Adverse effect of sitagliptin and exenatide (December 2009)

During the last month, the FDA has released reports of previously unreported adverse effects of sitagliptin (marketed as Januvia and Janumet) and exenatide (Byetta). The adverse effects will now be on the product labeling. These drugs used for treatment of Type 2 diabetes mellitus (T2DM) are not approved for those below 18 years and thus are not widely prescribed in Pediatric Endocrine practice. However, this information may be of use when deciding adjunct therapy in older pediatric Type 2 patients present in many pediatric diabetes practices.

Sitaglipin - Acute Pancreatitis: 88 cases of acute pancreatitis have been reported since October 2006. 95% of cases were in patients with another risk factor for kidney insufficiency Twenty percent of cases occurred within one month of beginning sitaglipin, and half of the cases were associated with another risk factor for pancreatitis (ie. hypertriglyceridemia ). Half of the cases resolved after sitaglipin was discontinued. It is unknown whether those with a history of pancreatitis before starting sitaglipin are at higher risk for sitaglipin-associated pancreatitis.

For further information visit: http://www.fda.gov/Drugs/DrugSafety/

Exenatide - Worsening of renal insufficiency: 78 cases of worsening kidney function have been reported since April 2005. 95% of patients had at least one other risk factor for renal insufficiency (cardiac insufficiency, hypertension, pancreatitis, rhabdomyolysis, urinary tract infection, concomitant medications such as antiretrovirals, antihypertensives, diuretics, and non-steroidal anti-inflammatory drugs (NSAIDs)). Since a significant percentage of these cases also reported nausea, vomiting, and diarrhea--known side effects of exenatide—it is unknown whether the renal insufficiency was secondary to exenatide or the volume depletion in these patients. Cases of acute renal failure or insufficiency occurred as soon as 3 days and up to 2 years after initiation of the drug. The patient ages ranged from 23 to 83 years, with an average age of 60 years.

The revised labeling for exenatide includes the following:

• Recommendations stating that exenatide should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease.
• Recommendations that caution should be applied when initiating or increasing doses of Byetta from 5 mcg to 10 mcg in patients with moderate renal impairment (creatinine clearance 30 to 50 ml/min).

For further information visit:
http://www.fda.gov/Drugs/DrugSafety/