What's the next step for a patient on Levetiracetam with elevated Alkaline Phosphatase and low normal AST and ALT?

Management of Elevated Alkaline Phosphatase in a Patient on Levetiracetam

Assessment of Current Laboratory Values

The patient should continue levetiracetam with close monitoring of liver enzymes in 2-5 days, as this is likely a drug-induced elevation of alkaline phosphatase that requires monitoring but not immediate discontinuation. 1, 2

The patient presents with:

• Elevated alkaline phosphatase (ALP): 136 U/L (reference range: 36-130 U/L)
• Normal AST: 20 U/L (reference range: 10-40 U/L)
• Normal ALT: 18 U/L (reference range: 10-40 U/L)

This pattern shows an isolated elevation of ALP with normal transaminases, which is consistent with a cholestatic pattern of liver injury rather than hepatocellular damage.

Significance and Likely Etiology

The pattern of isolated ALP elevation with normal transaminases suggests:

1. Drug-induced cholestatic pattern: Levetiracetam has been reported to cause elevated ALP levels, though this is rare 2
2. Mild cholestatic process: The elevation is only slightly above the upper limit of normal
3. Low risk of severe liver injury: Normal transaminases indicate minimal hepatocellular damage

Recommended Management Approach

1. Continue monitoring liver enzymes:

   • Repeat ALP, AST, ALT, total bilirubin in 2-5 days 3
   • Monitor for development of symptoms (fatigue, nausea, right upper quadrant pain)

2. Clinical assessment:

   • Evaluate for symptoms of liver dysfunction (jaundice, pruritus, right upper quadrant pain)
   • Review medication list for other potential hepatotoxic drugs

3. Additional testing to consider:

   • Gamma-glutamyl transferase (GGT) to confirm hepatic origin of ALP elevation 4
   • Total bilirubin to assess for biliary obstruction

4. Management decision tree:

   • If ALP continues to rise OR symptoms develop: Consider levetiracetam discontinuation
   • If ALP stabilizes or decreases: Continue current therapy with periodic monitoring
   • If transaminases become elevated (ALT ≥3× ULN): Consider drug discontinuation 3

Rationale for Continuing Levetiracetam

1. The FDA label for levetiracetam states: "There were no meaningful changes in mean liver function tests (LFT) in controlled trials in adult or pediatric patients; lesser LFT abnormalities were similar in drug and placebo treated patients in controlled trials (1.4%)" 1

2. The elevation is mild (only slightly above upper limit of normal)

3. Levetiracetam has minimal hepatic metabolism with predominantly renal clearance, making severe hepatotoxicity uncommon 5

4. According to guidelines for drug-induced liver injury, this pattern does not meet criteria for drug discontinuation, which would require:

   • ALT ≥5× ULN, or
   • ALP ≥2× ULN with elevated GGT, or
   • ALT ≥3× ULN with total bilirubin >2× ULN 3

Important Caveats and Monitoring

• If ALP continues to rise or if symptoms develop, levetiracetam should be reconsidered as the potential cause 2

• Although rare, cases of severe drug-induced liver injury from levetiracetam have been reported, typically occurring within days to 5 months after initiation 6

• The patient should be educated about warning signs of liver injury: jaundice, dark urine, light-colored stools, abdominal pain, or unusual fatigue

• If levetiracetam needs to be discontinued due to worsening liver function, consultation with neurology for alternative antiepileptic medication would be required

Follow-up Plan

• Repeat liver function tests in 2-5 days
• If ALP normalizes: continue regular monitoring every 3-6 months
• If ALP continues to rise: consider alternative antiepileptic medication
• Document the potential association between levetiracetam and ALP elevation in the patient's record for future reference