Pharm
Lamotrigine
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Lamotrigine
, Lamictal
Indications
Simple Partial Seizure
s
Lennox-Gastaut Syndrome
Complex Partial Seizure
s
Generalized Tonic Clonic Seizure
s
Bipolar Disorder
Mechanism
Phenyltriazine anticonvulsant
Enhances
Gamma-Aminobutyric Acid
(
GABA
) inhibitory activity
May also reduce pain transmission, inhibit voltage-gated
Sodium
channels, suppress
Glutamate
release, inhibit
Serotonin
reuptake
Pharmacokinetics
Oral
Bioavailability
: 98%
Elimination Half-Life
: 22 to 36 hours
Adverse Effects
Common (Dose related)
Dizziness
Incoordination
Tremor
Ataxia
Diplopia
Headache
Insomnia
Anxiety
Agitation
(esp. in
Autism
with
Cognitive Impairment
)
Somnolence
Blurred Vision
Nausea
or
Vomiting
Adverse Effects
Serious
Serious skin rash
DRESS Syndrome
Stevens Johnson Syndrome
or
Toxic Epidermal Necrolysis
Onset in first 2 to 8 weeks after starting medication
Incidence
0.3% in adults, 0.8% in children)
Higher risk when combined with
Valproic Acid
Prolonged QRS Interval
Increased risk of ventricular
Arrhythmia
or
Cardiac Arrest
Mechanism
Sodium Channel Blocker
Higher risk in underlying heart disease
Coronary Artery Disease
(prior
Myocardial Infarction
)
Structural heart disease
Atrioventricular Block
Heart Failure
Approach
Avoid in high risk cardiovascular patients
Consider baseline EKG in age over 60 years or
Cardiovascular Risk Factor
s
Avoid combining with other
Sodium Channel Blocker
s
References
(2021) Presc Lett 28(6):34
Aplastic Anemia
Thrombocytopenia
Neutropenia
Pancytopenia
Aseptic Meningitis
Serotonin Syndrome
Drug Interactions
Valproic Acid
(requires a decrease in Lamotrigine dose)
Enzyme-Inducing Anticonvulsants (require an increase in Lamotrigine dose)
Carbamazepine
Phenytoin
Phenobarbital
Primidone
Oral Contraceptive
s
Requires an increase in Lamotrigine dose to as much as double
Other Interactions
Rifampin
Precautions
Slow titration over 6 weeks or more reduces the risk of
Stevens-Johnson Syndrome
Dosing adjustments are needed when used with agents listed under
Drug Interaction
s
Decrease dose by 25% in moderate to severe hepatic
Impairment
(50% if
Ascites
present)
Dosing
Adults (age > 12 years)
Immediate Release
Initial: 25 mg orally daily for 2 weeks
Next: 50 mg orally daily for 2 weeks
Next: Titrate dose by 50 mg/day divided twice daily every 1 to 2 weeks
Typical dose: 225 to 375 mg/day divided orally twice daily
Maximum dose: 400 mg/day divided twice daily
Extended Release
Initial: 25 mg orally daily for 2 weeks
Next: 50 mg orally daily for 2 weeks
Next: 100 mg orally daily for 1 week
Next: Titrate dose by 50 mg/day taken daily every 1 week
Typical dose: 300 to 400 mg/day orally daily
Dose Adjustment when combined with a non-
Valproic Acid
, enzyme-inducing anticonvulsant drug or
Oral Contraceptive
s
Immediate Release Maximum Dose: 300 to 500 mg/day divided twice daily
Extended Release Maximum Dose: 400 to 600 mg/day
Dose Adjustment when combined with
Valproic Acid
Immediate Release
Initial: 25 mg orally every other day for 2 weeks
Next: 25 mg orally daily for 2 weeks
Next: Titrate dose by 25 to 50 mg/day daily or divided twice daily every 1 to 2 weeks
Typical dose: 100 to 200 mg/day daily or divided orally twice daily
Extended Release
Initial: 25 mg orally every other day for 2 weeks
Next: 25 mg orally daily for 2 weeks
Next: 50 mg orally daily for 1 week
Next: Titrate dose by 25 to 50 mg/day daily or divided twice daily every 1 to 2 weeks
Typical dose: 200 to 250 mg orally daily
Dosing
Children (age 2 to 12 years)
Immediate Release
Start: 0.3 mg/kg/day divided orally daily to twice daily for 2 weeks
Next: 0.6 mg/kg/day divided orally daily to twice daily for 2 weeks
Next: Titrate dose by 0.6 mg/kg/day divided twice daily every 1 to 2 weeks
Typical dose: 4.5 to 7.5 mg/kg/day divided orally twice daily
Maximum dose: 300 mg/day divided twice daily
Dose Adjustment when combined with a non-
Valproic Acid
, enzyme-inducing anticonvulsant drug
Start: 0.6 mg/kg/day divided orally daily to twice daily for 2 weeks
Next: 1.2 mg/kg/day divided orally daily to twice daily for 2 weeks
Next: Titrate dose by 1.2 mg/kg/day divided twice daily every 1 to 2 weeks
Typical dose: 5 to 15 mg/kg/day divided orally twice daily
Maximum dose: 400 mg/day divided twice daily
Dose Adjustment when combined with
Valproic Acid
Start: 0.15 mg/kg/day divided orally daily to twice daily for 2 weeks
Next: 0.3 mg/kg/day divided orally daily to twice daily for 2 weeks
Next: Titrate dose by 0.3 mg/kg/day divided twice daily every 1 to 2 weeks
Typical dose: 1 to 3 mg/kg/day divided orally twice daily
Maximum dose: 200 mg/day divided twice daily
Monitoring
Obtain labs monthly for the first 2 months and then every 3 to 12 months
Complete Blood Count
Liver Function Test
Approach
Toxicity or
Overdose
Evaluate as
Unknown Ingestion
Obtain other toxicologic screening including
Acetaminophen
level,
Serum Glucose
Electrocardiogram
Effects in
Overdose
Ventricular
Dysrhythmia
Lamictal inhibits voltage-gated
Sodium
channels
Wide
QRS Complex
Treat with
Sodium Bicarbonate
ampules until
QRS Complex
narrows
Serotonin Syndrome
Lamictal inhibits
Serotonin
reuptake
Neurologic Effects
Sedation (most common finding in
Overdose
)
Seizure
s
Paradoxical (as Lamictal is foremost an anticonvulsant)
Children may experience
Seizure
s at doses >30 mg/kg
Agitation
Increased
Deep Tendon Reflex
es (hyperreflexia)
Myoclonic Jerk
s
Miscellaneous
Nausea
or
Vomiting
Management
Activated Charcoal
Consider if <1 hour from time of ingestion, and patient without aspiration risk
QRS Widening
See above (regarding bicarbonate)
Seizure
s
See
Status Epilepticus
Benzodiazepine
s
Consider
Propofol
and intubation
Consider
Hemodialysis
Disposition
If asymptomatic at 4-6 hours after ingestion, may discharge home
References
Tomaszewski (2020) Crit Dec Emerg Med 34(1): 28
Safety
Pregnancy Category C
Risk of
Cleft Lip
and
Palate
No increase in
Autism
risk
Hernandez-Diaz (2024) N Engl J Med 390(12):1069-79 +PMID: 38507750 [PubMed]
Avoid in
Lactation
Risk of apnea, drowsiness and poor feeding
Resources
Lamotrigine (DailyMed)
https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=35aa48a2-2ce6-4a6e-bf5a-1bc6111d1234
References
(2022) Presc Lett, Resource #361206, Antiseizure Medications
Olson (2020) Clinical
Pharmacology
, Medmaster Miami, p. 56-7
Hamilton (2020) Tarascon Pocket Pharmacopoeia
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