Drugs are an often-overlooked cause of pancreatitis in hospitalized patients.1,2 Knowing which drugs are associated with acute pancreatic inflammation can help the hospitalist consider specific drugs as the cause within their differential diagnosis.
The two most common causes of acute pancreatitis are biliary disease (30%-60%) and chronic alcohol use (15%-30%). Drug-induced pancreatitis (DIP) has occurred with more than 100 prescribed medications.3,4
Most cases of acute pancreatitis are reversible and resolve on their own within three to seven days after treatment begins. A small number of patients develop severe complications, and their mortality rate nears 30%. Symptoms may last a few days and can include mild to severe epigastric pain that can radiate to the back, chest, flank, or lower abdomen.
Other symptoms can include nausea, vomiting, fever, abdominal tenderness, jaundice, or hypotension. Serum amylase and lipase levels usually rise to three times the upper limit of normal. Use of computerized tomography (CT) or ultrasound can help the diagnosis.
The mechanism of DIP is not known, but is thought to be predominantly due to an idiosyncratic reaction, and for a few agents/classes, to intrinsic drug toxicity.5 The incidence of DIP is approximately 1.4%-5%. Not knowing the exact number of prescriptions for each medication and the cases of pancreatitis from each impedes the determination of incidence.
Most data on DIP are from case reports or reviews of compiled cases. The validity and severity of DIP is unknown mostly because cases are underreported to MedWatch. Reasons for underreporting include:
- Low index of suspicion for DIP compared with drug- induced hepatotoxicity;
- Milder cases due to missed lower enzyme levels (not routinely ascertained in a metabolic panel);
- Missed latency of exposure; and
- Erroneous classification as alcoholic or biliary disease by default.
Drug-induced pancreatitis is more common in patients who have inflammatory bowel disease, AIDS, cancer, or gastrointestinal disease. It is also common in those who are geriatric, HIV positive, or who are on immunomodulating agents.6
An early compilation of DIP reports was published by Lankisch, et al. This was a retrospective evaluation that excluded all other pancreatitis etiologies (e.g., post-endoscopic retrograde cholangiopancreatography (ERCP), post-traumatic, post-operative, viral), except drugs. Out of 1,613 patients with acute pancreatitis, there were 22 cases of DIP due to the following agents: azathioprine (n=6), mesalamine/sulfasalazine (n=5) didanosine (ddI, n=4), estrogens (n=3), furosemide (n=2), hydrochlorothiazide (HCTZ, n=1), and rifampicin (n=1). Rechallenge was not attempted for ethical reasons. The mean hospital stay was 25.5 days (range two to 78 days), with an incidence of 1.2%. Two patients died (from AIDS and tuberculosis). The authors noted that other studies show a high fatality rate from azathioprine, ddI, furosemide, and HCTZ.
New Drugs
Granisetron injection (Kytril) has been tentatively FDA approved and is expected to receive final approval and go to market in December, upon patent expiration.
Raltegravir (Isentress), an oral integrase inhibitor, is in a new class of antiretrovirals. This agent was FDA approved for use in combination with other antiretroviral therapy for treating HIV infection in patients with ongoing viral replication despite treatment.
New Indications
Levofloxacin 750 mg IV injection and oral tablets (Levaquin) have been FDA approved as a five-day, once-daily course for the treatment of complicated urinary tract infections and acute pyelonephritis.
Raloxifene 60 mg tablets (Evista) have been FDA approved to reduce the risk of invasive breast cancer in two populations of postmenopausal women: those with osteoporosis and those at high risk for invasive breast cancer.