Antithyroid Drugs and Risk for Acute Pancreatitis: Is There a Link?

Medications and pancreas. Concept photo of pharmaceutical treatment of diseases associated with pancreas: pancreatitis, diabetes mellitus, enzyme deficiency, indigestion via pills, capsules with drugs
Based on a case-crossover analysis, there was an increased risk for acute pancreatitis associated with ongoing methimazole/carbimazole or propylthiouracil treatment.

In early 2019, the European Medicines Agency (EMA) issued a warning regarding the risk for acute pancreatitis associated with methimazole or carbimazole treatment. The risk for this adverse event is quite low; however, research findings supporting the warning were presented at the 89th Annual Meeting of the American Thyroid Association, held October 30 to November 3, 2019, in Chicago, Illinois.

Previous studies have reported that methimazole, carbimazole, and propylthiouracil may be associated with serious side effects, including agranulocytosis and hepatic dysfunction in 0.5% to 1.0% of patients. After 6 case reports of acute pancreatitis associated with methimazole/carbimazole, the EMA issued a special warning and an update to the product label to include acute pancreatitis as a possible serious side effect.

Because there are no similar reports of acute pancreatitis associated with propylthiouracil treatment, the goal of this nationwide controlled study was to explore the risk for acute pancreatitis associated with different antithyroid drugs.

The study included patients from Denmark who received ≥1 prescription of methimazole/carbimazole (103,852 patients) or propylthiouracil (14,824 patients) between 1995 and 2018. Cases were defined as hospitalization for first-time acute pancreatitis.

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The association between ongoing antithyroid drug use and acute pancreatitis was initially explored using a case-crossover technique, followed by a case-control study to assess the cumulative dose effect of the medications.

Of 43,580 cases of acute pancreatitis, 226 (0.5%) were noted among ongoing methimazole/carbimazole users and 19 (0.04%) were noted among ongoing propylthiouracil users.

Based on the case-crossover analysis, there was an increased risk for acute pancreatitis associated with ongoing methimazole/carbimazole treatment (odds ratio, 1.51; 95% CI, 1.12-2.02) and ongoing propylthiouracil treatment (odds ratio, 1.16; 95% CI, 0.46-2.93).

According to the case-control analysis, there was no evidence of a cumulative dose effect of methimazole/carbimazole or propylthiouracil on the risk for acute pancreatitis, when comparing the highest with the lowest quartile of cumulative dose or when exploring the effect of doubling of the cumulative dose of methimazole/carbimazole or propylthiouracil.

“In our view, the warning by The EMA is justified since the frequency of [acute pancreatitis] in [methimazole] users is of a similar magnitude as reported for agranulocytosis and hepatic dysfunction,” concluded the researchers.

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Hegedus L, Brix TH, Lund L, et al. The risk of acute pancreatitis is increased in users of antithyroid drugs, but differs between methimazole and propylthiouracil. Evidence from AF nationwide case-crossover study. Presented at: American Thyroid Association 2019 Annual Meeting; October 30-November 3, 2019; Chicago, IL. Short Call Oral 6.