EXENATIDE (BYETTA ) PROTOCOL, 5mcg and 10mcg SC injection pre-filled pens This document should be read in conjunction with the current Summary of Product Characteristics http://www.medicines.org.uk 1. Locally approved guidelines Exenatide is licensed to be given for of Type 2 diabetes in combination with: Metformin Sulphonylurea Thiazolidinediones Metformin and Sulphonylurea Metformin and a Thiazolidinediones In patients who have not achieved adequate glycaemic control on maximum tolerated doses of oral therapies. Exenatide has been approved for local use for the of Type 2 Diabetes, only in line with NICE CG87, Management of Type 2 Diabetes. NICE CG87, MAY 2009 MANAGEMENT OF TYPE 2 DIABETES: Consider adding Exenatide to metformin and a sulphonylurea if blood glucose control remains or becomes inadequate: Hba1c more than or equal to 7.5%/59mmols or other higher level agreed with the individual AND BMI 35kg/m2 or more in people of European decent (adjust for other ethnic groups) and there are problems associated with high weight OR BMI less than 35kg/m2 and insulin is unacceptable because of occupational implications of weight loss would benefit other co-morbidities Exenatide should only be continued if the patient has a beneficial metabolic response at 6months (Hba1c reduction by at least 1% AND initial bodyweight reduction by at least 3%) Diabetes Specialist Nurses October 2010 1
2. Therapeutic use and background Exenatide was the first glucagon like peptide (GLP-1) receptor agonist to be marketed in the UK GLP-1 is secreted in the intestine mostly in response to food intake. It stimulates the secretion of insulin and reduces hepatic glucose production GLP-1 also reduces GI motility and increases the feeling of being full GLP-1 agonists lower fasting and post-prandial blood glucose levels and are associated with weight loss Exenatide is given twice daily by subcutaneous injection GLP-1 agonists suppresses glucagon secretions which is inappropriately increased in Type 2 Diabetes 3. Contraindications hypersensitivity to the active ingredients or any of the excipients Type 1 Diabetes Severe renal impairment (egfr < 50 ml/min) Not recommended in severe inflammatory bowel disease or gastroparesis Previous history of pancreatitis Triglycerides > 10 (fasting) Pregnancy and breastfeeding (lack of data) Paediatric and adolescents < 18yr 4. Dosage Regime (adults) Subcutaneous injection into the abdomen or thigh Initial dose : 5mcg twice daily for 1 month to improve tolerability Subsequent dose: 10mcg twice daily Exenatide should be administered 30-60 minutes prior to the two main meals of the day, ensuring a minimum of 6hrs between these meals Exenatide SHOULD NOT be administered after a meal Increase in dose from 5mcg to 10mcg should be considered with caution in cases of moderate renal impairment 5. Drug Interactions NB: also refer to the BNF or Product Characteristics Summary Drugs with narrow therapeutic index and/or require clinical monitoring: Diabetes Specialist Nurses October 2010 2
Exenatide slows gastric emptying (amount of medicine absorbed and rate of absorption may be effected). Take other medicines 1hr before or 4hrs after Exenatide Gastro-resistant Formulations: Take 1hr before or 4hrs after Exenatide Sulphonylureas: Increased risk of hypoglycaemia therefore consider temporary dose reduction by 50% initially then titrate dose back up Initial blood glucose monitoring may be required Insulin: Currently not licensed for use with Exenatide and outside NICE guidelines Warfarin: Not known but INR has increased in some patients. Recommendation is to monitor INR more frequently Statins: Recommends monitoring of lipid profile in case of deterioration Oral Contraceptive Pill: Recommendation to be taken at least 1hr before Exenatide 6. Adverse Drug Reactions NB: also refer to BNF or Product Characteristics Summary Most serious toxicity is seen with long term use therefore may present to the GP first Common side effects Nausea Vomiting Diarrhoea Constipation Abdominal pain/distension Dyspepsia Headache Dizziness Nasopharyngitis Hypoglycaemia Less Common side effects Pancreatitis Altered renal function Diabetes Specialist Nurses October 2010 3
If the patient has symptoms of acute pancreatitis, (persistent, severe abdominal pain) they should stop immediately and seek medical attention urgently. Exenatide is a black triangle drug (at the time of writing), Any adverse reaction to a black triangle drug should be reported to the CHM via the yellow card scheme 7. Baseline Investigations Prior to commencing Exenatide the following should be undertaken Recent blood test within the last 3 months to include triglycerides/renal/hba1c Weight/BMI 8. Monitoring MONITORING FREQUENCY RESULTS ACTION BY Hba1c 2 monthly then 6 monthly At 6 months at least 1% reduction Bodyweight 6 monthly At 6 months at least 3% reduction U&E, egfr 1 monthly then 6 monthly Significant change Lipid profile 6 monthly Significant change 9. Prescribing Treatment with Exenatide may be initiated in secondary care and transferred to primary care once the patient is established Alternatively Exenatide may be initiated in primary care by a GP who has undergone extra training or following written request from a secondary care clinician Diabetes Specialist Nurses October 2010 4
10. Responsibility of Initiating Initiate Undertake baseline observations according to referral form Dose adjustment Monitor patients initial reaction and progress on the drug Continue to monitor the patient according to this protocol while the patient remains on this drug Monitor for risk of hypoglycaemia at 6months to assess outcomes outcomes against NICE CG 87 Provide patient with relevant drug information to enable Informed consent to therapy Understanding of potential side effects and appropriate action Understanding the role of monitoring 11. Responsibility of primary care To monitor and prescribe in collaboration with the specialist according to this protocol To ensure that monitoring and dosage record are kept up to date Symptoms or results are appropriately actioned, recorded and communicated to secondary care when necessary 12. Responsibility of Patients To attend hospital and GP clinic appointments Failure to attend may result in suspension of (on specialist advise) To report adverse effects to their specialist or GP 13. Additional Responsibilities Responsibility of all prescribers: any serious reactions to an established drug should be reported to CHM 14. GP referral letter attached Diabetes Specialist Nurses October 2010 5
15. Guideline date October 2010 16. Guideline review date October 2011 17. References Summary Of Product Characteristics (Byetta) Eli Lilly & Company Ltd. EMC last updated 06/08/2010 National Institute for Health and Clinical Excellence, 2009. Type 2 Diabetes newer agents, CG87. London. MHRA Drug Safety Update. vol 2, issue 8, March 2009: Exenatide (Byetta): risk for severe pancreatitis and renal failure Diabetes Specialist Nurses October 2010 6