Insulin Aspart

Registered South African indications:

• Diabetes mellitus

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypoglycaemia

Cautions

• Severe renal impairment or ESRD
• Severe hepatic impairment
• Elderly
• Dosing in children (especially in basal-bolus regimens)
• Risk factors for cardiac heart failure
• Hyperglycaemia
• Untreated hyperglycaemic events
• Conditions masking early warning symptoms of hypoglycaemia (e.g. intensified insulin therapy)
• Concomitant illness, especially infections and feverish conditions
• Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland
• Concomitant diseases or treatment where a delayed absorption of food is expected
• Presence of insulin antibodies
• Patients transferred between different types of insulin medicinal products
• Omission of a meal
• Unplanned, strenuous physical exercise
• Patient travelling between different time zones
• May impair ability to drive and operate machinery (as a result of hypoglycaemia)

Forms avail. in SA and covered in this monograph: inj

Insulin-dependent diabetes mellitus

• SC (inj): 0.5-1.0 unit/kg/day
• See link: General prescribing points on the principles of insulin dosing

The dosage should be determined according to the individual requirement of the patient, normally in combination with intermediate-acting or long-acting insulin

Administer subcutaneously by injection in the abdominal wall, the thigh, the upper arm, the deltoid region or the gluteal region. Alternatively, by infusion in the abdominal wall

Due to the faster onset of action, insulin aspart should generally be given immediately before a meal and, when necessary, soon after a meal

Insulin aspart may be administered intravenously, if applicable

Forms avail. in SA and covered in this monograph: inj

Insulin-dependent diabetes mellitus

• SC (inj): 0.5-1.0 unit/kg/day (>2 years)
• See link: General prescribing points on the principles of insulin dosing

Insulin aspart can be used in children and adolescents aged 1 year and older in preference to soluble human insulin when a rapid onset of action might be beneficial

The dosage should be determined according to the individual requirement of the patient, normally in combination with intermediate-acting or long-acting insulin

Administer subcutaneously by injection in the abdominal wall, the thigh, the upper arm, the deltoid region or the gluteal region. Alternatively, by infusion in the abdominal wall

Due to the faster onset of action, insulin aspart should generally be given immediately before a meal and, when necessary,  soon after a meal

Insulin aspart may be administered intravenously, if applicable

Pregnancy

• Safe
• Insulin aspart does not cross the placental barrier
• Data from two randomised controlled clinical trials do not indicate any adverse effect of insulin aspart on pregnancy or on the health of the foetus/newborn when compared to human insulin
• Intensified blood glucose control and monitoring of pregnant women with diabetes (type 1 diabetes, type 2 diabetes or gestational diabetes) are recommended throughout pregnancy and when contemplating pregnancy.Both hypo- and hyperglycaemia, which can occur in inadequately controlled diabetes therapy, may increase the risk of malformations and death in utero
• Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimester. After delivery, insulin requirements normally return rapidly to pre-pregnancy values

Breastfeeding

• Compatible
• There are no restrictions on breastfeeding as insulin aspart does not cross into breast milk
• Breastfeeding mothers may require adjustments in diet

Fertility

• Animal reproduction studies have not revealed any differences between insulin aspart and human insulin regarding fertility

Renal impairment

• eGFR ≥30-89 ml/min/1.73 m²: No dose adjustment recommended
• eGFR ≥11-29 ml/min/1.73 m² or ESRD: Caution; dose adjustment recommended
  Reduced recommended dose by up to 20%
  Monitor glucose target and renal function

Hepatic impairment

• Mild to moderate (Child-Pugh Classes A & B): No dose adjustment recommended
• Severe hepatic impairment (Child-Pugh Class C): Caution; dose adjustment recommended
  Adjust insulin dose according to blood glucose target

Elderly

• Caution; dose adjustment recommended
  Conservative initial dose is required to avoid risk of hypoglycaemia. Adjust dose by 10% to 15%
  Dosage must be titrated to achieve target glucose control

Porphyria information

• Not porphyrinogenic (NP)

Drugs in sport

• Prohibited - At all times

Central Nervous System Disorders

• Peripheral neuropathy
• Convulsions

Cardiovascular disorders

• Heart failure

Endocrine and Metabolic Disorders

• Hypoglycaemia
  - Cold sweats
  - Cool pale skin
  - Fatigue
  - Nervousness or tremor
  - Anxiousness
  - Unusual tiredness or weakness
  - Confusion
  - Difficulty in concentration
  - Drowsiness
  - Excessive hunger
  - Vision changes
  - Headache
  - Nausea
  - Palpitation
• Diabetic ketoacidosis
• Weight gain
• Excessive hunger

Skin and Subcutaneous Tissue Disorders

• Lipodystrophy
• Injection site reactions
  - Pain
  - Redness
  - Hives
  - Inflammation
  - Bruising
  - Swelling
  - Itching
• Urticaria
• Rash
• Eruptions

Immune, Blood and Lymphatic System Disorders

• Anaphylactic reactions
  - Generalised skin rash
  - Itching
  - Sweating
  - Gastrointestinal upset
  - Angioneurotic oedema
  - Difficulties in breathing
  - Palpitation
  - Decreased blood pressure
• Oedema

Sensory Disorders

• Refraction disorders
• Diabetic retinopathy

Others

• Unconsciousness

• Agents known to increase or reduce insulin requirements
• Oral contraceptives
• Thiazides
• Glucocorticoids
• Thyroid hormones
• Sympathomimetics
• Growth hormone
• Danazol
• Oral antidiabetic agents
• Monoamine oxidase inhibitors (MAOI)
• Non-selective beta-adrenergic blocking agents
• Angiotensin converting enzyme (ACE) inhibitors
• Angiotensin receptor blockers (ARBs)
• Salicylates
• Anabolic steroids
• Sulphonamides
• Pioglitazone
• Octreotide/lanreotide
• Alcohol

Diabetes mellitus

• Blood glucose
• Electrolytes
• HbA1c
• Renal function
• Hepatic function
• Weight

Gestational diabetes mellitus

• Blood glucose 4 times daily (1 fasting and 3 postprandial) until well-controlled

Dosing

• Blood glucose monitoring and insulin dose adjustments are recommended to achieve optimal glycaemic control
• Adjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness
• When injected subcutaneously into the abdominal wall, the onset of action will occur within 10–20 minutes of injection. The maximum effect is exerted between 1 and 3 hours after the injection. The duration of action is 3 to 5 hours

Method of administration

• Insulin aspart is administered subcutaneously by injection in the abdominal wall, the thigh, the upper arm, the deltoid region or the gluteal region. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy
• Subcutaneous injection in the abdominal wall ensures a faster absorption than other injection sites. Compared to soluble human insulin the faster onset of action of insulin aspart is maintained regardless of the injection site. The duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity
• Due to the faster onset of action, Insulin aspart should generally be given immediately before a meal. When necessary insulin aspart can be given soon after a meal

Continuous Subcutaneous Insulin Infusion (CSII)

• Insulin aspart may be used for CSII in pump systems suitable for insulin infusion. Patients using CSII should be comprehensively instructed in the use of the pump system and use the correct reservoir and tubing for the pump. The infusion set (tubing and cannula) should be changed in accordance with the instructions in the product information supplied with the infusion set
• CSII should be administered in the abdominal wall and infusion sites should be rotated
• When used, insulin aspart should not be mixed with any other insulin medicinal products
• Patients  must have an alternative insulin delivery method available in case of pump system failure

Vial - Intravenous use

• If necessary, insulin aspart can be administered intravenously which should be carried out by physicians or other healthcare staff
• For intravenous use, infusion systems with insulin aspart 100 units/ml at concentrations from 0.05 unit/ml to 1.0 unit/ml insulin aspart in the infusion fluids 0.9% sodium chloride, 5% dextrose or 10% dextrose including 40 mmol/l potassium chloride using polypropylene infusion bags, are stable at room temperature for 24 hours
• Although stable over time, a certain amount of insulin will be initially adsorbed to the material of the infusion bag
• Monitoring of blood glucose is necessary during insulin infusion

Transfer to another type or brand of insulin

• Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type, origin (animal, human insulin or human insulin analogue) and/or method of manufacture (recombinant DNA versus animal source insulin) may result in the need for a change in dose
• Patients transferred to insulin aspart from another type of insulin may require an increased number of daily injections or a change in dose from that used with their usual insulin medicinal products. If an adjustment is needed, it may occur with the first dose or during the first few weeks or months
• Close glucose monitoring is recommended during the transfer to another insulin product and in the initial weeks thereafter

Avoidance of medication errors

• Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between insulin aspart and other insulin products

Incompatibilities

• Substances added to insulin aspart may cause degradation of insulin aspart. This medicinal product must not be diluted or mixed with other medicinal products except for mixing with NPH (Neutral Protamine Hagedorn) insulin in a syringe for subcutaneous use, or with suitable infusion fluids

Special precautions for storage and handling

• Do not use this product if you notice that the solution is not clear, colourless and aqueous
• Insulin aspart that has been frozen must not be used
• Needles, syringes, cartridges, pre-filled pens and infusion sets must not be shared and the cartridge must not be refilled
• Unopened products should be stored in the refrigerator (between 2°C – 8°C). During use, store below 30°C for up to 4 weeks and do not expose to heat and sunlight
• Keep the vial/cartridge in the outer carton in order to protect from light

The blood glucose lowering effect of insulin aspart is due to the facilitated uptake of glucose following binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.

The substitution of amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin. Insulin aspart is therefore more rapidly absorbed from the subcutaneous layer compared to soluble human insulin.

Injection (per ml) 100u

• NovoRapid (Novo Nordisk) originator

Injection (per ml) 30u

• NovoRapid (Novo Nordisk) originator