- Drugs List
- Therapeutic Indications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
Control of type-2 diabetes when combined oral therapies inadequate
Treatment of type 2 diabetes in patients who are unable to achieve adequate glycaemic control at the maximum tolerated doses of oral hypoglycaemics in combination with:
a sulfonylurea or
a thiazolidinedione or
metformin and a sulfonylurea or
metformin and a thiazolidinedione
Exenatide injection is also indicated as adjunctive therapy to basal insulin with or without metformin and/or pioglitazone in adults who have not achieved adequate glycaemic control with these patients.
Initially 5 micrograms of exenatide per dose administered twice daily for a period of at least one month in order to improve tolerability.
The dose can then be increased to 10 micrograms of exenatide per dose administered twice daily if further glycaemic control is required.
Doses greater than 10 micrograms twice daily are not recommended.
If a dose is missed, treatment should continue with the next scheduled dose.
See also Additional Dosage Information .
Caution is advised when treating elderly patients.
Dosage increases from 5 micrograms to 10 micrograms should be carried out conservatively in patients over 70 years.
Limited clinical experience in treating patients over 75 years.
Patients with Renal Impairment
The Renal Drug Handbook notes that clearance of exenatide is reduced by 84% in patients with established renal failure.
Additional Dosage Information
Exenatide should only be used in combination with oral hypoglycaemic agents or basal insulin if other oral treatment is not appropriate ( see Therapeutic indications ).
When exenatide is used in combination with metformin or a thiazolidinedione, the current dose of metformin and/or the thiazolidinedione can be continued. No additional risk of hypoglycaemia is expected compared to metformin monotherapy.
When exenatide is used in combination with a sulfonylurea or insulin, the dose of sulfonylurea or insulin may need to be reduced in order to lower the risk of hypoglycaemia.
Dosage adjustment is not required on a day to day basis depending on self-monitored glycaemia. When adjusting the dose of sulfonylurea, glucose self monitoring may be required.
If an injection is missed the treatment should be continued with the next scheduled dose.
For subcutaneous injection only. The injection site may be the thigh, abdomen or upper arm.
Exenatide must be administered within a 1 hour period before the morning and evening meals (or two main meals of the day as long as the meals are approximately 6 hours apart).
Exenatide and basal insulin must be administered as two separate injections.
Children under 18 years
Renal impairment - creatinine clearance below 30 ml/minute
Severe gastrointestinal disorder
Precautions and Warnings
Body mass index less than 25kg per square metre
Patients over 70 years
Renal impairment - creatinine clearance 30-50ml/minute
Advise ability to drive/operate machinery may be affected by side effects
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Do not use if contents have been frozen
Use only if the solution is clear and colourless
Insulin dose adjustment: Reduce insulin dose gradually and monitor for DKA
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pancreatitis occurs
Discontinue if renal function deteriorates
Pregnancy confirmed: Change patient to insulin treatment
May affect the gastro-intestinal absorption of other drugs
Advise patient to eat meal less than 60 minutes after each dose
Advise patients to have glucose available in the event of hypoglycaemia
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk
There have been rare reports of altered renal function, including increased serum creatinine, renal impairment, exacerbation of chronic renal failure, acute renal failure (sometimes requiring haemodialysis) in patients receiving exenatide. In some cases, patients were experiencing events that could affect hydration, such as nausea, vomiting and/or diarrhoea, or were receiving concomitant drugs known to affect renal function and/or hydration such as ACE inhibitors, NSAIDs or diuretics.
In clinical trials, approximately 5% of patients experienced weight loss of more than 1.5kg/week. This rate of weight loss may have harmful consequences.
Pregnancy and Lactation
Exenatide is contraindicated in pregnancy.
When dieting alone is not successful, insulin is the treatment of choice for both Type 1 and Type 2 diabetes during pregnancy as it provides better control of maternal blood glucose than oral hypoglycaemics, and does not cross the placenta. Hyperglycaemia in the mother, particularly in the early stages of gestation, is associated with a number of foetal and maternal adverse effects, including foetal structural abnormalities. Carefully prescribed insulin therapy will provide better control of the mother's blood glucose thereby preventing the foetal and neonatal complications that occur with the disease (Briggs, 2011).
There are no data on the use of exenatide during human pregnancy. Animal studies have shown developmental toxicity including structural anomalies and neonatal death. Animal studies suggests moderate risk when exenatide is used during pregnancy, however, the absence of human data prevents a complete assessment. Ex vivo testing has concluded that exenatide is unlikely to cross the human placenta, however these results may not be representative of the whole gestation period.
Manufacturer recommends discontinuing treatment with exenatide and replacing with insulin therapy in the event of pregnancy.
The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Exenatide is contraindicated during breastfeeding.
There are no data on the use of exenatide during human breastfeeding. Low amounts of exenatide have been found to be excreted in the milk of rodents. Exenatide has a high molecular weight and a short elimination half-life, suggesting that it is unlikely to be secreted in breast milk in clinically significant amounts. If excreted in breast milk, it is considered unlikely that exenatide will be orally absorbed by the infant as it is likely to be digested in the stomach.
Manufacturer does not recommend the use of exenatide during breastfeeding. However, exenatide appears to present low risk during breastfeeding despite the lack of human data.
Insulin remains the drug of choice during breastfeeding, and if glycaemic control can be maintained, it is recommended that the mother is switched to insulin during nursing.
Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Advise patient of the appropriate handling procedures of this preparation.
Advise patient of the characteristic symptom of acute pancreatitis and to seek medical advice if this symptom occurs.
Advise patient to eat a meal less than 60 minutes after each dose.
Advise patient of the warning signs of hypoglycaemia.
Advise patients to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent hypoglycaemic episodes.
Inform the patient that he/she needs to inform the Driving and Vehicle Licensing Agency (DVLA) about the medication they are receiving. The Drivers Medical Group at the DVLA will be able to advise the patient on the legal issues surrounding the treatment of diabetes mellitus and driving.
The DVLA can be contacted by post at the following address:
Drivers Medical Group, DVLA, Swansea, SA99 1TU
By phone on 0870 600 0301; or by fax on 0845 850 0095
Detailed guidance on eligibility to drive, and precautions required, is available from the DVLA.
Further information concerning diabetes and driving may be obtained from the DVLA website at:
Acute renal failure
Gastroesophageal reflux disease
Injection site reactions
Serum creatinine increased
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Last Full Review Date: July 2013
British National Formulary, 65th Edition (March - September 2013) Pharmaceutical Press, London.
Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.
Medications and Mother's Milk, 14th edition (2010) Hale, T.W. Hale Publishing, Amarillo, Texas.
Summary of Product Characteristics: Byetta 5 micrograms solution for injection, prefilled pen. AstraZeneca Limited. Revised March 2013.
Summary of Product Characteristics: Byetta 10 micrograms solution for injection, prefilled pen. AstraZeneca Limited. Revised March 2013.
MHRA Drug Safety Update June 2019
Available at: https://www.mhra.gov.uk
Last accessed: 28 August 2019
MHRA Drug Safety Update
Volume 2 Issue 8, March 2009
Last accessed 12th July 2013
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