Drugs List

Therapeutic Indications

Uses

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:

metformin or
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.

Administration

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.

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Pregnancy
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
Contains metacresol
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

Pregnancy

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 ).

Lactation

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

Side Effects

Abdominal distension
Abdominal pain
Acute renal failure
Alopecia
Anaphylactic reaction
Angioneurotic oedema
Antibody formation
Asthenia
Constipation
Decreased appetite
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Eructation
Flatulence
Gastroesophageal reflux disease
Headache
Hyperhidrosis
Hypoglycaemia
Injection site reactions
Nausea
Nervousness
Pancreatitis
Pruritus
Rash
Renal impairment
Serum creatinine increased
Somnolence
Urticaria
Vomiting
Weight loss

Presentation

Exenatide injection

Drugs List

Therapeutic Indications

Uses

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:

metformin or
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.

Dosage

Adults

Elderly

Patients with Renal Impairment

Additional Dosage Information

Administration

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.

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Pregnancy
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
Contains metacresol
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

Pregnancy

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 ).

Lactation

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

Counselling

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.

https://www.gov.uk/government/publications/at-a-glance

Further information concerning diabetes and driving may be obtained from the DVLA website at:

https://www.gov.uk/government/organisations/driver-and-vehicle-licensing-agency

Side Effects

Abdominal distension
Abdominal pain
Acute renal failure
Alopecia
Anaphylactic reaction
Angioneurotic oedema
Antibody formation
Asthenia
Constipation
Decreased appetite
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Eructation
Flatulence
Gastroesophageal reflux disease
Headache
Hyperhidrosis
Hypoglycaemia
Injection site reactions
Nausea
Nervousness
Pancreatitis
Pruritus
Rash
Renal impairment
Serum creatinine increased
Somnolence
Urticaria
Vomiting
Weight loss

Overdosage

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 ).

Further Information

Last Full Review Date: July 2013

Reference Sources

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
https://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName=CON041213&RevisionSelectionMethod=LatestReleased
Last accessed 12th July 2013