General
Can change is manufactures affect blood levels?
yes! generic and brand can both be used, but do not change
What vitamins should be taken on all AEDs? Women of childbearing age? If taking Depakote? If taking lamotrigine and valproic acid (alopecia)?
Calcium and vitamin D
Folate
Carnitine?
if alopecia supplement with selenium and zinc
Compared to carbamazepine, what is different about oxacarbazepine?
fewer drug interactions, less adverse effects, no autoinduction, may work for carbamazepine non responders, increased incidence of hyponatremia, more expensive, still interacts with oral contraceptives.
Levetiracetam: Warnings? AEs? IV:PO ratio?
psychiatric rxns including psychotic sx, somnolence, fatigue, irritability and hostility
dizziness, vomiting
1:1 ratio
When does the phenytoin dose need corrected? What is the equation?
If albumin is <3.5 and CrCl is greater than or equal to 10 mL/min
(total phenytoin conc)/((0.2 x albumin) + 0.1)
What is the general principle for dosing anti-seizure meds?
start low, go slow
minimizes side effects, some potentially life threatening
What are the most important points for therapeutic drug monitoring for AEDs? What should be base our titrations off of? When are free levels beneficial for highly protein bound drugs?
Do not aim for specific drug target, treat the pt
Draw level at trough concentration, do not get daily levels and adjust dose daily (need to reach steady state)
elderly, pregnant, hypoalbuminemia, critically ill
How soon should you get a carbamazepine level? What is auto induction? What are the major drug interactions?
How is XR and SR formulations dosed?
2-3 weeks
Auto induction: SS in 21-28 days
DDIs: sertraline, carbapenems
XR and SR dosed BID to decrease AEs, improve QOL and seizure control, take with food
Topiramate: CI? Warnings and common AEs? Important DDI?
Pt w/ metabolic acidosis also taking metformin
Non-anion gap metabolic acidosis, nephrolithiasis, oligohidrosis (reduced sweating), fetal harm
AEs: sedation, weight loss, memory impairment, dysgeusia (feeling disgusted), paresthesias
Phenytoin: AEs? Monitoring?
AEs: dose related nystagmus, lethargy, ataxia, diplopia or blurred vision, chronic hair growth, hepatotoxicity, increased blood glucose
Monitor serum phenytoin conc., LFT, CBC, continuous cardiac and respi monitoring if IV, trough about 5 days after oral dose change
What is a big concern for all AEDs? Which patient population is most at risk?
increased risk of suicidality especially in pain and depression patients
What is hypersensitivity syndrome in this case? Which drugs are most and least likely to induce? What are risk factors?
Often maculopapular eruption on chest and inner elbows and knees, fever and systemic involvement
Most: Phenytoin and lamotrigine
Least: VPA, LEV, GBP
Risks: pediatric or old age, genetics, history of prior rxn, high initial dose and rapid titration, immune system disorder
What happens is lamotrigine is withheld for more than 3-5 days? When should we initially start with a lower dose? Higher dose?
Initial titration must be restarted
patients taking valproic acid
phenytoin, carbamazepine, phenobarbital
Valproic acid/divalproex: CI? BBW? Warnings and AEs?
CI: liver disease, mitochondrial disease, severe hematological abnormalities
BBW: hepatotoxicity, pancreatitis, fetal harm
Hyperammonemia (drug can induce carnitine depletion), dose related thrombocytopenia
Alopecia, weight gain, nausea, tremor, thrombocytopenia
AED Class Side Effects?
cognitive depression/impairment, drowsiness/sedation, blood dyscrasias, HA/N, weight changes, rash and hypersensitivity, fetal harm, neurotoxicity, osteoporosis, suicidality
What are some cognitive side effects of AEDs? Which 2 drugs have the most cognitive side effects? Least?
Drowsiness, dizziness, blurred or double vision, difficulty concentrating, memory and thinking problems, sedation, increased risk for impairments, falls, injury
Worst: phenobarbital and topiramate
Least: valproic acid/divalproex
What are the major drug interactions with AEDs?
Anti-hypertensives, cholesterol lowering, HIV, hormonal contraceptives, solid organ transplant meds, TB meds, Warfarin
Lamotrigine: BBW? Other warnings and AEs? Major DDI?
serious skin rxns (SJS/TEN), increased risk with fast titration up, starting dose too high or with VPA
Delayed hypersensitivity, suicidal ideation, N/V, tremor, alopecia (supplement)
Oral and injectable contraceptives
Divalproex/valproic acid: monitoring?
Conversion of depakote to depakote ER?
If also taking lamotrigine, what do we need to do?
LFTs, CBC, trough level in 2-4 days, once stable check every 6 months
increase total daily dose by 8-20%
reduce lamotrigine by 50%
Phenytoin/Fosphenytoin: BBW? Other warnings?
Phenytoin IV rate should not exceed 50 mg/min
Fosphenytoin IV should not exceed 150 mg PE/min or 2 mg PE/kg/min
Hypotension and cardiac arrhythmias can occur if given too quickly
Extravasion can lead to purple glove syndrome and possibly skin necrosis
What are some not cognitive related side effects of AEDs? Which drugs are most likely to cause?
RASH, hepatotoxicity, osteoporosis chronically and increase fracture risk (start vitamins)
Blood dyscrasias: felbamate most likely for aplastic anemia, carbamazepine most likely for agranulocytosis
Nausea, headache, instability
weight gain: valproic acid, carbamazepine (also gabapentin and pregabalin)
weight loss: topiramate and zonisamide
What is status epilepticus? What should be checked if possible? Treatment if GCSE (5-20 min)? Treatment if established (20-40 min)?
Seizure lasting more than 5 minutes or recurrent seizure activity without return to baseline mental status
Check glucose and electrolytes
GCSE: IV lorazepam 0.1 mg/kg/dose over 30-60 sec, max 4 mg/dose, can repeat in 5 min if no respionse
Established: IV Fosphenytoin 20 mg PE/kg once over 20 min, max <1500 mg PE/dose
Carbamazepine: BBW? Other warnings? Monitoring?
SJS/TEN, agranulocytosis and occasionally aplastic anemia
Hyponatremia, fetal harm, neurological AEs (dose limiting), GI disturbances
CBC with differential, LFTs, EKG, pregnancy, electrolytes
Important things to note about these meds:
Zonisamide, ethosuximide, phenobarbital, primidone, lacosamide
Zonisamide: weight loss
Ethosuximide: SJS/TEN, weight loss
Phenobarbital: significant CNS side effects
Primidone: pronounced drowsiness
Lacosamide: arrhythmia (monitor EKG)
AEDs side effects:
Most overall, cognitive (most and least), blood dyscrasias, skin rash (highest and lowest risk), weight changes (gain and loss)
Overall: lamotrigine and topiramate
Cognitive: phenobarb and topiramate (most), VPA (least)
Blood: Felbamate (anemia), carbamazepine (agranulocytosis)
Skin rash: Phenytoin and lamotrigine (highest risk), levetiracetam and VPA (lowest)
Weight: VPA and carbamazepine (gain), topiramate and zonisamide (loss)