Drugs List

Therapeutic Indications

Uses

Monotherapy

For the treatment of type 2 diabetes in patients inadequately controlled by diet and exercise alone and when metformin is inappropriate due to contraindications or tolerance.

Combination therapy

For the treatment of type 2 diabetes in combination with metformin, when maximum tolerated dose of metformin monotherapy does not provide adequate glycaemic control.

For the treatment of type 2 diabetes in combination with a sulfonylurea, when maximum tolerated dose of sulfonylurea monotherapy does not provide adequate glycaemic control and where metformin is either contraindicated or poorly tolerated.

For the treatment of type 2 diabetes in combination with a thiazolidinedione, when treatment with a thiazolidinedione is appropriate but does not provide adequate glycaemic control.

For the treatment of type 2 diabetes in combination with a sulfonylurea and metformin, when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control.

For the treatment of type 2 diabetes in combination with insulin (with or without metformin) when diet and exercise plus a stable dose of insulin do not provide adequate glycaemic control.

Administration

For oral administration.

Tablets may be taken with or without a meal.

Contraindications

Hepatic impairment
AST or ALT greater than three times the upper limit of normal
Children under 18 years
Severe congestive cardiac failure (NYHA class 3 or 4)
Galactosaemia
Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

Precautions and Warnings

Vildagliptin should not be used as a substitute for insulin in patients with type 1 diabetes or in the treatment of diabetic ketoacidosis.

Creatinine clearance less than 50ml/min or end stage renal disease on haemodialysis - see Dosage - renal impairment

Liver function tests should be carried out prior to initiation of therapy, in order to establish the patient's baseline value. Liver function should be monitored every three months during the first year of treatment and then periodically thereafter throughout treatment with vildagliptin. Any patients developing raised transaminase levels should undergo a second test to confirm the finding and then receive periodic liver function testing until the disturbance is corrected. If an increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels to greater than 3 times the upper limit of normal occurs and persists, treatment with vildagliptin should be discontinued.

Vildagliptin therapy should be discontinued in any patient who develops jaundice or other signs suggestive of liver dysfunction. Advise patients to seek prompt medical attention if symptoms such as nausea, vomiting, abdominal pain, fatigue and dark urine develop. Treatment should not be reinstated following withdrawal, even once liver function has returned to normal.

Caution is advised when treating patients with congestive cardiac failure (NYHA class 1 or 2) due to limited clinical experience.

Reports of acute pancreatitis have been reported post-marketing. Resolution of the pancreatitis has been observed after discontinuation of vildagliptin. Advise patients to report severe, persistent abdominal pain and discontinue vildagliptin if pancreatitis is suspected.

Skin disorders including ulceration and blistering were reported during animal studies with vildagliptin. Experience with diabetic patients with skin complications is limited. Manufacturers recommend that patients should be monitored for skin disorders as part of routine patient care.

When used in combination with a sulfonylurea, a lower dose of the sulfonylurea may be considered to reduce the risk of hypoglycaemia.

Tablets contain lactose. Patients with glucose-galactose malabsorption syndrome or lactose intolerance should be treated with caution.

Pregnancy and Lactation

Pregnancy

Contraindicated during pregnancy.

Animal studies have shown reproductive toxicity when vildagliptin is administered at high doses. The potential risk to humans is unknown.

When dieting alone is not successful, 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 than oral hypoglycaemics, and does not cross the placenta. Hyperglycaemia in the mother, particularly in the early stages of gestation, is associated with a number of foetal and maternal adverse effects, including foetal structural abnormalities. Carefully prescribed insulin therapy will provide better control of the mother's blood glucose thereby preventing the foetal and neonatal complications that occur with the disease (Briggs, 2011).

Insulin is the treatment of choice for patients with type 2 diabetes during pregnancy as it provides a more stable control of blood sugar than oral antidiabetics.

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 14-17 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

Contraindicated during breastfeeding.

Animal studies have shown that vildagliptin is excreted in breast milk. It is not known whether this is also true for humans.

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

Increase of liver transaminases Angioedema Tremor Headache Dizziness Fatigue Nausea Hypoglycaemia Nasopharyngitis Constipation Asthenia Weight gain Peripheral oedema Upper respiratory tract infection Arthralgia Hepatitis Hepatic impairment Urticaria Pancreatitis Decreased blood glucose Chills Gastroesophageal reflux disease Diarrhoea Flatulence Hyperhidrosis Skin lesions

Presentation

Tablets containing 50mg vildagliptin.

Drugs List

Therapeutic Indications

Uses

Monotherapy

For the treatment of type 2 diabetes in patients inadequately controlled by diet and exercise alone and when metformin is inappropriate due to contraindications or tolerance.

Combination therapy

For the treatment of type 2 diabetes in combination with metformin, when maximum tolerated dose of metformin monotherapy does not provide adequate glycaemic control.

For the treatment of type 2 diabetes in combination with a sulfonylurea, when maximum tolerated dose of sulfonylurea monotherapy does not provide adequate glycaemic control and where metformin is either contraindicated or poorly tolerated.

For the treatment of type 2 diabetes in combination with a thiazolidinedione, when treatment with a thiazolidinedione is appropriate but does not provide adequate glycaemic control.

For the treatment of type 2 diabetes in combination with a sulfonylurea and metformin, when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control.

For the treatment of type 2 diabetes in combination with insulin (with or without metformin) when diet and exercise plus a stable dose of insulin do not provide adequate glycaemic control.

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration.

Tablets may be taken with or without a meal.

Contraindications

Hepatic impairment
AST or ALT greater than three times the upper limit of normal
Children under 18 years
Severe congestive cardiac failure (NYHA class 3 or 4)
Galactosaemia
Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section

Precautions and Warnings

Vildagliptin should not be used as a substitute for insulin in patients with type 1 diabetes or in the treatment of diabetic ketoacidosis.

Creatinine clearance less than 50ml/min or end stage renal disease on haemodialysis - see Dosage - renal impairment

Liver function tests should be carried out prior to initiation of therapy, in order to establish the patient's baseline value. Liver function should be monitored every three months during the first year of treatment and then periodically thereafter throughout treatment with vildagliptin. Any patients developing raised transaminase levels should undergo a second test to confirm the finding and then receive periodic liver function testing until the disturbance is corrected. If an increase in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels to greater than 3 times the upper limit of normal occurs and persists, treatment with vildagliptin should be discontinued.

Vildagliptin therapy should be discontinued in any patient who develops jaundice or other signs suggestive of liver dysfunction. Advise patients to seek prompt medical attention if symptoms such as nausea, vomiting, abdominal pain, fatigue and dark urine develop. Treatment should not be reinstated following withdrawal, even once liver function has returned to normal.

Caution is advised when treating patients with congestive cardiac failure (NYHA class 1 or 2) due to limited clinical experience.

Reports of acute pancreatitis have been reported post-marketing. Resolution of the pancreatitis has been observed after discontinuation of vildagliptin. Advise patients to report severe, persistent abdominal pain and discontinue vildagliptin if pancreatitis is suspected.

Skin disorders including ulceration and blistering were reported during animal studies with vildagliptin. Experience with diabetic patients with skin complications is limited. Manufacturers recommend that patients should be monitored for skin disorders as part of routine patient care.

When used in combination with a sulfonylurea, a lower dose of the sulfonylurea may be considered to reduce the risk of hypoglycaemia.

Tablets contain lactose. Patients with glucose-galactose malabsorption syndrome or lactose intolerance should be treated with caution.

Pregnancy and Lactation

Pregnancy

Contraindicated during pregnancy.

Animal studies have shown reproductive toxicity when vildagliptin is administered at high doses. The potential risk to humans is unknown.

When dieting alone is not successful, 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 than oral hypoglycaemics, and does not cross the placenta. Hyperglycaemia in the mother, particularly in the early stages of gestation, is associated with a number of foetal and maternal adverse effects, including foetal structural abnormalities. Carefully prescribed insulin therapy will provide better control of the mother's blood glucose thereby preventing the foetal and neonatal complications that occur with the disease (Briggs, 2011).

Insulin is the treatment of choice for patients with type 2 diabetes during pregnancy as it provides a more stable control of blood sugar than oral antidiabetics.

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 14-17 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

Contraindicated during breastfeeding.

Animal studies have shown that vildagliptin is excreted in breast milk. It is not known whether this is also true for humans.

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

Effects on Ability to Drive and Operate Machinery

No studies have been performed.

Patients experiencing dizziness during treatment should be advised to avoid driving or operating machinery.

Counselling

Advise patients to avoid driving or operating machinery if affected by dizziness during treatment.

Advise patient to seek medical attention if they experience signs of hepatic dysfunction (nausea, vomiting, abdominal pain, fatigue or dark urine) or of pancreatitis (severe, persistent abdominal pain)

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

Increase of liver transaminases Angioedema Tremor Headache Dizziness Fatigue Nausea Hypoglycaemia Nasopharyngitis Constipation Asthenia Weight gain Peripheral oedema Upper respiratory tract infection Arthralgia Hepatitis Hepatic impairment Urticaria Pancreatitis Decreased blood glucose Chills Gastroesophageal reflux disease Diarrhoea Flatulence Hyperhidrosis Skin lesions

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 ).

Shelf Life and Storage

Store in original packaging
Protect from moisture

Further Information

Last Full Review Date: February 2012

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

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.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of product characteristics: Galvus tablets 50mg. Novartis Pharmaceuticals. October 2013.