Insulin Glulisine

Registered South African indications:

• Diabetes mellitus

Contraindications

South African manufacturer recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Children <4 years

International manufacturer recommendations

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

Cautions

South African manufacturer recommendations

• Pregnancy
• Renal impairment
• Hepatic impairment
• Elderly
• Intercurrent conditions
  - Illness
  - Emotional disturbances
  - Stress
• Change of insulin (e.g. change in strength, manufacturer, type, species, method of manufacture)
• Change in treatment regimen
• Autonomic neuropathy
• Long history of diabetes 
• Medication errors between insulins
• Handling errors
• Visual impairment
• Patients with reduced or absent awareness of the warning symptoms of hypoglycaemia
• Frequent episodes of hypoglycaemia
• May impair ability to drive and operate machinery

International manufacturer recommendations

• Pregnancy
• Renal impairment
• Hepatic impairment
• Elderly
• Change of insulin (e.g. change in strength, brand, type, origin, method of manufacture)
• Lipodystrophy
• Cutaneous amyloidosis
• Change in injection site
• Inadequate doses
• Treatment discontinuation
• Change in treatment regimen
• Long duration of diabetes
• Intensified insulin therapy
• Diabetic nerve disease
• Increased physical activity
• Changes to usual meal plan
• Exercising immediately after a meal
• Uncorrected hypoglycaemic or hyperglycaemic reactions
• Illness
• Emotional disturbances
• Handling errors
• Use of non-recommended pens (cat)
• Sensitivity to metacresol
• Visual impairment 
• Patients with reduced or absent awareness of the warning symptoms of hypoglycaemia
• Frequent episodes of hypoglycaemia
• Coadministration with pioglitazone
  - Risk factors for development of cardiac heart failure 
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: cat, ped, sus

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Diabetes mellitus, where treatment with insulin is required

• SC/IV: Individualised dosages
  See link: General prescribing points on the principles of insulin dosing

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The dosage should be individualised and determined based on the healthcare professional advice in accordance with the needs of the patient 

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Because of the short duration of action, patients also require a longer-acting insulin or basal insulin analogue to maintain adequate glucose control

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Should be given within 15 minutes before or immediately after a meal

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See additional prescribing points

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International manufacturer recommendations

Diabetes mellitus, where treatment with insulin is required

• SC/IV: Individualised dosages
  See link: General prescribing points on the principles of insulin dosing

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The potency of this preparation is stated in units. These units are exclusive to insulin glulisine and are not the same as IU or the units used to express the potency of other insulin analogues

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Should be used in regimens that include an intermediate or long acting insulin or basal insulin analogue and can be used with oral hypoglycaemic agents

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Should be given shortly (0-15 minutes) before or soon after meals

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See additional prescribing points

Paed. forms avail. in SA and covered in this monograph: cat, ped, sus

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Diabetes mellitus, where treatment with insulin is required

Younger than 4 years

• Not established for use 

Older than 4 years

• See adult dosages

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International manufacturer recommendations

Diabetes mellitus, where treatment with insulin is required

Younger than 6 years

• Not established for use 

Older than 6 years

• See adult dosages

Pregnancy

South African manufacturer recommendations

• Caution
• Safety and efficacy in pregnancy have not been established
• It is essential for patients with diabetes or a history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. Insulin requirements may decrease during the first trimester, generally increase during the second and third trimesters and rapidly decline after delivery. Careful monitoring of glucose control is essential in such patients. Patients with diabetes must inform their doctor if they are pregnant or are contemplating pregnancy

International manufacturer recommendations

• Caution
• There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of insulin glulisine in pregnant women
• Animal reproduction studies have not revealed any differences between insulin glulisine and human insulin regarding pregnancy, embryonal/foetal development, parturition or postnatal development
• Caution should be exercised when prescribing to pregnant women. Careful monitoring of glucose control is essential. It is essential for patients with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly

Breastfeeding

South African manufacturer recommendations

• Compatible
• It is unknown whether insulin glulisine is excreted in human milk
• Breastfeeding women may require adjustments in insulin dose and diet

International manufacturer recommendations

• Compatible
• It is unknown whether insulin glulisine is excreted in human milk, but in general insulin does not pass into breast milk and is not absorbed after oral administration
• Breastfeeding mothers may require adjustments in insulin dose and diet

Fertility

South African manufacturer recommendations 

• No information available 

International manufacturer recommendations

• Animal reproduction studies with insulin glulisine have not revealed any adverse effects on fertility

Renal Impairment

• Caution; no dose adjustment recommended  
  Insulin requirements may be reduced

Hepatic Impairment

• Caution; no dose adjustment recommended 
  Insulin requirements may be diminished due to a reduced capacity for gluconeogenesis and reduced insulin metabolism

Elderly

• Caution; no dose adjustment recommended 
  Hypoglycaemia may be difficult to recognise
  Deterioration of renal function may lead to a decrease in insulin requirements

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Temporary or permanent impairment of brain function or death as a result of severe hypoglycaemia
• Unconsciousness and/or seizures as a result of severe hypoglycaemia

Cardiovascular Disorders

• Cardiac failure (in combination with pioglitazone)

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
• Hyperglycaemia (potentially leading to diabetic ketoacidosis (vial only)) 
• Weight gain (in combination with pioglitazone)

Skin and Subcutaneous Tissue Disorders

• Injection site reactions
• Local hypersensitivity reactions at injection site
  - Redness
  - Swelling
  - Itching
• Lipodystrophy
• Cutaneous amyloidosis

Immune, Blood and Lymphatic System Disorders

• Systemic hypersensitivity reactions
  - Urticaria
  - Chest tightness
  - Dyspnoea
  - Allergic dermatitis
  - Pruritus
• Severe generalised allergy
  - Anaphylactic reaction
• Oedema (in combination with pioglitazone)

• Beta blockers
• Clonidine
• Lithium salts
• Pentamidine
• Sympatholytic agents
• Guanethidine
• Reserpine
• Oral antidiabetic agents 
• Angiotensin converting enzyme (ACE) inhibitors
• Disopyramide
• Fibrates
• Fluoxetine
• Monoamine oxidase inhibitors (MAOIs)
• Salicylates
• Sulphonamide antibiotics
• Pentoxifylline
• Propoxyphene
• Corticosteroids
• Danazol
• Diazoxide
• Diuretics
• Glucagon
• Isoniazid
• Phenothiazine derviatives
• Somatropin
• Sympathomimetics
• Epinephrine (adrenaline)
• Salbutamol
• Terbutaline
• Thyroid hormones
• Oestrogens
• Progestins (e.g. in oral contraceptives) 
• Protease inhibitors
• Atypical antipsychotics
• Olanzapine
• Clozapine

Other interactions

• Alcohol

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

Traceability
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded

Preparation and handling 

• Before first use, insulin glulisine must be kept at room temperature for 1-2 hours
• Must only be used if the solution is clear, colourless, with no solid particles visible and if it is of water-like consistency

Administration

• Insulin glulisine in cartridges is only suitable for subcutaneous injections from a reusable pen. Insulin glulisine in a disposable pen is only suitable for subcutaneous injections. If administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used
• Insulin glulisine may be used for continuous subcutaneous insulin infusion (CSII) in pump systems suitable for insulin infusion
• The infusion set and reservoir used with insulin glulisine must be changed at least every 48 hours
• Should be administered subcutaneously in the abdominal wall, thigh or deltoid or by continuous infusion in the abdominal wall
• Injection sites and infusion sites within an injection area (abdomen, thigh or deltoid) should be rotated from one injection to the next in order to reduce the risk of lipodystrophy and cutaneous amyloidosis
• The rate of absorption, and consequently, the onset and duration of action may be affected by the injection site, exercise and other variables
• Subcutaneous injection in the abdominal wall ensures a slightly faster absorption than other injection sites
• Care should be taken to ensure that a blood vessel has not been entered
• After injection, the injection site should not be massaged
• Patients must be educated to use proper injection techniques

Mixing with insulins 

• When administered as a subcutaneous injection, insulin glulisine must not be mixed with other medicinal products except neutral protamine Hagedorn (NPH) human insulin
• When used with an insulin infusion pump, insulin glulisine must not be mixed with diluents or any other insulin

Insulin glulisine is a recombinant human insulin analogue that is equipotent to regular human insulin. Insulin glulisine has a more rapid onset of action and a shorter duration of action than regular human insulin. 

The primary activity of insulins and insulin analogues, including insulin glulisine, is regulation of glucose metabolism. Insulins lower blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis in the adipocyte, inhibits proteolysis and enhances protein synthesis. Studies in healthy volunteers and patients with diabetes demonstrated that insulin glulisine is more rapid in onset of action and of shorter duration of action than regular human insulin when given subcutaneously. When insulin glulisine is injected subcutaneously, the glucose lowering activity will begin within 10-20 minutes. After intravenous administration, a faster onset and shorter duration of action, as well as a greater peak response were observed as compared with subcutaneous administration. The glucose-lowering activities of insulin glulisine and regular human insulin are equipotent when administered by intravenous route. 

One unit of insulin glulisine has the same glucose-lowering activity as one unit of regular human insulin. 

Cartridge (per ml) 100iu

• Apidra (Sanofi Aventis) originator

Disposable pen (per ml) 100iu

• Apidra (Sanofi Aventis) originator

Suspension (vial) (per ml) 100iu

• Apidra (Sanofi Aventis) originator