What are the common and serious adverse effects of Trileptal (oxcarbazepine) and how should they be monitored?

Adverse Effects of Trileptal (Oxcarbazepine)

Trileptal commonly causes central nervous system and gastrointestinal adverse effects, with hyponatremia being the most clinically significant serious adverse reaction requiring monitoring.

Most Common Adverse Effects

The most frequent adverse effects (occurring in ≥10% more than placebo) include 1:

• Dizziness (most common cause of discontinuation at 6.4%)
• Somnolence/drowsiness (discontinuation rate 3.8%)
• Diplopia (double vision, discontinuation rate 5.9%)
• Fatigue (discontinuation rate 2.1%)
• Nausea and vomiting (discontinuation rates 4.9% and 5.1% respectively)
• Ataxia (coordination problems, discontinuation rate 5.2%)
• Headache (discontinuation rate 2.9%)
• Abnormal vision (discontinuation rate 2.1%)
• Nystagmus (involuntary eye movements)
• Tremor (discontinuation rate 1.8%)
• Abnormal gait (discontinuation rate 1.7%)

Approximately 23% of adult patients discontinue treatment due to adverse reactions 1. Research confirms these effects are dose-dependent and often transient 2, 3.

Serious Adverse Effects Requiring Monitoring

Hyponatremia (Low Sodium)

This is the most important adverse effect to monitor, as it occurs frequently and can be symptomatic:

• Severe hyponatremia (sodium ≤125 mmol/L) occurs in approximately 11.1% of patients 4
• Symptomatic hyponatremia occurs in 6.8% of patients, with clinically significant symptomatic cases in 2.8% 4
• Develops gradually during the first months of therapy in approximately 3% of patients with previously normal sodium 3
• Patients with hyponatremia have a 7-fold increased risk of adverse effects compared to those with normal sodium levels 5

Symptoms of hyponatremia include 5:

• Dizziness (28% vs 6% in normal sodium)
• Tiredness (22% vs 7%)
• Instability (19% vs 3%)
• Diplopia (16% vs 4%)

Risk factors for severe/symptomatic hyponatremia 4:

• Older age (independent risk factor)
• Concomitant use of diuretics (5.6-fold increased risk for severe hyponatremia)
• Antiepileptic drug polytherapy (1.5-fold increased risk)
• Medications that lower sodium (oral contraceptives, NSAIDs)
• Pre-existing renal disease

Dermatological Reactions

• Rash occurs in <5% of patients (discontinuation rate 1.4%) 1, 6
• Serious dermatological reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis can occur 1
• Cross-hypersensitivity with carbamazepine occurs in approximately 25-30% of patients with prior carbamazepine hypersensitivity 1

Other Serious Reactions

• Anaphylactic reactions and angioedema 1
• Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multi-Organ Hypersensitivity 1
• Hematologic events (blood cell abnormalities) 1
• Suicidal behavior and ideation 1
• Cognitive/neuropsychiatric adverse reactions 1

Monitoring Recommendations

Baseline monitoring 3:

• Serum sodium measurement is not routinely required unless the patient has:
  • Renal disease
  • Takes medications that lower sodium (diuretics, oral contraceptives, NSAIDs)
  • Clinical symptoms of hyponatremia

During maintenance therapy 3, 4:

• Monitor serum sodium regularly, especially in:
  • Elderly patients
  • Patients on AED polytherapy
  • Patients taking concomitant diuretics
  • When adding medications known to decrease sodium
  • If symptoms of hyponatremia develop

Other monitoring 3:

• Oxcarbazepine does not require routine monitoring of liver function, renal function, or hematological parameters in most patients
• No therapeutic drug level monitoring needed (unlike carbamazepine)

Pediatric Considerations

In children, adverse effects are similar to adults, with the exception that infections and infestations are more frequently seen in younger children (1 month to <4 years old) 1. Approximately 11% of pediatric patients discontinue treatment due to adverse reactions 1.

Clinical Pitfalls to Avoid

• Do not assume all CNS symptoms are drug-related - they may indicate hyponatremia requiring sodium measurement 5
• Do not overlook drug interactions - oxcarbazepine decreases effectiveness of oral contraceptives and increases phenytoin levels 6
• Do not ignore symptoms in elderly patients on diuretics - this combination dramatically increases hyponatremia risk 4
• Recognize that 65% of patients with hyponatremia experience adverse effects compared to only 21% with normal sodium 5