Does use of Vimpat (lacosamide) or oxcarbazepine cause elevation of alkaline phosphatase?

Alkaline Phosphatase Elevation with Vimpat (Lacosamide) and Oxcarbazepine

Neither lacosamide (Vimpat) nor oxcarbazepine is commonly associated with alkaline phosphatase elevation; however, both anticonvulsants can induce gamma-glutamyl transferase (GGT) elevation through hepatic enzyme induction, which may be mistaken for cholestatic liver injury if not properly differentiated.

Lacosamide (Vimpat) and Liver Enzymes

Lacosamide does not typically elevate alkaline phosphatase. The most relevant evidence comes from a 2024 study demonstrating that switching from carbamazepine to lacosamide actually improved liver enzyme profiles in patients with elevated GGT 1. In this study of 12 epilepsy patients with controlled focal seizures and elevated GGT on carbamazepine, abruptly switching to lacosamide resulted in:

• Significant GGT reduction from median 141.5 to 63.5 IU/L within one month 1
• Decreased proportion of patients with abnormal GGT from 100% to 66.7% 1
• No increase in seizure recurrence during the transition 1

This evidence strongly suggests that lacosamide has a favorable hepatic enzyme profile compared to older anticonvulsants and is unlikely to cause alkaline phosphatase elevation 1.

Oxcarbazepine and Liver Enzymes

Oxcarbazepine, like other anticonvulsants, can induce hepatic enzymes—particularly GGT—but isolated alkaline phosphatase elevation is not a characteristic finding. Anticonvulsants as a class are recognized as enzyme inducers that can raise alkaline phosphatase through induction mechanisms rather than true cholestatic injury 2. However, the elevation is typically mild and accompanied by GGT elevation, which helps distinguish drug-induced enzyme induction from primary hepatobiliary disease 3.

Distinguishing Drug-Induced Enzyme Induction from Cholestatic Disease

When evaluating alkaline phosphatase elevation in patients on anticonvulsants, the following approach is critical:

Confirm Hepatic Origin

• Measure GGT concurrently to confirm hepatobiliary origin; elevated GGT with elevated alkaline phosphatase suggests hepatic source, while normal GGT suggests bone origin 3
• If GGT is unavailable, obtain alkaline phosphatase isoenzyme fractionation to determine the percentage derived from liver versus bone 3

Assess Pattern and Severity

• Calculate the R value: (ALT/ULN)/(ALP/ULN) to classify injury pattern 3
  • Cholestatic: R ≤2
  • Mixed: R >2 and <5
  • Hepatocellular: R ≥5
• Severity classification 3:
  • Mild: <5× upper limit of normal (ULN)
  • Moderate: 5-10× ULN
  • Severe: >10× ULN (requires expedited workup)

Drug-Induced Enzyme Induction Pattern

• Anticonvulsant-induced enzyme elevation typically shows:
  • Mild alkaline phosphatase elevation (<2× ULN) 2
  • Proportionate or greater GGT elevation (GGT is more sensitive to enzyme induction) 3
  • Normal or minimally elevated transaminases 2
  • Normal bilirubin (elevated bilirubin suggests true cholestatic injury) 3

Clinical Pitfalls to Avoid

1. Do not assume anticonvulsants are the cause of significant alkaline phosphatase elevation (>5× ULN) without excluding serious pathology such as biliary obstruction, infiltrative disease, or malignancy 4, 5

2. Do not overlook alternative causes in older patients (≥60 years), who are particularly susceptible to cholestatic drug-induced liver injury, accounting for up to 61% of cases in this age group 3, 6

3. Recognize that isolated alkaline phosphatase elevation of unclear etiology is most commonly due to malignancy (57% of cases), particularly infiltrative intrahepatic malignancy or bone metastases, not drug effects 4

Recommended Diagnostic Approach

For patients on lacosamide or oxcarbazepine with elevated alkaline phosphatase:

1. Obtain GGT, complete liver panel (ALT, AST, total and direct bilirubin, albumin), and calculate R value 3

2. If alkaline phosphatase is >2× ULN or accompanied by elevated bilirubin:

   • Perform abdominal ultrasound as first-line imaging to assess for biliary obstruction, gallstones, or infiltrative lesions 3
   • If ultrasound is negative but alkaline phosphatase remains elevated, proceed to MRI with MRCP, which is superior for detecting intrahepatic biliary abnormalities 3

3. If alkaline phosphatase is mildly elevated (<2× ULN) with proportionate GGT elevation and normal bilirubin:

   • This pattern is consistent with enzyme induction 2
   • Repeat testing in 1-3 months to confirm stability 3
   • Consider medication review and alternative anticonvulsant if clinically appropriate 1

4. If GGT is normal despite elevated alkaline phosphatase:

   • Suspect bone origin and evaluate for bone disease, particularly in postmenopausal women or patients with malignancy 3
   • Consider bone-specific alkaline phosphatase measurement or bone imaging if symptomatic 3

Monitoring Recommendations

• For patients on anticonvulsants with baseline normal liver enzymes, monitor alkaline phosphatase, AST, and ALT periodically for the first 3 months 6
• Repeat alkaline phosphatase within 7-10 days if initial elevation is detected to confirm reproducibility and direction of change 3
• Expedite workup if alkaline phosphatase is >10× ULN, as this is highly associated with serious pathology including sepsis, malignant obstruction, and infiltrative disease 5