Drugs List

Therapeutic Indications

Uses

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

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Debilitation
Patients over 75 years
Hepatic impairment
Malnutrition
Renal impairment - glomerular filtration rate below 20ml/minute

Advise patient to take precautions to avoid hypoglycaemia whilst driving
Monitor blood glucose periodically
Monitor patients for signs of adverse cardiovascular effects
Monitoring of glycosylated haemoglobin is recommended
Secondary failure: Reduction in hypoglycaemic effect over time can occur
Pregnancy confirmed: Change patient to insulin treatment
Temporary discontinuation & use of insulin may be needed at times of stress
Advise patient that transient visual disturbances may occur initially
Advise patient they have to inform the DVLA of antidiabetic medication
Advise patients of the warning signs of hypoglycaemia
Advise patients on adequate dietary control

As with other insulin secretagogues, repaglinde can cause hypoglycaemia.

The blood glucose lowering effect of oral hypoglycaemic agents reduces in many patients over time. This is known as secondary failure, to distinguish it from primary failure, where the drug is ineffective in an individual patient when first given. Before confirming a patient as secondary failure, adjustment of dose and adherence to diet and exercise should be assessed.

Pregnancy and Lactation

Pregnancy

Repaglinide is contraindicated in pregnancy.

At the time of writing there are no adequate, well controlled studies regarding the use of repaglinide in pregnant women and the potential risk in human pregnancies is unknown. It is not known whether repaglinide crosses the placenta, but transfer to the foetus should be expected due to a low molecular weight. Animal data suggests moderate risk and studies have shown skeletal deformities (shortening, thickening and bending of the humerus) during the postnatal period when repaglinide was administered at high doses during the latter part of pregnancy and during breastfeeding. Limited data from reproduction studies in animals indicate that repaglinide is not teratogenic.

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.

Lactation

Repaglinide is contraindicated in breastfeeding.

At the time of writing, there are no studies regarding the use of repaglinide in women who are breastfeeding. Skeletal deformities including shortening, thickening and bending of the humerus have been observed during the postnatal period in animals when the mother was exposed to high doses during the latter stages of pregnancy and during breastfeeding. Repaglinide has been detected in the milk of experimental animals. It is not known whether repaglinide is excreted in human breast milk but it should be expected as it has a low molecular weight. Due to the unknown potential for toxicity and hypoglycaemia in a breast-fed infant, repaglinide should be avoided by women who are breastfeeding.

Side Effects

Abdominal pain
Anaphylactic reaction
Cardiovascular disturbances
Constipation
Diarrhoea
Erythema
Hepatic impairment
Hypersensitivity reactions
Hypoglycaemia
Increases in hepatic enzymes
Itching
Nausea
Pruritus
Rash
Urticaria
Vasculitis
Visual disturbances
Vomiting

Presentation

Oral formulations of repaglinide

Drugs List

Therapeutic Indications

Uses

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

Dosage

Short-term administration of repaglinide may be sufficient during periods of transient loss of control in Type 2 diabetic patients usually controlled well on diet.

Adults

Contraindications

Children under 18 years
Breastfeeding
Diabetic ketoacidosis
Pregnancy
Severe hepatic impairment

Precautions and Warnings

Debilitation
Patients over 75 years
Hepatic impairment
Malnutrition
Renal impairment - glomerular filtration rate below 20ml/minute

Advise patient to take precautions to avoid hypoglycaemia whilst driving
Monitor blood glucose periodically
Monitor patients for signs of adverse cardiovascular effects
Monitoring of glycosylated haemoglobin is recommended
Secondary failure: Reduction in hypoglycaemic effect over time can occur
Pregnancy confirmed: Change patient to insulin treatment
Temporary discontinuation & use of insulin may be needed at times of stress
Advise patient that transient visual disturbances may occur initially
Advise patient they have to inform the DVLA of antidiabetic medication
Advise patients of the warning signs of hypoglycaemia
Advise patients on adequate dietary control

As with other insulin secretagogues, repaglinde can cause hypoglycaemia.

The blood glucose lowering effect of oral hypoglycaemic agents reduces in many patients over time. This is known as secondary failure, to distinguish it from primary failure, where the drug is ineffective in an individual patient when first given. Before confirming a patient as secondary failure, adjustment of dose and adherence to diet and exercise should be assessed.

Pregnancy and Lactation

Pregnancy

Repaglinide is contraindicated in pregnancy.

At the time of writing there are no adequate, well controlled studies regarding the use of repaglinide in pregnant women and the potential risk in human pregnancies is unknown. It is not known whether repaglinide crosses the placenta, but transfer to the foetus should be expected due to a low molecular weight. Animal data suggests moderate risk and studies have shown skeletal deformities (shortening, thickening and bending of the humerus) during the postnatal period when repaglinide was administered at high doses during the latter part of pregnancy and during breastfeeding. Limited data from reproduction studies in animals indicate that repaglinide is not teratogenic.

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.

Lactation

Repaglinide is contraindicated in breastfeeding.

At the time of writing, there are no studies regarding the use of repaglinide in women who are breastfeeding. Skeletal deformities including shortening, thickening and bending of the humerus have been observed during the postnatal period in animals when the mother was exposed to high doses during the latter stages of pregnancy and during breastfeeding. Repaglinide has been detected in the milk of experimental animals. It is not known whether repaglinide is excreted in human breast milk but it should be expected as it has a low molecular weight. Due to the unknown potential for toxicity and hypoglycaemia in a breast-fed infant, repaglinide should be avoided by women who are breastfeeding.

Counselling

Advise patient to take immediately before meals (not more than 30 minutes before a meal) and to add or skip a dose if a meal is added or skipped.

Advise patients on adequate dietary control.

Advise patients that transient visual disturbances may occur initially. Advise patients of the warning signs of hypoglycaemia.
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 reaction
Cardiovascular disturbances
Constipation
Diarrhoea
Erythema
Hepatic impairment
Hypersensitivity reactions
Hypoglycaemia
Increases in hepatic enzymes
Itching
Nausea
Pruritus
Rash
Urticaria
Vasculitis
Visual disturbances
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: September 2021

Reference Sources

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.

Joint Formulary Committee. British National Formulary. 70th ed. London: BMJ Group and Pharmaceutical Press; 2015.

The Renal Drug Handbook. Fifth Edition (2019) ed. Ashley, C. and Dunleavy, A. Radcliffe Publishing Ltd, London.

Summary of Product Characteristics: Prandin 0.5mg, 1mg, 2mg Tablets. Novo Nordisk Limited. Last revised November 2015.

Summary of Product Characteristics: Repaglinide 0.5 mg Tablets. Actavis UK LTD. Last revised April 2013.
Summary of Product Characteristics: Repaglinide 1 mg Tablets. Actavis UK LTD. Last revised April 2013.
Summary of Product Characteristics: Repaglinide 2 mg Tablets. Actavis UK LTD. Last revised April 2013.

Summary of Product Characteristics: Enyglid 0.5mg tablets. Consilient Health Ltd. Last revised January 2021.
Summary of Product Characteristics: Enyglid 1mg tablets. Consilient Health Ltd. Last revised January 2021.
Summary of Product Characteristics: Enyglid 2mg tablets. Consilient Health Ltd. Last revised January 2021.

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
Repaglinide. Last revised: 10 March 2015
Last accessed: 12 February 2016