Seizures/ Epilepsy

Question 1

Class:
Indications:
MOA:
Dosage forms:
Dosing:
Max dose:
Contraindications:
Warnings:
Side Effects:
Monitoring:
Pearls/Notes:
Drug-Drug/Food interactions:

Question 2

Seizure: a sudden, uncontrolled surge of excitatory neuronal activity within the brain.

Epilepsy: a chronic seizure disorder.

Question 3

(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.

Question 4

-
-

Answer 4

• fever
• infection
• alcohol withdrawal
• hypoglycemia
• electrolyte abnormalities
• head injury
• drug induced

Question 5

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!

Answer 5

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

Question 6

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.

Question 7

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).

Answer 7

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.

Question 8

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.

Answer 8

(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)

Question 9

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

Answer 9

Focal seizures are classified based on this level of awareness.

Question 10

Focal aware seizures:

Answer 10

• no loss of consciousness.
• so patients are aware they are seizing
• previously known as “simple partial seizure”

Question 11

Focal seizures with impaired awareness:

Answer 11

• means patient has a loss of consciousness
• patient not aware they are seizing
• previously known as “complex partial seizures”

Question 12

Generalized seizures with non-motor symptoms are referred to as _________________.

Answer 12

absence seizures

-typically include starring spells with no movement.

Question 13

Acute Seizure Management:

seizures can vary by -

1)
2)
3)

Answer 13

1) Type
2) Duration
3) Treatment options

Question 14

Acute Seizures:

There are 2 types-

Answer 14

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.

Question 15

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

Question 16

Status Epilepticus treatment:

• Is divided into phases
  1)
  2)
  3)
  4)

Answer 16

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)

Question 17

Status Epilepticus treatment:

1) Stabilization Phase (0-5 minutes)

what should take place here?

Answer 17

• 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

Question 18

Status Epilepticus treatment:

2) Initial Treatment Phase (5-20 minutes):

what should take place here?

Answer 18

• ## 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.

Question 19

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?

Answer 19

• 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.

Question 20

Status Epilepticus treatment:

3) Second Treatment Phase (20-40 minutes):

what should take place here?

Answer 20

• ## 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

Question 21

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?

Answer 21

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.

Question 23

Dispensing Requirements for pharmacists:

Diastat Acudial:

dispensing steps include:

1)
2)
3)
4)

Answer 23

• 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.

Question 25

Chronic Seizure Management: When it comes to chronic seizure management, what are our goals?

Answer 25

1)- control seizures with minimal treatment side effects - we can help improve patients quality of life by accomplishing these 2 things.

Question 26

Chronic Seizure Management: Treatment Primary Tx: Adjuvant Tx:

Answer 26

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. Adjuvant Tx: - - 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 - cheese ------------------------------------------------------------------------------------------------------------ There 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. ============================================================= Foods to AVOID when following a ketogenic diet - - Fried Foods - Coffee creamers - Baked goods - Microwavable meals "processed food products" - Pastas - Potatoes

Question 27

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?

Answer 27

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.

Question 28

Antiseizure Medications Overview: How and why certain antiseizure medications work- There are 2 classifications for antiseizure medications: 1) 2)

Answer 28

1) we can classify AED based on the types of seizures they treat 2) we can classify AED by their mechanism of action

Question 29

Antiseizure Medications Overview: 1) Classification of Antiseizure medications based on seizures they treat: - Broad spectrum: - Narrow spectrum:

Answer 29

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. =========================================================== 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.

Question 30

Antiseizure Medications Overview: "another way to classify antiseizure medications" 2) (MOA) mechanisms of action - - -

Answer 30

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)

Question 31

Antiseizure Medications Overview: Ion channels that are primarily involved in propagating neuronal signals or electrical impulses across the neuron are ________________.

Answer 31

Na Ca Cl

Question 32

Antiseizure Medications Overview: Blocking ___ channels = decreases excitatory transmission (glutamate).

Answer 32

Na - anything that decreases glutamate activity decreases seizure activity.

Question 33

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).

Answer 33

Cl Cl chloride

Question 34

Antiseizure Medications Overview: Major Mechanisms of Common Antiseizure Medications- - Benzodiazepines - Phenobarbital both work on-

Answer 34

- enhancing GABA effects

Question 35

Antiseizure Medications Overview: Major Mechanisms of Common Antiseizure Medications- - Valproate

Answer 35

is believed to work by blocking Na channels and increasing GABA concentrations within the brain.

Question 36

Antiseizure Medications Overview: Major Mechanisms of Common Antiseizure Medications- - Levetiracetam ?

Answer 36

*Inhibits vesicle fusion by binding to SV2A proteins. this is thought to interfere with neurotransmitter transport. - - - Ca channel blocker and increases GABA- - -???

Question 37

Antiseizure Medications Overview: Major Mechanisms of Common Antiseizure Medications- - carbamazepine - phenytoin/fosphenytoin - topiramate

Answer 37

work by primarily blocking Na channels. *remember*- blocking those sodium channels, blocks the effects of glutamate.

Question 38

Antiseizure Medications Overview: Major Mechanisms of Common Antiseizure Medications- ethosuximide

Answer 38

blocks T-type Ca channels

Question 39

Antiseizure Medications Overview: Major Mechanisms of Common Antiseizure Medications- - Lamotrigine

Answer 39

- blocks Na channels and decreases glutamate concentrations.

Question 40

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

Question 41

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

Answer 41

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 recommended**for 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.

Question 42

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:

Answer 42

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:

Question 43

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:

Answer 43

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:

Question 44

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:

Answer 44

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:

Question 45

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:

Answer 45

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:

Question 46

Keppra Keppra XR Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 46

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**

Question 47

Roweepra Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 47

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:

Question 48

Spritam Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 48

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:

Question 49

Topamax Topamax Sprinkle Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 49

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). -* 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*

Question 50

Qudexy XR Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 50

topiramate extended release capsules Contraindications: - patients with metabolic acidosis who are taking metformin

Question 51

Trokendi XR Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 51

topiramate extended release capsules Contraindications: - alcohol use 6 hours before or after dose

Question 52

Valproate products are considered Broad spectrum antiseizure medications

Question 53

Which antiepileptic drugs have an indication for migraine prophylaxis?

Answer 53

- valproic acid - topiramate

Question 54

Which antiepileptic medications have an indication for treating bipolar disorder?

Answer 54

- lamotrigine - valproate - carbamazepine (Equetro)

Question 55

which antiepileptic medications have an indication for trigeminal neuralgia?

Answer 55

- carbamazepine

Question 56

Depakene* Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 56

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. *- valproate increases warfarin concentrations, it can increase the INR and bleeding risk in patients on warfarin. - *- [DRUGS that can DECREASE valproate]- includes carbapenems, estrogen-containing contraceptives.

Question 57

Depacon* Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 57

valproate sodium Class: Indications: Seizure Coverage: MOA: Dosage forms: IV Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Question 58

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:

Answer 58

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.

Question 59

Tegretol Tegretol XR Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 59

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-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). -* 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:

Question 60

Epitol Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 60

carbamazepine

Question 61

Carbatrol Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 61

carbamazepine

Question 62

Equetro

Answer 62

carbamazepine but for bipolar disorder

Question 63

Trileptal Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 63

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: -* can decrease levels of hormonal contraceptives, patients should use non-hormonal contraception when on treatment. - - 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.

Question 64

Oxtellar XR Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 64

oxcarbazepine Extended-release tablet XR tablet - take on empty stomach 1 hour before or 2 hours after a meal

Question 65

Dilantin Dilantin Infatabs Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 65

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.

Question 66

Cerebyx Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 66

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.

Question 67

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. - ___________________________________________________________________________________ NG-tube phenytoin - - Enteral feedings decrease phenytoin absorption - - Hold feeding 1-2 hours before and after administration - - -

Answer 67

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 - - - ___________________________________________________________________________________________

Question 68

Michaelis-Menten kinetics (aka Saturable Kinetics): - - - 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? _____________

Answer 68

Enzyme saturation + Increase dose = Increased Increased Phenytoin levels - - 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 - -

Question 69

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.

Answer 69

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.

Question 70

Vimpat Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 70

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:

Question 71

Phenytek Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 71

phenytoin

Question 72

Sesquient Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 72

fosphenytoin

Question 73

phenobarbital Class: Indications: Seizure Coverage: MOA: Dosage forms: Dosing: Max dose: Contraindications: Warnings: Side Effects: Monitoring: Pearls/Notes: Drug-Drug/Food interactions:

Answer 73

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.

Question 74

Related Antiseizure Medications: (all these drugs can cause) - carbamazepine - oxcarbazepine - eslicarbazepine [the active metabolite of eslicarbazepine IS oxcarbazepine]

Answer 74

- all end in -azepine - Rash - Hyponatremia (low sodium levels) - enzyme induction (so can speed up the metabolism of other drugs)

Question 75

Related Antiseizure Medications: - phenobarbital - primidone

Answer 75

- 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

Question 76

Related Antiseizure Medications: - Gabapentin - Pregabalin

Answer 76

- pregabalin (Lyrica) C-V - gabapentin (Neurotin) - *weight gain - *peripheral edema - *mild euphoria - Used primarily for neuropathic pain* - *somnolence

Question 77

Related Antiseizure Medications: - Topiramate - Zonisamide

Answer 77

- zonisamide (Zonegran): Is Contraindicated with a Sulfonamide Allergy** - weight loss - metabolic acidosis -nephrolithiasis (kidney stones) - oligohidrosis (impaired sweating)/hyperthermia (in children) -

Question 78

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

Answer 78

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]

Question 79

Briviact

Answer 79

brivaracetam

Question 80

Epidiolex

Answer 80

cannabidiol

Question 81

Xcopri

Answer 81

cenobamate

Question 82

Aptiom

Answer 82

eslicarbazepine

Question 83

Zarontin

Answer 83

ethosuximide - capsule, oral solution - Used only for absence seizures - Warnings: - can cause serious skin reactions (eg SJS/TEN) - blood dyscrasias

Question 84

Felbatol

Answer 84

felbamate - -- - *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***

Question 85

Fintepla

Answer 85

fenfluramine C-IV - - 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

Question 86

Gralise

Question 87

Neurontin

Answer 87

gabapentin

Question 88

Horizant

Question 89

Fycompa

Answer 89

perampanel

Question 90

Lyrica

Answer 90

pregabalin

Question 91

Mysoline

Answer 91

primidone

Question 92

Banzel

Answer 92

rufinamide

Question 93

Diacomit

Answer 93

dtiripentol

Question 94

Gabitril

Answer 94

tiagabine

Question 95

Vigadrone

Answer 95

vigabatrin

Question 95

Sabril

Answer 95

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

Question 96

Zonegran

Answer 96

zonisamide

Question 98

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

Answer 98

1) Ensure efficacy 2) minimize adverse effects

Question 99

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.

Answer 99

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!!

Question 100

General Principles on Monitoring & Drug Interactions: For Antiseizure medications Organ & hematologic function

Answer 100

- some antiseizure medications can cause blood dyscrasias or hematologic changes. - Monitor LFTs, CBC with differential

Question 101

General Principles on Monitoring & Drug Interactions: For Antiseizure medications Some Antiseizure medications have: Therapeutic drug levels that needed to be monitored are for: - - - - When do therapeutic levels need to be monitored? obtained? for antiseizure medications. Do they need to be obtained for every patient? - - 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.

Answer 101

- 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)

Question 102

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.]

Answer 102

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

Question 103

General Principles on Monitoring & Drug Interactions: For Antiseizure medications Enzyme Inducers:

Answer 103

- carbamazepine - oxcarbazepine - phenytoin - fosphenytoin - phenobarbital - primidone

Question 104

General Principles on Monitoring & Drug Interactions: For Antiseizure medications Enzyme Inhibitors:

Answer 104

- valproate [UGT- the enzyme primarily responsible for lamotrigine metabolism]

Question 105

Seizures & Epilepsy: Special Populations- Pregnancy & Pediatrics

Answer 105

antiseizure medication levels generally decline during pregnancy

Question 106

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 The most common teratogenic effect with antiseizure medications is -

Answer 106

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.

Question 107

Seizures & Epilepsy: Special Populations- Pediatrics

Answer 107

- 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