Drugs List

Therapeutic Indications

Uses

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

Contraindications

Children under 12 years
Breastfeeding
Diabetic ketoacidosis
Porphyria
Pregnancy
Severe adrenal insufficiency
Severe hepatic impairment
Severe hypothyroidism

Precautions and Warnings

Children aged 12 to 18 years
Debilitation
Moderate hepatic impairment
Renal impairment

Advise patient to take precautions to avoid hypoglycaemia whilst driving
Cross sensitivity to sulfonamides and derivatives may occur
Oral anti-diabetics should be omitted on the morning of surgery
Perform blood counts if signs of persistent infection exist
Risk of hypoglycaemia may be increased by exercise or ingestion of alcohol
Pregnancy confirmed: Change patient to insulin treatment
Temporary discontinuation & use of insulin may be needed at times of stress
Not licensed for use in children under 18 years
Advise patient that alcohol ingestion may cause a disulfiram-like reaction
Advise patient that photosensitivity possible
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
Advise patients to have glucose available in the event of hypoglycaemia

Blood abnormalities may develop during treatment with tolbutamide. Platelet and white blood cell counts should be performed in patients who develop unexplained fever or sore throat during treatment and as indicated.

Pregnancy and Lactation

Pregnancy

Tolbutamide is contraindicated in pregnancy.

The use of tolbutamide in human gestation does not appear to be related to structural abnormalities, although teratogenicity has been seen in some animal studies. Tolbutamide does cross the placenta and there is a risk of prolonged hypoglycaemia in newborns. If therapy with oral antidiabetics does occur during pregnancy, it is not an indication for termination but a detailed ultrasound examination is recommended to confirm normal morphological development. If used during pregnancy, tolbutamide should be discontinued and replaced with insulin therapy at least four days before delivery to reduce the possibility of prolonged hypoglycaemia in the neonate.

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.

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

Tolbutamide is contraindicated in breastfeeding.

Tolbutamide is excreted in low levels in breast milk. The effect on the infant is unknown though hypoglycaemia is a potential toxicity. Insulin is the treatment of choice in diabetic patients wishing to breastfeed. UK licensed product information recommends that tolbutamide should not be used in breastfeeding mothers. Monitoring of blood glucose in the breastfed infant is advised during maternal therapy with oral hypoglycaemic agents. Observe infant closely for signs of jaundice and hypoglycaemia.

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

Agranulocytosis
Alcohol intolerance
Allergic skin reactions
Anorexia
Aplastic anaemia
Cholestatic jaundice
Constipation
Diarrhoea
Erythema multiforme
Exfoliative dermatitis
Fever
Haemolytic anaemia
Headache
Hepatic failure
Hepatitis
Hypersensitivity reactions
Hypoglycaemia
Increased appetite
Jaundice
Leucopenia
Liver function disturbances
Nausea
Pancytopenia
Paraesthesia
Photosensitivity
Thrombocytopenia
Tinnitus
Vomiting
Weight gain

Presentation

Tablets containing tolbutamide

Drugs List

Therapeutic Indications

Uses

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

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Additional Dosage Information

Contraindications

Children under 12 years
Breastfeeding
Diabetic ketoacidosis
Porphyria
Pregnancy
Severe adrenal insufficiency
Severe hepatic impairment
Severe hypothyroidism

Precautions and Warnings

Children aged 12 to 18 years
Debilitation
Moderate hepatic impairment
Renal impairment

Advise patient to take precautions to avoid hypoglycaemia whilst driving
Cross sensitivity to sulfonamides and derivatives may occur
Oral anti-diabetics should be omitted on the morning of surgery
Perform blood counts if signs of persistent infection exist
Risk of hypoglycaemia may be increased by exercise or ingestion of alcohol
Pregnancy confirmed: Change patient to insulin treatment
Temporary discontinuation & use of insulin may be needed at times of stress
Not licensed for use in children under 18 years
Advise patient that alcohol ingestion may cause a disulfiram-like reaction
Advise patient that photosensitivity possible
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
Advise patients to have glucose available in the event of hypoglycaemia

Blood abnormalities may develop during treatment with tolbutamide. Platelet and white blood cell counts should be performed in patients who develop unexplained fever or sore throat during treatment and as indicated.

Pregnancy and Lactation

Pregnancy

Tolbutamide is contraindicated in pregnancy.

The use of tolbutamide in human gestation does not appear to be related to structural abnormalities, although teratogenicity has been seen in some animal studies. Tolbutamide does cross the placenta and there is a risk of prolonged hypoglycaemia in newborns. If therapy with oral antidiabetics does occur during pregnancy, it is not an indication for termination but a detailed ultrasound examination is recommended to confirm normal morphological development. If used during pregnancy, tolbutamide should be discontinued and replaced with insulin therapy at least four days before delivery to reduce the possibility of prolonged hypoglycaemia in the neonate.

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.

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

Tolbutamide is contraindicated in breastfeeding.

Tolbutamide is excreted in low levels in breast milk. The effect on the infant is unknown though hypoglycaemia is a potential toxicity. Insulin is the treatment of choice in diabetic patients wishing to breastfeed. UK licensed product information recommends that tolbutamide should not be used in breastfeeding mothers. Monitoring of blood glucose in the breastfed infant is advised during maternal therapy with oral hypoglycaemic agents. Observe infant closely for signs of jaundice and hypoglycaemia.

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 that ill health, trauma, surgery, physical exercise and emotional upsets, for example, may affect blood-glucose levels. Dosage adjustment may be necessary and they should consult their physician.

Ensure patient is aware of the need for a healthy diet for optimum blood sugar control, and provide dietary advice if required.

Advise patients to always have sugar available in the event of hypoglycaemia.

Advise patient to monitor blood-glucose level regularly.

Patients should be advised to avoid alcohol due to the risk of a possible disulfiram-type reaction.

Advise patients that their ability to drive or operate machinery may be impaired.

Inform the patient that he/she needs to inform the Driving and Vehicle Licensing Agency (DVLA) about the medication they are receiving. The Drivers Medical Group at the DVLA will be able to advise the patient on the legal issues surrounding the treatment of diabetes mellitus and driving.

The DVLA can be contacted by post at the following address:

Drivers Medical Group, DVLA, Swansea, SA99 1TU

By phone on 0870 600 0301; or by fax on 0845 850 0095

Detailed guidance on eligibility to drive, and precautions required, is available from the DVLA.

https://www.gov.uk/government/publications/at-a-glance

Further information concerning diabetes and driving may be obtained from the DVLA website at:

https://www.gov.uk/government/organisations/driver-and-vehicle-licensing-agency

Side Effects

Agranulocytosis
Alcohol intolerance
Allergic skin reactions
Anorexia
Aplastic anaemia
Cholestatic jaundice
Constipation
Diarrhoea
Erythema multiforme
Exfoliative dermatitis
Fever
Haemolytic anaemia
Headache
Hepatic failure
Hepatitis
Hypersensitivity reactions
Hypoglycaemia
Increased appetite
Jaundice
Leucopenia
Liver function disturbances
Nausea
Pancytopenia
Paraesthesia
Photosensitivity
Thrombocytopenia
Tinnitus
Vomiting
Weight gain

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: July 2014

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.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Tolbutamide 500 mg tablets. Actavis UK Ltd. Revised November 2009.
Summary of Product Characteristics: Tolbutamide 500 mg tablets. Kent Pharmaceuticals Ltd. Revised May 2012.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 04 September 2017

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Last accessed: July 21, 2014.

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
Tolbutamide Last revised: September 7, 2013.
Last accessed: July 21, 2014.