Monitoring Liver Function Tests in Patients on Lamotrigine
Patients on lamotrigine should have baseline liver function tests (LFTs) before starting treatment and periodic monitoring during therapy, especially in the first few months of treatment when the risk of hepatotoxicity is highest.
Background on Lamotrigine and Hepatotoxicity
Lamotrigine is an anticonvulsant medication used to treat epilepsy and bipolar disorder. While generally considered safe, there have been documented cases of severe hepatotoxicity associated with lamotrigine use.
Monitoring Recommendations
Initial Assessment
- Obtain baseline LFTs before starting lamotrigine therapy
- Screen for pre-existing liver disease
- Document concurrent medications that may affect liver function
Monitoring Schedule
- Check LFTs at 2-4 weeks after initiation
- Repeat at 3 months
- Continue monitoring every 3-6 months during the first year
- After the first year, monitor at least annually if LFTs remain normal
Higher Risk Patients
More frequent monitoring (monthly for the first 3-6 months) is recommended for:
- Patients on polytherapy with other antiepileptic drugs
- Patients with pre-existing liver disease
- Children on multiple medications
- Patients with rapid titration schedules
Evidence for Hepatotoxicity
Several case reports document lamotrigine-associated hepatotoxicity:
- A 43-year-old woman developed severe transaminitis with AST 6079 IU/L and ALT 6900 IU/L after starting lamotrigine, which resolved after discontinuation 1
- A 33-year-old male patient developed fatal hepatic failure after taking lamotrigine for 15 days 2
- Three children on lamotrigine developed reversible hepatotoxicity, with one experiencing severe hepatic failure requiring aggressive therapy 3
- An 8-year-old boy developed acute hepatic failure with jaundice, elevated liver enzymes, and coagulopathy while on lamotrigine 4
- A 3-year-old female who ingested lamotrigine tablets developed transient elevation of liver function tests 5
Warning Signs and Management
Warning Signs Requiring Immediate LFT Testing
- Jaundice
- Rash (especially if accompanied by fever)
- Nausea/vomiting
- Abdominal pain
- Fatigue or malaise
- Dark urine
Management of Abnormal LFTs
- For mild elevations (<3× ULN): Continue monitoring more frequently (every 2 weeks)
- For moderate elevations (3-5× ULN): Consider dose reduction and increase monitoring frequency
- For severe elevations (>5× ULN): Discontinue lamotrigine immediately and provide supportive care
Important Considerations
- Hepatotoxicity risk appears higher when lamotrigine is used in polytherapy regimens
- Rapid titration may increase risk of adverse reactions including hepatotoxicity
- The risk of severe hepatotoxicity appears to be highest within the first 8 weeks of treatment
- Patients with complicated acute systemic conditions (fever, status epilepticus, encephalitis) may be at higher risk
Conclusion
While lamotrigine-induced hepatotoxicity is rare, it can be severe and potentially fatal. Regular monitoring of liver function is essential, particularly during the initial months of therapy. The pattern of monitoring should be similar to that recommended for other potentially hepatotoxic medications such as azathioprine, where regular LFT monitoring is standard practice 6.