What medications can increase lipase levels?

Medications That Can Increase Lipase Levels

Several medications can cause elevated serum lipase levels, with the most common being pancreatic enzyme replacement therapy (PERT) products, which directly introduce exogenous lipase into the body.

Primary Medications That Increase Lipase

Pancreatic Enzyme Replacement Therapy (PERT)

• FDA-approved PERT formulations contain high concentrations of lipase and are the most direct cause of increased serum lipase levels 1
• Available PERT products and their lipase content:
  • Creon: 3,000-36,000 USP units of lipase
  • Zenpep: 3,000-40,000 USP units of lipase
  • Pancreaze: 2,600-37,000 USP units of lipase
  • Pertzye: 4,000-24,000 USP units of lipase
  • Viokace: 10,444-20,880 USP units of lipase
  • Relizorb: In-line lipase cartridge for enteral feeding formulas

Lipase Inhibitors (Paradoxical Effect)

• Orlistat (Tetrahydrolipstatin) - while primarily a lipase inhibitor, can cause compensatory increases in pancreatic enzyme production 1
• 4-bromophenylboronic acid - another lipase inhibitor that may trigger compensatory lipase production 1

Other Medications Associated with Elevated Lipase

Medications That May Cause Pancreatitis

Medications that can cause drug-induced pancreatitis will indirectly increase lipase levels:

• Asparaginase - can cause pancreatitis with elevated amylase and lipase 1
• Certain antibiotics (tetracyclines, metronidazole)
• Immunosuppressants (azathioprine)
• Diuretics (furosemide, thiazides)
• Valproic acid
• Estrogens

Medications That Reduce Lipase Clearance

• Medications causing renal impairment can lead to reduced lipase clearance and elevated serum levels 2
• Nephrotoxic drugs (aminoglycosides, NSAIDs with prolonged use)

Clinical Significance and Interpretation

Diagnostic Considerations

• Serum lipase is considered more specific than amylase for diagnosing acute pancreatitis 1, 3
• A serum lipase level >3 times the upper limit of normal has a sensitivity of 100% and specificity of 99% for diagnosing acute pancreatitis 3
• However, elevated lipase can occur in non-pancreatic conditions, particularly when <3 times the upper limit of normal 4

Monitoring Considerations

• When monitoring patients on PERT, lipase levels may be elevated without clinical significance
• For patients with suspected pancreatitis, lipase is the most sensitive laboratory test for detection of pancreatic inflammation 1
• Procalcitonin is more sensitive for detecting pancreatic infection 1

Clinical Approach to Elevated Lipase

1. Determine the magnitude of elevation:

   • 3x upper limit of normal: Highly suggestive of pancreatitis

   • <3x upper limit of normal: Consider medication effect or non-pancreatic causes

2. Review medication history:

   • Check for PERT products
   • Identify medications known to cause pancreatitis
   • Evaluate for medications affecting renal function

3. Assess for symptoms:

   • Asymptomatic elevations are more likely medication-related
   • Abdominal pain with elevated lipase >3x normal suggests pancreatitis

4. Consider alternative causes if no medication correlation:

   • Renal impairment
   • Macrolipase formation
   • Hepatobiliary disease
   • Intestinal disorders
   • Critical illness

Important Caveats

• Lipase elevations from PERT are expected and generally not concerning
• When diagnosing pancreatitis, clinical symptoms should be correlated with laboratory findings
• Isolated lipase elevation without symptoms may not require intervention if medication-related
• Discontinuing the causative medication should normalize lipase levels if drug-induced

Human pancreatic lipase has lower activity on meal triglycerides than previously thought, which explains why higher doses of PERT are often needed to prevent steatorrhea in pancreatic insufficiency 5.