Fiasp 100 units/mL solution for injection in vial

Treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above.

Posology

Fiasp is a mealtime insulin for subcutaneous administration up to 2 minutes before the start of the meal, with the option to administer up to 20 minutes after starting the meal (see section 5.1).

Dosing with Fiasp is individual and determined in accordance with the needs of the patient. Fiasp given by subcutaneous injection should be used in combination with intermediate-acting or long-acting insulin given at least once a day. In a basal-bolus treatment regimen approximately 50% of this requirement may be provided by Fiasp and the remaining by intermediate-acting or long-acting insulin.

The individual total daily insulin requirement in adults, adolescents and children may vary and is usually between 0.5 and 1 unit/kg/day.

Blood glucose monitoring and insulin dose adjustment 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. Blood glucose levels should be monitored adequately under these conditions.

The duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity.

Patients on basal-bolus treatment who forget a mealtime dose are advised to monitor their blood glucose level to decide if an insulin dose is needed. Patients should resume their usual dosing schedule at the next meal.

The potency of insulin analogues, including Fiasp, is expressed in units. One (1) unit of Fiasp corresponds to 1 international unit of human insulin or 1 unit of other fast-acting insulin analogues.

The early onset of action must be considered when prescribing Fiasp (see section 5.1).

Initiation

Patients with type 1 diabetes mellitus

The recommended starting dose in insulin naï ve patients with type 1 diabetes is approximately 50% of the total daily insulin dose and should be divided between the meals based on the size and composition of the meals. The remainder of the total daily insulin dose should be administered as intermediate-acting or long-acting insulin. As a general rule, 0.2 to 0.4 units of insulin per kilogram of body weight can be used to calculate the initial total daily insulin dose in insulin naï ve patients with type 1 diabetes.

Patients with type 2 diabetes mellitus

Suggested initial dose is 4 units at one or more meals. Number of injections and subsequent titration will depend on the individual glycaemic target and the size and composition of the meals.

Dose adjustment may be considered daily based on self-measured plasma glucose (SMPG) on the previous day(s) according to Table 1.

• Pre-breakfast dose should be adjusted according to the pre-lunch SMPG the previous day

• Pre-lunch dose should be adjusted according to the pre-dinner SMPG the previous day

• Pre-dinner dose should be adjusted according to the bedtime SMPG the previous day

Special populations

Elderly patients (≥ 65 years old)

The safety and efficacy of Fiasp have been established in elderly patients aged 65 to 75 years. Close glucose monitoring is recommended and the insulin dose should be adjusted on an individual basis (see section 5.1 and 5.2). The therapeutic experience in patients ≥ 75 years of age is limited.

Renal impairment

Renal impairment may reduce the patient's insulin requirements. In patients with renal impairment, glucose monitoring should be intensified and the dose adjusted on an individual basis (see section 5.2).

Hepatic impairment

Hepatic impairment may reduce the patient's insulin requirements. In patients with hepatic impairment, glucose monitoring should be intensified and the dose adjusted on an individual basis (see section 5.2).

Paediatric population

Fiasp can be used in adolescents and children from the age of 1 year (see section 5.1). There is no clinical experience with the use of Fiasp in children below the age of 2 years.

Fiasp is recommended to be administered prior to the meal (0-2 minutes), with the flexibility to administer up to 20 minutes after starting the meal in situations, when there is uncertainty about the meal intake.

Transfer from other insulin medicinal products

Close glucose monitoring is recommended during the transfer from other mealtime insulins and in the initial weeks thereafter. Converting from another mealtime insulin can be done on a unit-to-unit basis. Transferring a patient from another type, brand or manufacturer of insulin to Fiasp must be done under strict medical supervision and may result in the need for a change in dose.

Doses and timing of concurrent intermediate-acting or long-acting insulin medicinal products or other concomitant antidiabetic treatment may need to be adjusted.

Method of administration

Subcutaneous injection

Fiasp is recommended to be administered subcutaneously by injection in the abdominal wall or the upper arm (see section 5.2). Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections 4.4 and 4.8).

Fiasp 100 units/mL solution for injection in vial

Administration with a syringe

The vial is to be used with insulin syringes with the corresponding unit scale (units-100 or 100 units/mL).

Continuous subcutaneous insulin infusion (CSII)

Fiasp solution for injection in vial can be used for CSII in pumps suitable for insulin infusion and will cover both the bolus insulin requirement (approximately 50%) and basal insulin. It can be administered in accordance with the instructions provided by the pump manufacturer, preferably in the abdomen. When used with an insulin infusion pump, it should not be diluted or mixed with any other insulin medicinal products.

Patients using CSII should be instructed in the use of the pump and use the correct reservoir and tubing for pump (see section 6.6). The infusion set (tubing and cannula) should be changed in accordance with the instructions in the product information supplied with the infusion set.

Patients administering Fiasp by CSII must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.

Intravenous use

Fiasp 100 units/mL solution for injection in vial

If necessary, Fiasp can be administered intravenously by health care professionals.

For intravenous use, it should be used at concentrations from 0.5 unit/mL to 1 unit/mL insulin aspart in infusion systems – using polypropylene infusion bags.

Fiasp must not be mixed with any other insulin or any other medicinal product except those mentioned in section 6.6. For instructions on dilution of the medicinal product before administration, see section 6.6.

Monitoring of blood glucose is necessary during insulin infusion. Care should be taken to ensure that the insulin is injected into the infusion bag and not simply the entry port.

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

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.

Hypoglycaemia

Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.

Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement (see sections 4.8 and 4.9).

Patients, whose blood glucose control is greatly improved, e.g. by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia and should be advised accordingly. Usual warning symptoms may disappear in patients with long-standing diabetes.

The timing of hypoglycaemia usually reflects the time-action profile of the administered insulin formulation. Hypoglycaemia may occur earlier after an injection/infusion when compared to other mealtime insulins due to the earlier onset of action of Fiasp (see section 5.1).

Since Fiasp should be administered up to 2 minutes before the start of the meal with the option to administer up to 20 minutes after starting the meal, the time to onset of action must be taken into account when prescribing to patients with concomitant diseases or treatment where a delayed absorption of food might be expected.

Paediatric population

Close monitoring of blood glucose levels is recommended if administering this medicinal product after the start of the last meal of the day, in order to avoid nocturnal hypoglycaemia.

Hyperglycaemia and diabetic ketoacidosis

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

Continuous subcutaneous insulin infusion (CSII)

Pump or infusion set malfunctions can lead to a fast onset of hyperglycaemia and ketosis. Prompt identification and correction of the cause of hyperglycaemia or ketosis is necessary. Interim therapy with subcutaneous injection may be required.

Skin and subcutaneous tissue disorders

Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site from an affected to an unaffected area, and dose adjustment of antidiabetic medicinal products may be considered.

Transfer from other insulin medicinal products

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 Fiasp from another type of insulin may require a change in dose from that used with their usual insulin medicinal products.

Concomitant illness

Concomitant illness, especially infections and feverish conditions, usually increases the patient's insulin requirements. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland may require changes in the insulin dose.

Combination of pioglitazone and insulin medicinal products

Cases of congestive heart failure have been reported when pioglitazone were used in combination with insulin, especially in patients with risk factors for development of congestive heart failure. This should be kept in mind if treatment with the combination of pioglitazone and insulin medicinal products is considered. If the combination is used, patients should be observed for signs and symptoms of congestive heart failure, weight gain and oedema. Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.

Insulin initiation and glucose control intensification

Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, acute painful peripheral neuropathy and peripheral oedema. However, long-term glycaemic control decreases the risk of diabetic retinopathy and neuropathy.

Insulin antibodies

Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper- or hypoglycaemia.

Avoidance of accidental mix-ups/medication errors

Patients must be instructed to always check the insulin label before each injection to avoid accidental mix-ups between this medicinal product and other insulin medicinal products.

Patients must visually verify the units of the dose prior to administering. Therefore, the requirement for patients to self-administer is that they can read the dose scale. Patients, who are blind or have poor vision, must be instructed to always get assistance from another person who has good vision and is trained in administration of insulins.

Travelling between time zones

Before travelling between different time zones, the patient should seek the doctor's advice.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.

A number of medicinal products are known to interact with the glucose metabolism.

The following substances may reduce insulin requirement:

Oral antidiabetics, monoamine oxidase inhibitors (MAOIs), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids, sulphonamides and GLP-1 receptor agonist.

The following substances may increase insulin requirement:

Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics, growth hormone and danazol.

Beta-blocking agents may mask the symptoms of hypoglycaemia.

Octreotide/lanreotide may either increase or decrease the insulin requirement.

Alcohol may intensify or reduce the hypoglycaemic effect of insulin.

Pregnancy

Fiasp can be used in pregnancy.

Data from two randomised controlled clinical trials conducted with insulin aspart (322 + 27 exposed pregnancies) do not indicate any adverse effect of insulin aspart on pregnancy or on the health of the foetus/new born when compared to soluble 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. Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimesters. After delivery, insulin requirements normally return rapidly to pre-pregnancy values.

Breast-feeding

There are no restrictions on treatment with Fiasp during breast-feeding. Insulin treatment of the breast-feeding mother presents no risk to the baby. However, the dose may need to be adjusted.

Fertility

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

The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g., driving a car or using machines).

Patients should be advised to take precautions to avoid hypoglycaemia while driving. This is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.

Summary of safety profile

The most frequently reported adverse reaction during treatment is hypoglycaemia (see section 'Description of selected adverse reactions' below).

Tabulated list of adverse reactions

Adverse reactions listed below (Table 2) are based on data from 6 completed therapeutic confirmatory trials in adults. Frequency categories are defined according to the following convention: 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) and not known (cannot be estimated from the available data).

Table 2 Adverse reactions from clinical trials

^† ADR from postmarketing sources.

Description of selected adverse reactions

Allergic reactions

Allergic skin manifestations reported with Fiasp (1.8% vs. 1.5% for comparator) include eczema, rash, rash pruritic, urticaria and dermatitis.

With Fiasp generalised hypersensitivity reactions (manifested by generalised skin rash and facial oedema) was reported uncommonly (0.2% vs. 0.3% for comparator).

Hypoglycaemia

Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. The 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 (see sections 4.4 and 5.1). Hypoglycaemia may occur earlier after an injection/infusion of Fiasp compared to other mealtime insulins due to the earlier onset of action.

Skin and subcutaneous tissue disorders

Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Lipodystrophy was reported at the injection/infusion site in patients treated with Fiasp (0.5% vs. 0.2% in comparator). Continuous rotation of the injection site within the given injection area may help to reduce or prevent these reactions (see section 4.4).

Injection/infusion site reactions

Injection site reactions (including rash, redness, inflammation, pain and bruising) were reported in patients treated with Fiasp (1.3% vs. 1.0% in comparator). In patients using CSII (N=261): Infusion site reactions (including redness, inflammation, irritation, pain, bruising and itching) were reported in patients treated with Fiasp (10.0% vs. 8.3% in comparator). These reactions are usually mild and transitor