Source: European Medicines Agency (EU) Revision Year: 2020 Publisher: Sanofi-Aventis Deutschland GmbH, D-65926, Frankfurt am Main, Germany
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypoglycaemia.
Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, neutral protamine Hagedorn [NPH], lente, long-acting, etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need for a change in dose. Concomitant oral antidiabetic treatment may need to be adjusted.
The use of inadequate doses or discontinuation of treatment, especially in insulin-dependent diabetic, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.
The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and may, therefore, change when the treatment regimen is changed.
Conditions which may make the early warning symptoms of hypoglycaemia different or less pronounced include long duration of diabetes, intensified insulin therapy, diabetic nerve disease, medicinal products such as beta blockers or after transfer from animal-source insulin to human insulin.
Adjustment of dose may be also necessary if patients undertake increased physical activity or change their usual meal plan. Exercise taken immediately after a meal may increase the risk of hypoglycaemia.
When compared with soluble human insulin, if hypoglycaemia occurs after an injection with rapid acting analogues, it may occur earlier.
Uncorrected hypoglycaemic or hyperglycaemic reactions can cause loss of consciousness, coma, or death.
Insulin requirements may be altered during illness or emotional disturbances.
Pens to be used with Apidra 100 units/ml solution for injection in a cartridge Apidra 100 units/ml in cartridges is only suitable for subcutaneous injections from a reusable pen. If administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used.
The Apidra cartridges should only be used with the following pens:
These cartridges should not be used with any other reusable pen as the dosing accuracy has only been established with the listed pens (see section 4.2 and 6.6). Not all of these pens may be marketed in your country.
Medication errors have been reported in which other insulins, particularly long-acting insulins, have been accidentally administered instead of insulin glulisine. Insulin label must always be checked before each injection to avoid medication errors between insulin glulisine and other insulins.
Continuous subcutaneous insulin infusion.
Malfunction of the insulin pump or infusion set or handling errors can rapidly lead to hyperglycaemia, ketosis and diabetic ketoacidosis. Prompt identification and correction of the cause of hyperglycaemia or ketosis or diabetic ketoacidosis is necessary.
Cases of diabetic ketoacidosis have been reported when Apidra has been given in continuous subcutaneous insulin infusion in pump systems. Most of the cases were related to handling errors or pump system failure. Interim subcutaneous injections with Apidra may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternative insulin delivery system available in case of pump system failure (see section 4.2 and 4.8).
This medicinal product contains less than 1 mmol (23 mg) sodium per dose, i.e. it is essentially ‘sodium-free’. Apidra contains metacresol, which may cause allergic reactions.
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. This should be kept in mind if treatment with the combination of pioglitazone and Apidra is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.
Handling of the SoloStar pre-filled pen: Apidra SoloStar 100 units/ml in pre-filled pen is only suitable for subcutaneous injections. If administration by syringe, intravenous injection or infusion pump is necessary, a vial should be used. Before using SoloStar, the Instructions for use included in the Package leaflet must be read carefully. SoloStar has to be used as recommended in these Instructions for use (see section 6.6).
Studies on pharmacokinetic interactions have not been performed. Based on empirical knowledge from similar medicinal products, clinically relevant pharmacokinetic interactions are unlikely to occur.
A number of substances affect glucose metabolism and may require dose adjustment of insulin glulisine and particularly close monitoring.
Substances that may enhance the blood-glucose-lowering activity and increase susceptibility to hypoglycaemia include oral antidiabetic medicinal products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors (MAOIs), pentoxifylline, propoxyphene, salicylates and sulphonamide antibiotics.
Substances that may reduce the blood-glucose-lowering activity include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somatropin, sympathomimetic medicinal products (e.g. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, oestrogens, progestins (e.g. in oral contraceptives), protease inhibitors and atypical antipsychotic medicinal products (e.g. olanzapine and clozapine).
Beta-blockers, clonidine, lithium salts or alcohol may either potentiate or weaken the blood-glucose-lowering activity of insulin. Pentamidine may cause hypoglycaemia, which may sometimes be followed by hyperglycaemia.
In addition, under the influence of sympatholytic medicinal products such as beta-blockers, clonidine, guanethidine and reserpine, the signs of adrenergic counter-regulation may be reduced or absent.
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 (see section 5.3).
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.
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.
Breast-feeding mothers may require adjustments in insulin dose and diet.
Animal reproduction studies with insulin glulisine have not revealed any adverse effects on fertility.
The patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machines). Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.
Hypoglycaemia, the most frequent adverse reaction of insulin therapy, may occur if the insulin dose is too high in relation to the insulin requirement.
The following related adverse reactions from clinical studies were listed below by system organ class and in order of decreasing incidence (very common: ≥1/10; common: ≥1/100 to <1/10; uncommon: ≥1/1,000 to <1/100; rare: ≥1/10,000 to <1/1,000; very rare: <1/10,000), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Very common: Hypoglycaemia
Unknown: Hyperglycaemia (potentially leading to Diabetic ketoacidosis1)
Common: Injection site reactions, Local hypersensitivity reactions
Rare: Lipodystrophy
Uncommon: Systemic hypersensitivity reactions
1Apidra 100 Units/ml solution for injection in a vial: Most of the cases were related to handling errors or pump system failure when Apidra was used with CSII.
Symptoms of hypoglycaemia usually occur suddenly. They may include 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 and palpitation. Hypoglycaemia can become severe and may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death.
Cases of hyperglycaemia have been reported with Apidra when used with CSII (see section 4.4) that has led to Diabetic Ketoacidosis (DKA); most of the cases were related to handling errors or pump system failure. The patient should always follow the Apidra specific instructions and always have access to alternative insulin delivery system in case of pump system failure.
Local hypersensitivity reactions (redness, swelling and itching at the injection site) may occur during treatment with insulin. These reactions are usually transitory and normally they disappear during continued treatment.
Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
Systemic hypersensitivity reactions may include urticaria, chest tightness, dyspnoea, allergic dermatitis and pruritus. Severe cases of generalized allergy, including anaphylactic reaction, may be life-threatening.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except NPH human insulin.
When used with an insulin infusion pump, Apidra must not be mixed with other medicinal products.
Apidra was found to be incompatible with Glucose 5% solution and Ringer’s solution and, therefore, must not be used with these solution fluids. The use of other solutions has not been studied.
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