How to manage isolated Serum Glutamic-Pyruvic Transaminase (SGPT) elevation in patients on flecainide?

Management of Isolated SGPT Elevation in Patients on Flecainide

For patients with isolated SGPT elevation while on flecainide therapy, close monitoring should be continued without discontinuing the medication unless the elevation is severe (>5x ULN) or accompanied by symptoms of liver dysfunction.

Assessment of Liver Function in Patients on Flecainide

• Flecainide is listed as a medication that requires caution in patients with hepatic dysfunction according to ACC/AHA/HRS guidelines 1
• Isolated SGPT (ALT) elevation should be evaluated within the context of overall liver function and categorized by severity:
  • Grade 1 (>ULN to 3.0x ULN): Continue flecainide with monitoring 1
  • Grade 2 (>3.0 to 5.0x ULN): Consider temporary hold and more frequent monitoring 1
  • Grade 3 (>5.0 to 20x ULN): Temporarily discontinue flecainide 1
  • Grade 4 (>20x ULN): Permanently discontinue flecainide 1

Management Algorithm

For Grade 1 Elevation (>ULN to 3.0x ULN):

• Continue flecainide therapy 1
• Monitor liver enzymes every 1-2 weeks 1
• Rule out other causes of liver enzyme elevation (medications, alcohol, viral hepatitis) 1
• Consider checking gamma-glutamyl transferase (GGT) to confirm hepatic origin 1

For Grade 2 Elevation (>3.0 to 5.0x ULN):

• Consider temporary hold of flecainide if elevation persists 1
• Increase monitoring frequency to every 3 days 1
• Evaluate for other hepatotoxic medications and discontinue if possible 1
• Resume flecainide when levels improve to ≤ Grade 1 1

For Grade 3-4 Elevation (>5.0x ULN):

• Discontinue flecainide temporarily (Grade 3) or permanently (Grade 4) 1
• Consider hepatology consultation 1
• Evaluate for alternative antiarrhythmic options 1

Special Considerations

• Patients with pre-existing liver disease are at higher risk for flecainide accumulation due to reduced hepatic biotransformation 2
• The plasma half-life of flecainide is significantly longer in patients with cirrhosis (mean t1/2 of 42.2 hours vs. 11.7 hours in healthy subjects) 2
• Flecainide is primarily metabolized by the liver, with approximately 40% excreted unchanged in urine in healthy individuals 2

Monitoring Recommendations

• Baseline liver function tests should be obtained before starting flecainide 1
• For patients with isolated SGPT elevation:
  • Grade 1: Monitor every 1-2 weeks until stabilized 1
  • Grade 2: Monitor every 3 days 1
  • Consider monitoring flecainide plasma levels, keeping trough plasma levels below 0.7-1.0 mcg/mL 1

Alternative Antiarrhythmic Options

• If flecainide must be discontinued due to hepatotoxicity, consider:
  • For supraventricular tachycardia: Beta-blockers, calcium channel blockers (diltiazem, verapamil) 1
  • For atrial fibrillation: Propafenone (although also has hepatic metabolism), amiodarone, or sotalol based on patient characteristics 1
  • Catheter ablation may be considered as a non-pharmacological alternative 1

Clinical Pearls and Pitfalls

• Flecainide has been used extensively worldwide with a favorable safety profile in patients without significant left ventricular disease or coronary heart disease 3
• Extracardiac adverse effects of flecainide are most commonly dizziness (30%) and visual disturbances (28%), with hepatotoxicity being relatively uncommon 4
• Avoid flecainide in patients with structural heart disease, as it has been associated with increased mortality in patients with prior myocardial infarction 5, 3
• Always consider drug interactions that may increase flecainide levels when evaluating liver enzyme abnormalities 1