Drugs List

Therapeutic Indications

Uses

Treatment of insulin-dependent diabetes mellitus.

Insulin glulisine has a rapid onset and short duration of action.

Administration

To be injected subcutaneously in the abdominal wall, the thigh, the deltoid region or gluteal region or by continuous infusion in the abdominal wall. The injection site must be rotated within the same region.

Insulin glulisine should be given shortly (0-15 minutes) before a meal. When necessary, insulin glulisine can be given soon after the meal.

Onset and duration of action will vary according to injection site, dose, blood flow, temperature and physical activity or lifestyle factors.

Insulin glulisine vials are for us with corresponding insulin syringes or continuous subcutaneous insulin pumps.

Patients using continuous subcutaneous insulin infusion (CSII) should be comprehensively instructed in the use of the pump system. The infusion set and reservoir should be changed every 48 hours using aseptic technique. Patients should have alternative insulin available in case of pump system failure. Insulin glulisine should not be mixed with any other insulin in an infusion pump.

Insulin glulisine cartridges are for use with compatible insulin pens.

The fastest absorption is seen when insulin glulisine is injected subcutaneously into the abdominal wall.

Insulin glulisine is indicated for subcutaneous use only.

Compatibilities

Do not mix with any preparations other than NPH (Neutral Protamine Hagedorn) human insulin.

If used in an infusion pump, do NOT mix with any other insulin.

Contraindications

Hypoglycaemia

Children under 6 years (see Dosage - Children)

Precautions and Warnings

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 insulin glulisine may require altered dosage of any concurrent oral antidiabetic medications.

Inadequate dosing or discontinuation of treatment may, especially in Type I diabetes (insulin-dependent diabetes mellitus) lead to hyperglycaemia and diabetic ketoacidosis. The first symptoms of hyperglycaemia usually come on gradually, over a period of hours or days. They include nausea, vomiting, drowsiness, flushed dry skin, dry mouth, increased urination, thirst and loss of appetite as well as acetone breath.

Patients should be aware of circumstances where warning symptoms of hypoglycaemia are diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain risk groups. These include patients:
in whom glycaemic control is markedly improved
in whom hypoglycaemia develops gradually
who are elderly
in whom an autonomic neuropathy is present
with a long history of diabetes
suffering from a psychiatric illness
receiving concurrent treatment with certain other medicinal products such as beta blockers
after transfer from animal insulin to human insulin

Adherence of the patient to the dosage and dietary regimen, correct insulin administration and awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors increasing the susceptibility to hypoglycaemia require particularly close monitoring and may necessitate dosage adjustment. These include:
change of the injection area
improved insulin sensitivity (e.g. by removal of stress factors)
unaccustomed, increased or prolonged physical activity
intercurrent illness (e.g. vomiting, diarrhoea)
inadequate food intake
missed meals
alcohol consumption
certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or adrenocortical insufficiency)
concurrent treatment with certain other medicinal products

Dose adjustment may be required if a patient undertakes increased physical exercise or alters their diet. Exercise directly after a meal may increase the risk of hypoglycaemia.

A consequence of the pharmacodynamics of rapidly acting insulin analogues is that if hypoglycaemia occurs, it may occur earlier after an injection when compared with soluble human insulin.

Insulin glulisine should be administered in immediate relation to a meal. The fast onset of action should therefore be considered in patients with concurrent diseases or medication where a delayed absorption of food might be expected.

Untreated hyperglycaemic or hypoglycaemic events can cause loss of consciousness, coma or death.

Concomitant illness (especially infections) and emotional disturbances usually increases the patient's insulin requirements.

In patients with renal impairment, insulin requirements may be diminished due to reduced insulin metabolism. In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin requirements.

In severe hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism.

Pregnancy (see 'Pregnancy' section).
Breastfeeding (see 'Lactation' section).

Alcohol may intensify and prolong the hypoglycaemic effect of insulin.

Contains metacresol, which may cause allergic reactions.

In case of insufficient glucose control or a tendency for hypo- or hyperglycaemia, the patient's adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered.

Advise patient not to use if the solution is not clear and colourless.

There have been reports of medication errors when other insulins, particularly long acting, have been administered in place of insulin glulisine. Remind patient to check the label before each injection.

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/CG63/NiceGuidance/pdf/English .

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. There is inadequate human data to support such statements for insulin glulisine. However, Briggs (2008) concludes that there is no reason to believe that insulin glulisine would pose a risk to the embryo or foetus different from that of other insulins.

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.

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 ).

Licensed in pregnancy? - No

Recommended for use in pregnancy? - No

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 (Briggs, 2008) and is thought to contribute to intestinal maturation and decrease the risk of contracting type 1 diabetes in breastfed infants (Lactmed, via Toxnet).

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

Drug excreted in breast milk? - Insulin is a natural component breast milk

UK Drugs in Lactation Advisory Service Classification - This drug may be administered to breastfeeding mothers.

Side Effects

Hypoglycaemia is the most frequently occurring undesirable effect and usually occurs suddenly. Symptoms include:
Cold sweat
Coolness of skin
Fatigue
Nervousness
Tremor
Anxiety
Tiredness
Weakness
Confusion
Concentration difficulties
Drowsiness
Excessive hunger
Visual disturbances
Headache
Nausea
Palpitations

Severe hypoglycaemia may lead to:
Unconsciousness
Convulsions
Temporary or permanent impairment of brain function
Death

Systemic hypersensitivity reaction - symptoms include:
Urticaria
Chest tightness
Dyspnoea
Allergic dermatitis
Pruritis
Generalized allergy
Anaphylactic reaction

Other side effects include:
Injection site reactions
Stinging, redness and swelling at injection site (local hypersensitivity reactions)
Lipodystrophy
Oedema (usually transitory)
Rash

Presentation

Solution for injection containing 100 units per ml of insulin glulisine presented in either a 3ml cartridge (containing 300 units), a 3ml disposable pen (containing 300 units) or a 10ml vial (containing 1000 units).

Insulin glulisine is a short acting insulin analogue produced by recombinant DNA technology using Escherichia coli.

Drugs List

Therapeutic Indications

Uses

Treatment of insulin-dependent diabetes mellitus.

Insulin glulisine has a rapid onset and short duration of action.

Dosage

Insulin glulisine should normally be used in combination with intermediate-acting or long-acting insulin or basal insulin analogue or oral hypoglycaemic agent. (but see Additional dosage)

Dose may need adjusting according to physical activity or diet changes or if the patient is pregnant or lactating.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

To be injected subcutaneously in the abdominal wall, the thigh, the deltoid region or gluteal region or by continuous infusion in the abdominal wall. The injection site must be rotated within the same region.

Insulin glulisine should be given shortly (0-15 minutes) before a meal. When necessary, insulin glulisine can be given soon after the meal.

Onset and duration of action will vary according to injection site, dose, blood flow, temperature and physical activity or lifestyle factors.

Insulin glulisine vials are for us with corresponding insulin syringes or continuous subcutaneous insulin pumps.

Patients using continuous subcutaneous insulin infusion (CSII) should be comprehensively instructed in the use of the pump system. The infusion set and reservoir should be changed every 48 hours using aseptic technique. Patients should have alternative insulin available in case of pump system failure. Insulin glulisine should not be mixed with any other insulin in an infusion pump.

Insulin glulisine cartridges are for use with compatible insulin pens.

The fastest absorption is seen when insulin glulisine is injected subcutaneously into the abdominal wall.

Insulin glulisine is indicated for subcutaneous use only.

Compatibilities

Do not mix with any preparations other than NPH (Neutral Protamine Hagedorn) human insulin.

If used in an infusion pump, do NOT mix with any other insulin.

Contraindications

Hypoglycaemia

Children under 6 years (see Dosage - Children)

Precautions and Warnings

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 insulin glulisine may require altered dosage of any concurrent oral antidiabetic medications.

Inadequate dosing or discontinuation of treatment may, especially in Type I diabetes (insulin-dependent diabetes mellitus) lead to hyperglycaemia and diabetic ketoacidosis. The first symptoms of hyperglycaemia usually come on gradually, over a period of hours or days. They include nausea, vomiting, drowsiness, flushed dry skin, dry mouth, increased urination, thirst and loss of appetite as well as acetone breath.

Patients should be aware of circumstances where warning symptoms of hypoglycaemia are diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain risk groups. These include patients:
in whom glycaemic control is markedly improved
in whom hypoglycaemia develops gradually
who are elderly
in whom an autonomic neuropathy is present
with a long history of diabetes
suffering from a psychiatric illness
receiving concurrent treatment with certain other medicinal products such as beta blockers
after transfer from animal insulin to human insulin

Adherence of the patient to the dosage and dietary regimen, correct insulin administration and awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors increasing the susceptibility to hypoglycaemia require particularly close monitoring and may necessitate dosage adjustment. These include:
change of the injection area
improved insulin sensitivity (e.g. by removal of stress factors)
unaccustomed, increased or prolonged physical activity
intercurrent illness (e.g. vomiting, diarrhoea)
inadequate food intake
missed meals
alcohol consumption
certain uncompensated endocrine disorders (e.g. in hypothyroidism and in anterior pituitary or adrenocortical insufficiency)
concurrent treatment with certain other medicinal products

Dose adjustment may be required if a patient undertakes increased physical exercise or alters their diet. Exercise directly after a meal may increase the risk of hypoglycaemia.

A consequence of the pharmacodynamics of rapidly acting insulin analogues is that if hypoglycaemia occurs, it may occur earlier after an injection when compared with soluble human insulin.

Insulin glulisine should be administered in immediate relation to a meal. The fast onset of action should therefore be considered in patients with concurrent diseases or medication where a delayed absorption of food might be expected.

Untreated hyperglycaemic or hypoglycaemic events can cause loss of consciousness, coma or death.

Concomitant illness (especially infections) and emotional disturbances usually increases the patient's insulin requirements.

In patients with renal impairment, insulin requirements may be diminished due to reduced insulin metabolism. In the elderly, progressive deterioration of renal function may lead to a steady decrease in insulin requirements.

In severe hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism.

Pregnancy (see 'Pregnancy' section).
Breastfeeding (see 'Lactation' section).

Alcohol may intensify and prolong the hypoglycaemic effect of insulin.

Contains metacresol, which may cause allergic reactions.

In case of insufficient glucose control or a tendency for hypo- or hyperglycaemia, the patient's adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered.

Advise patient not to use if the solution is not clear and colourless.

There have been reports of medication errors when other insulins, particularly long acting, have been administered in place of insulin glulisine. Remind patient to check the label before each injection.

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/CG63/NiceGuidance/pdf/English .

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. There is inadequate human data to support such statements for insulin glulisine. However, Briggs (2008) concludes that there is no reason to believe that insulin glulisine would pose a risk to the embryo or foetus different from that of other insulins.

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.

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 ).

Licensed in pregnancy? - No

Recommended for use in pregnancy? - No

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 (Briggs, 2008) and is thought to contribute to intestinal maturation and decrease the risk of contracting type 1 diabetes in breastfed infants (Lactmed, via Toxnet).

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

Drug excreted in breast milk? - Insulin is a natural component breast milk

UK Drugs in Lactation Advisory Service Classification - This drug may be administered to breastfeeding mothers.

Effects on Ability to Drive and Operate Machinery

Diabetic patient's ability to concentrate and react may be impaired as a result of hyperglycaemia or hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance, for example driving or operating machinery.

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving or operating machinery.

Drivers treated with insulin or oral antidiabetic drugs are required to inform the DVLA of their condition. See counselling section for further information.

Counselling

As insulin glulisine is usually prescribed in conjunction with other insulins, remind patients to check the label on the container before each injection.

Patients using continuous subcutaneous insulin infusion (CSII) should be comprehensively instructed in the use of the pump system, including the need to change the infusion set and reservoir every 48 hours using aseptic technique.

Patients using CSII should be informed of the need to have alternative insulin available in case of pump failure.

Diabetic patients should be advised to carry a source of sugar, for example some sugar lumps or a few biscuits.

Patients should be advised to avoid hypoglycaemia while driving and this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in such circumstances.

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

Hypoglycaemia is the most frequently occurring undesirable effect and usually occurs suddenly. Symptoms include:
Cold sweat
Coolness of skin
Fatigue
Nervousness
Tremor
Anxiety
Tiredness
Weakness
Confusion
Concentration difficulties
Drowsiness
Excessive hunger
Visual disturbances
Headache
Nausea
Palpitations

Severe hypoglycaemia may lead to:
Unconsciousness
Convulsions
Temporary or permanent impairment of brain function
Death

Systemic hypersensitivity reaction - symptoms include:
Urticaria
Chest tightness
Dyspnoea
Allergic dermatitis
Pruritis
Generalized allergy
Anaphylactic reaction

Other side effects include:
Injection site reactions
Stinging, redness and swelling at injection site (local hypersensitivity reactions)
Lipodystrophy
Oedema (usually transitory)
Rash

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 a refrigerator (2 - 8 degrees C)
Keep in outer cartons to protect from light.
Do not freeze
Protect from direct heat.

Once in use the product may be stored for a maximum of 4 weeks not above 25 degrees C.

Further Information

Last Full Review Date: March 2011

Reference Sources

British National Formulary, 60th edition (2010) 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, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Apidra 100 units/ml, Solution for Injection. Sanofi Aventis. Revised January 2011.
Summary of Product Characteristics: Apidra 100units/ml solution for Injection in Opticlik cartridge. Sanofi Aventis. Revised January 2011.
Summary of Product Characteristics: Apidra 100units/ml Solostar solution for Injection in a pre-filled pen. Sanofi Aventis. Revised January 2011.

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.ukmicentral.nhs.uk/drugpreg/qrg_p1.asp
Last accessed: March 10, 2011

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: December 7, 2010
Last accessed: March 10, 2011