenobarbital
What pregnancy category is Primidone?
D
What unique seizure disorder is Rufinamide (Banzel) indicated for?
Lennox-Gastaut/ Refactory seizures
What are the contraindications and warnings of Rufinamide?
Familial short QT syndrome
Warning: Multiorgan sensitivity reactions (DRESS), SJS, TEN
Tiagabine (Gabitril) dosing needs to be adjusted when taken with certain drugs. How is it dosed for enzyme inducing drugs?
Valproate therapy?
Concomitant enzyme inducing drugs: 4mg once daily, increase by 4-8mg/day once weekly
Concomitant valproate therapy: 4mg every other day increase by 4-8mg / day every 2 wks.
What are the goal serum concentrations for Tiagabine?
0.02 -0.2mcg/mL
What patients should Tiagabine be used in caution with?
For patients without seizure disorder and with hepatic disease, may trigger seizures.
What is a major Adverse effect of Tiagabine?
Cognitive impairement
What is the P450 impact of Tiagabine?
P450 3A4 substrate: major
What is the dose for Topiramate (Topamax)?
25-50mg/day, increase by 25-50mg/day once weekly
What is the renal dosing for Topiramate?
CrCl
What is the dosing for SE for Topiramate?
200-400mg per nasogastric tube or PO: 300 - 1600mg/day orally in 2-4 divided doses
What patients do you use Topiramate with caution in?
nephrolithiasis, renal impairment, hepatic disease
What are the warnings for Topiramate?
CNS depression, metabolic acidosis, oligohydrosis/hyperthermia, acute mhopia, secondary angle-closure glaucoma, nephrolithiasis, visual field defects, cognitive impairment, hyperchloremic non anion,gap metabolic acidosis
What is the preg category and metabolism of P450 enzymes?
Category D
P450 2C19 inhibitor moderate
P450 3A4 substrate/inducer; moderate-strong (dose dependant)
What are monitoring parameters for Topiramate?
Basic metabolic profile, urinalysis every 3-6 months
What type of seizures is Vigabatrin (Sabril) used for and what is the dose?
Refactory seizures:
500mg BID, increase by 500mg daily
What is the renal dosing for Vigabatrin?
CrCl 50 - 80ml/min: reduce dose by 25%
CrCl 30 -50: reduce by 50%
CrCl 10 - 30: reduce dose by 75%
Vigabatrin is contraindicated in which patients?
BLACK BOX for VISION LOSS. So don’t use if patient has other risk factors for irreversible vision loss
What are the adverse effects of Vigabatrin?
Depression, weight gain, insomnia, permanent loss of peripheral vision
What are the monitoring parameters for Vigabatrin?
SCr, vision assessment at baseline and every 3-6 months
What type of seizures is Ethosuximide (Zarontin) used to treat?
Absence
What are the contraindications and warnings with Ethosuximide?
Avoid in renal/hepatic dysfunction
Warnings: Systemic Lupus Erythematosus, SJS/TEN
What are the adverse effects associated with Ethosuximide?
Leukopenia, eosinophilia, psychiatric and sleep disturbances, aggression, hiccups
What are the monitoring parameters and P450 metabolism?
P450 3A4 Substrate: major
CBC with differential and platelets, basic metabolic profile baseline and every 3 months
