Insulin Soluble

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
• Changes in insulin strength, type (e.g. insulin human injection, human insulin isophane suspension), species (beef, pork, beef-pork, human, human insulin analog), or method of manufacture (recombinant DNA versus animal-source insulin)
• Greatly improved blood glucose
• Long duration of diabetes
• Diabetic nerve disease
• Diseases of the adrenal, pituitary or thyroid glands
• Concomitant illness
• Emotional disturbances
• Changes to physical activity
• Changes to usual diet (e.g. skipped meals)
• Driving and use of machinery

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

Insulin-dependent diabetes mellitus 

• SC (inj): Initial: 0.4-0.5 units/kg/day; Maintenance: 0.4-1.0 units/kg/day in divided doses
• See link: General prescribing points on the principles of insulin dosing

For patients at higher risk of hypoglycaemia (on sulfonylurea antidiabetic agents, malnutrition, elderly, and low cognitive status), conservative initial doses of 0.2-0.4 units/kg/day may be considered to avoid the potential for hypoglycaemia

Higher initial doses may be required in patients who are obese, sedentary, or presenting with ketoacidosis

Insulin soluble may be administered by subcutaneous, intramuscular or intravenous injection

The dosage should be determined by the healthcare professional, according to the requirements of the patient

See Additional Prescribing Points

Paed. forms avail. in SA and covered in this monograph: inj

Insulin-dependent diabetes mellitus

Insulin regimens should be individualised according to age and maturity to achieve glycaemic goals without causing hypoglycaemia. The daily doses presented are expressed as the total units/kg/day of all insulin formulations combined

• SC (inj): Initial: 0.2-0.4 units/kg/day
  Conservative initial doses are often recommended to avoid the potential for hypoglycaemia
• SC (inj): Maintenance: 0.5-1.0 unit/kg/day in divided doses
  Doses must be individualised; however, an estimate can be determined based on phase of diabetes and level of maturity
• See link:  General prescribing points on the principles of insulin dosing

During puberty, requirements may substantially increase to >1.2-2.0 units/kg/day

Pregnancy

• Safe
• It is essential to maintain good control of the insulin treated (insulin-dependent or gestational diabetes) patient throughout pregnancy
• Insulin requirements usually fall during the first trimester and increase during the second and third trimesters
• Patients with diabetes should be advised to inform their doctors if they are pregnant or are contemplating pregnancy
• Careful monitoring of glucose control, as well as general health, is essential in pregnant patients with diabetes

Breastfeeding

• Compatible
• Insulin is a naturally-occurring constituent of the blood and is excreted into breast milk
• In a study, milk samples were obtained from breastfeeding mothers. The results showed that insulin, both endogenous and exogenous, are actively transported from the blood into milk and is protected from degradation and, presumably, has a functional or developmental role in the infant
• No metabolic effects of insulin ingested insulin on the breastfed newborn/infant are anticipated since insulin as a peptide, is digested into amino acids in the human gastrointestinal tract
• Breastfeeding women may require adjustments in insulin dose and diet

Fertility

• No information available

Renal impairment

• eGFR >30-89 ml/min/1.73m²: No dose adjustment recommended
• eGFR <29 ml/min/1.73m² or ESRD: Caution; dose adjustment recommended
  Reduce recommended dose by up to 50%. Monitor glucose target and renal function
• Patients on haemodialysis: No dose adjustment recommended 

Hepatic impairment

• Mild-to-moderate: (Child-Pugh Classes A & B): No dose adjustment recommended
• Severe (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 for hypoglycaemia. Reduce the initial recommended dose by 10%-20%
  
  Severe hypoglycaemia
  Dosage reductions of 25%-50% have been recommended
  Control of geriatric patient's blood glucose needs to be individualised
  Avoid intensive glucose control (risk for hypoglycaemia and CVS-related mortality

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Endocrine and Metabolic Disorders

• Hypoglycaemia (mild to severe)

Skin and Subcutaneous Tissue Disorders

• Injection site reactions
  - Redness
  - Swelling
  - Itching
• Injection site lipodystrophy

Immune, Blood and Lymphatic System Disorders

• Systemic allergy
  - Rash over the whole body
  - Shortness of breath
  - Wheezing
  - Reduction in blood pressure
  - Fast pulse
  - Sweating

Others

• Oedema

• Thiazolidinediones
• Pioglitazone
• Beta-blockers
• Somatostatin analogues
• Octreotide
• Lanreotide
• Glucocorticoids
• Thyroid hormones
• Growth hormone
• Danazol
• Beta 2-sympathomimetics
• Ritodrine
• Salbutamol
• Terbutaline
• Thiazides
• Hydrochlorothiazide
• Oral hypoglycaemics
• Metformin
• Salicylates
• Acetylsalicylic acid
• Monoamine oxidase inhibitors (MAOIs)
• Angiotensin converting enzyme (ACE) inhibitors
• Captopril
• Enalapril
• Angiotensin II receptor blockers
• Losartan
• Non-selective beta-blocking agents
• Alcohol

Diabetes mellitus

• Blood glucose
• HbA1c
• Renal function
• Hepatic function

Gestational diabetes mellitus

• Blood glucose 4 times daily (1 fasting and 3 after meals) until well controlled, then as appropriate

Method of administration

• Insulin soluble should be given by subcutaneous injection but may, although not recommended, also be given by intramuscular injection or intravenous administration
• Subcutaneous administration should be in the upper arms, thighs, buttocks or abdomen. Use of injection sites should be rotated so that the same site is not used more than approximately once a month
• After any insulin injection, the injection site should not be massaged
• Patients must be educated to use proper injection techniques
• Insulin soluble may be administered in combination with insulin isophane  (see below Instructions for use and handling)
• After the dose is prepared, the injection should be made promptly to avoid clogging of the needle

Instructions for use and handling

1. Insulin soluble solution does not require resuspension and should be clear and colourless. Do not use if insulin soluble appears cloudy, thickened, slightly coloured or if solid particles are visible
2. Mixing of insulins: The shorter-acting insulin should be drawn into the syringe first, to prevent contamination of the vial by the longer-acting preparation. It is advisable to inject directly after mixing. However, if a delay is necessary, a consistent routine must be followed
   Alternatively, a separate syringe, or separate cartridges of insulin soluble and insulin isophane can be used for administration of the correct amount of each formulation
3. Prepare your syringe prior to injection, as directed by your doctor or diabetes specialist nurse
4. Use an insulin syringe marked for the strength of insulin being administered
5. Inject the correct dose of insulin as directed by your doctor or diabetes specialist nurse
6. Use of the injection sites should be rotated so that the same is not used more than approximately one month

Hypoglycaemia

• May occur as a result of excess insulin relative to food intake and energy expenditure
• Associated with listlessness, confusion, palpitations, headache, sweating and vomiting
• Mild hypoglycaemic episodes will respond to oral administration of glucose or sugar products
• Correction of moderately severe hypoglycaemia can be accomplished by intramuscular or subcutaneous administration of glucagon, followed by oral carbohydrate when the patient recovers sufficiently. Patients who fail to respond to glucagon must be given glucose solution intravenously
• If the patient is comatose, glucagon should be administered intramuscularly or subcutaneously. If the patient fails to respond to glucagon or if glucagon is not available, then glucose solution must be given intravenously. The patient should be given a meal as soon as consciousness is recovered
• Sustained carbohydrate intake and observation may be necessary because hypoglycaemia may occur after apparent clinical recovery

Incompatibilities

• Insulin soluble should not be mixed with insulins produced by other manufacturers or with animal insulin preparations

Special precautions for storage

• Store in a refrigerator (2^oC - 8^oC)
• After the first use, store below 30 ^oC
• After the first use, discard after 28 days
• Do not freeze or expose to excessive heat or direct sunlight

Special precautions for disposal and other handling

• Do not reuse needles
• Do not share needles
• Vials can be used until empty, then properly discard
• Any unused medicinal product or waste material should be disposed of in accordance with local requirements

Insulin soluble is a short-acting preparation that replaces the insufficiency of insulin secreted by the β-cells of the pancreas to regulate glucose metabolism.Insulin stimulates the cellular uptake of amino acids and increases cellular permeability to several ions, including potassium, magnesium, and phosphate. By activating sodium-potassium ATPases, insulin promotes the intracellular movement of potassium.

Injection (per ml) 100u

• Actrapid HM (ge) (Novo Nordisk) originator
• Biosulin R (Dezzo Pharma)
• Humulin R (Eli Lilly) originator