Lamotrigine

Aka: Lamotrigine, Lamictal

1. Indications
   1. Simple Partial Seizures
   2. Complex Partial Seizures
   3. Generalized Tonic Clonic Seizures
   4. Bipolar Disorder
2. Mechanism
   1. Phenyltriazine anticonvulsant
3. Pharmacokinetics
   1. Oral bioavailability: 98%
   2. Elimination half-life: 22 to 36 hours
4. Adverse Effects: Dose related
   1. Dizziness
   2. Incoordination
   3. Tremor
   4. Ataxia
   5. Diplopia
   6. Headache
   7. Insomnia
   8. Somnolence
   9. Blurred Vision
   10. Nausea or Vomiting
5. Adverse Effects: Other
   1. Serious skin rash (Incidence 0.08% in adults)
      1. Stevens Johnson Syndrome
      2. Toxic Epidermal Necrolysis
   2. Prolonged QRS Interval
      1. Increased risk of ventricular Arrhythmia or Cardiac Arrest
      2. Mechanism
         1. Sodium Channel Blocker
      3. Higher risk in underlying heart disease
         1. Coronary Artery Disease (prior Myocardial Infarction)
         2. Structural heart disease
         3. Atrioventricular Block
         4. Heart Failure
      4. Approach
         1. Avoid in high risk cardiovascular patients
         2. Consider baseline EKG in age over 60 years or Cardiovascular Risk Factors
         3. Avoid combining with other Sodium Channel Blockers
      5. References
         1. (2021) Presc Lett 28(6):34
   3. Aplastic Anemia
   4. Thrombocytopenia
   5. Neutropenia
   6. Pancytopenia
   7. Aseptic Meningitis
   8. Serotonin Syndrome
6. Drug Interactions
   1. Valproic Acid
   2. Carbamazepine
   3. Phenytoin
   4. Phenobarbital
   5. Primidone
   6. Rifampin
   7. Oral Contraceptives
7. Dosing: Adults
   1. Initial: 25 mg every other day for 2 weeks
   2. Next: 25 mg orally daily for 2 weeks
   3. Target dose: 50-100 mg orally twice daily
   4. Maximum dose: 400 mg/day
   5. Precautions
      1. Slow titration over 6 weeks or more reduces the risk of Stevens-Johnson Syndrome
      2. Dosing adjustments are needed when used with agents listed under Drug Interactions
8. Monitoring
   1. Obtain labs monthly for the first 2 months and then every 3 to 12 months
   2. Complete Blood Count
   3. Liver Function Test
9. Approach: Toxicity or Overdose
   1. Evaluate as Unknown Ingestion
      1. Obtain other toxicologic screening including Acetaminophen level, Serum Glucose
      2. Electrocardiogram
   2. Effects in Overdose
      1. Ventricular Dysrhythmia
         1. Lamictal inhibits voltage-gated Sodium channels
         2. Wide QRS Complex
            1. Treat with Sodium Bicarbonate ampules until QRS Complex narrows
      2. Serotonin Syndrome
         1. Lamictal inhibits Serotonin reuptake
      3. Neurologic Effects
         1. Sedation (most common finding in Overdose)
         2. Seizures
            1. Paradoxical (as Lamictal is foremost an anticonvulsant)
            2. Children may experience Seizures at doses >30 mg/kg
         3. Agitation
         4. Increased Deep Tendon Reflexes (hyperreflexia)
         5. Myoclonic Jerks
      4. Miscellaneous
         1. Nausea or Vomiting
   3. Management
      1. Activated Charcoal
         1. Consider if <1 hour from time of ingestion, and patient without aspiration risk
      2. QRS Widening
         1. See above (regarding bicarbonate)
      3. Seizures
         1. See Status Epilepticus
         2. Benzodiazepines
         3. Consider Propofol and intubation
         4. Consider Hemodialysis
   4. Disposition
      1. If asymptomatic at 4-6 hours after ingestion, may discharge home
   5. References
      1. Tomaszewski (2020) Crit Dec Emerg Med 34(1): 28