Drugs List

Therapeutic Indications

Uses

Insulin-dependent diabetes mellitus

Administration

To be injected subcutaneously in the upper arms, thighs, buttocks or abdomen. Injection sites should be rotated so that the same site is not used more than approximately once a month.

When administered, care should be taken to check that a blood vessel has not been entered. After injection, the site should not be massaged.

Patients must be educated to ensure the proper injection technique.

Insulin lispro has a rapid onset of action (approximately 10 to 20 minutes), thus allowing it to be given close to mealtime. Insulin lispro protamine has a duration of action similar to that of a basal insulin.

For subcutaneous administration only, other routes are contra-indicated.

Insulin suspensions are not to be used in insulin infusion pumps.

Contraindications

Hypoglycaemia

Precautions and Warnings

Children under 12 years
Elderly
Infection
Breastfeeding
Delayed food absorption
Hepatic impairment
Pregnancy
Renal impairment

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
Contains metacresol
Change in injection site area may necessitate dose adjustment
Consider cutaneous amyloidosis if injection site subcutaneous lumps occur
For single patient use only
For subcutaneous use only
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
Advise patient to report cutaneous amyloidosis symptoms
Consider dose reduction to prevent hypoglycaemia if dietary intake reduced
Exercise immediately after a meal may increase risk of hypoglycaemia
Risk of hypoglycaemia may be increased by exercise or ingestion of alcohol
Consider dosage modification if diet or exercise levels are changed
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 patients of the warning signs of hypoglycaemia

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. Compared to other biphasic human insulins, biphasic insulin lispro may have a stronger hypoglycaemic effect up to 6 hours after injection. This may have to be compensated for in the individual patient, through adjustment of insulin dose and/or food intake.

Transferring a patient to a new type or brand of insulin should be done under strict medical supervision as any change (brand, type species, method of manufacture) may require a change in dose. Patients using biphasic insulin lispro may require a change in dose from that used with the previous insulin. If such a change in dose is required, it may occur with the first dose or during the first weeks or months.

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.

Pregnancy and Lactation

Pregnancy

Use insulin lispro biphasic with caution in 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.

Rapid acting insulin analogues aspart and lispro are structurally very similar to human insulin and present a low risk factor when used in pregnancy and they are recommended in current national guidelines.

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

Use insulin lispro biphasic with caution in breastfeeding.

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 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

Anaphylactic reaction
Angioneurotic oedema
Anxiety
Breathing difficulties
Cognitive impairment
Cold sweat
Concentration difficulties
Confusion
Convulsions
Coolness of skin
Cutaneous amyloidosis
Death
Decrease in blood pressure
Drowsiness
Erythema at injection site
Fatigue
Gastro-intestinal disturbances
Headache
Hunger
Hypersensitivity reactions
Hypoglycaemia
Increased pulse rate
Itching
Itching sensation (local)
Lipodystrophy (injection site)
Localised and generalised rash
Nausea
Nervousness
Oedema
Palpitations
Peripheral neuropathy
Pruritus
Refraction anomalies
Skin eruption
Slurred speech
Stinging, redness and swelling at injection site
Sweating
Tiredness
Tremor
Unconsciousness
Urticaria
Visual disturbances
Weakness
Worsening of diabetic retinopathy (temporary)

Presentation

Injections of insulin lispro with insulin lispro protamine

These products have been produced by recombinant technology using E.coli.

Drugs List

Therapeutic Indications

Uses

Insulin-dependent diabetes mellitus

Dosage

Dosage is individual and determined on the basis of the physician's advice in accordance with the needs of the patient.

Adults

Elderly

Children

Administration

To be injected subcutaneously in the upper arms, thighs, buttocks or abdomen. Injection sites should be rotated so that the same site is not used more than approximately once a month.

When administered, care should be taken to check that a blood vessel has not been entered. After injection, the site should not be massaged.

Patients must be educated to ensure the proper injection technique.

Insulin lispro has a rapid onset of action (approximately 10 to 20 minutes), thus allowing it to be given close to mealtime. Insulin lispro protamine has a duration of action similar to that of a basal insulin.

For subcutaneous administration only, other routes are contra-indicated.

Insulin suspensions are not to be used in insulin infusion pumps.

Contraindications

Hypoglycaemia

Precautions and Warnings

Children under 12 years
Elderly
Infection
Breastfeeding
Delayed food absorption
Hepatic impairment
Pregnancy
Renal impairment

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
Contains metacresol
Change in injection site area may necessitate dose adjustment
Consider cutaneous amyloidosis if injection site subcutaneous lumps occur
For single patient use only
For subcutaneous use only
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
Advise patient to report cutaneous amyloidosis symptoms
Consider dose reduction to prevent hypoglycaemia if dietary intake reduced
Exercise immediately after a meal may increase risk of hypoglycaemia
Risk of hypoglycaemia may be increased by exercise or ingestion of alcohol
Consider dosage modification if diet or exercise levels are changed
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 patients of the warning signs of hypoglycaemia

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia. Compared to other biphasic human insulins, biphasic insulin lispro may have a stronger hypoglycaemic effect up to 6 hours after injection. This may have to be compensated for in the individual patient, through adjustment of insulin dose and/or food intake.

Transferring a patient to a new type or brand of insulin should be done under strict medical supervision as any change (brand, type species, method of manufacture) may require a change in dose. Patients using biphasic insulin lispro may require a change in dose from that used with the previous insulin. If such a change in dose is required, it may occur with the first dose or during the first weeks or months.

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.

Pregnancy and Lactation

Pregnancy

Use insulin lispro biphasic with caution in 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.

Rapid acting insulin analogues aspart and lispro are structurally very similar to human insulin and present a low risk factor when used in pregnancy and they are recommended in current national guidelines.

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

Use insulin lispro biphasic with caution in breastfeeding.

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 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

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.

Advise patients of the warning signs of hypoglycaemia.

Patients with diabetic nerve disease, or long standing diabetes or 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 female patients to consult their GP if pregnancy is suspected or planned.

Patients should be advised to take precautions to avoid hypoglycaemia before driving, especially in patients who have reduced or absent warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia

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 enquiries, DVLA, Swansea, SA99 1TU

By phone on 0300 790 6806; 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

Anaphylactic reaction
Angioneurotic oedema
Anxiety
Breathing difficulties
Cognitive impairment
Cold sweat
Concentration difficulties
Confusion
Convulsions
Coolness of skin
Cutaneous amyloidosis
Death
Decrease in blood pressure
Drowsiness
Erythema at injection site
Fatigue
Gastro-intestinal disturbances
Headache
Hunger
Hypersensitivity reactions
Hypoglycaemia
Increased pulse rate
Itching
Itching sensation (local)
Lipodystrophy (injection site)
Localised and generalised rash
Nausea
Nervousness
Oedema
Palpitations
Peripheral neuropathy
Pruritus
Refraction anomalies
Skin eruption
Slurred speech
Stinging, redness and swelling at injection site
Sweating
Tiredness
Tremor
Unconsciousness
Urticaria
Visual disturbances
Weakness
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 2016

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. 71st ed. London: BMJ Group and Pharmaceutical Press; 2016.

Paediatric Formulary Committee. BNF for Children 2015-2016. London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; 2015.

Summary of Product Characteristics: Humalog Mix25 100U/ml suspension for injection in vial/cartridge/Pen/KwikPen. Mix50 100U/ml suspension for injection in cartridge/Pen/KwikPen, Eli Lilly and Co Ltd. revised January 2016.

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

UK Drugs in Lactation Advisory Service.
Available at: https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1
Last accessed: 18 April 2016

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: 26 February 2016
Last accessed: 18 April 2016