What medications can cause pancreatitis?

Medications That Can Cause Pancreatitis

Multiple medications can cause pancreatitis, with the strongest evidence for didanosine, azathioprine, valproic acid, pentamidine, mercaptopurine, and several others in Class I medications (those with >20 reported cases and documented recurrence upon rechallenge). 1

High-Risk Medications (Class I)

These medications have the strongest evidence for causing pancreatitis:

• Didanosine - An antiretroviral medication with clear FDA warnings about pancreatitis risk 2
• Azathioprine/6-mercaptopurine - Immunomodulators used in inflammatory bowel disease and transplant medicine 3
• Valproic acid - An anticonvulsant with well-documented pancreatitis risk, especially in children 4, 5
• Pentavalent antimonials - Used for leishmaniasis treatment 3
• Pentamidine - Used for pneumocystis pneumonia and leishmaniasis 3
• Estrogen preparations
• Opiates
• Tetracycline
• Cytarabine
• Corticosteroids
• Trimethoprim/sulfamethoxazole
• Sulfasalazine/mesalamine - Used in inflammatory bowel disease
• Furosemide
• Sulindac 1

Moderate-Risk Medications (Class II)

Medications implicated in >10 cases of acute pancreatitis:

• Rifampin
• Lamivudine
• Octreotide
• Carbamazepine
• Acetaminophen
• Enalapril
• Hydrochlorothiazide
• Erythromycin 1

Special Attention to Newer Medications

GLP-1 Receptor Agonists

• Liraglutide and Semaglutide carry warnings about pancreatitis risk 3, 6
• Pancreatitis has been reported in clinical trials, though causality hasn't been definitively established
• Discontinue if pancreatitis is suspected 3

Tirzepatide (Dual GIP/GLP-1 Receptor Agonist)

• Similar pancreatitis warnings as GLP-1 receptor agonists
• Discontinue if pancreatitis is suspected 3

Monitoring and Management

Risk Assessment

• Identify patients at higher risk:
  • Children with seizure disorders, acute lymphocytic leukemia, or Crohn's disease 7
  • Patients on multiple medications, especially the elderly
  • HIV+ patients
  • Cancer patients
  • Patients on immunomodulating agents 1

Laboratory Monitoring

• For high-risk medications like azathioprine/6-mercaptopurine:
  • Monitor serum chemistry values including lipase/amylase weekly during initiation
  • Continue periodic monitoring throughout treatment 3

Clinical Vigilance

• Watch for symptoms of pancreatitis:
  • Abdominal pain (often radiating to the back)
  • Nausea/vomiting
  • Elevated lipase/amylase

Management of Drug-Induced Pancreatitis

• Discontinue the offending medication immediately
• For pentavalent antimonials: interrupt therapy if moderate-to-severe clinical pancreatitis develops 3
• For thiopurines: thoughtfully differentiate true drug toxicity from extraintestinal manifestations of IBD 3

Special Considerations

Children

• Valproic acid is particularly associated with pancreatitis in children under 11 years 7, 4
• Children with drug-associated pancreatitis often require longer hospital stays and more intensive management 7

HIV Patients

• Didanosine carries specific warnings about pancreatitis risk
• Risk increases when combined with other medications like tenofovir disoproxil fumarate 2

Common Pitfalls

1. Failure to recognize drug-induced pancreatitis - Consider medication review in all cases of unexplained pancreatitis
2. Rechallenge with offending agent - Avoid reintroducing medications previously associated with pancreatitis in a patient
3. Overlooking drug interactions - Combinations like didanosine with tenofovir can increase pancreatitis risk 2
4. Delayed discontinuation - Early withdrawal of the offending agent is critical for improved outcomes 4
5. Missing valproic acid-induced pancreatitis in children - Can be mistaken for abdominal trauma 5

Remember that drug-induced pancreatitis is often idiosyncratic and can occur at any time during treatment. Prompt recognition and discontinuation of the offending agent are essential for favorable outcomes.