RX414 Focal and Generalized Tonic-Clonic Seizure Medications

What should be monitored with any "-azepine" drug?

Sodium

What are the concentration-dependent adverse effects of carbamazepine (Tegretol)?

- Diplopia (double vision)

- Nystagmus (rapid eye movement)

- CNS effects

- GI effects

What are the concentration-independent adverse effects of carbamazepine (Tegretol)?

- Leukopenia

- Hyponatremia (SIADH)

- Severe rashes (HLA-B*1502)

- Decreased bone density

- Vitamin D deficiency

- Thrombocytopenia

- Anemia

What are the black box warnings for carbamazepine (Tegretol)?

- Severe rashes

- Aplastic anemia

- Agranulocytosis

What CYP enzyme does carbamazepine (Tegretol) interact with?

- CYP3A4

- Major inducer (autoinducer)

- May have to titrate up since it eats itself

What are the monitoring parameters for carbamazepine (Tegretol)?

- HLA-B*1502

- Renal function

- CMP

- BMP

- Drug levels

- Sodium

What are the clinical pearls of carbamazepine (Tegretol)?

- May worsen absence seizures

- May precipitate tonic-clonic seizures in patients with other generalized seizures

- Fetal harm

- Used in bipolar disorder

- Used in trigeminal neuralgia

- Higher risk of rashes with faster titrations

What are the adverse effects of oxcarbazepine (Trileptal)?

- Hyponatremia (SIADH)

- Severe rashes

- Diplopia (double vision)

- Nystagmus (rapid eye movement)

- Decreased bone density

What are the CYP interactions of oxcarbazepine (Trileptal)?

- CYP3A4 inducer

- CYP2C19 inhibitor (high doses)

What are the monitoring parameters for oxcarbazepine (Trileptal)?

- BMP

- CBC

- Renal function

- Thyroid function

- Sodium

What are the clinical pearls of oxcarbazepine (Trileptal)?

- Higher risk of SIADH compared to carbamazepine

- Prodrug

- 30% cross-reactivity if rash with carbamazepine

What are the adverse effects of eslicarbazepine (Aptiom)?

- Diplopia (double vision)

- Hyponatremia (SIADH)

What are the interactions of eslicarbazepine (Aptiom)?

- CYP2C19 inhibitor

- UGT1A1 inducer

What are the monitoring parameters for eslicarbazepine (Aptiom)?

- Renal function

- Sodium

What are the clinical pearls of eslicarbazepine (Aptiom)?

- Reserve for failure of other agents

- Taken once daily

- Lower risk of SIADH

- Prodrug

What is the black box warning of phenytoin (Dilantin)?

Cardiovascular risk with rapid infusion

What are the adverse effects of phenytoin (Dilantin)?

- Gingival hyperplasia

- Hirsutism and acne

- Purple glove syndrome and skin thickening

- Decreased bone density

- Neuropathy

- Agranulocytosis

What are the interactions of phenytoin (Dilantin)?

- CYP2C9 substrate and inducer

- CYP2C19 substrate and inducer

- Tube feeds

- Strong CYP3A4 inducer

What are the monitoring parameters of phenytoin (Dilantin)?

- Liver function

- CBC

- Drug levels

What are the clinical pearls of phenytoin (Dilantin)?

- Fetal harm

- Saturable/zero-order pharmacokinetics

- Low albumin

- Dosage form considerations (salt conversions)

- Decreases folic acid absorption

- Highly protein-bound

How does fosphenytoin compare to phenytoin?

- IV only

- Fast infusion rate

- Less extravasation risk

- Less cardiac side effects (no PG)

- D5W or NS

What are the adverse effects of phenobarbital (Luminal)?

- Respiratory depression

- Cognitive effects and agitation

- Agranulocytosis

- Hypotension

- Paradoxical hyperactivity

- Severe rashes

- Liver dysfunction

What is the CYP enzyme interaction for phenobarbital (Luminal)?

CYP2C9 substrate/inducer

What are the monitoring parameters for phenobarbital (Luminal)?

- Liver function

- CBC

- Behavior

- Renal function

- Drug levels

What are the clinical pearls of phenobarbital (Luminal)?

- C-IV

- Paradoxical agitation with acute/chronic pain

- Fetal harm

- Has a prodrug (primidone)

What seizure medications need drug level monitoring?

- Valproic acid

- Carbamazepine

- Phenytoin

- Phenobarbital

What are the advantages of carbamazepine (Tegretol)?

- Well-studied

- Multiple dosage forms

- Minimal risk of cognitive impairment

What are the disadvantages of carbamazepine (Tegretol)?

- Auto-induction

- Many drug interactions

- Fetal harm

- Decreases bone mineral density

- May cause vitamin D deficiency

What is the place in therapy of carbamazepine (Tegretol)?

- Considered first-line in many seizure types

- May worsen absence seizures

- May precipitate tonic-clonic seizures in patients with other generalized seizure types

What are the advantages of oxcarbazepine (Trileptal)?

- Useful even if patient did not respond to carbamazepine

- Efficacy comparable to other agents

- Well-tolerated

What are the disadvantages of oxcarbazepine (Trileptal)?

- More hyponatremia

- Cross-reactivity with carbamazepine

- Drug interactions

What is the place in therapy of oxcarbazepine (Trileptal)?

- Monotherapy or adjunctive

- Treats focal seizures

- Can be first-line

What is the main advantage of eslicarbazepine (Aptiom)?

Less hyponatremia and adverse effects

What is the main disadvantage of eslicarbazepine (Aptiom)?

New drug with minimal data

What is the place in therapy of eslicarbazepine (Aptiom)?

- Reserve for failure of other agents

- Monotherapy or adjunctive

- Treats focal onset seizures

What is the main advantage of phenytoin (Dilantin)?

Available IV for emergencies

What are the disadvantages of phenytoin (Dilantin)?

- Many chronic side effects

- Narrow therapeutic window

- Many drug interactions

What is the place in therapy of phenytoin (Dilantin)?

- Treats focal onset seizures

- Treats generalized tonic-clonic seizures

- Monotherapy or adjunctive

- Limited by side effects

What is the main advantage of phenobarbital (Luminal)?

Been in use the longest

What are the disadvantages of phenobarbital (Luminal)?

- Sedation and cognitive impairment

- Significant drug interaction potential

What is the place in therapy of phenobarbital (Luminal)?

- Reserve for second-line

- Treats focal onset and generalized seizures

- Monotherapy or adjunctive

What are the adverse effects of lacosamide (Vimpat)?

- Diplopia (double vision)

- PR prolongation

- Bradycardia/heart block

- Itching

- Liver enzyme elevation

What are the monitoring parameters of lacosamide (Vimpat)?

- ECG

- Renal function

- Liver function

What are the clinical pearls of lacosamide (Vimpat)?

- C-V

- May cause AV conduction abnormalities

- Minimal drug interactions

What are the adverse effects of gabapentin (Neurontin)?

- Peripheral edema

- Weight gain

What is the monitoring parameter for gabapentin (Neurontin)?

Renal function

What are the clinical pearls of gabapentin (Neurontin)?

- Consider with comorbid neuropathic pain

- Often used as adjunct

- Available in liquid form

- Frequent dosing

- Risk for withdrawal effects

- Minimal drug interactions

What are the adverse effects of pregabalin (Lyrica)?

- Peripheral edema

- Weight gain

- Elevated creatinine kinase

- Dry mouth

What are the monitoring parameters for pregabalin (Lyrica)?

- Myopathy

- Renal function

What are the clinical pearls of pregabalin (Lyrica)?

- C-V

- Risk for withdrawal effects

- Minimal drug interactions

What is the black box warning for perampanel (Fycompa)?

Serious psychiatric and behavioral reactions

What are the adverse effects of perampanel (Fycompa)?

- Agitation

- Anxiety/paranoia

- Euphoria

- SIADH

- Weight gain

What is the CYP enzyme interaction of perampanel (Fycompa)?

CYP3A4 substrate and inducer

What are the monitoring parameters for perampanel (Fycompa)?

- Behavior

- BMP

- Liver function

What are the clinical pearls of perampanel (Fycompa)?

- C-III

- Risk for aggression

What are the adverse effects of tiagabine (Gabitril)?

- Spike-wave stupor

- Asthenia (weakness)

What are the drug interactions of tiagabine (Gabitril)?

- CYP3A4 substrate

- Naproxen/salicylates

- Valproic acid

What is the monitoring parameter of tiagabine (Gabitril)?

Liver function

What are the clinical pearls of tiagabine (Gabitril)?

- Highly protein-bound

- Use with caution in absence seizures

- Can worsen refractory seizures

What is the black box warning for vigabatrin (Sabril)?

Permanent vision loss

What are the adverse effects for vigabatrin (Sabril)?

- Blindness

- Weight gain

- Upper respiratory tract infection

What is the CYP interaction for vigabatrin (Sabril)?

CYP2C19 inducer

What are the monitoring parameters for vigabatrin (Sabril)?

- Behavioral

- Vision

- Renal function

- CBC

What are the clinical pearls of vigabatrin (Sabril)?

- Used for infantile spasms

- REMS program

What is the black box warning for clobazam (Onfi) and clonazepam (Klonopin)?

Concomitant opioid use may cause dependence

What are the adverse effects of clobazam (Onfi)?

- Behavioral changes

- Amnesia

- Respiratory depression

- Drooling

What are the CYP interactions for clobazam (Onfi)?

- CYP2C19 substrate

- CYP3A4 substrate

- CYP2D6 inhibitor

- CYP3A4 inducer

What are the monitoring parameters for clobazam (Onfi)?

- Behavioral

- Respiratory depression

- Liver function

What are the clinical pearls of clobazam (Onfi)?

- C-IV

- Withdrawal effects with abrupt discontinuation

What are the adverse effects of clonazepam (Klonopin)?

- Behavioral problems

- Respiratory depression

What is the CYP interaction for clonazepam (Klonopin)?

CYP3A4 substrate

What are the monitoring parameters for clonazepam (Klonopin)?

- Respiratory depression

- Liver function

What are the clinical pearls for clonazepam (Klonopin)?

- C-IV

- Contraindicated in severe liver dysfunction

What are the black box warnings for felbamate (Felbatol)?

- Aplastic anemia

- Liver failure

What are the adverse effects of felbamate (Felbatol)?

- Anorexia

- Weight loss

What CYP enzyme does felbamate (Felbatol) interact with?

CYP3A4

What are the monitoring parameters for felbamate (Felbatol)?

- Liver function

- CBC

What is the clinical pearl of felbamate (Felbatol)?

Consent needed

What is the place in therapy of lacosamide (Vimpat)?

- Monotherapy or adjunctive

- Treats focal onset seizures

- Reserve for second- or third-line

- Few drug interactions but no strong evidence

What are the advantages of gabapentin (Neurontin)?

- Minimal drug interactions

- Broad therapeutic range

- Rapid dose titration

- Available in liquid form

What are the disadvantages of gabapentin (Neurontin)?

- Frequent dosing

- Poorly efficacious

What is the place in therapy of gabapentin (Neurontin)?

- Treats focal onset seizures with or without secondary generalization

- Considered second-line

- Helpful for neuropathic pain

What are the advantages of pregabalin (Lyrica)?

- More potent than gabapentin

- Minimal CNS effects

- No drug interactions

- Less dose-limiting GI absorption

What is the place in therapy of pregabalin (Lyrica)?

- Adjunctive for focal onset seizures

- Reserve for failure of other agents

- Helpful for comorbid conditions

What are the advantages of perampanel (Fycompa)?

- Novel mechanism

- Dosed once daily

What are the disadvantages of perampanel (Fycompa)?

- Limited data

- Controlled substance

What is the place of perampanel (Fycompa)?

- Monotherapy or adjunctive for focal onset seizures

- Adjunctive treatment for primary generalized tonic-clonic

- Reserve for failure of other agents

What is the main disadvantage of tiagabine (Gabitril)?

Increased seizure frequency and status epilepticus

What is the place in therapy of tiagabine (Gabitril)?

- Adjunctive treatment of focal onset seizures

- Reserve for failure of other agents

What are the disadvantages of vigabatrin (Sabril)?

- Significant adverse effects

- Available only through SHARE program

What is the place in therapy of vigabatrin (Sabril)?

- Monotherapy for infantile spasms

- Third-line adjunctive for refractory focal epilepsy

What are the advantages of clobazam (Onfi)?

- More effective for Lennox-Gastaut syndrome than clonazepam

- Less likely to develop tolerance

What are the disadvantages of clobazam (Onfi)?

- Controlled substance

- Must be tapered off slowly

- Less effective for myoclonic jerks and absence seizures than clonazepam

What is the place in therapy of clobazam (Onfi)?

- Adjunctive for Lennox-Gastaut syndrome

- May treat focal onset epilepsies

- Reserve for failure of other agents in other generalized epilepsies

What is the advantage of clonazepam (Klonopin)?

Long half-life

What are the disadvantages of clonazepam (Klonopin)?

- Risk with concomitant opioids

- CNS effects

- Potential for tolerance and dependence

What is the place in therapy of clonazepam (Klonopin)?

- Monotherapy or adjunctive

- Lennox-Gastaut syndrome

- Akinetic seizures

- Myoclonic seizures

- Absence seizures

What is the place in therapy of felbamate (Felbatol)?

- Monotherapy or adjunctive

- Focal onset seizures

- Lennox-Gastaut syndrome in children

- Reserve for failure of other agents

Which seizure medications should be reserved for failure of other agents?

- Felbamate

- Pregabalin

- Perampanel

- Tiagabine

- Clobazam (generalized)