Drugs List

Therapeutic Indications

Uses

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

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 alogliptin and metformin.

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

With Insulin:
For the treatment of type 2 diabetes in combination with 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
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

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

Reduce dose in patients with moderate renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Test vit B12 levels if deficiency is suspected or risk factors are present
Monitor renal function before treatment and regularly during treatment
If hepatic impairment symptoms occur monitor LFT & consider discontinuation
Monitor for development of lactic acidosis
Monitor hepatic function
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 patient/carer to report immediately symptoms of lactic acidosis
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Discontinue permanently if acute pancreatitis occurs
Withhold until at least 48hrs after general, spinal or epidural anaesthesia
Discontinue if lactic acidosis is suspected
Discontinue if pancreatitis is suspected
If dehydration occurs, discontinue treatment until patient has recovered
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.

Special caution should be exercised in situations where renal function may become impaired, e.g. when starting therapy with a non-steroidal anti-inflammatory drug (NSAID).

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

Alogliptin with metformin is contraindicated in pregnancy.
Manufacturer advises to avoid the use of alogliptin with metformin during pregnancy.
At the time of writing there are no data from the use of alogliptin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Metformin is generally considered to present a low risk when used during pregnancy (Briggs, 2015) and animal data generally do not indicate harmful effects on pregnancy, embryonal or foetal development, parturition or postnatal development. Rare cases of neural tube defects and malformations of the heart and eye have been seen in animals though studies in pregnant women indicate a low risk to the foetus. The manufacturer states that metformin is not recommended for the treatment of diabetes in pregnancy as it does not provide adequate maternal glycaemic control and insulin therapy is preferred.
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

Alogliptin with metformin is contraindicated in breastfeeding.
Manufacturer advises that a decision must be made to either stop breastfeeding or discontinue alogliptin with metformin.
It is unknown whether alogliptin is excreted in human breast milk. Animal studies have shown excretion of alogliptin and/or metabolite in milk, a risk to the nursing infant cannot be excluded.
Metformin is known to be excreted in breast milk, and has occasionally been detected in low-levels in the serum of breastfed infants, although studies have found no adverse effects in infants breastfed by women taking metformin. LactMed recommends that caution be used in mothers with newborn and premature infants, and infants with renal impairment when metformin is taken.

Side Effects

Abdominal pain
Abnormal liver function tests
Acute pancreatitis
Anaphylactic reaction
Angioedema
Bullous pemphigoid
Decreased appetite
Decreased vitamin-B12 absorption
Diarrhoea
Erythema
Erythema multiforme
Exfoliative dermatitis
Gastritis
Gastro-enteritis
Gastroesophageal reflux disease
Headache
Hepatic failure
Hepatic impairment
Hepatitis
Hypersensitivity reactions
Lactic acidosis
Metallic taste
Nasopharyngitis
Nausea
Pruritus
Rash
Stevens-Johnson syndrome
Upper respiratory tract infection
Urticaria
Vomiting

Presentation

Tablets containing alogliptin and metformin.

Drugs List

Therapeutic Indications

Uses

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

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 alogliptin and metformin.

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

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

Dosage

Adults

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Acute alcohol intoxication
Children under 18 years
Severe infection
Shock
Within 48 hours of using iodinated contrast media
Alcoholism
Breastfeeding
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

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

Reduce dose in patients with moderate renal impairment
Advise ability to drive/operate machinery may be affected by side effects
Test vit B12 levels if deficiency is suspected or risk factors are present
Monitor renal function before treatment and regularly during treatment
If hepatic impairment symptoms occur monitor LFT & consider discontinuation
Monitor for development of lactic acidosis
Monitor hepatic function
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 patient/carer to report immediately symptoms of lactic acidosis
Advise patients to report symptoms of acute pancreatitis immediately
Discontinue if pemphigus-type reactions develop
Discontinue permanently if acute pancreatitis occurs
Withhold until at least 48hrs after general, spinal or epidural anaesthesia
Discontinue if lactic acidosis is suspected
Discontinue if pancreatitis is suspected
If dehydration occurs, discontinue treatment until patient has recovered
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.

Special caution should be exercised in situations where renal function may become impaired, e.g. when starting therapy with a non-steroidal anti-inflammatory drug (NSAID).

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

Alogliptin with metformin is contraindicated in pregnancy.
Manufacturer advises to avoid the use of alogliptin with metformin during pregnancy.
At the time of writing there are no data from the use of alogliptin in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Metformin is generally considered to present a low risk when used during pregnancy (Briggs, 2015) and animal data generally do not indicate harmful effects on pregnancy, embryonal or foetal development, parturition or postnatal development. Rare cases of neural tube defects and malformations of the heart and eye have been seen in animals though studies in pregnant women indicate a low risk to the foetus. The manufacturer states that metformin is not recommended for the treatment of diabetes in pregnancy as it does not provide adequate maternal glycaemic control and insulin therapy is preferred.
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

Alogliptin with metformin is contraindicated in breastfeeding.
Manufacturer advises that a decision must be made to either stop breastfeeding or discontinue alogliptin with metformin.
It is unknown whether alogliptin is excreted in human breast milk. Animal studies have shown excretion of alogliptin and/or metabolite in milk, a risk to the nursing infant cannot be excluded.
Metformin is known to be excreted in breast milk, and has occasionally been detected in low-levels in the serum of breastfed infants, although studies have found no adverse effects in infants breastfed by women taking metformin. LactMed recommends that caution be used in mothers with newborn and premature infants, and infants with renal impairment when metformin is taken.

Counselling

Advise patient to report symptoms of acute pancreatitis (severe, persistent abdominal pain).

Advise patient to avoid alcohol during treatment.

Advise patient that the ability to drive or operate machinery may be impaired.

Advise patient 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 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 pancreatitis
Anaphylactic reaction
Angioedema
Bullous pemphigoid
Decreased appetite
Decreased vitamin-B12 absorption
Diarrhoea
Erythema
Erythema multiforme
Exfoliative dermatitis
Gastritis
Gastro-enteritis
Gastroesophageal reflux disease
Headache
Hepatic failure
Hepatic impairment
Hepatitis
Hypersensitivity reactions
Lactic acidosis
Metallic taste
Nasopharyngitis
Nausea
Pruritus
Rash
Stevens-Johnson syndrome
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: March 2019

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. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Vipdomet 12.5mg/1000mg film coated tablets. Takeda UK Ltd. Revised March 2021.

EMA Safety Update December 2016
Available at: https://www.ema.europa.eu/ema/
Last accessed: 18 January 2017

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Metformin. Last revised: 31 October 2018
Last accessed: 18 March 2019

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