Drugs List

Therapeutic Indications

Uses

Insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus where a medium to long duration of action is required.

Dosage

Insulin isophane porcine may be given alone or mixed with a fast acting insulin. In intensive insulin therapy it may be used as a basal insulin (evening and/or morning), in combination with a short or rapid acting insulin given at meal times.

Dosage is individual and determined by the physician in accordance with the needs of the patient.

The desired blood glucose levels, the insulin preparations to be used and the insulin dosage (doses and timings) must be determined individually and adjusted to suit the patient's diet, physical activity and life-style.

Administration

For subcutaneous or intramuscular injection only.

Subcutaneous:
Insulin is usually injected into the upper arms, thighs, buttocks or abdomen. Absorption from a limb site may be increased if used in vigorous exercise after injection.

After subcutaneous administration onset of action occurs in approximately 2 hours, a peak action between 6 to 12 hours and an overall duration of 18 to 24 hours.

Intramuscular:
Intramuscular administration generally results in a faster onset but shorter duration than is seen with subcutaneous injections and physical activity alters the absorption.

Contraindications

Hypoglycaemia

Precautions and Warnings

Elderly
Breastfeeding
Hepatic impairment
Pregnancy
Severe renal impairment

Insulin requirements may be diminished by renal or hepatic impairment
Insulin requirements may decrease in coeliac disease
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Evaluate patient's ability to drive/operate machinery regularly
Contains metacresol
Change in injection site area may necessitate dose adjustment
Consider cutaneous amyloidosis if injection site subcutaneous lumps occur
Do not use if contents have been frozen
Follow storage and handling guidelines
Once in use, store cartridges below 25 degrees C, but do not refrigerate
Rotate injection sites within a given area to avoid lipodystrophy
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
Compensatory response to hypoglycaemia may be impaired
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 be reduced in the elderly
Insulin requirements may increase during illness,puberty or emotional upset
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

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.

Insulin resistance frequently occurs in patients with lipid disorders, hypertension and ischaemic heart disease. More than 200 units of insulin daily are usually required in patients with insulin resistance. Greatly increased insulin requirements may be due to factors including antibody formation, infections, endocrine hyperfunctional states (e.g. acromegaly, Cushing's syndrome, thyrotoxicosis) or stress.

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.

When changing between pork and human-sequence insulins, a dose change is not usually needed, but careful monitoring is still advised.

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.

The use of insulin of animal origin is not recommended during pregnancy, as it is believed to cross the human placenta via an insulin-antibody complex. Studies have also shown an association between levels of animal insulin in the cord blood and development of foetal macrosomia, though further study into this area is required.

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 14-17 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 (Briggs, 2011) 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

Side Effects

Cutaneous amyloidosis
Generalised oedema
Hypersensitivity reactions
Hypoglycaemia
Hypokalaemia
Insulin antibodies
Insulin resistance
Lipodystrophy (injection site)
Local reaction at injection site
Neuropathic pain
Weight gain

Presentation

Suspension for injection containing 100 units/ml of isophane porcine insulin

Drugs List

Therapeutic Indications

Uses

Insulin-dependent diabetes mellitus

Insulin-dependent diabetes mellitus where a medium to long duration of action is required.

Dosage

Insulin isophane porcine may be given alone or mixed with a fast acting insulin. In intensive insulin therapy it may be used as a basal insulin (evening and/or morning), in combination with a short or rapid acting insulin given at meal times.

Dosage is individual and determined by the physician in accordance with the needs of the patient.

The desired blood glucose levels, the insulin preparations to be used and the insulin dosage (doses and timings) must be determined individually and adjusted to suit the patient's diet, physical activity and life-style.

Administration

For subcutaneous or intramuscular injection only.

Subcutaneous:
Insulin is usually injected into the upper arms, thighs, buttocks or abdomen. Absorption from a limb site may be increased if used in vigorous exercise after injection.

After subcutaneous administration onset of action occurs in approximately 2 hours, a peak action between 6 to 12 hours and an overall duration of 18 to 24 hours.

Intramuscular:
Intramuscular administration generally results in a faster onset but shorter duration than is seen with subcutaneous injections and physical activity alters the absorption.

Contraindications

Hypoglycaemia

Precautions and Warnings

Elderly
Breastfeeding
Hepatic impairment
Pregnancy
Severe renal impairment

Insulin requirements may be diminished by renal or hepatic impairment
Insulin requirements may decrease in coeliac disease
Advise patient to take precautions to avoid hypoglycaemia whilst driving
Evaluate patient's ability to drive/operate machinery regularly
Contains metacresol
Change in injection site area may necessitate dose adjustment
Consider cutaneous amyloidosis if injection site subcutaneous lumps occur
Do not use if contents have been frozen
Follow storage and handling guidelines
Once in use, store cartridges below 25 degrees C, but do not refrigerate
Rotate injection sites within a given area to avoid lipodystrophy
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
Compensatory response to hypoglycaemia may be impaired
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 be reduced in the elderly
Insulin requirements may increase during illness,puberty or emotional upset
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

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.

Insulin resistance frequently occurs in patients with lipid disorders, hypertension and ischaemic heart disease. More than 200 units of insulin daily are usually required in patients with insulin resistance. Greatly increased insulin requirements may be due to factors including antibody formation, infections, endocrine hyperfunctional states (e.g. acromegaly, Cushing's syndrome, thyrotoxicosis) or stress.

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.

When changing between pork and human-sequence insulins, a dose change is not usually needed, but careful monitoring is still advised.

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.

The use of insulin of animal origin is not recommended during pregnancy, as it is believed to cross the human placenta via an insulin-antibody complex. Studies have also shown an association between levels of animal insulin in the cord blood and development of foetal macrosomia, though further study into this area is required.

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 14-17 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 (Briggs, 2011) 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

Counselling

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

Advise patients of the warning signs of hypoglycaemia.

Patients should be aware that emotional upset or concurrent illness, especially infection and fever, will usually increase insulin requirements.

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

Patients should carry glucose tablets or other suitable form of sugar with them to take in the event of hypoglycaemia and should be advised of the warning signs that they may experience.

Patient should be advised that injection sites should be rotated within the same area to minimise the risk of developing lipodystrophy.

Advise patient to seek medical advice regarding dosage if they are intending to travel between different time zones.

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

Cutaneous amyloidosis
Generalised oedema
Hypersensitivity reactions
Hypoglycaemia
Hypokalaemia
Insulin antibodies
Insulin resistance
Lipodystrophy (injection site)
Local reaction at injection site
Neuropathic pain
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: March 2013

Reference Sources

British National Formulary, 64th Edition (2012) Pharmaceutical Press, London.

BNF for Children (2012-2013) 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, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Hypurin Porcine Isophane Cartridges. Wockhardt UK Ltd. Revised January 2013.

Summary of Product Characteristics: Hypurin Porcine Isophane Vials. Wockhardt UK Ltd. Revised January 2013.

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: January 15, 2013
Last accessed: March 13, 2013