Drugs List

Therapeutic Indications

Uses

Insulin-dependent diabetes mellitus

Administration

Human soluble insulin is usually administered subcutaneously, in the upper arm, thigh or abdominal wall. If convenient the gluteal region or the deltoid region may be used. Injection sites must be rotated within a given injection area from one injection to the next.

Injection into the abdominal wall ensures a faster absorption than from other injection sites. Injection into a lifted skin fold minimises the risk of intramuscular injection. The injection site should not be massaged after administration.

Some products are suitable for intramuscular or intravenous administration but only under the close guidance of a physician.

When combination with intermediate or long acting insulin is necessary, follow the manufacturer's instructions.

Subcutaneous injection should be followed by a meal or snack containing carbohydrates within 15 to 30 minutes.

Some brands maybe given by continuous subcutaneous infusion using a portable infusion device which delivers a continuous basal insulin infusion and also allows patient triggered bolus doses at meal times.

Contraindications

Hypoglycaemia

Precautions and Warnings

Elderly
Breastfeeding
Hepatic impairment
Pregnancy
Renal impairment

Consider increased dose during intercurrent illness/trauma/surgery
Insulin requirements may be diminished by renal or hepatic impairment
Advise impaired alertness may affect ability to drive or operate machinery
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Some formulations contain metacresol
Change in injection site area may necessitate dose adjustment
Consider cutaneous amyloidosis if injection site subcutaneous lumps occur
Do not use if any signs of precipitate or particulate matter apparent
Do not use if contents have been frozen
Only the recommended brands should be used in infusion pumps
Rotate injection sites within a given area to avoid lipodystrophy
Solution must not be drawn from cartridge or pre-filled pen into a syringe
Use designated delivery device only
Hypoglycaemic symptoms may be masked or altered in long duration diabetes
Hypoglycaemic symptoms may be masked/altered in diabetic nerve disease
Hypoglycaemic symptoms may be masked/altered in intensified insulin therapy
Monitor blood or urinary glucose
Monitor urine of diabetic patients for ketones
Advise patient to report cutaneous amyloidosis symptoms
Antibodies to ingredient may develop
Exercise immediately after a meal may increase risk of hypoglycaemia
Hypoglycaemic symptoms may be masked/altered with beta blockers
Increased activity: insulin requirements may occasionally be increased
Risk of hypoglycaemia may be increased by exercise or ingestion of alcohol
Insulin requirements may increase during illness,puberty or emotional upset
Removal of stress factors may necessitate dose adjustment
Transfer from other brands of insulin may involve dosage adjustment
Pregnancy & breastfeeding: Insulin requirements may vary
Advise patient they have to inform the DVLA of antidiabetic medication
Advise patient to contact doctor if travel between time zones is planned
Advise patient to read the leaflet in the pack
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
Transfer from animal insulin may alter usual hypoglycaemia warning symptoms

Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for cardiac failure. If this combination is prescribed, patients should be observed for symptoms of heart failure, including weight gain and oedema. Pioglitazone should be discontinued if there is any deterioration in cardiac symptoms.

Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (rapid acting insulin, intermediate acting insulin, long acting insulin etc) species (human insulin analogue, animal), and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change of dose. If such a change in dose is required, it may occur with the first dose or during the first weeks or months.

Some preparations are designed for the use in Hoechst Infusor and H-Tron insulin pumps. Only tetrafluoroethylene or polyethylene catheters must be used. Peristaltic pumps with silicone tubing must be avoided.

Pregnancy and Lactation

Pregnancy

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 .

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.

Human insulin is considered safe to use during pregnancy and extensive experience with human insulin during pregnancy does not indicate any embryotoxic potential. Human insulin is often the first line treatment for diabetes and the benchmark used when comparing the safety of other insulins during pregnancy.

Infants of diabetic mothers are at an increased risk of congenital abnormalities, the rate of which appears to be related to maternal glycaemic control during the first trimester. Careful control of maternal blood glucose is required throughout pregnancy. Good maternal glycaemic control during labour and birth is important in preventing adverse neonatal outcomes including neonatal hypoglycaemia and respiratory stress.

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

Insulin is a natural component of breast milk and insulin treatment of breastfeeding mothers should represent no risk to the infant. Insulin in breast milk is digested by the infant's gut and is thought to contribute to intestinal maturation and decrease the risk of contracting type 1 diabetes in breastfed infants.

Proper insulin levels are required for lactation. Good glycaemic control decreases the delay in establishment of lactation that is observed in diabetic mothers as well as enhancing maternal serum and milk prolactin concentrations.

No adverse effects have been reported relating the use of insulin to breastfeeding, therefore it is considered safe to for diabetic mothers receiving insulin to continue breastfeeding.

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

Allergic reaction
Angioneurotic oedema
Anxiety
Behavioural disturbances
Blurred vision
Breathing difficulties
Cognitive impairment
Coma
Confusion
Convulsions
Cool pale skin
Cutaneous amyloidosis
Death
Disturbances of appetite
Drowsiness
Generalised oedema
Headache
Hypersensitivity reactions
Hypoglycaemia
Hypotension
Insulin antibodies
Insulin resistance
Itching
Lipodystrophy (injection site)
Local reaction at injection site
Nausea
Pallor
Palpitations
Paraesthesia
Peripheral neuropathy
Rash
Refraction anomalies
Slurred speech
Stinging, redness and swelling at injection site
Sweating
Tiredness
Tremor
Urticaria
Vomiting
Worsening of diabetic retinopathy (temporary)

Presentation

Solution for injection containing soluble (neutral) insulin

Drugs List

Therapeutic Indications

Uses

Insulin-dependent diabetes mellitus

Dosage

Soluble human insulin is a fast acting insulin and may be used in combination with long-acting insulins.

Adults

Elderly

Children

Administration

Human soluble insulin is usually administered subcutaneously, in the upper arm, thigh or abdominal wall. If convenient the gluteal region or the deltoid region may be used. Injection sites must be rotated within a given injection area from one injection to the next.

Injection into the abdominal wall ensures a faster absorption than from other injection sites. Injection into a lifted skin fold minimises the risk of intramuscular injection. The injection site should not be massaged after administration.

Some products are suitable for intramuscular or intravenous administration but only under the close guidance of a physician.

When combination with intermediate or long acting insulin is necessary, follow the manufacturer's instructions.

Subcutaneous injection should be followed by a meal or snack containing carbohydrates within 15 to 30 minutes.

Some brands maybe given by continuous subcutaneous infusion using a portable infusion device which delivers a continuous basal insulin infusion and also allows patient triggered bolus doses at meal times.

Contraindications

Hypoglycaemia

Precautions and Warnings

Elderly
Breastfeeding
Hepatic impairment
Pregnancy
Renal impairment

Consider increased dose during intercurrent illness/trauma/surgery
Insulin requirements may be diminished by renal or hepatic impairment
Advise impaired alertness may affect ability to drive or operate machinery
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Some formulations contain metacresol
Change in injection site area may necessitate dose adjustment
Consider cutaneous amyloidosis if injection site subcutaneous lumps occur
Do not use if any signs of precipitate or particulate matter apparent
Do not use if contents have been frozen
Only the recommended brands should be used in infusion pumps
Rotate injection sites within a given area to avoid lipodystrophy
Solution must not be drawn from cartridge or pre-filled pen into a syringe
Use designated delivery device only
Hypoglycaemic symptoms may be masked or altered in long duration diabetes
Hypoglycaemic symptoms may be masked/altered in diabetic nerve disease
Hypoglycaemic symptoms may be masked/altered in intensified insulin therapy
Monitor blood or urinary glucose
Monitor urine of diabetic patients for ketones
Advise patient to report cutaneous amyloidosis symptoms
Antibodies to ingredient may develop
Exercise immediately after a meal may increase risk of hypoglycaemia
Hypoglycaemic symptoms may be masked/altered with beta blockers
Increased activity: insulin requirements may occasionally be increased
Risk of hypoglycaemia may be increased by exercise or ingestion of alcohol
Insulin requirements may increase during illness,puberty or emotional upset
Removal of stress factors may necessitate dose adjustment
Transfer from other brands of insulin may involve dosage adjustment
Pregnancy & breastfeeding: Insulin requirements may vary
Advise patient they have to inform the DVLA of antidiabetic medication
Advise patient to contact doctor if travel between time zones is planned
Advise patient to read the leaflet in the pack
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
Transfer from animal insulin may alter usual hypoglycaemia warning symptoms

Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for cardiac failure. If this combination is prescribed, patients should be observed for symptoms of heart failure, including weight gain and oedema. Pioglitazone should be discontinued if there is any deterioration in cardiac symptoms.

Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (rapid acting insulin, intermediate acting insulin, long acting insulin etc) species (human insulin analogue, animal), and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change of dose. If such a change in dose is required, it may occur with the first dose or during the first weeks or months.

Some preparations are designed for the use in Hoechst Infusor and H-Tron insulin pumps. Only tetrafluoroethylene or polyethylene catheters must be used. Peristaltic pumps with silicone tubing must be avoided.

Pregnancy and Lactation

Pregnancy

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 .

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.

Human insulin is considered safe to use during pregnancy and extensive experience with human insulin during pregnancy does not indicate any embryotoxic potential. Human insulin is often the first line treatment for diabetes and the benchmark used when comparing the safety of other insulins during pregnancy.

Infants of diabetic mothers are at an increased risk of congenital abnormalities, the rate of which appears to be related to maternal glycaemic control during the first trimester. Careful control of maternal blood glucose is required throughout pregnancy. Good maternal glycaemic control during labour and birth is important in preventing adverse neonatal outcomes including neonatal hypoglycaemia and respiratory stress.

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

Insulin is a natural component of breast milk and insulin treatment of breastfeeding mothers should represent no risk to the infant. Insulin in breast milk is digested by the infant's gut and is thought to contribute to intestinal maturation and decrease the risk of contracting type 1 diabetes in breastfed infants.

Proper insulin levels are required for lactation. Good glycaemic control decreases the delay in establishment of lactation that is observed in diabetic mothers as well as enhancing maternal serum and milk prolactin concentrations.

No adverse effects have been reported relating the use of insulin to breastfeeding, therefore it is considered safe to for diabetic mothers receiving insulin to continue breastfeeding.

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

Each cartridge/pre-filled pen must be used by one patient only, even if the needle is changed, to prevent the possible transmission of disease.

Patients should be shown the container to confirm the version is the one they are expecting.

The patient should be advised to read and follow the instructions which accompany the product.

The patient should be advised to rotate injection site so that the same site is not used more than approximately once a month.

Advise patients to dispose of needles and any unused product in accordance with local requirements.

Advise patients of the warning signs of hypoglycaemia.

Patients whose blood glucose is greatly improved, e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia and should be advised accordingly.

Advise patient to consult their GP before travelling between different time zones, since this will result in meals at different times.

Advise female patients to consult their GP if pregnancy is suspected or planned.

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

Advise patient to report cutaneous amyloidosis symptoms.

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

Allergic reaction
Angioneurotic oedema
Anxiety
Behavioural disturbances
Blurred vision
Breathing difficulties
Cognitive impairment
Coma
Confusion
Convulsions
Cool pale skin
Cutaneous amyloidosis
Death
Disturbances of appetite
Drowsiness
Generalised oedema
Headache
Hypersensitivity reactions
Hypoglycaemia
Hypotension
Insulin antibodies
Insulin resistance
Itching
Lipodystrophy (injection site)
Local reaction at injection site
Nausea
Pallor
Palpitations
Paraesthesia
Peripheral neuropathy
Rash
Refraction anomalies
Slurred speech
Stinging, redness and swelling at injection site
Sweating
Tiredness
Tremor
Urticaria
Vomiting
Worsening of diabetic retinopathy (temporary)

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: April 2015

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 (online) London: BMJ Group and Pharmaceutical Press. Accessed on 24 April 2015.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 24 April 2015.

Summary of Product Characteristics: Actrapid 100 international units/ml, Solution for Injection in a Vial. Novo Nordisk Ltd. Revised March 2018.

Summary of Product Characteristics: Humulin S (Soluble) 100IU/ml suspension for injection in cartridge. Eli Lilly and Company Limited. Revised July 2018.
Summary of Product Characteristics: Humulin S (Soluble) 100IU/ml suspension for injection in vial. Eli Lilly and Company Limited. Revised March 2018.

Summary of Product Characteristics: Insuman Rapid (100 IU/ml) Cartridges. SANOFI. Revised August 2020.

Summary of Product Characteristics: Insuman Infusat 100 IU/ml solution for injection in a cartridge. SANOFI. Revised August 2020.

MHRA Drug Safety Update September 2020
Available at: https://www.mhra.gov.uk
Last accessed: 16 December 2020

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
Insulin. Last revised: 10 March 2015
Last accessed: 24 April 2015