Table 1.
Antiseizure medications formulations, mechanisms of action with additional considerations and reported TRE seizure response rates.4,55–57 Reported response rates are for patients with tumor-related epilepsy and may include tumors other than gliomas including meningiomas and brain metastases. Mo, month; SE, side effect; SJS, Stevens Johnson Syndrome
| Antiseizure medication | Formulation/approved for children | Primary mechanism of action | Most commonly reported side effects | Serious side effects | Reported efficacy for use as monotherapy in TRE | Additional considerations |
|---|---|---|---|---|---|---|
| Brivaracetam | Tablet, liquid, IV/ Yes |
Binds to SV2A (a synaptic vesicle glycoprotein) |
Fatigue, dizziness, anxiety, agitation, depression | Hypersensitivity reactions | Not reported | — |
| Carbamazepine | Tablet, liquid/ Yes |
Na+ channel blocking |
Transaminitis, hyponatremia, blood dyscrasias, rash/SJS, nausea, vomiting |
Aplastic anemia, hepatotoxicity, hyponatremia, rash/ TEN/SJS, hypersensitivity reactions, decreased bone density (use > 10 years) | 6 mo seizure freedom: 28%1 12 mo seizure freedom: 30–55%1 |
CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP1A2, UGT1A4 inducer May cause bone marrow suppression |
| Cenobamate | Tablet/ No |
Na + channel blocking Enhancing GABA |
Fatigue, dizziness, hyperkalemia | QT shortening, drug reaction with eosinophilia | Not reported | CYP2C19 inhibitor, CYP3A4/5, CYP2B6 inducer |
| Clobazam | Tablet, liquid/ Yes |
GABAA-receptor agonist | Fatigue, dizziness, dry mouth, nausea |
Somnolence, sedation | Not reported | N-desmethylclobazam, the metabolite can be monitored for toxicity |
| Eslicarbazepine | Tablet, liquid/ Yes |
Na+ channel blocking |
Hyponatremia, rash/SJS, somnolence, nausea, fatigue |
Rash/TEN/SJS, hyponatremia, hepatotoxicity, blood dyscrasias, decreased T3/T4 |
Not reported | CYP2C9 inhibitor |
| Gabapentin | Tablet, liquid/ Yes |
Binding α2δ Ca channel subunit | Dizziness, fatigue, peripheral edema, weight gain, ataxia | None | Not reported | Substrate for a protein transporter likely reducing brain availability2 |
| Lacosamide | Tablet, liquid, IV/ Yes |
Na+ channel blocking |
Dizziness, gait instability, headache, fatigue, prolonged PR interval |
PR prolongation, syncope, rash/TEN/SJS, dizziness, ataxia | 6 mo seizure freedom: 55%-67%3 | Monitor for arrhythmias |
| Lamotrigine | Tablet, oral dissolving tablet/ Yes |
Na+ channel blocking |
Rash/SJS insomnia (if taken at night as bid dosing), blood dyscrasias |
Rash/TEN/SJS, blood dyscrasias, angioedema, bronchospasm | Not reported | Need for slow titration May be beneficial for mood Relatively safe in pregnancy |
| Levetiracetam | Tablet, liquid, IV/ Yes |
Binds to SV2A (a synaptic vesicle glycoprotein) |
Irritability, depression, anxiety, aggression, fatigue, lightheadedness | Suicidal ideation, depression | 6 mo seizure freedom: 39-96%1 6 mo seizure reduction≥50%: 71–100%1 |
Higher risk of psychiatric side effects in frontal lobe tumors4 Relatively safe in pregnancy |
| Oxcarbazepine | Tablet, liquid/ Yes |
Na+ channel blocking |
Hyponatremia, fatigue, lightheadedness, weight gain, alopecia, nausea | Hyponatremia, rash/TEN/SJS | 12 mo seizure freedom: 40% 12 mo seizure reduction≥50%: 88%1 |
CYP2C19 inhibitor and weakly induces CYP3A4 |
| Perampanel | Tablet, liquid/ Yes |
AMPA antagonism | Dizziness, vertigo, fatigue, aggressiveness, agitation, irritability, anxiety, nausea | Psychiatric side effects, homicidal/suicidal ideation | No studies | |
| Phenobarbital | Tablet, liquid, IV/ Yes |
Enhancing GABA | Drowsiness, fatigue, vertigo, habit forming, blood dyscrasias, cognitive slowing, rash/SJS |
Withdrawal seizures, hepatotoxicity, CNS depression, rash/TEN/SJS, blood dyscrasias | No studies |
CYP1A, CYP2A6, CYP2B, CYP2C, CYP3 A, UGT inducer Increases steroid clearance2 |
| Phenytoin | Tablet, liquid, IV/ Yes |
Na+ channel blocking |
Transaminitis, rash/SJS ataxia, dysarthria | Rash/TEN/SJS, hepatotoxicity, blood dyscrasias, gingival hyperplasia, lymphadenopathy, arrhythmias | 12 mo seizure freedom: 49–64%1 | Enzyme-inducing agent Increases steroid clearance2 Risk of birth defects |
| Pregabalin | Tablet, liquid/ Yes |
Binding α2δ Ca channel subunit | Drowsiness, sedation, weight gain, blood dyscrasias |
Peripheral edema, angioedema, hypersensitivity reactions | 12 mo seizure freedom: 75%1 | – |
| Primidone | Tablet/ Yes |
Enhancing GABA | N/A | Hypersensitivity reaction, thrombocytopenia, megaloblastic anemia | N/A | Not recommended due to similar SEs as phenobarbital and more difficult to monitor |
| Tiagabine | Tablet/ Yes, >12 years old |
Enhancing GABA | Lightheadedness, fatigue, anxiety, tremor, diarrhea, depression | CNS depression, rash | No studies | Side effects are commonly reported |
| Topiramate | Tablet, sprinkles/ Yes |
Na+ channel blocking, enhancing GABA, AMPA antagonism | Weight loss, word-finding difficulty, psychomotor slowing, metabolic acidosis, parasthesias, glaucoma | Acute angle closure glaucoma, nephrolithiasis, rash/TEN/SJS, oligohydrosis with heat stroke | 6 mo seizure freedom: 59% 12 mo seizure freedom: 57–71%1 |
CYP3A4 inducer |
| Valproic acid | Tablet, liquid, IV/ Yes > 10 years old |
Na+ channel blocking, enhancing GABA, blocking T-type Ca channels |
Weight gain, hair loss, fatigue, hyperammonemia, transaminitis, tremor, thrombocytopenia, rash/SJS | Hyperammonemia, hepatotoxicity, rash/TEN/SJS thrombocytopenia | 6 mo seizure freedom: 65% 6 mo seizure reduction≥50%: 77% 12 mo seizure freedom: 30–57% 12 mo seizure reduction ≥ 50%: 75–86%1 |
CYP2C9, UGT1A4 inhibitor (and weak inhibitor of CYP2C19 and CYP3A4) Significant risk of birth defects |
| Zonisamide | Tablet/ Yes > 16 years old |
Na+ channel blocking, blocking T-type Ca channels |
Somnolence, weight loss, lightheadedness, word-finding difficulty, renal calculi, oligohydrosis, rash | Rash/TEN/SJS, glaucoma, nephrolithiasis | No studies | Avoid in patients with history of nephrolithiasis Avoid in patients with sulfa allergies |