Drugs List

Therapeutic Indications

Uses

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

Monotherapy
For the treatment of type 2 diabetes controlled inadequately by diet and exercise alone and metformin is not advised due to intolerance or contraindication.

Dual therapy
For the treatment of type 2 diabetes in combination with metformin when diet, exercise and metformin monotherapy provide inadequate glycaemic control.

For the treatment of type 2 diabetes in combination with a sulfonylurea when diet, exercise and sulfonylurea monotherapy at maximum provide inadequate glycaemic control and metformin is inappropriate due to contraindication or intolerance.

For the treatment of type 2 diabetes in combination with a thiazolidinedione when diet, exercise and thiazolidinedione monotherapy provide inadequate glycaemic control.

Triple therapy
For the treatment of type 2 diabetes in combination with metformin and sulfonylurea when diet, exercise and dual therapy provide inadequate glycaemic control.

For the treatment of type 2 diabetes in combination with thiazolidinedione and metformin when diet, exercise and dual therapy provide inadequate glycaemic control.

With insulin
For the treatment of type 2 diabetes in combination with insulin (with or without metformin) when diet, exercise and stable insulin dosing provide inadequate glycaemic control.

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Pregnancy

Precautions and Warnings

History of pancreatitis
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic impairment

Reduce dose in patients with creatinine clearance below 50ml/min
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient somnolence may affect ability to drive or operate machinery
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Monitor renal function before treatment and regularly during treatment
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Discontinue if hypersensitivity reactions occur
Discontinue if pancreatitis occurs
Pregnancy confirmed: Change patient to insulin treatment
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Pregnancy and Lactation

Pregnancy

Sitagliptin is contraindicated in pregnancy.

At the time of writing there is limited published information regarding the use of sitagliptin during pregnancy. Animal research have shown reproductive toxicity when taken at high doses.

Briggs and Freeman (2015) states the possibility of sitagliptin crossing the placenta.

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

Sitagliptin contraindicated in breastfeeding.

At the time of writing there is limited published information regarding the use of sitagliptin during breastfeeding. Animal research have shown that sitagliptin is excreted in breast milk.

Briggs and Freeman (2015) also states that sitagliptin is excreted into breast milk. This is based in the molecular weight of about 505, low metabolism of about 21%, plasma protein binding of about 38% and the prolonged half-life elimination of about 12.4 hours. Monitoring for hypoglycaemia is recommended although it is not expected to occur. Hale (2014) agrees that the levels of excreted milk is low based on the molecular size of sitagliptin and its kinetics.

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 renal failure
Anaphylaxis
Angioedema
Anorexia
Arthralgia
Arthropathy
Back pain
Bullous pemphigoid
Constipation
Cutaneous vasculitis
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Exfoliative dermatitis
Extremity pain
Flatulence
Headache
Hypersensitivity reactions
Hypoglycaemia
Influenza
Myalgia
Nasopharyngitis
Nausea
Osteoarthritis
Pancreatitis
Peripheral oedema
Pruritus
Rash
Renal impairment
Somnolence
Stevens-Johnson syndrome
Upper abdominal pain
Upper respiratory tract infection
Urticaria
Vomiting

Presentation

Film-coated tablets containing sitagliptin

Drugs List

Therapeutic Indications

Uses

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

Monotherapy
For the treatment of type 2 diabetes controlled inadequately by diet and exercise alone and metformin is not advised due to intolerance or contraindication.

Dual therapy
For the treatment of type 2 diabetes in combination with metformin when diet, exercise and metformin monotherapy provide inadequate glycaemic control.

For the treatment of type 2 diabetes in combination with a sulfonylurea when diet, exercise and sulfonylurea monotherapy at maximum provide inadequate glycaemic control and metformin is inappropriate due to contraindication or intolerance.

For the treatment of type 2 diabetes in combination with a thiazolidinedione when diet, exercise and thiazolidinedione monotherapy provide inadequate glycaemic control.

Triple therapy
For the treatment of type 2 diabetes in combination with metformin and sulfonylurea when diet, exercise and dual therapy provide inadequate glycaemic control.

For the treatment of type 2 diabetes in combination with thiazolidinedione and metformin when diet, exercise and dual therapy provide inadequate glycaemic control.

With insulin
For the treatment of type 2 diabetes in combination with insulin (with or without metformin) when diet, exercise and stable insulin dosing provide inadequate glycaemic control.

Dosage

Adults

Elderly

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Pregnancy

Precautions and Warnings

History of pancreatitis
Renal impairment - creatinine clearance below 50ml/minute
Severe hepatic impairment

Reduce dose in patients with creatinine clearance below 50ml/min
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient somnolence may affect ability to drive or operate machinery
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Monitor renal function before treatment and regularly during treatment
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Discontinue if hypersensitivity reactions occur
Discontinue if pancreatitis occurs
Pregnancy confirmed: Change patient to insulin treatment
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Pregnancy and Lactation

Pregnancy

Sitagliptin is contraindicated in pregnancy.

At the time of writing there is limited published information regarding the use of sitagliptin during pregnancy. Animal research have shown reproductive toxicity when taken at high doses.

Briggs and Freeman (2015) states the possibility of sitagliptin crossing the placenta.

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

Sitagliptin contraindicated in breastfeeding.

At the time of writing there is limited published information regarding the use of sitagliptin during breastfeeding. Animal research have shown that sitagliptin is excreted in breast milk.

Briggs and Freeman (2015) also states that sitagliptin is excreted into breast milk. This is based in the molecular weight of about 505, low metabolism of about 21%, plasma protein binding of about 38% and the prolonged half-life elimination of about 12.4 hours. Monitoring for hypoglycaemia is recommended although it is not expected to occur. Hale (2014) agrees that the levels of excreted milk is low based on the molecular size of sitagliptin and its kinetics.

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 to take sitagliptin with or without food.

Advise patient to report any signs of pancreatitis: severe, persistent abdominal pain.

Advise patient to take precautions to avoid hypoglycaemia whilst driving.

Advise patient to avoid driving or skilled tasks if affected by side effects such as dizziness, drowsiness or somnolence.

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

Acute renal failure
Anaphylaxis
Angioedema
Anorexia
Arthralgia
Arthropathy
Back pain
Bullous pemphigoid
Constipation
Cutaneous vasculitis
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Exfoliative dermatitis
Extremity pain
Flatulence
Headache
Hypersensitivity reactions
Hypoglycaemia
Influenza
Myalgia
Nasopharyngitis
Nausea
Osteoarthritis
Pancreatitis
Peripheral oedema
Pruritus
Rash
Renal impairment
Somnolence
Stevens-Johnson syndrome
Upper abdominal pain
Upper respiratory tract infection
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 : January 2017

Reference Sources

Joint Formulary Committee. British National Formulary. 72nd ed. London: BMJ Group and Pharmaceutical Press; 2016.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.

Summary of Product Characteristics: Januvia film-coated tablets. Merck Sharp and Dohme Ltd. Revised June 2017.