Bydureon BCise Special Precautions

Prolonged-release exenatide should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Prolonged-release exenatide is not a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent patients after rapid discontinuation or dose reduction of insulin (see Dosage & Administration).
Prolonged-release exenatide must not be administered by intravenous or intramuscular injection.
Renal impairment: In patients with end stage renal disease receiving dialysis, single doses of immediate release exenatide increased frequency and severity of gastrointestinal adverse reactions; therefore, prolonged release exenatide formulations are not recommended for use in patients with end-stage renal disease or severe renal impairment (creatinine clearance <30 ml/min). The clinical experience in patients with moderate renal impairment is limited and the use of prolonged-release exenatide is not recommended.
There have been uncommon events of altered renal function with exenatide, including increased serum creatinine, renal impairment, worsened chronic renal failure and acute renal failure, sometimes requiring haemodialysis. Some of these events occurred in patients experiencing events that may affect hydration, including nausea, vomiting, and/or diarrhoea and/or receiving medicinal products known to affect renal function/hydration status. Concomitant medicinal products included angiotensin converting enzymes inhibitors, angiotensin-II antagonists, non-steroidal anti-inflammatory medicinal products and diuretics. Reversibility of altered renal function has been observed with supportive treatment and discontinuation of potentially causative medicinal products, including exenatide.
Severe gastrointestinal disease: Prolonged-release exenatide has not been studied in patients with severe gastrointestinal disease, including gastroparesis. Its use is commonly associated with gastrointestinal adverse reactions, including nausea, vomiting, and diarrhoea. Therefore, the use of this medicinal product is not recommended in patients with severe gastrointestinal disease.
Acute pancreatitis: Use of GLP-1 receptor agonists has been associated with a risk of developing acute pancreatitis. In clinical studies of Bydureon BCise, acute pancreatitis occurred in 0.4% of patients. There have been spontaneously reported events of acute pancreatitis with prolonged-release exenatide. Resolution of pancreatitis has been observed with supportive treatment, but very rare cases of necrotising or haemorrhagic pancreatitis and/or death have been reported. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, the use of this medicinal product should be discontinued; if acute pancreatitis is confirmed, it should not be restarted. Caution should be exercised in patients with a history of pancreatitis.
Concomitant medicinal products: The concurrent use of prolonged-release exenatide formulations with D-phenylalanine derivatives (meglitinides), alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors or other GLP-1 receptor agonists has not been studied. The concurrent use of a formulation of prolonged-release and immediate-release exenatide has not been studied and is not recommended.
Interaction with warfarin: There have been spontaneously reported cases of increased INR (International Normalized Ratio), sometimes associated with bleeding, with concomitant use of warfarin and exenatide (see Interactions).
Hypoglycaemia: The risk of hypoglycaemia was increased when prolonged-release exenatide was used in combination with a sulphonylurea in clinical studies. Furthermore, in the clinical studies, patients on a sulphonylurea combination with mild renal impairment had an increased incidence of hypoglycaemia compared to patients with normal renal function. To reduce the risk of hypoglycaemia associated with the use of a sulphonylurea, reduction in the dose of sulphonylurea should be considered.
Rapid weight loss: Rapid weight loss at a rate of > 1.5 kg per week has been reported in patients treated with exenatide. Weight loss of this rate may have harmful consequences. Patients with rapid weight loss should be monitored for signs and symptoms of cholelithiasis.
Discontinuation of treatment: After discontinuation, the effect of prolonged-release exenatide may continue as plasma levels of exenatide decline over 10 weeks. Choice of other medicinal products and dose selection should be considered accordingly, as adverse reactions may continue and efficacy may, at least partly, persist until exenatide levels decline.
Effects on ability to drive and use machines: Prolonged-release exenatide has minor influence on the ability to drive and use machines. When used in combination with a sulphonylurea, patients should be advised to take precautions to avoid hypoglycaemia while driving and using machines.