DrugInduced Pancreatitis

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Drug-Induced Pancreatitis

• Christi Riley
• Pharm.D. Candidate 2009
• October 16, 2008
• University of Kentucky College of Pharmacy

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Objectives

• Understand the diagnosis and etiology of acute
  pancreatitis
• Understand the drugs implicated in
  drug-induced pancreatitis
• Understand treatments and complications
  associated with drug-induced pancreatitis

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Physiology

• Pancreas is responsible for the production of
  insulin and digestive enzymes
• Major enzymes
• Amylase
• Lipase
• Trypsin

Whitcomb, N Engl J Med. 2006 May
18354(20)2142-50
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Pathophysiology

• Acute pancreatitis results from inappropriate
  activation of trypsinogen to trypsin
• Failure to eliminate active trypsin
• Digestive enzymes cause pancreatic injury and
  inflammation
• The acute inflammatory response can cause tissue
  damage, a systemic inflammatory response
  syndrome, multi-organ failure, or death

Whitcomb, N Engl J Med. 2006 May
18354(20)2142-50
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Acute Pancreatitis

• Incidence
• 220,000 patients in 2007
• Mortality - 10-30
• African Americans gt Caucasians
• Males gt Females
• Males Alcohol
• Females Biliary tract disease
• Age varies from 30-70 years

Whitcomb, N Engl J Med. 2006 May
18354(20)2142-50
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Risk Factors

• Biliary tract disease (40)
• Alcohol (35)
• Post-ERCP (4)
• Drugs (2)
• Trauma (1.5)
• Idiopathic (10)

Gardner, TB, Acute Pancreatitis, Jun 10, 2008,
http//www.emedicine.com
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I Get Smashed

• I - idiopathic
• G - gallstones
• E - ethanol (alcohol)
• T - trauma
• S - steroids
• M - mumps and other viruses
• A - autoimmune disease
• S - scorpion sting/ snake bite
• H - hypercalcemia, hyperlipidemia
• E - ERCP
• D - drugs

Gardner, TB, Acute Pancreatitis, Jun 10, 2008,
http//www.emedicine.com
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Signs and Symptoms

• Abdominal pain Cardinal Symptom
• Dull, boring, and steady
• Sudden onset, gradually intensifies
• Epigastric region
• Lasting more than one day
• Nausea/Vomiting/Diarrhea
• Elevated Pancreatic Enzymes
• Physical examination findings
• Fever
• Tachycardia
• Muscular guarding
• Abdominal distension

Journal of Gastroenterology and Hepatology (2002)
17 (Suppl.) S15S39
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Amylase and Lipase

• KEY enzymes in diagnosis of AP
• Serum levels begin to rise 2 to 12 hours from
  onset
• Lipase can remain elevated up to 14 days
• Lipase levels 2.5-3x Amylase indicates
  pancreatitis due to alcohol
• Lipase levels will remain normal in some
  non-pancreatic conditions

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Drug-Induced Pancreatitis

• Medications account for 2 of AP
• Difficult to make definitive diagnosis
• DIP is relatively rare when compared to number of
  potentially toxic drugs
• Many isolated and sporadic reports of DIP

Whitcomb, N Engl J Med. 2006 May
18354(20)2142-50
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DIP Diagnostic Algorithm
J Clin Gastroenterology, September 2005
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Medications associated with DIP

• Most common
• Azathioprine
• Valproic acid
• Mesalamine
• Estrogens
• Furosemide
• HMG-CoA reductase inhibitors
• Isoniazid
• Mercaptopurine

Trivedi, Drug-Induced Pancreatitis An Update, J
Clin Gastroenterology, 2005, Sep, 39 (8) 709-716
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Medications associated with DIP

• Less common drugs
• Rifampin
• Lamivudine
• Hydrochlorothiazide
• Cisplatin
• Carbamazepine
• Acetaminophen
• Octreotide

Trivedi, Drug-Induced Pancreatitis An Update, J
Clin Gastroenterology, 2005, Sep, 39 (8) 709-716
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Byetta (exenatide)

• FDA ALERT on the topic of acute pancreatitis in
  patients taking Byetta
• Information for Healthcare Professionals
  Exenatide
• Update 8/18/2008  Since October 2007, FDA has
  received reports of 6 cases of hemorrhagic or
  necrotizing pancreatitis in patients taking
  Byetta. Of the 6 cases of hemorrhagic or
  necrotizing pancreatitis, all patients required
  hospitalization, two patients died and four
  patients were recovering at time of reporting.
• FDA ALERT 10/2007  FDA has reviewed 30
  postmarketing reports of acute pancreatitis in
  patients taking Byetta.  An association between
  Byetta and acute pancreatitis is suspected in
  some of these cases.  Healthcare professionals
  should instruct patients taking Byetta to seek
  prompt medical care if they experience
  unexplained persistent severe abdominal pain
  which may or may not be accompanied by vomiting. 
  If pancreatitis is suspected, Byetta should be
  discontinued.  If pancreatitis is confirmed,
  Byetta should not be restarted unless an
  alternative etiology is identified.

FDA, http//www.fda.gov/CDER/Drug/InfoSheets/
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Complications of Pancreatitis

• Acute fluid collections
• Pseudocyst
• Intra-abdominal infections
• Intestinal flora are the predominant source of
  bacteria
• Pancreatic necrosis
• Death

Gardner, TB, Acute Pancreatitis, Jun 10, 2008,
http//www.emedicine.com
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Treatments

• Pain Control
• IV pain medications, avoid exacerbations
• Bowel Rest and IV Hydration
• Supportive Care
• Blood glucose monitoring
• Nutritional Support
• Enteral feedings or TPN
• ERCP
• Antibiotics
• Surgery

Journal of Gastroenterology and Hepatology (2002)
17 (Suppl.) S15S39
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Antibiotics

• Use of Abx is controversial
• Prophylactic Abx is not recommended
• Reserved for Necrotizing Pancreatitis
• Abx are appropriate for fever, leukocytosis, and
  organ failure with confirmed positive cultures

Whitcomb, N Engl J Med. 2006 May
18354(20)2142-50
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Antibiotics

• Coverage of Gram and Gram bacteria
• Fluoroquinolones
• Imipenem-cilastatin
• Metronidazole
• Ciprofloxacin
• Zosyn or Unasyn
• Intrabdominal infections

Gastroenterologist. 1997 Jun5(2)157-64
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Pharmacist Role

• Be aware of potential for DIP
• Rule out medications as cause
• Suggest appropriate therapies
• Glucose monitoring/interventions
• Reporting of Adverse Drug events to track
  incidence and severity of DIP
• FDA Center for Drug Evaluation and Research
  http//www.fda.gov/cder/index.html

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Summary

• Acute pancreatitis can be a medical emergency
• Proper medical attention and treatment is
  necessary
• Many times, cause is unknown, therefore we must
  rule out all possible etiologies including
  medications

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Drug-Induced Pancreatitis

• Christi Riley
• Pharm.D. Candidate 2009
• October 16, 2008
• University of Kentucky College of Pharmacy