What to monitor in a patient on Lamotrigine (Lamictal) and Oxcarbazepine (Trileptal)?

From the Guidelines

When monitoring a patient on lamotrigine and oxcarbazepine, clinicians should prioritize regular assessments of complete blood counts, liver function, electrolytes (particularly sodium), and kidney function to minimize the risk of adverse effects and optimize therapeutic outcomes. Monitoring should include baseline labs before starting therapy, with follow-up testing at 1-3 month intervals initially, then every 6-12 months once stable 1. It is crucial to monitor serum sodium levels closely as oxcarbazepine commonly causes hyponatremia, and watch for signs of serious skin reactions with lamotrigine, particularly rash, which can progress to Stevens-Johnson syndrome or toxic epidermal necrolysis, especially during the first 8 weeks of treatment or after dose increases 1. Some key points to consider when monitoring these patients include:

• Regular assessment of therapeutic efficacy and side effects at each visit
• Evaluation for dizziness, headache, diplopia, ataxia, and cognitive effects
• Checking drug levels if toxicity is suspected or to assess adherence, though routine monitoring is not always necessary
• Careful monitoring of the combination of these medications, as oxcarbazepine can decrease lamotrigine levels through enzyme induction, potentially requiring lamotrigine dose adjustments 1. Patients should be educated about potential drug interactions, including with oral contraceptives, which may have reduced efficacy when used with these anticonvulsants. Given the potential for serious adverse effects, individualized treatment and adequate communication regarding the prognosis of the disease, the adverse effects of the medication, and the expected outcome of the treatment is warranted before the use of medication 1.

From the FDA Drug Label

5.1 Hyponatremia Clinically significant hyponatremia (sodium <125 mmol/L) can develop during oxcarbazepine use. Measurement of serum sodium levels should be considered for patients during maintenance treatment with oxcarbazepine, particularly if the patient is receiving other medications known to decrease serum sodium levels (e.g., drugs associated with inappropriate ADH secretion) or if symptoms possibly indicating hyponatremia develop (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, or increase in seizure frequency or severity). 5.7 Cognitive/Neuropsychiatric Adverse Reactions Use of oxcarbazepine has been associated with central nervous system-related adverse reactions The most significant of these can be classified into 3 general categories: 1) cognitive symptoms including psychomotor slowing, difficulty with concentration, and speech or language problems, 2) somnolence or fatigue, and 3) coordination abnormalities, including ataxia and gait disturbances Patients should be monitored for these signs and symptoms and advised not to drive or operate machinery until they have gained sufficient experience on oxcarbazepine to gauge whether it adversely affects their ability to drive or operate machinery.

When a patient is on lamotrigine and Oxcarbazepine, the following should be monitored:

• Serum sodium levels: due to the risk of hyponatremia associated with oxcarbazepine use 2
• Cognitive function: including psychomotor slowing, difficulty with concentration, and speech or language problems 2
• Somnolence or fatigue: as oxcarbazepine has been associated with somnolence or fatigue 2
• Coordination abnormalities: including ataxia and gait disturbances 2
• Signs of suicidal thoughts or behavior: as antiepileptic drugs, including oxcarbazepine, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication 2
• Skin reactions: as oxcarbazepine has been associated with serious skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) 2

From the Research

Monitoring Parameters

When a patient is on lamotrigine and oxcarbazepine, the following parameters should be monitored:

• Liver function, including liver enzymes such as AST, ALT, and alkaline phosphatase, as well as total bilirubin 3, 4
• International normalized ratio (INR) to assess coagulation 3
• Clinical signs of hepatotoxicity, such as jaundice and pruritic macular rash 3
• Seizure outcome and frequency to assess the efficacy of the treatment 5
• Adverse effects, such as headache, dizziness, nausea, and somnolence, which may be more frequent with combination therapy 6
• Serum concentrations of lamotrigine and oxcarbazepine to monitor pharmacokinetic variability, especially in patients with age-related changes or those taking concomitant medications 6, 7

Laboratory Tests

Regular laboratory tests should be performed to monitor:

• Liver function tests, including AST, ALT, alkaline phosphatase, and total bilirubin 3, 4
• Complete blood count and electrolyte panel to assess for any adverse effects on hematologic or electrolyte parameters
• Serum concentration measurements of lamotrigine and oxcarbazepine to guide dose adjustments and minimize adverse effects 6, 7

Patient Factors

Patient factors that may affect monitoring include:

• Age, as pharmacokinetic variability may be greater in younger children and the elderly 7
• Concomitant medications, which may affect the clearance of lamotrigine and oxcarbazepine 6, 7
• Presence of underlying liver disease or other medical conditions that may affect liver function or increase the risk of adverse effects 3, 4