Insulin and analogues

Glulisine

Each ml contains 100 U insulin glulisine (equivalent to 3.49 mg). Each vial contains 10 ml of solution for injection, equivalent to 1000 U. Each cartridge contains 3 ml of solution for injection, equivalent to 300 U. Each pen contains 3 ml of solution for injection, equivalent to 300 U. Insulin glulisine is produced by recombinant DNA technology in Escherichia coli.

Apidra 100 Units/ml, solution for injection in a pre-filled pen. SoloStar. Clear, colourless, aqueous solution.

Treatment of adults, adolescents and children, 6 years or older with diabetes mellitus, where treatment with insulin is required.

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

Apidra should be given shortly (0-15 min) before or soon after meals.

Apidra 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.

The dosage of Apidra should be individually adjusted.

Administration

Apidra should be given by subcutaneous injection or by continuous subcutaneous pump infusion.

Apidra 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. 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 site of injection should not be massaged. Patients must be educated to use proper injection techniques.

Mixing with insulins

In the absence of compatibility studies, insulin glulisine must not be mixed with other medicinal products except NPH human insulin.

Before using OptiSet, the Instructions for Use included in the Package Leaflet must be read carefully.

Continuous subcutaneous infusion pump

When used with an insulin infusion pump, Apidra must not be mixed with diluents or any other insulin.

Special populations

Renal impairment

The pharmacokinetic properties of insulin glulisine are generally maintained in patients with renal impairment. However, insulin requirements may be reduced in the presence of renal impairment

Hepatic impairment

The pharmacokinetic properties of insulin glulisine have not been investigated in patients with decreased liver function. In patients with hepatic impairment, insulin requirements may be diminished due to reduced capacity for gluconeogenesis and reduced insulin metabolism. 

Children and adolescents

There is insufficient clinical information on the use of Apidra in children younger than the age of 6 years.

Limited pharmacokinetic data are available in elderly patients with diabetes mellitus. Deterioration of renal function may lead to a decrease in insulin requirements.

Hypersensitivity to insulin glulisine or to any of the excipients. Hypoglycaemia.

Transferring a patient to a new type or brand of insulin should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, etc.), species (animal) and/or method of manufacturing may result in a change in dosage. Concomitant oral antidiabetic treatment may need to be adjusted.

The use of inadequate dosages or discontinuation of treatment, especially in insulin-dependent diabetic, may lead to hyperglycaemia and diabetic ketoacidosis; conditions which are potentially lethal.

Switching a patient to another type or brand of insulin should be done under strict medical supervision and may require change in dose.

Hypoglycaemia

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 dosage 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.

Handling of the OptiSet pen

Before using OptiSet, the Instructions for Use included in the Package Leaflet must be read carefully. OptiSet has to be used as recommended in these Instructions for Use.

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 agents, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamide oxidase inhibitors (MAOIs), pentoxifylline, propoxyphene, salicylates and sulfonamide antibiotics.

Substances that may reduce the blood-glucose-lowering activity include corticosteroids, danazol, diazoxide, diuretics, glucagon, isoniazid, phenothiazine derivatives, somatropin, sympathomimetic agents (e.g. epinephrine [adrenaline], salbutamol, terbutaline), thyroid hormones, estrogens, 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.

Hypoglycaemia, the most frequent undesirable effect 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 investigations were listed below by system organ class and in order of decreasing incidence (very common: >1/10; common: >1/100, <1/10; uncommon: > 1/1,000, < 1/100; rare: >1/10,000, <1/1,000; very rare: < 1/10,000).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Metabolism and nutrition disorders

Very common: Hypoglycaemia

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.

Skin and subcutaneous tissue disorders

Common: injection site reactions and local hypersensitivity reactions.

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.

Rare: Lipodystrophy

Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.

General disorders

Uncommon: Systemic hypersensitivity reactions

Systemic hypersensitivity reactions may include urticaria, chest tightness, dyspnea, allergic dermatitis and pruritus. Severe cases of generalized allergy, including anaphylactic reaction, may be life-threatening.

Sanofi-Aventis

(POM)

11 August 2009