Pharm

Lamotrigine

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Lamotrigine, Lamictal

  • Indications
  1. Simple Partial Seizures
  2. Lennox-Gastaut Syndrome
  3. Complex Partial Seizures
  4. Generalized Tonic Clonic Seizures
  5. Bipolar Disorder
  • Mechanism
  1. Phenyltriazine anticonvulsant
  2. Enhances Gamma-Aminobutyric Acid (GABA) inhibitory activity
  3. May also reduce pain transmission, inhibit voltage-gated Sodium channels, suppress Glutamate release, inhibit Serotonin reuptake
  • Pharmacokinetics
  1. Oral Bioavailability: 98%
  2. Elimination Half-Life: 22 to 36 hours
  • Adverse Effects
  • Common (Dose related)
  1. Dizziness
  2. Incoordination
  3. Tremor
  4. Ataxia
  5. Diplopia
  6. Headache
  7. Insomnia
  8. Anxiety
  9. Agitation (esp. in Autism with Cognitive Impairment)
  10. Somnolence
  11. Blurred Vision
  12. Nausea or Vomiting
  • Adverse Effects
  • Serious
  1. Serious skin rash
    1. DRESS Syndrome
    2. Stevens Johnson Syndrome or Toxic Epidermal Necrolysis
      1. Onset in first 2 to 8 weeks after starting medication
      2. Incidence 0.3% in adults, 0.8% in children)
      3. Higher risk when combined with Valproic Acid
  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
  • Drug Interactions
  1. Valproic Acid (requires a decrease in Lamotrigine dose)
  2. Enzyme-Inducing Anticonvulsants (require an increase in Lamotrigine dose)
    1. Carbamazepine
    2. Phenytoin
    3. Phenobarbital
    4. Primidone
  3. Oral Contraceptives
    1. Requires an increase in Lamotrigine dose to as much as double
  4. Other Interactions
    1. Rifampin
  • 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
  3. Decrease dose by 25% in moderate to severe hepatic Impairment (50% if Ascites present)
  • Dosing
  • Adults (age > 12 years)
  1. Immediate Release
    1. Initial: 25 mg orally daily for 2 weeks
    2. Next: 50 mg orally daily for 2 weeks
    3. Next: Titrate dose by 50 mg/day divided twice daily every 1 to 2 weeks
    4. Typical dose: 225 to 375 mg/day divided orally twice daily
    5. Maximum dose: 400 mg/day divided twice daily
  2. Extended Release
    1. Initial: 25 mg orally daily for 2 weeks
    2. Next: 50 mg orally daily for 2 weeks
    3. Next: 100 mg orally daily for 1 week
    4. Next: Titrate dose by 50 mg/day taken daily every 1 week
    5. Typical dose: 300 to 400 mg/day orally daily
  3. Dose Adjustment when combined with a non-Valproic Acid, enzyme-inducing anticonvulsant drug or Oral Contraceptives
    1. Immediate Release Maximum Dose: 300 to 500 mg/day divided twice daily
    2. Extended Release Maximum Dose: 400 to 600 mg/day
  4. Dose Adjustment when combined with Valproic Acid
    1. Immediate Release
      1. Initial: 25 mg orally every other day for 2 weeks
      2. Next: 25 mg orally daily for 2 weeks
      3. Next: Titrate dose by 25 to 50 mg/day daily or divided twice daily every 1 to 2 weeks
      4. Typical dose: 100 to 200 mg/day daily or divided orally twice daily
    2. Extended Release
      1. Initial: 25 mg orally every other day for 2 weeks
      2. Next: 25 mg orally daily for 2 weeks
      3. Next: 50 mg orally daily for 1 week
      4. Next: Titrate dose by 25 to 50 mg/day daily or divided twice daily every 1 to 2 weeks
      5. Typical dose: 200 to 250 mg orally daily
  • Dosing
  • Children (age 2 to 12 years)
  1. Immediate Release
    1. Start: 0.3 mg/kg/day divided orally daily to twice daily for 2 weeks
    2. Next: 0.6 mg/kg/day divided orally daily to twice daily for 2 weeks
    3. Next: Titrate dose by 0.6 mg/kg/day divided twice daily every 1 to 2 weeks
    4. Typical dose: 4.5 to 7.5 mg/kg/day divided orally twice daily
    5. Maximum dose: 300 mg/day divided twice daily
  2. Dose Adjustment when combined with a non-Valproic Acid, enzyme-inducing anticonvulsant drug
    1. Start: 0.6 mg/kg/day divided orally daily to twice daily for 2 weeks
    2. Next: 1.2 mg/kg/day divided orally daily to twice daily for 2 weeks
    3. Next: Titrate dose by 1.2 mg/kg/day divided twice daily every 1 to 2 weeks
    4. Typical dose: 5 to 15 mg/kg/day divided orally twice daily
    5. Maximum dose: 400 mg/day divided twice daily
  3. Dose Adjustment when combined with Valproic Acid
    1. Start: 0.15 mg/kg/day divided orally daily to twice daily for 2 weeks
    2. Next: 0.3 mg/kg/day divided orally daily to twice daily for 2 weeks
    3. Next: Titrate dose by 0.3 mg/kg/day divided twice daily every 1 to 2 weeks
    4. Typical dose: 1 to 3 mg/kg/day divided orally twice daily
    5. Maximum dose: 200 mg/day divided twice daily
  • 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
  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
  • Safety
  1. Pregnancy Category C
    1. Risk of Cleft Lip and Palate
    2. No increase in Autism risk
      1. Hernandez-Diaz (2024) N Engl J Med 390(12):1069-79 +PMID: 38507750 [PubMed]
  2. Avoid in Lactation
    1. Risk of apnea, drowsiness and poor feeding
  • Resources
  1. Lamotrigine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=35aa48a2-2ce6-4a6e-bf5a-1bc6111d1234
  • References
  1. (2022) Presc Lett, Resource #361206, Antiseizure Medications
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 56-7
  3. Hamilton (2020) Tarascon Pocket Pharmacopoeia