Exenatide (Byetta ▼): risk of severe pancreatitis and renal failure
- Medicines and Healthcare products Regulatory Agency
- 1 March 2009
- Therapeutic area:
- Endocrinology, diabetology and metabolism
There have been reports of necrotising and haemorrhagic pancreatitis in people taking exenatide some of which were fatal - stop exenatide treatment if pancreatitis is diagnosed.
Article date: March 2009
Exenatide (Byetta ▼), the first-in-class incretin mimetic, is a glucagon-like-peptide-1 analogue that stimulates insulin release from pancreatic β cells in a glucose-dependent manner.
Exenatide is indicated for treatment of type 2 diabetes mellitus in combination with metformin, with or without sulphonylureas in patients who have not achieved adequate glycaemic control on maximally tolerated doses of these oral therapies. Exenatide should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. It should not be used in patients with type 2 diabetes who require insulin therapy due to β-cell failure.
Treatment with exenatide should be initiated at 5 µg twice daily for at least 1 month to improve tolerability. The dose can then be increased to 10 µg twice daily to further improve glycaemic control. Doses higher than 10 µg twice daily are not recommended.
Exenatide was first marketed in the EU in November 2006 and since then the MHRA in conjunction with the European Medicines Agency (EMA) has monitored its safety. Acute pancreatitis is a known adverse effect of exenatide, but continued reporting of serious and fatal cases has led to re-evaluation of this issue.
An estimated 8000 patients in the UK were prescribed exenatide in the 12-month period up to September 2008 and usage is increasing rapidly (data derived from IMS Disease Analyzer 10/07–09/08 by the MHRA). Up to February 2009, we have received 6 case reports of pancreatitis and a further 3 cases of acute pancreatitis in the UK. There have been approximately 800,000 patient-years of exposure worldwide since licensing. 396 case reports of pancreatitis have been received worldwide in association with exenatide up to September 2008 (mostly from the USA). 80% of these reports were considered to be possibly related to exenatide, and in several cases there was evidence of positive rechallenge. 9 reports of necrotising or haemorrhagic pancreatitis have been received worldwide, 2 of which had a fatal outcome. After a Europe-wide review, product information for exenatide is being updated to contain further information about this risk.
Case reports of renal impairment, including several UK reports of renal failure, have been received in association with exenatide. Up to Jan 30, 2009 we have received seven case reports of acute renal failure in the UK. This medicine is not recommended for use in patients with end-stage renal disease or severe renal impairment (creatinine clearance <30 mL/min). Clinical experience in patients with moderate renal impairment is very limited.
Advice for healthcare professionals:
- There have been reports of necrotising and haemorrhagic pancreatitis with exenatide, some of which were fatal
- If pancreatitis is suspected, treatment with exenatide should be suspended immediately; if pancreatitis is diagnosed, exenatide should be permanently discontinued
- Diagnosed pancreatitis with an unexpectedly prolonged course, haemodynamic instability, fever, failure of medical therapy, or presence of fluid collections on CT suggest possible necrosis
- Exenatide is not recommended for use in patients with end-stage renal disease or severe renal impairment (creatinine clearance <30 mL/min)
Reporting of suspected adverse reactions to exenatide ▼
As with all medicines, the safety of exenatide remains under close review. Please continue to report to the MHRA and the Commission on Human medicines all suspected adverse reactions to exenatide via the Yellow Card Scheme.
Article citation: Drug Safety Update March 2009, vol 2 issue 8: 6.
Diagnosis and management of acute pancreatitis: Munoz A, Katerndahl DA. Am Fam Physician 2000; 62: 164–74.
Pancreatic necrosis and pancreatic abscess: Thomson ABR, Frizzell ER. 2008, Pancreatic Necrosis and Pancreatic Abscess.
Published: 1 March 2009
Therapeutic area: Endocrinology, diabetology and metabolism