Drugs List

Therapeutic Indications

Uses

Control of type-2 diabetes when combined oral therapies inadequate

Treatment of type 2 (non insulin dependent) diabetes mellitus, when dietary management and exercise in combination with oral glucose-lowering medicinal product and/or basal insulin does not result in adequate glycaemic control.

Lixisenatide is used in combination therapy with other oral antidiabetics and/or basal insulin.

Not to be given in triple combination with basal insulin and a sulfonylurea.

Administration

For subcutaneous injection only. The injection site may be the thigh, abdomen or upper arm.

Lixisenatide may be administered any time within a 1 hour period before a meal, preferably before the same meal every day.

Administration before meals is essential.

Lixisenatide and basal insulin must be administered as two separate injections.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Severe gastrointestinal disorder

Precautions and Warnings

Patients over 75 years
History of pancreatitis
Renal impairment - creatinine clearance 30-50ml/minute

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
Consider glucose monitoring when given in combination
Insulin dose adjustment: Reduce insulin dose gradually and monitor for DKA
Advise patient to seek medical advice if symptoms of dehydration occur
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pancreatitis occurs
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

Pregnancy and Lactation

Pregnancy

Lixisenatide is contraindicated in pregnancy.

At the time of writing there is limited published information regarding the use of lixisenatide during pregnancy. Animal studies have shown reproductive toxicity. The risk to humans is unknown.

Detailed guidance on the treatment of diabetes during pregnancy is available from the National Institute for Health and Clinical Excellence (NICE) at https://www.nice.org.uk/guidance/ng3

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 compared to oral hypoglycaemics. It is believed that human insulin and insulin analogues do not cross the placenta, however there may be endogenous carrier proteins allowing passage of insulin to the embryo during early gestation; animal insulin is believed to cross the human placenta. The foetus produces its own insulin once insulin-secreting cells in the foetal pancreas become differentiated at the end of the first trimester.

Human insulin is considered safe to use during pregnancy and extensive experience with human insulin during pregnancy does not indicate any embryotoxic potential. Human insulin is often the first line treatment for diabetes and the benchmark used when comparing the safety of other insulins during pregnancy.

Infants of diabetic mothers are at an increased risk of congenital abnormalities, the rate of which appears to be related to maternal glycaemic control during the first trimester. Careful control of maternal blood glucose is required throughout pregnancy. Good maternal glycaemic control during labour and birth is important in preventing adverse neonatal outcomes including neonatal hypoglycaemia and respiratory stress.

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

Lixisenatide is contraindicated in breastfeeding.

It is unknown whether lixisenatide is excreted in breast milk, therefore a risk to the nursing infant cannot be excluded.

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

Acute pancreatitis
Anaphylactic reaction
Back pain
Cardiac arrhythmias
Cystitis
Dehydration
Diarrhoea
Dizziness
Dyspepsia
Headache
Hypersensitivity reactions
Hypoglycaemia
Influenza
Injection site reactions
Nausea
Palpitations
Somnolence
Tachycardia
Upper respiratory tract infection
Urticaria
Viral infection
Vomiting

Presentation

Solution for injection containing lixisenatide

Drugs List

Therapeutic Indications

Uses

Control of type-2 diabetes when combined oral therapies inadequate

Treatment of type 2 (non insulin dependent) diabetes mellitus, when dietary management and exercise in combination with oral glucose-lowering medicinal product and/or basal insulin does not result in adequate glycaemic control.

Lixisenatide is used in combination therapy with other oral antidiabetics and/or basal insulin.

Not to be given in triple combination with basal insulin and a sulfonylurea.

Dosage

Adults

Elderly

Additional Dosage Information

Administration

For subcutaneous injection only. The injection site may be the thigh, abdomen or upper arm.

Lixisenatide may be administered any time within a 1 hour period before a meal, preferably before the same meal every day.

Administration before meals is essential.

Lixisenatide and basal insulin must be administered as two separate injections.

Contraindications

Children under 18 years
Breastfeeding
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Severe gastrointestinal disorder

Precautions and Warnings

Patients over 75 years
History of pancreatitis
Renal impairment - creatinine clearance 30-50ml/minute

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
Consider glucose monitoring when given in combination
Insulin dose adjustment: Reduce insulin dose gradually and monitor for DKA
Advise patient to seek medical advice if symptoms of dehydration occur
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pancreatitis occurs
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

Pregnancy and Lactation

Pregnancy

Lixisenatide is contraindicated in pregnancy.

At the time of writing there is limited published information regarding the use of lixisenatide during pregnancy. Animal studies have shown reproductive toxicity. The risk to humans is unknown.

Detailed guidance on the treatment of diabetes during pregnancy is available from the National Institute for Health and Clinical Excellence (NICE) at https://www.nice.org.uk/guidance/ng3

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 compared to oral hypoglycaemics. It is believed that human insulin and insulin analogues do not cross the placenta, however there may be endogenous carrier proteins allowing passage of insulin to the embryo during early gestation; animal insulin is believed to cross the human placenta. The foetus produces its own insulin once insulin-secreting cells in the foetal pancreas become differentiated at the end of the first trimester.

Human insulin is considered safe to use during pregnancy and extensive experience with human insulin during pregnancy does not indicate any embryotoxic potential. Human insulin is often the first line treatment for diabetes and the benchmark used when comparing the safety of other insulins during pregnancy.

Infants of diabetic mothers are at an increased risk of congenital abnormalities, the rate of which appears to be related to maternal glycaemic control during the first trimester. Careful control of maternal blood glucose is required throughout pregnancy. Good maternal glycaemic control during labour and birth is important in preventing adverse neonatal outcomes including neonatal hypoglycaemia and respiratory stress.

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

Lixisenatide is contraindicated in breastfeeding.

It is unknown whether lixisenatide is excreted in breast milk, therefore a risk to the nursing infant cannot be excluded.

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 characteristic symptom of acute pancreatitis and to seek medical advice if this symptom occurs.

Advise patient to seek medical advice if symptoms of dehydration occur.

Advise patient to eat a meal less than 60 minutes after each dose.

Advise patient if a dose of lixisenatide is missed, it should be injected within the hour prior to the next meal.

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.

Advise the patient that they need to inform the Driving and Vehicle Licensing Agency (DVLA) about the medication they are receiving. The Drivers' medical enquiries 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 enquiries, DVLA, Swansea, SA99 1TU

By phone on 0300 790 6806; 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

Acute pancreatitis
Anaphylactic reaction
Back pain
Cardiac arrhythmias
Cystitis
Dehydration
Diarrhoea
Dizziness
Dyspepsia
Headache
Hypersensitivity reactions
Hypoglycaemia
Influenza
Injection site reactions
Nausea
Palpitations
Somnolence
Tachycardia
Upper respiratory tract infection
Urticaria
Viral infection
Vomiting

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: March 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, 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.

Joint Formulary Committee. British National Formulary. 70th ed. London: BMJ Group and Pharmaceutical Press; 2015.

Summary of Product Characteristics: Lyxumia 10 micrograms solution for injection. Sanofi. Revised April 2016.
Summary of Product Characteristics: Lyxumia 20 micrograms solution for injection. Sanofi. Revised April 2016.
Summary of Product Characteristics: Lyxumia Treatment Initiation Pack. Sanofi. Revised April 2016.

MHRA Drug Safety Update June 2019
Available at: https://www.mhra.gov.uk
Last accessed: 28 August 2019