Seizures/ Epilepsy Flashcards
Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Seizure: a sudden, uncontrolled surge of excitatory neuronal activity within the brain.
Epilepsy: a chronic seizure disorder.
(EEG)-electroencephalogram- records electrical activity within the brain.
- can be used to identify abnormal firing patterns.
- very useful in the outpatient and inpatient care settings.
-
-
- fever
- infection
- alcohol withdrawal
- hypoglycemia
- electrolyte abnormalities
- head injury
- drug induced
Key drugs that can lower the seizure threshold:
“if a patient has a past history of epilepsy, we want to avoid these medications”
- if patient has a drug induced seizure, we want to know what drug to look for!
Theophylline, Varenicline, acyclovir, valacyclovir, metoclopramide
[analgesics]
opioids - (tramadol, meperidine) *
[anti-infectives]
- quinolones, carbapenems, cephalosporins, penicillin’s*, lindane, mefloquine
[psychiatric medications]
- bupropion, antipsychotics: clozapine, lithium, tricyclic antidepressants,
—————————————————————————————————————
- patients on High doses of these drugs or have renal impairment are at an even greater risk of having a seizure
First Aid for Seizures:
1) Prevent injury by clearing the area around the person of anything hard or sharp.
2) Ease the person to the floor and put something soft and flat, like a folded jacket, under the head. Turn the person gently onto one side. This will help keep the airway clear.
3) Remove eyeglasses and loosen ties or anything around the neck that may make breathing difficult.
4) Time the seizure. If the seizure continues for longer than 5 minutes without signs of slowing down, or if the person has trouble breathing, appears to be injured, in pain or has an unusual recovery, call 911.
5) Do not hold people down or try to stop their movements.
6) Contrary to popular belief, it is not true that people having a seizure can swallow their tongue. Do not put anything in the person’s mouth.
7) Do not attempt artificial respiration except in the unlikely event that a person does not start breathing after the seizure has stopped.
Classification of Seizures:
- one way to classify seizures is based off of where they start in the brain [LOCATION].
- seizures can occur in a part of the brain, one side of the brain (focal) or they can occur across the entire brain (generalized).
Focal Seizures: occur on one side of the brain and can spread to the other side.
Generalized Seizures: start on both sides of the brain.
Classification of Seizures:
- another way to classify seizures is based on the [SYMPTOMS] the patient has during the active seizure.
- seizures patients have, can have certain (MOTOR symptoms) during an active seizure.
(motor symptoms)
- uncontrolled jerking movements
- muscle twitching
- rigid or tense muscles
- limp
Tonic = rigid Tense muscles
Clonic = unControlled jerking movements
Myoclonus = brief Muscle twitching
Atonic = limp (no tone)
Classification of Seizures:
- seizures patients have, can have certain (Non-MOTOR symptoms) during an active seizure.
- Awareness/consciousness of the active seizure
OR
- Loss of consciousness/unaware of the active seizure
Focal seizures are classified based on this level of awareness.
Focal aware seizures:
- no loss of consciousness.
- so patients are aware they are seizing
- previously known as “simple partial seizure”
Focal seizures with impaired awareness:
- means patient has a loss of consciousness
- patient not aware they are seizing
- previously known as “complex partial seizures”
Generalized seizures with non-motor symptoms are referred to as _________________.
absence seizures
-typically include starring spells with no movement.
Acute Seizure Management:
seizures can vary by -
1)
2)
3)
1) Type
2) Duration
3) Treatment options
Acute Seizures:
There are 2 types-
1) typical Seizures
Duration: - self-limiting, lasts a couple minutes at most, less than < 5min
Treatment: - treatment may or may not be needed.
2) (SE) Status Epilepticus
Duration: - lasts greater than or equal to > 5min
Treatment: - emergency care = can be FATAL
both differ in how long they last and how we approach treating them.
Status epilepticus - is a seizure that lasts 5 minutes or more because the normal mechanisms that terminate seizures are not working.
- this is a medical emergency and emergency treatment should be given with any seizure that lasts longer than 5 minutes.
- negative consequences include causing cardiac arrhythmias, hypoxia, and permanent cognitive or neurological damage.
- can be fatal
Status Epilepticus treatment:
- Is divided into phases
1)
2)
3)
4)
1) Stabilization phase (0-5 minutes)
2) Initial Treatment Phase (5-20 minutes)
3) Second Treatment Phase (20-40 minutes)
4) Third Treatment Phase (Refractory)
Status Epilepticus treatment:
1) Stabilization Phase (0-5 minutes)
what should take place here?
- here emergency treatment should be done as soon as possible beginning in the stabilization phase.
- during this time, keep track of how long the patient has been seizing. (TIME THE SEIZURE)
- MONITOR THE PATIENTS VITALS (drug levels for AEDs, electrolytes, glucose)
- Assess patients oxygen levels & start ECG readings at this time.
- look for any reversible causes of seizures, like low blood sugars. (treat with D25 - D50)
-IV access should also be attempted at this phase so labs can be drawn
- No need to wait for labs to begin treatment, this can contribute to patient harm
Status Epilepticus treatment:
2) Initial Treatment Phase (5-20 minutes):
what should take place here?
- ## drug should be given within the first 20 minutes of receiving the patient for care.
- these are all preferred drugs because they all have a very fast onset of action!
Options:
IV lorazepam (Ativan)
IM midazolam (Versed)
IV diazepam - these drugs slow neuronal firing very quickly
- remember it is all about optimizing our time and treating patients quickly.
Status Epilepticus treatment:
2) Initial Treatment Phase (5-20 minutes):
If NONE of the preferred options are available
IV lorazepam (Ativan)
IM midazolam (Versed)
IV diazepam
then what are the alternative we can use?
- if NONE of these preferred options are available then we can use:
— IV phenobarbital
— rectal (PR-per rectum) diazepam (Diastat Acudial)
— intranasal or buccal midazolam.
Status Epilepticus treatment:
3) Second Treatment Phase (20-40 minutes):
what should take place here?
- ## if seizures continue after the initial treatment phase, then we move into the Second Phase of Treatment.
- for this phase we give IV Antiseizure medications
Possible Options include:
- IV fosphenytoin
- IV valproic acid
- IV levetiracetam
- IV phenobarbital
Status Epilepticus treatment:
3) Second Treatment Phase (20-40 minutes):
But, what do you do when none of this works and the patient continues to have seizures?
If seizure persists despite giving an injectable benzodiazepine AND IV antiseizure medication
Then Third Treatment Phase (Refractory):
- there is No clear evidence to guide therapy
- best option would be to repeat second line therapy or give midazolam, pentobarbital, or propofol with continuous EEG monitoring.
Dispensing Requirements for pharmacists:
Diastat Acudial:
dispensing steps include:
1)
2)
3)
4)
- a rectal diazepam gel used to stop an active seizure.
- it is commonly used as an adjunctive treatment in patients with refractory epilepsy, who experience random episodes of increased seizure activity.
- a caregiver usually administers it outside of a healthcare setting and sometimes may be given in a longer health care facility.
- Each Kit comes with 2 prefilled rectal syringes
- Pharmacist MUST dial AND lock correct prescribed dose before dispensing to a patient or caregiver. - ## syringes come in 2.5, 10, and 20mg
1) Hold the barrel of syringe in one hand with cap facing downward and dose window visible.
2) To dial the dose- Twist cap to adjust dose being careful not to remove it. Confirm correct dose is visible in dosing window.
3) Lock dose, by grasping locking ring at bottom of syringe barrel and pushing it upwards. Green “READY” band is revealed once dose is locked.
4) Repeat steps for second syringe in kit.
- When counseling, check both syringes with the patient before they leave the pharmacy to ensure they are dialed and locked.
Chronic Seizure Management:
When it comes to chronic seizure management, what are our goals?
1)- control seizures with minimal treatment side effects
- we can help improve patients quality of life by accomplishing these 2 things.
Chronic Seizure Management: Treatment
Primary Tx:
Adjuvant Tx:
Primary Tx:
- think of the mainstay treatments for the patients with epilepsy.
- 1st line treatment for epilepsy: (AED) Antiepileptic Drugs
eg. [lamotrigine, valproate, levetiracetam]
- Do NOT stop these drugs abruptly, can precipitate a seizure to occur.
- If need to stop an agent then tamper.
- ## Cannabis-derived products, often used in patients with certain refractory seizures. Cannabidiol or (CBD- Epidiolex) was the first approved cannabis derived medication approved by the FDA to treat rare forms of epilepsy.
- ## Neurostimulation is an adjuvant nondrug treatment that can be beneficial in drug resistant epilepsy. It involves using a device that delivers electromagnetic energy to stimulate different targeted areas of the nervous system. With a goal of altering the conduction pathway to reduce seizures. Device can be implanted or can be external.
- Ketogenic diet is used to help reduce seizure frequency especially in refractory seizures. The diet contains high fats, normal proteins and low carbohydrates (usually a 4:1 ratio of fats to combined protein and carbohydrates). [This forces the body to break down fatty acids into ketone bodies as an energy source. ketone bodies pass into the brain and replace glucose. The body burning ketones for energy instead of glucose].
- The diet mimics a starvation state and induces ketogenesis- the breakdown of fatty acids into ketones, as the bodies primary energy source. This shift to ketones is thought to play a role in its anticonvulsant effect.
HIGH fat, LOW carb, with protein diet
Foods that would be encouraged in diet: “High fat foods & animal proteins.”
- eggs,
- leafy vegetables
- Pork, poultry, beef
- Nuts, seeds
- Olive oil, coconut oil
- seafood
- ## cheeseThere are modifications of the ketogenic diet that exist
ex. modified Atkins diet is a version of the ketogenic diet that allows for more flexibility in food selection.
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Foods to AVOID when following a ketogenic diet
-
- Fried Foods
- Coffee creamers
- Baked goods
- Microwavable meals “processed food products”
- Pastas
- Potatoes
Chronic Seizure Management:
Because the ketogenic diet is very restrictive.
Nutritional deficits can happen if not careful.
*Supplementation with ___________ is essential for ALL patients on a ketogenic diet.
For patients on a ketogenic diet, what is recommended for patients to take?
multivitamins
calcium
Vitamin D
*Choosing a low carbohydrate multivitamin is recommended and should include selenium. (prevent alopecia from AED like lamotrigine and valproic acid)
- some antiseizure medications can increase the risk of bone fractures, making calcium and vitamin D supplements necessary. For ALL AED, patients should supplement with calcium and vitamin D.
Antiseizure Medications Overview:
How and why certain antiseizure medications work-
There are 2 classifications for antiseizure medications:
1)
2)
1) we can classify AED based on the types of seizures they treat
2) we can classify AED by their mechanism of action
Antiseizure Medications Overview:
1) Classification of Antiseizure medications based on seizures they treat:
- Broad spectrum:
- Narrow spectrum:
Broad spectrum: antiseizure medications that treat Focal seizures and any Generalized seizures.
(e.g. lamotrigine, levetiracetam, topiramate, valproate)
-valproic acid: therapeutic range [50-100 mcg/mL (up to 150mcg/mL in some patients)] IF albumin LOW (<3.5g/dL), then calculate a corrected level using same equation for phenytoin.
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Narrow spectrum: antiseizure medications are NOT used to treat both. They primarily treat one type of seizure and that is usually Focal seizures.
(e.g. carbamazepine, phenytoin)
carbamazepine: therapeutic range [4-12 mcg/mL]
phenytoin:
therapeutic range [10-20 mcg/mL] total level, [1-2.5mcg/mL] free level;
IF albumin LOW then calculate a corrected phenytoin level.
fosphenytoin: “dosed in phenytoin equivalents (PE)”
1mg (PE) phenytoin equivalent = 1mg phenytoin
1mg (PE) phenytoin equivalent = 1.5mg fosphenytoin
- narrow spectrum agents also include a drug that treats a specific generalized seizure type called absence seizures. (e.g. ethosuximide)
There are no motor symptoms with this type of seizure.
Antiseizure Medications Overview:
“another way to classify antiseizure medications”
-
-
1- Alter ion channels or proteins (that are involved with neuronal firing or transmission of electrical activity)
2- Increase (GABA) gamma-aminobutyric acid (inhibitory neurotransmitter), so slows down neuronal firing.
3- Decrease glutamate activity (excitatory neurotransmitter)
Antiseizure Medications Overview:
Ion channels that are primarily involved in propagating neuronal signals or electrical impulses across the neuron are ________________.
Na
Ca
Cl
Antiseizure Medications Overview:
Blocking ___ channels = decreases excitatory transmission (glutamate).
Na
- anything that decreases glutamate activity decreases seizure activity.
Antiseizure Medications Overview:
Increasing GABA activity, promotes the activation of ___________ ion channels on the receiving neuron. This Causes an increase in inhibitory neurotransmission. Resulting in decreased seizure activity.
Activating ________ channels = leads to increasing inhibitory transmission (GABA).
Cl
Cl chloride
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Benzodiazepines
- Phenobarbital
both work on-
- enhancing GABA effects
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Valproate
is believed to work by blocking Na channels and increasing GABA concentrations within the brain.
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Levetiracetam
?
*Inhibits vesicle fusion by binding to SV2A proteins. this is thought to interfere with neurotransmitter transport.
- Ca channel blocker and increases GABA- - -???
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- carbamazepine
- phenytoin/fosphenytoin
- topiramate
work by primarily blocking Na channels.
remember- blocking those sodium channels, blocks the effects of glutamate.
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
ethosuximide
blocks T-type Ca channels
Antiseizure Medications Overview:
Major Mechanisms of Common Antiseizure Medications-
- Lamotrigine
- blocks Na channels and decreases glutamate concentrations.
Antiseizure Medications Overview:
Major Mechanisms of action in Common Antiseizure Medications-
1) Increase GABA (inhibitory neurotransmitter)
2) Decrease Glutamate (excitatory neurotransmitter)
3) Ca channel blockers
4) Na channel blockers
Common Adverse Effects of antiseizure medications:
- although there are many different antiseizure medications, they have a few adverse effects that are similar between them.
This is related to how they work:
What are the 4 common adverse effects across all types of seizure medications:
-1
-2
-3
-4
since seizures result from uncontrolled neuronal firing. Antiseizure medications decreasing neuronal activity through CNS depression is beneficial in stopping seizures. However, there are unwanted effects.
1) CNS depression: confusion, sedation, poor coordination, falls (increased risk), impaired cognition.
- - - patients starting antiseizure medications should be warned that these medications may also impair there focus or reaction time.
2) Suicide risk: can increase risk of suicidal thoughts or behaviors.
– both patients and caregivers should be advised to Monitor changes in mood or behavior when starting an antiseizure medication.
– something to be mindful of especially in patients with psychiatric conditions like depression.
3) Bone loss: increased risk of fractures.
- antiseizure medications can reduce bone mineral density, alter vitamin D metabolism, and affect bone remodeling. Although this can happen with almost all antiseizure medications, enzyme inducing antiseizure medications ARE the MOST common culprit for this adverse effect. The enzyme induction causes increased vitamin D metabolism to inactive metabolites. Leading to less active vitamin D available and decreased gut absorption of calcium.
- patients on antiseizure medications are at an increased risk for fractures due to bone loss.
- Calcium AND Vitamin D supplementation is recommendedfor all patients on antiseizure medications to reduce the risk of fractures.
4) Rash: benign or life-threatening (eg SJS, TEN, DRESS) [Stevens-Johnson Syndrome, Toxic Epidermal Necrolysis, Drug Reaction with eosinophilia and Systemic Symptoms].
- antiseizure medications can cause a rash. They range from benign to life threatening.
- the risk of rash is dose dependent. Typically develops early on in treatment, but can happen anytime during treatment.
- the risk of rash can be further increased with dose escalation or with certain combinations of antiseizure medications.
DRESS is another hypersensitivity reaction that has cutaneous manifestations.
Lamictal
Lamictal ODT
Lamictal XR
Chewable tablet
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lamotrigine
Class: antiepileptic
Indications: seizures
- also used in bipolar disorder
Seizure Coverage: Broad spectrum coverage
MOA: blocks Na channels and decreases glutamate concentrations
Dosage forms:
*Dosing: [Titrating medication very important to prevent serious skin reactions].
- *(initial dosing can vary based on interacting drugs)
Initial: 25mg daily for Week 1 and Week 2
Titrate: 50mg daily for Week 3 and Week 4
Weeks 5 and on: Can increase daily dose by 50mg every 1-2 weeks.
Maintenance Dose: 300-400mg daily, divide BID unless using XR (daily).
Boxed Warnings:
- Serious skin reactions, including: (Stevens-Johnson syndrome/toxic epidermal necrolysis. [These are life threatening conditions]. The rate of rash is greater in pediatrics than adults. Rash is spread across whole body with painful skin sloughing and lesions.
There is increased risk with:
- higher dosing than recommended starting doses
- dose escalation
- when used with valproate
Contraindications:
Warnings:
- risk of aseptic meningitis, blood dyscrasias, cardiac rhythm abnormalities, multiorgan hypersensitivity (DRESS) reactions, [Drug Reaction with Eosinophilia Systemic Symptoms]
*Side Effects:
- rash,
- *Alopecia “hair loss”- if this occurs, (supplement with selenium, biotin, and zinc)- to help reduce this side effect.
- N/V, ataxia (lack of balance/coordination), tremor, insomnia, blurred vision,
*Monitoring:
- rash, fever
- **general monitoring of seizure frequency, CNS depression, depressed mood and suicidality.
Pearls/Notes:
Safety Considerations:
**- advise patient or caregiver when starting the medication if any rash develops to contact medical care provider as soon as possible.
**- if patient develops a rash or signs and symptoms of hypersensitivity, then patient should stop taking medication and seek immediate medical attention.
- Always use a starter kit when initiating treatment.
- **If discontinued for greater or equal to 5 half-lives (~6 days), restart initial dosing titration. Use a starter kit.
Drug-Drug/Food interactions:
Lamictal Starter Kit [orange]
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
When would we use this starter kit?
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lamotrigine Orange Starter Kit
[Standard starting dose kit]
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
[Orange Kit contents and dosing schedule]
Week 1: 25mg daily
Week 2: 25mg daily
Week 3: 50mg daily (two 25mg tablets)
Week 4: 50mg daily (two 25mg tablets)
Week 5: 100mg daily (1 tablet)
[42 tablets of 25mg & 7 tablets of 100mg]
-** then can continue to increase daily dose by 50mg every 1-2 weeks**
When would we use this starter kit?
-** patient has NO interacting medications**
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Lamictal Starter Kit [blue]
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
When would we use this starter kit?
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lamotrigine Blue Starter Kit = “Blue for Below” starting dose
[Lower Starting dose titration]
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
[Blue Kit contents and dosing schedule]
Week 1: 25mg (EOD) every other day
Week 2: 25mg (EOD) every other day
Week 3: 25mg daily
Week 4: 25mg daily
Week 5: 50mg daily (two of the 25mg tabs)
[35 tablets of 25mg]
*When would we use this starter kit?
- Use if patient is taking VALPROIC ACID
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Lamictal Starter Kit [green]
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
When would we use this starter kit?
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lamotrigine Green Starter Kit = “Green for Greater than” starting dose
[Higher starting dose kit]
Class:
Indications:
Seizure Coverage:
MOA: inhibits the release of Glutamate (an excitatory neurotransmitter) and inhibits voltage sensitive Na channels, which stabilizes neuronal membranes.
Dosage forms:
Dosing:
[Green Kit contents and dosing schedule]
Week 1: 50mg daily (two of the 25mg tabs)
Week 2: 50mg daily (two of the 25mg tabs)
Week 3: 100mg daily (50mg AM and 50mg PM) (two of the 25mg tabs AM and two 25mg tablets PM)
Week 4: 100mg daily (50mg AM and 50mg PM) (two of the 25mg tabs AM and two 25mg tablets PM)
Week 5: 200mg daily (100mgAM and 100mg PM) (100mg tablet AM and PM)
[84 tablets of 25mg, and 14 tablets of 100mg]
When would we use this starter kit?
- Use if patient is taking an enzyme inducer and NOT taking valproic acid.
{e.g. carbamazepine, phenytoin, phenobarbital, primidone)
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Keppra
Keppra XR
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
levetiracetam
Class: antiseizure
Indications:
Seizure Coverage: Broad spectrum
MOA: Inhibits vesicle fusion by binding SV2A proteins. this is thought to interfere with neurotransmitter transport.
Dosage forms: tablet, injection, ODT, oral solution
XR formulations - only approved for ages 12 and older.
Dosing:
Initial: 500mg BID for IR
Initial: 1000mg daily XR
*If CrCl is less than or equal too 80mL/min then: Decrease Dose
**Max dose: 3000mg/day
Contraindications:
Warnings:
**- psychiatric reactions, including psychotic symptoms, somnolence, fatigue.
- severe skin reactions (SJS/TEN), anemias, decreased seizure control in pregnancy, withdrawal seizures, increased BP, suicidal behavior, angioedema, coordination difficulties.
Side Effects:
- behavior changes, irritability, dizziness, weakness, asthenia (physical weakness or lack of energy),
Monitoring:
Pearls/Notes:
-* IV:PO ratio is 1:1
-
**levetiracetam is Preferred in:
1) pediatrics- can be used in infants (comes in several formulations that would be easy to administer to kids).
2) pregnancy it is preferred. Carries the lowest risk of fetal harm. Plasma levels can change during pregnancy. So, drug level monitoring and dose level adjustments are needed when appropriate.
3) Ideal when you have a patient with epilepsy on other drugs with a high interaction risk profile. [No significant drug interactions].
(ex. antiseizure medications are known to interact with hormonal contraceptives but levetiracetam has no significant drug interactions).
- can be used in patients on transplant medications
Drug-Drug/Food interactions:
** No significant drug reactions**
Roweepra
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
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Drug-Drug/Food interactions:
levetiracetam
Class: antiseizure
Indications:
Seizure Coverage: Broad spectrum
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Spritam
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
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Drug-Drug/Food interactions:
levetiracetam
Class: antiseizure
Indications:
Seizure Coverage: Broad spectrum
MOA:
Dosage forms: tablets for oral suspension
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Topamax
Topamax Sprinkle
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
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Drug-Drug/Food interactions:
topiramate
Class: antiepileptic
Indications: seizures
- also used for migraine prophylaxis
Seizure Coverage: Broad Spectrum (Focal and Generalized seizures)
MOA:
- Works by primarily blocking Na channels.
remember- blocking those sodium channels, blocks the effects of glutamate.
- it also blocks carbonic anhydrase, an enzyme that plays a key role in systemic acid base regulation.
Dosage forms: IR and ER formulations
Dosing:
Initial:
IR Week 1: 25mg BID
XR Week 1: 50mg daily
IR Weeks 2-4: Increase dose by 25mg BID each week.
XR Weeks 2-4: Increase dose by 50mg each week.
Week 2: 100mg daily
Week 3: 150mg daily
Week 4: 200mg daily
IR Week 5 and on: Increase dose by 100mg weekly until max dose or therapeutic
XR Week 5 and on: Increase dose by 100mg weekly until max dose / therapeutic
*If CrCl is less than 70mL/min: Decrease Dose 50%
Max dose: 400mg/day*
Contraindications:
Warnings:
-* fetal harm
- Acid/Base disturbances/issues:
- - metabolic acidosis (occurs due to increased renal excretion of bicarbonate)
**- - hyperammonemia: high/increased levels of ammonia (NH3) “alone & with valproic acid”.
** Valproate can also increase ammonia (NH3). Topiramate can increase ammonia levels on its own as well.
*- - nephrolithiasis (kidney stones): which occurs when carbonic anhydrase inhibition leads to increased urinary pH and reduced urinary citrate excretion. This promotes calcium phosphate stone formation in the kidneys.
- Oligohidrosis (reduced perspiration). - rare
- normal perspiration serves a purpose. When body senses an increase in temperature, it causes vasodilation and perspiration to help displace the heat. This results in decreased body temperature. When Carbonic anhydrase inhibition alters sweat composition and decreases sweat rate.
So instead of sweating and cooling, the body experiences continued hyperthermia (high body temperature).
- normal perspiration serves a purpose. When body senses an increase in temperature, it causes vasodilation and perspiration to help displace the heat. This results in decreased body temperature. When Carbonic anhydrase inhibition alters sweat composition and decreases sweat rate.
-* Visual problems (reversible)
- - acute myopia
- - angle closure glaucoma (caused by a blockage that leads to a sudden sharp increase in intraocular pressure) [Medical Emergency]- that requires surgery.
Side Effects:
relate to “CNS depressant” think DOPE -amax
dopy - brain fog
Pronounced CNS effects:
- - *somnolence
- - dizziness
- - psychomotor slowing
- - *difficulty with memory/concentration/attention
- *weight loss, anorexia
Monitoring:
- electrolytes especially bicarbonate (HCO3)
- eye exam (intraocular pressure)
- renal function, hydration status
Pearls/Notes:
- patient should report to provider with any changes in vision. Due to risk of eye damage.
Drug-Drug/Food interactions:
- ** Can decrease the effectiveness of oral contraceptives (especially doses greater or equal to 200mg daily). Non-hormonal contraception is recommended*
Qudexy XR
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
topiramate extended release capsules
Contraindications:
- patients with metabolic acidosis who are taking metformin
Trokendi XR
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
topiramate extended release capsules
Contraindications:
- alcohol use 6 hours before or after dose
Valproate products are considered Broad spectrum antiseizure medications
Which antiepileptic drugs have an indication for migraine prophylaxis?
- valproic acid
- topiramate
Which antiepileptic medications have an indication for treating bipolar disorder?
- lamotrigine
- valproate
- carbamazepine (Equetro)
which antiepileptic medications have an indication for trigeminal neuralgia?
- carbamazepine
Depakene*
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
valproic acid
Class: antiepileptic
Indications: epilepsy
- bipolar disorder
- migraine prophylaxis
Seizure Coverage: BROAD spectrum
MOA:
- causes increased availability of GABA, an inhibitory neurotransmitter, to brain neurons or may enhance the action of GABA.
- is believed to work by blocking Na channels ( which results in suppression of high-frequency repetitive neuronal firing) and increasing GABA concentrations within the brain.
Dosage forms: capsule, syrup
Dosing:
Initial: 10-15mg/kg/day
**[Therapeutic range]: 50 - 100 mcg/mL (total level)
Max dose: 60mg/kg/day
Boxed Warnings:
**- Hepatic failure: usually during the first 6 months of therapy, children less than < 2 years old and patients with mitochondrial disorders [mutations in mitochondrial DNA polymerase gamma gene (POLG)] are at increased risk;
-* fetal harm (neural tube defects and decreased IQ scores)
- pancreatitis
Contraindications:
Warnings:
-**Hyperammonemia: can develop because valproate also decreases carnitine, a compound that prevents the accumulation of ammonia by converting it to urea for excretion. Symptoms of hyperammonemia include: nausea, vomiting, abdominal pain, and balance or coordination issues (also known as ataxia).
(Treat with carnitine or lactulose in symptomatic adults only).
-**does-related thrombocytopenia (increased bleeding risk). [Valproate can disrupt hematologic processes by causing antibody mediated decreases in thrombocytes, bone marrow toxicity, and increased platelet destruction, leading to thrombocytopenia. Which increases risk of bleeding.
- hypothermia, multiorgan hypersensitivity (DRESS) reactions.
Side Effects:
- somnolence——– caused by CNS depression
- tremor
- *weight changes (weight gain more likely)
- nausea, vomiting
- *alopecia (supplement with selenium, zinc and biotin supplements can help reduce hair loss)
Monitoring:
- *LFTs (baseline and frequently in the first 6 months)
[as mentioned in the Boxed Warnings, Valproate derivatives can cause hepatic failure]
- *(CBC) Complete Blood Count with differential [due to the risk of thrombocytopenia, the lower the platelet count, the greater the risk of bleeding].
Pearls/Notes:
*- Across all antiepileptic medications, Valproate has the highest risk of congenital disorders and can cause major malformations, such as neural tube defects. It can also cause decreased cognitive scores in offspring.
*- Avoid using in pregnant patients.
- alopecia is more common in women than men and is a dose related side effect.
- Valproate is an enzyme inhibitor and can displace certain drugs from protein binding sites.
- If the albumin level is low (less than < 3.5 g/dL), the true valproic acid level will be higher than it appears - adjust with the same formula used for phenytoin.
Drug-Drug/Food interactions:
*- Valproate can INCREASE levels of: [lamotrigine, phenobarbital, phenytoin, warfarin].
- - - - the interaction between LAMOTRIGINE & VALPROATE is caused by valproate inhibiting UGT= (glucuronosyltransferase): an enzyme involved in glucuronidation. This is lamotrigine’s primarily means of metabolism. This interaction can increase the risk of a serious rash**. This is WHY we use a lower starting dose on patients taking both lamotrigine & valproate.
*- [DRUGS that can DECREASE valproate]- includes carbapenems, estrogen-containing contraceptives.
Depacon*
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
valproate sodium
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms: IV
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
Depakote
Depakote Sprinkle
Depakote ER
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
divalproex- delayed release (DR) tablet—————–(valproic acid)
divalproex- extended release (ER) tablet——————–(valproic acid)
[DR and ER formulations are not bioequivalent, increase total daily dose 8-20% when converting from DR to ER tablets.]
- divalproex is a valproic acid derivative with the same side effect profile and CYP enzyme/protein binding interactions as the valproic acid formulations.
Tegretol
Tegretol XR
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
carbamazepine
Class: antiepileptic
Indications: seizures
- also used in trigeminal neuralgia (neuropathic pain that occurs at trigeminal nerve, located on the side of the face)
Seizure Coverage: Narrow Spectrum antiepileptic
MOA: Block (Na) sodium channels
Dosage forms: capsule, tablet, chewable tablet, oral suspension
Dosing:
Initial: 200mg BID (or divided QID for suspension)
Maximum: 1600mg/day (some patients can require more)
Therapeutic Range: * 4 - 12 mcg/mL
Boxed Warning:
- Serious Skin reactions (eg SJS/TEN): this risk is increased in those containing the HLA-B1502 allele (Human Leukocyte Antigen complex). This allele is more common in Asian descent and should be tested for prior to initiation. If (+) positive for this allele, carbamazepine cannot be used (unless benefit clearly outweighs risk).
- aplastic anemia (when the bone marrow cannot make enough red blood cells for the body to function)
-* agranulocytosis (a severe form of neutropenia, having absolute neutrophil counts (ANC) less than 100 neutrophils per microliter of blood.)
- discontinue if significant myelosuppression occurs
Contraindications:
*Myelosuppression
- hypersensitivity to TCAs
- Use of MAO inhibitors within past 14 days
- Use with nefazodone or NNRTIs that are substrates of CYP3A4
Warnings:
** -Fetal Harm
** -Hyponatremia [It does this by increasing ADH antidiuretic hormone and the sensitivity of renal vasopressin V2 receptors to antidiuretic hormone. This is known as (SIADH) Syndrome of Inappropriate Antidiuretic Hormone Release.
- liver damage
Side Effects:
- dizziness, drowsiness, ataxia (impaired coordination), N/V, pruritus, photosensitivity, blurred vision, increased LFTs, alopecia
Monitoring:
- serum sodium
- platelets [ CBC with differential prior to and during therapy]
- LFTs
- eye exam
- thyroid function tests
Pearls/Notes:
-* can decrease levels of hormonal contraceptives, patients should use non-hormonal contraception when on treatment.
-* carbamazepine is a STRONG Inducer of many CYP enzymes [CYP1A2, 2C19, 2C8, 2C9, 3A4] and P-gp.
-* It is also an autoinducer, induces its own metabolism. So decreases level of itself.
Drug-Drug/Food interactions:
Epitol
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
carbamazepine
Carbatrol
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
carbamazepine
Equetro
carbamazepine
but for bipolar disorder
Trileptal
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
oxcarbazepine
Class: antiepileptic
Indications:
Seizure Coverage: NARROW spectrum antiepileptic (Focal) seizures
MOA: Block (Na) sodium channels
Dosage forms: oral suspension, tablet
Dosing:
Initial:
300mg BID (Trileptal)
600mg daily (Oxtellar XR)
If CrCl < 30 mL/min, then Start 300mg daily.
Max dose: 2400mg/day
Warnings:
**- Serious Skin reactions (eg SJS/TEN): this risk is increased in those containing the HLA-B*1502 allele (Human Leukocyte Antigen complex). This allele is more common in Asian descent and should be tested for prior to initiation. If (+) positive for this allele, carbamazepine cannot be used (unless benefit clearly outweighs risk).
- hypersensitivity reactions to carbamazepine have 25-30% cross-sensitivity to oxcarbazepine.
** -Hyponatremia [It does this by increasing ADH antidiuretic hormone and the sensitivity of renal vasopressin V2 receptors to antidiuretic hormone. This is known as (SIADH) Syndrome of Inappropriate Antidiuretic Hormone Release.
Contraindications:
- hypersensitivity to eslicarbazepine
Side Effects:
- somnolence, dizziness, N/V, diplopia (double vision), ataxia (impaired coordination), tremor
Monitoring:
- Serum Na levels, especially during first 3 months of therapy, CBC, thyroid function
Pearls/Notes:
- structurally similar to carbamazepine
-** NOT an autoinducer
-** NO BOXED WARNING for aplastic anemia, agranulocytosis
- oral suspension must be used within 7 weeks once original container is opened.
Drug-Drug/Food interactions:
- oxcarbazepine doses greater or equal to 1200mg daily can significantly increase phenytoin levels. Phenytoin levels should be monitored carefully as dose reductions may be needed.
- oxcarbazepine and its active metabolite, MHD, can increase levels of fosphenytoin, phenytoin, and phenobarbital.
Oxtellar XR
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
oxcarbazepine Extended-release tablet
XR tablet - take on empty stomach 1 hour before or 2 hours after a meal
Dilantin
Dilantin Infatabs
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
phenytoin
Class: antiepileptic
Indications:
Seizure Coverage: NARROW spectrum
MOA: Na channel blocker
Dosage forms: oral formulations (capsule, chewable, oral suspension) and injection (IV only)
Dosing:
Loading Dose: 15-20 mg/kg
Maintenance Dose: up to 300-600mg/day
*Max dose: IV: 50mg/min (slow infusion)
Boxed Warnings:
- Hypotension, cardiac arrhythmias with rapid infusion.[Phenytoin IV administration should NOT exceed 50mg/min].**
- if given faster, hypotension and cardiac arrhythmias can occur**
- Follow infusion rates.
Contraindications:
previous hepatotoxicity due to phenytoin
Warnings:
- **Extravasation (which can lead to purple glove syndrome, characterized by edema, pain and bluish discoloration of the skin, which can sometimes lead to tissue necrosis).
- [similar to carbamazepine and oxcarbazepine], AVOID use in HLA-B*1502 positive patients and in patients who have had a severe rash with carbamazepine, multiorgan hypersensitivity (DRESS) reactions.
-Fetal harm
Side Effects:
- Acute: ataxia (poor coordination), diplopia (double vision), nystagmus (a vision condition in which the eyes make repetitive, uncontrolled movements).
- slurred speech, dizziness, somnolence, confusion, lethargy (lack of energy).[DOSE-related toxicities]
- Chronic: gingival hyperplasia (overgrowth of the gums), hair growth, hepatotoxicity
Monitoring:
- Serum phenytoin levels
- LFTs
- For IV formulations: Cardiac and respiratory monitoring
Therapeutic range:
10 - 20 mcg/mL (total level) = recommended range for total drug levels
1 - 2 mcg/mL (free level) = free drug levels in blood**
Pearls/Notes:
- *IV:PO ration 1:1
- genetic testing is not required before starting treatment with phenytoin.
- *should be avoided in pregnancy when possible
- phenytoin is a highly protein bound drug, meaning some drug binds to albumin in the plasma, while some drug remains free or unbound in the tissues. The bound drug to albumin is inactive, while the unbound drug or free drug is active/available to do its job.
[Dosed in phenytoin equivalents (PE)]
1 mg of PE = 1 mg of phenytoin
1 mg of PE = 1.5 mg of fosphenytoin
- specific administration requirements
- dose adjustments based on low albumin levels*
**- To properly adjust phenytoin levels: MUST understand Michaelis-Menten kinetics (also called saturable kinetics). - Remember Calcium AND vitamin D for ALL AEDs
Drug-Drug/Food interactions:
** Strong Inducer of CYP enzymes: CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, P-gp (P-glycoprotein), and UGT1A1.
- Can decrease hormonal contraceptives. Should be advised to use non-hormonal contraceptives.
Cerebyx
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
fosphenytoin **prodrug of phenytoin.
Class: antiepileptic
Indications:
Seizure Coverage: NARROW spectrum coverage
MOA: Na channel blocker
Dosage forms: Injection (IV/IM)
Dosing: [Dosed in phenytoin equivalents (PE)]***
1 mg of PE = 1 mg of phenytoin
1 mg of PE = 1.5 mg of fosphenytoin
**Max dose: IV 150 mg PE/min ***
Boxed Warnings:
- Hypotension, cardiac arrhythmias with rapid infusion. [Fosphenytoin IV should NOT exceed 150 mg PE/min or 2 mg PE/kg/min (use the slower rate)].
- if given faster, hypotension and cardiac arrhythmias can occur
Contraindications:
- previous hepatotoxicity due to phenytoin
Warnings:
- **Extravasation (which can lead to purple glove syndrome, characterized by edema, pain and bluish discoloration of the skin, which can sometimes lead to tissue necrosis).
- [similar to carbamazepine and oxcarbazepine], AVOID use in HLA-B*1502 positive patients and in patients who have had a severe rash with carbamazepine, multiorgan hypersensitivity (DRESS) reactions.
-Fetal harm
Side Effects:
- Acute: ataxia, diplopia, nystagmus (a vision condition in which the eyes make repetitive, uncontrolled movements).
Monitoring:
- Serum phenytoin levels
- LFTs
- For IV formulations: Cardiac and respiratory monitoring
Therapeutic range:
10 - 20 mcg/mL (total level) = recommended range for total drug levels
1 - 2 mcg/mL (free level) = free drug levels in blood**
Pearls/Notes:
- lower risk of purple glove syndrome
- *IV:PO ration 1:1
- genetic testing is not required before starting treatment with phenytoin.
- *should be avoided in pregnancy when possible
- phenytoin is a highly protein bound drug, meaning some drug binds to albumin in the plasma, while some drug remains free or unbound in the tissues. The bound drug to albumin is inactive, while the unbound drug or free drug is active/available to do its job.
[Dosed in phenytoin equivalents (PE)]
1 mg of PE = 1 mg of phenytoin
1 mg of PE = 1.5 mg of fosphenytoin
- Remember Calcium AND vitamin D for ALL AEDs
Drug-Drug/Food interactions:
** Strong Inducer of CYP enzymes: CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, P-gp (P-glycoprotein), and UGT1A1.
- Can decrease hormonal contraceptives. Should be advised to use non-hormonal contraceptives.
Specific administration requirements:
IV Phenytoin
- Both REQUIRE a SLOW infusion (less than or equal to 50 mg/min)
-
- Monitoring for both infusion products is the SAME, (BP, ECG and respiratory monitoring)
-
- Dilute in NS (normal saline), is stable for 4 hours. Do NOT refrigerate, can cause precipitation in IV bag.
-
- An in-line FILTER is required when administering.
-
___________________________________________________________________________________
- ## Enteral feedings decrease phenytoin absorption
- ## Hold feeding 1-2 hours before and after administration-
-
Specific administration requirements:
IV Fosphenytoin
- Both REQUIRE a SLOW infusion (less than or equal to 150 mg PE/min)
-
- Monitoring for both infusion products is the SAME, (BP, ECG and respiratory monitoring)
-
- Lower risk of purple glove syndrome
-
-
-
___________________________________________________________________________________________
-
- To account for kinetic differences due to changes in albumin. We use the Phenytoin Correction formula:
- What is Formula?
- When do we Use this formula? _____________
- If enzymes before saturated, then an increase in dose can cause a much larger increase in phenytoin concentration.
- ## This can lead to toxicity
- ## since phenytoin is highly protein bound. Patient with LOW albumin levels have an increased fraction of free phenytoin. This can also increase risk of toxicity.-
Phenytoin Correction = Total Phenytoin measured / (0.2 x albumin) + 0.1 - ## directly drawn Free Levels do not require correction
- ## Use ONLY for albumin < 3.5 g/dL with a CrCl > greater or equal to 10 mL/min-
Practice case question:
The medical team is discussing a patient with epilepsy during rounds. The patients lab results are as follows: total phenytoin level 16mcg/mL, SCr 0.9mg/dL, albumin 2.9 g/dL. What is the corrected phenytoin level? (round final answer to the nearest tenth)
the SCr is 0.9 mg/dL which is considered normal.
Phenytoin Correction = Total phenytoin measured / (0.2 x albumin level) + 0.1
*** Use only when Albumin < 3.5 g/dL WITH a CrCl > or equal to 10mL/min
Phenytoin Correction = 16 / (0.2 x 2.9) + 0.1
Phenytoin Correction = 16 / (0.58) + 0.1
Phenytoin Correction = 16 / 0.68
Phenytoin Correction = 23.529 = 23.5
This means our patient is slightly Supra-Therapeutic, we would likely recommend a dose reduction to reduce the risk of toxicity.
Vimpat
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
lacosamide C-V
Class: antiepileptic
Indications:
Seizure Coverage: NARROW spectrum
MOA: drug works on (Na) sodium channels.
- which are also involved in cardiac conduction.
(remember class 1 antiarrhythmics are also Na channel blockers)
Dosage forms: tablet, oral solution, injection
Dosing:
Initial: 50 - 100mg BID
If CrCl is less than < 30mL/min THEN Max dose 300mg/day
Max dose: 400mg/day
Contraindications:
Warnings:
**Cardiac effects:
- Prolongs PR interval
- Increases risk of arrhythmias; (obtain baseline & steady-state ECG in at-risk patients)
- dizziness, ataxia
Side Effects:
- blurred vision, diplopia = (double vision - when seeing 2 images of a single thing)
- tremor
- euphoria (is related why it is a scheduled C-V controlled substance)
Monitoring:
Pearls/Notes:
- IV:PO ratio 1:1
V = <3, so cardiac effects
- Should be avoided in patients with cardiac conduction issues when possible.
- Use Caution with drugs that affect PR interval (e.g. beta-blockers, calcium channel blockers, digoxin)
Drug-Drug/Food interactions:
Phenytek
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
phenytoin
Sesquient
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
fosphenytoin
phenobarbital
Class:
Indications:
Seizure Coverage:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:
C-IV
Class: barbiturate
Indications: antiepileptic
Seizure Coverage: Narrow Spectrum Antiepileptic
MOA: Enhances the effect of GABA (an inhibitory neurotransmitter)
Dosage forms: oral (tablet, oral solution, elixir) and injectable formulations
Dosing:
Initial: 50-100mg BID or TID
Therapeutic Range:
20-40 mcg/mL (adults)
Max dose:
Contraindications:
- previous addiction to sedative hypnotics
- severe hepatic impairment
- dyspnea or airway obstruction
Warnings:
-* respiratory depression (dose related adverse effect)
-* Fetal harm
-* potential for drug dependency
- serious skin reactions (SJS/TEN)
Side Effects:
- *residual sedation or “next day drowsiness” = “Hangover effect”
- *dependence, *tolerance [Use Caution in Hx of Substance Use Disorder]
- somnolence, cognitive impairment, dizziness, ataxia, depression, folate deficiency.
Monitoring:
- LFTS
- CBC with differential
Pearls/Notes:
- not commonly used due to its harsh effects
- phenobarbital levels are typically obtained when toxicity is expected or if there are concerns for decreased serum concentrations due to drug interactions.
- should not be used in pregnant patients
-** Primidone is a prodrug of phenobarbital. “meaning primidone is converted to phenobarbital in the body”
- **Strong Enzyme Inducer
Drug-Drug/Food interactions:
- Can decrease levels of hormonal contraceptives. Non-hormonal contraception is recommended.
Related Antiseizure Medications: (all these drugs can cause)
- carbamazepine
- oxcarbazepine
- eslicarbazepine [the active metabolite of eslicarbazepine IS oxcarbazepine]
- all end in -azepine
- Rash
- Hyponatremia (low sodium levels)
- enzyme induction (so can speed up the metabolism of other drugs)
Related Antiseizure Medications:
- phenobarbital
- primidone
- these drugs are considered barbiturates
- Primidone is the prodrug of phenobarbital
- ## enzyme inducers
- Sedation
- dependence/tolerance/overdose risk
- should be used cautiously in patients with a hx of substance misuse
Related Antiseizure Medications:
- Gabapentin
- Pregabalin
- pregabalin (Lyrica) C-V
- gabapentin (Neurotin)
- *weight gain
- *peripheral edema
- *mild euphoria
- Used primarily for neuropathic pain*
- *somnolence
Related Antiseizure Medications:
- Topiramate
- Zonisamide
- zonisamide (Zonegran): Is Contraindicated with a Sulfonamide Allergy**
- weight loss
- metabolic acidosis
-nephrolithiasis (kidney stones) - ## oligohidrosis (impaired sweating)/hyperthermia (in children)
Benzodiazepines, including:
> clobazam (Onfi- tablet, Sympazan-oral film)
> diazepam (Valtoco)- nasal spray
-5mg
- 1 nasal spray device (1 dose per unit)
Diastat AcuDial (rectal gel)
> midazolam (Nayzilam) - nasal spray
- 5mg
- 2 nasal spray units (1 dose per unit)
midazolam (Versed) - intranasal injection
> lorazepam
C-IV
- can cause dependence
- All come in a variety of fast acting formulations
[oral formulations, rectal gel, intranasal spray, injection]
- Used to stop an Active seizure or in Refractory Epilepsy.
- clobazam is an exception and is a chronic treatment for patients with NOX gasto or refractory epilepsy.
Boxed Warnings:
- profound sedation, respiratory depression or death with opioids
[Opioids and benzodiazepines should NOT be given together]
Briviact
brivaracetam
Epidiolex
cannabidiol
Xcopri
cenobamate
Aptiom
eslicarbazepine
Zarontin
ethosuximide
- capsule, oral solution
- Used only for absence seizures
-
Warnings:
- can cause serious skin reactions (eg SJS/TEN)
- blood dyscrasias
Felbatol
–
- it can impair the bone marrow’s ability to make red blood cells and white blood cells, leading to pancytopenia
- patients that develop this side effect are at increased risk of serious bleeding or an infection
Boxed Warnings
- hepatic failure
- aplastic anemia or pancytopenia with bone marrow failure**
Fintepla
- patients with underlying pulmonary artery conditions should not use this medication
- echocardiogram required before, during and after treatment
Boxed Warnings: - valvular heart disease**
- pulmonary hypertension**
[available only through a restricted distribution program/REMS]**
Warnings:
- decreased appetite*
- weight loss*
- serotonin syndrome
- increased blood pressure
- angle closure glaucoma
Contraindications:
- MAO inhibitors
Gralise
Neurontin
gabapentin
Horizant
Fycompa
perampanel
Lyrica
pregabalin
Mysoline
primidone
Banzel
rufinamide
Diacomit
dtiripentol
Gabitril
tiagabine
Vigadrone
vigabatrin
Sabril
vigabatrin
[only available through a restricted program called the Vigabatrin REMS Program]
tablet, packet for solution.
Boxed Warnings:
- causes permanent vision loss (in greater than or equal to 30% of patients).**
Monitoring:
- Eye exam at baseline, every 3 months during therapy and 3-6 months after discontinuation
Zonegran
zonisamide
General Principles on Monitoring & Drug Interactions: For Antiseizure medications
2 main reasons we monitor antiseizure medications
1)
2)
- a variety of tests and strategies can be used to monitor antiseizure medications. Like monitoring seizure frequency
1) Ensure efficacy
2) minimize adverse effects
General Principles on Monitoring & Drug Interactions: For Antiseizure medications
Patients with Epilepsy or caregivers are encouraged to keep a seizure diary or track when a seizure occurs, how long it lasts, or any unusual symptoms or triggers they notice.
This serves as a way to determine if the patients seizure control is improving or worsening with there current regimen.
There is an APP for that!!
General Principles on Monitoring & Drug Interactions: For Antiseizure medications
Organ & hematologic function
- some antiseizure medications can cause blood dyscrasias or hematologic changes.
- Monitor LFTs, CBC with differential
General Principles on Monitoring & Drug Interactions: For Antiseizure medications
Some Antiseizure medications have:
-
-
-
- because changes in metabolism occur during pregnancy
serum drug levels for antiseizure medications are often obtained to guide dosing therapy. - metabolic changes occur also after pregnancy (postpartum). Drug levels are also obtained to ensure appropriate dosing and minimize the risk of adverse effects.
- serum drug levels may be obtained before or after [dose changes] for anyone. This can help ensure the change in dose is just right.
- serum drug levels can be ordered to check adherence when non-adherence is suspected. (serum concentrations below the serum therapeutic range coupled with poor seizure control, may indicated the patient has been non-adherent with their medications)
-therapeutic drug levels or other monitoring may be ordered when there is a suspected drug toxicity. (Drug levels above the concentration range can increase the risk of adverse effects and may help further confirm toxicity in symptomatic patients). Toxicity can be caused by organ dysfunction, the drug dose being to high for the patient or a drug interaction.
- Carbamazepine
Therapeutic range: 4-12 mcg/mL - Phenytoin
Therapeutic range: 10-20 mcg/mL (total level) / 1-2.5 mcg/mL (free level) - Phenobarbital
Therapeutic range: 20-40 mcg/mL (adults) - Valproic acid
Therapeutic range 50-100 mcg/mL (total level)
-(eg. low albumin levels can affect phenytoin kinetics and patients can have supratherapeutic levels)
General Principles on Monitoring & Drug Interactions: For Antiseizure medications
DRUG INTERACTIONS with Antiseizure medications:
“Antiseizure medications interact with other drugs through 2 main mechanisms”
1) Protein binding:
- drug binds to plasma proteins in the blood (mainly albumin) r
- remember think of the bound drug to protein, as too busy to too its job. Its bound to protein and has other business.
- the free unbound drug is free to do its job.
- antiseizure drugs that are highly protein bound can displace other drugs from protein binding sites on albumin (Competitive drug displacement)
2) Enzyme effects: (antiseizure medications effects on enzymes)
- enzyme effects include altering metabolism related enzymes like CYP and UGT and transporters like (eg P-glycoprotein).
- inducer or inhibitor, know that this is likely referring to multiple enzyme types
[Overall, Protein Binding & Enzyme Effects of antiseizure medications can increase or decrease their efficacy or toxicity as well as the efficacy or toxicity of other drugs.]
examples of antiseizure medications that are highly protein bound and can displace other drugs from protein binding sites are:
- clobazam
- phenytoin
- valproic acid
Inducers: increase the metabolism of substrate drugs
Inhibitors: reduce the metabolism of substrate drugs
General Principles on Monitoring & Drug Interactions: For Antiseizure medications
Enzyme Inducers:
- carbamazepine
- oxcarbazepine
- phenytoin
- fosphenytoin
- phenobarbital
- primidone
General Principles on Monitoring & Drug Interactions: For Antiseizure medications
Enzyme Inhibitors:
- valproate [UGT- the enzyme primarily responsible for lamotrigine metabolism]
Seizures & Epilepsy: Special Populations- Pregnancy & Pediatrics
antiseizure medication levels generally decline during pregnancy
Seizures & Epilepsy: Special Populations- Pregnancy
Antiseizure medications in pregnancy:
The biggest concern with antiseizure medications is the risk of fetal harm or
teratogenic risk.
The risk of fetal harm is greatest with older antiseizure medications:
- carbamazepine
- valproate [Highest risk]- AVOID in pregnant patients
- phenytoin
- primidone
levetiracetam = lowest risk [preferred antiseizure medication in pregnancy]
Neural tube defects and decreased IQ or cognitive scores
Daily folate supplementation is recommended while daily antiseizure medications for patients of childbearing potential.
Seizures & Epilepsy: Special Populations- Pediatrics
- cognitive difficulty can occur for children taking antiseizure medications. Can impact learning and development.
- can also have coordination issues
For children there are some unique adverse effects with certain medications:
Topiramate & Zonisamide = oligohidrosis (reduced sweating), sun exposure should be limited to minimize this risk
Lamotrigine = Rash life threatening severe
Unique formulations needed:
- may cannot swallow tablets and capsules
- ODTs, chewable tablets, oral solutions are preferred
