Lamotrigine

Aka: Lamotrigine, Lamictal

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II. Indications

  1. Simple Partial Seizures
  2. Lennox-Gastaut Syndrome
  3. Complex Partial Seizures
  4. Generalized Tonic Clonic Seizures
  5. Bipolar Disorder (mood stabilizer)

III. Mechanism

  1. Phenyltriazine anticonvulsant (broad spectrum) indicated in both generalized and Focal Seizures
  2. Enhances Gamma-Aminobutyric Acid (GABA) inhibitory activity
  3. Other effects
    1. Reduce pain transmission
    2. Inhibits voltage-gated Sodium channels (see toxicity below)
    3. Suppresses Glutamate release
    4. Inhibits Serotonin reuptake
    5. Inhibits MAO reuptake

IV. Pharmacokinetics

  1. Oral Bioavailability: 98%
  2. Elimination Half-Life: 22 to 36 hours
  3. Peak Activity (extended in Overdose)
    1. Immediate Release: 2 hours after ingestion
    2. Extended Release: 6 hours after ingestion
  4. Metabolism
    1. Glucuronidation (slowed in Gilbert Syndrome, and with Valproic Acid)
    2. Elimination in the urine
    3. No active metabolites

V. 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

VI. 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

VII. Drug Interactions

  1. Valproic Acid
    1. Slows Lamotrigine Glucuronidation
    2. 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

VIII. 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)

IX. 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

X. 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

XI. 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

XII. Approach: Toxicity or Overdose

  1. See Lamotrigine Toxicity

XIII. 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

XIV. Resources

  1. Lamotrigine (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=35aa48a2-2ce6-4a6e-bf5a-1bc6111d1234

XV. 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

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Cost: Medications

lamotrigine (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LAMOTRIGINE 100 MG TABLET Generic $0.05 each
LAMOTRIGINE 150 MG TABLET Generic $0.07 each
LAMOTRIGINE 200 MG TABLET Generic $0.08 each
LAMOTRIGINE 25 MG DISPER TAB Generic $0.19 each
LAMOTRIGINE 25 MG TABLET Generic $0.03 each
LAMOTRIGINE 5 MG DISPER TABLET Generic $0.25 each
LAMOTRIGINE ER 100 MG TABLET Generic $1.26 each
LAMOTRIGINE ER 200 MG TABLET Generic $1.08 each
LAMOTRIGINE ER 25 MG TABLET Generic $0.91 each
LAMOTRIGINE ER 250 MG TABLET Generic $3.61 each
LAMOTRIGINE ER 300 MG TABLET Generic $2.99 each
LAMOTRIGINE ER 50 MG TABLET Generic $0.75 each
LAMOTRIGINE ODT 100 MG TABLET Generic $3.05 each
LAMOTRIGINE ODT 200 MG TABLET Generic $4.18 each
LAMOTRIGINE ODT 25 MG TABLET Generic $3.43 each
LAMOTRIGINE ODT 50 MG TABLET Generic $3.57 each
lamictal (on 1/1/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LAMICTAL 100 MG TABLET Generic $0.05 each
LAMICTAL 150 MG TABLET Generic $0.07 each
LAMICTAL 200 MG TABLET Generic $0.08 each
LAMICTAL 25 MG DISPER TABLET Generic $0.19 each
LAMICTAL 25 MG TABLET Generic $0.03 each
LAMICTAL ODT 100 MG TABLET Generic $3.05 each
LAMICTAL ODT 200 MG TABLET Generic $4.18 each
LAMICTAL ODT 50 MG TABLET Generic $3.57 each
LAMICTAL XR 100 MG TABLET Generic $1.26 each
LAMICTAL XR 200 MG TABLET Generic $1.08 each
LAMICTAL XR 300 MG TABLET Generic $2.99 each
LAMICTAL XR 50 MG TABLET Generic $0.75 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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