Drugs List

Therapeutic Indications

Uses

Oral combination treatment of type 2 diabetes

Dual therapy:
For the treatment of type 2 diabetes as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on their maximal tolerated dose of metformin alone or those already treated with combination of sitagliptin and metformin.

Triple therapy:
For the treatment of type 2 diabetes in combination with a sulfonylurea as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a sulfonylurea.

For the treatment of type 2 diabetes in combination with a thiazolidinedione as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and thiazolidinedione.

With Insulin:
For the treatment of type 2 diabetes in addition to insulin when diet, exercise and stable dosage of insulin and metformin alone do not provide adequate glycaemic control.

Contraindications

Acute alcohol intoxication
Children under 18 years
Severe infection
Shock
Within 48 hours of using iodinated contrast media
Alcoholism
Breastfeeding
Decompensated cardiac failure
Dehydration
Diabetic ketoacidosis
Diabetic pre-coma
Hepatic impairment
Hypoxia
Lactic acidosis
Pregnancy
Recent myocardial infarction
Renal impairment - glomerular filtration rate below 30ml/minute
Respiratory failure

Precautions and Warnings

Elderly
History of pancreatitis
Renal impairment - glomerular filtration rate 30 to 59 ml/minute

Reduce dose in patients with moderate renal impairment
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Caution when adding a drug likely to impair renal function (NSAID,diuretic)
Test vit B12 levels if deficiency is suspected or risk factors are present
Monitor renal function prior to initiating treatment
Monitor for development of lactic acidosis
Monitor renal function 3 to 6 monthly in elderly patients
Monitor renal function 3- 6 monthly if renal function is borderline normal
Monitor renal function annually in patients with normal renal function
Advise patient to report symptoms of low vitamin B12 levels
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Discontinue treatment if Stevens-Johnson Syndrome suspected
Withhold until at least 48hrs after general, spinal or epidural anaesthesia
Discontinue if hypersensitivity reactions occur
Discontinue if lactic acidosis is suspected
Discontinue if pancreatitis occurs
If dehydration occurs, discontinue treatment until patient has recovered
Pregnancy confirmed: Change patient to insulin treatment
Advise patient to avoid alcohol during treatment
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Lactic acidosis can occur due to metformin accumulation. To reduce the incidence of this occurring, patients should be assessed for risk factors associated with the development of lactic acidosis and monitored regularly. Symptoms of lactic acidosis include acidotic dyspnoea, abdominal pain, hypothermia and coma. Risk factors for lactic acidosis include poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic impairment and any condition associated with hypoxia.

A diagnosis of lactic acidosis should be considered in the presence of non-specific symptoms such as muscle cramps, digestive disorders, abdominal pain or severe asthenia. Lactic acidosis is also indicated by decreased blood pH, plasma lactate levels above 5mmol/L and an increased anion gap and lactate pyruvate ratio.

Patients with heart failure are at an increased risk of hypoxia and renal insufficiency. Treatment is contraindicated in patients with acute or unstable heart failure but may be used in patients with stable chronic heart failure provided cardiac and renal function is regularly monitored.

Pregnancy and Lactation

Pregnancy

Sitagliptin with metformin is contraindicated during pregnancy.

The manufacturer advises sitagliptin with metformin should not be used during pregnancy. Animal studies with sitagliptin have shown reproductive toxicity and transfer across the placenta. At the time of writing there is limited published experience concerning the use of sitagliptin during human pregnancy. Potential risks are unknown.

Metformin have shown to cross the placenta. Rare cases of neural tube defects and malformations of the heart and eye has been observed in animals though studies in pregnant women indicate a low risk to the foetus.

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.

Lactation

Sitagliptin with metformin is contraindicated during breastfeeding.

The manufacturer states that at the time of writing, there is limited published experience concerning the use of sitagliptin during breastfeeding. Animal studies have shown significant excretion of sitagliptin and metformin in breast milk and low levels of metformin has been detected in the serum of breastfed infants.

Side Effects

Abdominal pain
Abnormal liver function tests
Acute renal failure
Anaphylaxis
Angioedema
Arthralgia
Arthropathy
Bullous pemphigoid
Constipation
Cutaneous vasculitis
Decreased appetite
Decreased vitamin-B12 absorption
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Erythema
Exfoliative dermatitis
Extremity pain
Fungal infection
Headache
Hepatitis
Hypersensitivity reactions
Hypoglycaemia
Interstitial lung disease
Lactic acidosis
Metallic taste
Myalgia
Nasopharyngitis
Nausea
Osteoarthritis
Pancreatitis
Peripheral oedema
Pruritus
Rash
Renal impairment
Somnolence
Stevens-Johnson syndrome
Thrombocytopenia
Upper respiratory tract infection
Urticaria
Vomiting

Presentation

Oral formulation of sitagliptin with metformin hydrochloride.

Drugs List

Therapeutic Indications

Uses

Oral combination treatment of type 2 diabetes

Dual therapy:
For the treatment of type 2 diabetes as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on their maximal tolerated dose of metformin alone or those already treated with combination of sitagliptin and metformin.

Triple therapy:
For the treatment of type 2 diabetes in combination with a sulfonylurea as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a sulfonylurea.

For the treatment of type 2 diabetes in combination with a thiazolidinedione as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and thiazolidinedione.

With Insulin:
For the treatment of type 2 diabetes in addition to insulin when diet, exercise and stable dosage of insulin and metformin alone do not provide adequate glycaemic control.

Dosage

The dose of sitagliptin with metformin should be individualised on the basis of the patient's current regimen, effectiveness and tolerability while not exceeding the maximum recommended daily dose of 100mg sitagliptin.

Adults

Patients with Renal Impairment

Contraindications

Acute alcohol intoxication
Children under 18 years
Severe infection
Shock
Within 48 hours of using iodinated contrast media
Alcoholism
Breastfeeding
Decompensated cardiac failure
Dehydration
Diabetic ketoacidosis
Diabetic pre-coma
Hepatic impairment
Hypoxia
Lactic acidosis
Pregnancy
Recent myocardial infarction
Renal impairment - glomerular filtration rate below 30ml/minute
Respiratory failure

Precautions and Warnings

Elderly
History of pancreatitis
Renal impairment - glomerular filtration rate 30 to 59 ml/minute

Reduce dose in patients with moderate renal impairment
Advise patient dizziness may affect ability to drive or operate machinery
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Caution when adding a drug likely to impair renal function (NSAID,diuretic)
Test vit B12 levels if deficiency is suspected or risk factors are present
Monitor renal function prior to initiating treatment
Monitor for development of lactic acidosis
Monitor renal function 3 to 6 monthly in elderly patients
Monitor renal function 3- 6 monthly if renal function is borderline normal
Monitor renal function annually in patients with normal renal function
Advise patient to report symptoms of low vitamin B12 levels
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Discontinue treatment if Stevens-Johnson Syndrome suspected
Withhold until at least 48hrs after general, spinal or epidural anaesthesia
Discontinue if hypersensitivity reactions occur
Discontinue if lactic acidosis is suspected
Discontinue if pancreatitis occurs
If dehydration occurs, discontinue treatment until patient has recovered
Pregnancy confirmed: Change patient to insulin treatment
Advise patient to avoid alcohol during treatment
Patient to inform DVLA if fitness to drive impaired or hypoglycaemic risk

Lactic acidosis can occur due to metformin accumulation. To reduce the incidence of this occurring, patients should be assessed for risk factors associated with the development of lactic acidosis and monitored regularly. Symptoms of lactic acidosis include acidotic dyspnoea, abdominal pain, hypothermia and coma. Risk factors for lactic acidosis include poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol intake, hepatic impairment and any condition associated with hypoxia.

A diagnosis of lactic acidosis should be considered in the presence of non-specific symptoms such as muscle cramps, digestive disorders, abdominal pain or severe asthenia. Lactic acidosis is also indicated by decreased blood pH, plasma lactate levels above 5mmol/L and an increased anion gap and lactate pyruvate ratio.

Patients with heart failure are at an increased risk of hypoxia and renal insufficiency. Treatment is contraindicated in patients with acute or unstable heart failure but may be used in patients with stable chronic heart failure provided cardiac and renal function is regularly monitored.

Pregnancy and Lactation

Pregnancy

Sitagliptin with metformin is contraindicated during pregnancy.

The manufacturer advises sitagliptin with metformin should not be used during pregnancy. Animal studies with sitagliptin have shown reproductive toxicity and transfer across the placenta. At the time of writing there is limited published experience concerning the use of sitagliptin during human pregnancy. Potential risks are unknown.

Metformin have shown to cross the placenta. Rare cases of neural tube defects and malformations of the heart and eye has been observed in animals though studies in pregnant women indicate a low risk to the foetus.

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.

Lactation

Sitagliptin with metformin is contraindicated during breastfeeding.

The manufacturer states that at the time of writing, there is limited published experience concerning the use of sitagliptin during breastfeeding. Animal studies have shown significant excretion of sitagliptin and metformin in breast milk and low levels of metformin has been detected in the serum of breastfed infants.

Counselling

Advise patient to report severe, persistent abdominal pain.

Advise patient to avoid alcohol and alcohol containing medications.

Advise patients to report symptoms of lactic acidosis such as acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia.

Advise patient to report symptoms of low vitamin B12 levels.

Advise patients to temporarily discontinue treatment in case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake) and to contact a healthcare professional for advice.

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
Abnormal liver function tests
Acute renal failure
Anaphylaxis
Angioedema
Arthralgia
Arthropathy
Bullous pemphigoid
Constipation
Cutaneous vasculitis
Decreased appetite
Decreased vitamin-B12 absorption
Diarrhoea
Dizziness
Drowsiness
Dry mouth
Erythema
Exfoliative dermatitis
Extremity pain
Fungal infection
Headache
Hepatitis
Hypersensitivity reactions
Hypoglycaemia
Interstitial lung disease
Lactic acidosis
Metallic taste
Myalgia
Nasopharyngitis
Nausea
Osteoarthritis
Pancreatitis
Peripheral oedema
Pruritus
Rash
Renal impairment
Somnolence
Stevens-Johnson syndrome
Thrombocytopenia
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 Date: August 2020

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

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.

Summary of Product Characteristics: Janumet 50mg/1000mg film-coated tablets. Merck Sharp and Dohme Ltd. Revised May 2020.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 22 July 2020

MHRA Drug Safety Update June 2022
Available at: https://www.mhra.gov.uk
Last accessed: 21 July 2022