Drugs List

Therapeutic Indications

Uses

Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone

Indicated in adult patients with type 2 diabetes mellitus to improve glycaemic control:

In monotherapy, when metformin is inappropriate and diet and exercise alone does not provide adequate glycaemic control.

In combination with metformin, when metformin alone, with diet and exercise, does not provide adequate glycaemic control.

In combination with a sulfonylurea, when the sulfonylurea alone, with diet and exercise, does not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate.

In combination with a thiazolidinedione, when the thiazolidinedione alone with diet and exercise, does not provide adequate glycaemic control in patients for whom use of a thiazolidinedione is considered appropriate.

In combination with metformin and a sulfonylurea, when this regimen alone with diet and exercise, does not provide adequate glycaemic control.

In combination with insulin (with or without metformin), when this regimen alone with diet and exercise, does not provide adequate glycaemic control.

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Haemodialysis
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Elderly
Immunosuppressed transplant recipients
Glucose-galactose malabsorption syndrome
History of cardiac failure
History of pancreatitis
Immunodeficiency syndromes
Lactose intolerance
Moderate hepatic impairment
Moderate renal impairment
New York Heart Association class III failure
New York Heart Association class IV failure

Not suitable for treatment of diabetic ketoacidosis
Not suitable for treatment of Type 1 diabetes mellitus
Reduce dose in patients with renal impairment
Advise patient dizziness may affect ability to drive or operate machinery
Contains lactose
Exclude pregnancy prior to initiation of treatment
Monitor renal function prior to initiating treatment
Monitor skin changes
Advise patient to report new or worsening signs of cardiac failure
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Risk of pancreatitis
Advise patient to seek advice at first indications of pregnancy
Discontinue if pancreatitis occurs
Discontinue if severe hypersensitivity reactions occur
Pregnancy confirmed: Change patient to insulin treatment
Advise patient not to take St John's wort concurrently
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Cases of bullous pemphigoid requiring hospitalisation have been reported with saxagliptin use. If bullous pemphigoid is suspected or development of blisters or erosions occur, discontinue treatment and referral to a dermatologist should be considered.

Pregnancy and Lactation

Pregnancy

Saxagliptin is contraindicated in pregnancy.

There is no data from the use of saxagliptin during pregnancy. Animal studies have shown reproductive toxicity at high doses. The potential risk for 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/CG63/NiceGuidance/pdf/English .

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

Saxagliptin is contraindicated in breastfeeding.

It is unknown whether saxagliptin is excreted in human breast milk. Animal studies have shown excretion of saxagliptin and/or metabolite in milk, 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

Abdominal pain
Anaphylactic shock
Angioedema
Arthralgia
Bullous pemphigoid
Dermatitis
Diarrhoea
Dizziness
Dyslipidaemia
Dyspepsia
Erectile dysfunction
Fatigue
Flatulence
Gastritis
Gastro-enteritis
Headache
Hypersensitivity reactions
Hypertriglyceridaemia
Hypoglycaemia
Myalgia
Nasopharyngitis
Nausea
Pancreatitis
Peripheral oedema
Pruritus
Rash
Sinusitis
Upper respiratory tract infection
Urinary tract infections
Urticaria
Vomiting

Presentation

Tablets containing saxagliptin (as saxagliptin hydrochloride).

Drugs List

Therapeutic Indications

Uses

Type 2 diabetes (NIDDM) not controlled by diet,weight loss & exercise alone

Indicated in adult patients with type 2 diabetes mellitus to improve glycaemic control:

In monotherapy, when metformin is inappropriate and diet and exercise alone does not provide adequate glycaemic control.

In combination with metformin, when metformin alone, with diet and exercise, does not provide adequate glycaemic control.

In combination with a sulfonylurea, when the sulfonylurea alone, with diet and exercise, does not provide adequate glycaemic control in patients for whom use of metformin is considered inappropriate.

In combination with a thiazolidinedione, when the thiazolidinedione alone with diet and exercise, does not provide adequate glycaemic control in patients for whom use of a thiazolidinedione is considered appropriate.

In combination with metformin and a sulfonylurea, when this regimen alone with diet and exercise, does not provide adequate glycaemic control.

In combination with insulin (with or without metformin), when this regimen alone with diet and exercise, does not provide adequate glycaemic control.

Dosage

Adults

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Galactosaemia
Haemodialysis
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Elderly
Immunosuppressed transplant recipients
Glucose-galactose malabsorption syndrome
History of cardiac failure
History of pancreatitis
Immunodeficiency syndromes
Lactose intolerance
Moderate hepatic impairment
Moderate renal impairment
New York Heart Association class III failure
New York Heart Association class IV failure

Not suitable for treatment of diabetic ketoacidosis
Not suitable for treatment of Type 1 diabetes mellitus
Reduce dose in patients with renal impairment
Advise patient dizziness may affect ability to drive or operate machinery
Contains lactose
Exclude pregnancy prior to initiation of treatment
Monitor renal function prior to initiating treatment
Monitor skin changes
Advise patient to report new or worsening signs of cardiac failure
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Risk of pancreatitis
Advise patient to seek advice at first indications of pregnancy
Discontinue if pancreatitis occurs
Discontinue if severe hypersensitivity reactions occur
Pregnancy confirmed: Change patient to insulin treatment
Advise patient not to take St John's wort concurrently
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Cases of bullous pemphigoid requiring hospitalisation have been reported with saxagliptin use. If bullous pemphigoid is suspected or development of blisters or erosions occur, discontinue treatment and referral to a dermatologist should be considered.

Pregnancy and Lactation

Pregnancy

Saxagliptin is contraindicated in pregnancy.

There is no data from the use of saxagliptin during pregnancy. Animal studies have shown reproductive toxicity at high doses. The potential risk for 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/CG63/NiceGuidance/pdf/English .

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

Saxagliptin is contraindicated in breastfeeding.

It is unknown whether saxagliptin is excreted in human breast milk. Animal studies have shown excretion of saxagliptin and/or metabolite in milk, 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 female patients to consult their GP if pregnancy is suspected or planned.

Advise patients that they should not self-medicate with St John's Wort during treatment as the hypoglycaemic effect of saxagliptin may be reduced.

Advise patient to report new or worsening signs of cardiac failure.

Advise patients that their ability to drive or operate machinery may be impaired.

Advise patient to report to DVLA if there is a risk of hypoglycaemia, or if fitness to drive may be impaired due to diabetes complications. Guidance can be found by accessing Gov.uk website.

Side Effects

Abdominal pain
Anaphylactic shock
Angioedema
Arthralgia
Bullous pemphigoid
Dermatitis
Diarrhoea
Dizziness
Dyslipidaemia
Dyspepsia
Erectile dysfunction
Fatigue
Flatulence
Gastritis
Gastro-enteritis
Headache
Hypersensitivity reactions
Hypertriglyceridaemia
Hypoglycaemia
Myalgia
Nasopharyngitis
Nausea
Pancreatitis
Peripheral oedema
Pruritus
Rash
Sinusitis
Upper respiratory tract infection
Urinary tract infections
Urticaria
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: October 2014

Reference Sources

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 (online) London: BMJ Group and Pharmaceutical Press. Accessed on 06 October 2014.

Summary of Product Characteristics: Onglyza 2.5 mg and 5 mg film-coated tablets. AstraZeneca UK Ltd. Revised March 2020.