Fiasp 100 U/ml Solution for injection

Maintenance treatment of diabetes mellitus in adults, adolescents and children aged 1 year and above, used alone or in combination with other insulins or metformin.

Posology

Dosage Fiasp u00ae is a mealtime insulin for subcutaneous administration at the start of a meal or post-meal (within 20 minutes after starting a meal).

Fiasp can be used for continuous subcutaneous insulin infusion (CSII) in pumps or be administrated intravenously by healthcare professionals. The potency of Fiasp u00ae , is expressed in units. One (1) unit of Fiasp u00ae corresponds to 1 international unit of human insulin or 1 unit of other fast-acting insulin analogues.

Dosing with Fiasp u00ae is individual and determined in accordance with the needs of the patient.

Injection therapy: Fiasp u00ae 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 u00ae and the remainder by intermediate acting or long-acting insulin.

Continuous subcutaneous insulin infusion (CSII): Fiasp u00ae can be used for continuous subcutaneous insulin infusion (CSII) in pumps. In this case, Fiasp u00ae will cover both the need for bolus insulin (approximately 50 %) and basal insulin. Blood glucose monitoring and insulin dose adjustment are recommended to achieve optimal glycaemic control.

The individual total daily insulin requirement in adults, adolescents and children, may vary and is usually between 0,5 and 1,0 unit/kg/day. 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.

Initiation

Patients with type 1 diabetes mellitus The recommended starting dose of Fiasp u00ae in insulin nau00efve patients with type 1 diabetes is approximately 50 % of the total daily insulin dose and should be divided between each daily meal. 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 nau00efve 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 individual glycaemic target.

Transfer from other insulin medicines 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. Due to the fast onset of insulin action, Fiasp u00ae should be injected at the start of a meal or post-meal (within 20 minutes after starting a meal). Transferring a patient from another type, brand or manufacturer of insulin to Fiasp u00ae must be done under medical supervision and may result in the need for a change in dosage. Doses and timing of concurrent intermediate or long-acting insulin products or other concomitant antidiabetic treatment may need to be adjusted.

Patients with type 2 diabetes mellitus Fiasp u00ae adjustment may be considered daily based on mealtime and bedtime SMPG (Self Monitoring Plasma Glucose) on the previous day according to Table 1 u2022 Pre-breakfast Fiasp u00ae should be adjusted according to the pre-lunch SMPG (Self Monitoring Plasma Glucose) the previous day u2022 Pre-lunch Fiasp u00ae should be adjusted according to the pre-dinner SMPG the previous day u2022 Pre-dinner Fiasp u00ae should be adjusted according to the bedtime SMPG the previous day.

Elderly (u2265 65 years old) The safety and efficacy of Fiasp u00ae has been established in elderly patients. Close glucose monitoring is recommended and the insulin dose should be adjusted on an individual basis ( see PD, PK sections and clinical efficacy and safety data).

Renal and hepatic impairment Renal or hepatic impairment may reduce the patientu2019s insulin requirements. In patients with renal or hepatic impairment, glucose monitoring should be intensified and the dose adjusted on an individual basis ( see PK section ).

Paediatric population Fiasp u00ae can be used in adolescents and children aged 1 year and above ( see section 3.1 ).

Method of administration

Subcutaneous injection: Fiasp u00ae is administered subcutaneously by injection in the abdominal wall, the upper arm or the thigh. Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy and cutaneous amyloidosis ( see sections 4.2 and 4.3 ). The duration of action of Fiasp u00ae may vary according to the dose, injection site, blood flow, temperature and level of physical activity.

Continuous Subcutaneous Insulin Infusion (CSII): Fiasp u00ae has been used in limited number of patients for Continuous Subcutaneous Insulin Infusion (CSII) in pumps suitable for insulin infusion. Fiasp u00ae can be administered in accordance with the instructions provided by the pump manufacturer, preferably in the abdomen. Infusion sites should be rotated within the same region to reduce the risk of lipodystrophy. When used with an insulin infusion pump, Fiasp u00ae should not be diluted or mixed with any other insulin medicines. Patients using CSII should be instructed in the use of the pump and use the correct reservoir and tubing for pump. The infusion set (tubing and cannula) should be changed in accordance with the instructions in the medicine information supplied with the infusion set. Patients administering Fiasp u00ae by CSII must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure.

Intravenous use: If necessary, Fiasp u00ae can be administered intravenously by health care professionals. For intravenous use Fiasp u00ae should be used at concentrations from 0,5 unit/ml to 1,0 unit/ml insulin aspart in infusion systems using polypropylene infusion bags. Fiasp u00ae has been shown to be stable at room temperature for 24 hours in the infusion fluids such as 0,9 % sodium chloride or 5 % dextrose. 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. Substances added to Fiasp u00ae may cause degradation of insulin aspart. Fiasp u00ae must not be diluted or mixed with any other products except infusion fluids as described in method of administration.

Missed dose 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.

• Hypersensitivity to the insulin aspart or any of the excipients listed under u201cCompositionu201d.
• During episodes of hypoglycaemia

The safe use of Fiasp in treatment of ketoacidosis has not been established.

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 u201c OVERDOSE u201d). 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 concentrating, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation. 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 longstanding diabetes. The timing of hypoglycaemia usually reflects the time-action profile of the administered insulin formulation. Fiasp u00ae has a distinct time action profile, which impacts the timing of hypoglycaemia. A consequence of the pharmacodynamics of Fiasp u00ae is that if hypoglycaemia occurs, it may occur earlier after an injection/infusion when compared to other mealtime insulins. Since Fiasp u00ae should be administered at the start of a meal or postmeal (within 20 minutes after starting a meal), the fast onset of action should therefore be considered in patients with delayed gastric emptying.

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

Hyperglycaemia 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. The first symptoms of hyperglycaemia usually come on gradually, over a period of hours or days. They include nausea, vomiting, drowsiness, flushed dry skin, dry mouth, increased urination, thirst and loss of appetite as well as acetone breath.

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.

Clinical safety data with use of Fiasp by continuous subcutaneous insulin infusion (CSII) in pumps is limited.

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 medicines Cases of congestive heart failure have been reported when pioglitazone was 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 medicines 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. 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 Fiasp u00ae and other insulin medicines. Patients must visually verify the units of the dose prior to administering Fiasp u00ae. 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.

Allergic reactions Anaphylactic reactions may occur. Immediate-type allergic reactions to either insulin itself or the excipients may potentially be life-threatening.

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 medicine may be considered.

A number of medicines are known to interact with the glucose metabolism. The following substances may reduce insulin requirement: Oral antidiabetic medicines, monoamine oxidase inhibitors (MAOIs), beta-blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids, angiotensin receptor blockers (ARBu2019s), 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 medicines 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 Safety in pregnancy has not been established. Insulin aspart does not cross the placental barrier. Intensified blood glucose control and monitoring of pregnant women with diabetes (Type 1, Type 2 or gestational diabetes) are recommended throughout pregnancy and when contemplating pregnancy. Both hypoglycaemia and hyperglycaemia which can occur in inadequately controlled diabetes therapy may increase the risk of malformations and death in utero. Insulin requirements usually fall in the first trimester and increase subsequently during the second and third trimesters. After delivery, insulin requirements return rapidly to pre-pregnancy levels.

Breast-feeding Safety during breast-feeding has not been established. There are no restrictions on treatment with Fiasp during breastfeeding as insulin aspart does not cross into breast milk. However, the Fiasp dosage may need to be adjusted.

The patientu2019s 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 operating machinery). Patients should be advised to take precautions to avoid hypoglycaemia while driving. This is particularly important in those patients 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.

(a) Summary of the safety profile The most frequently reported side effect during treatment is hypoglycaemia (see section u2018Description of selected side effects below).

(b) Tabulated summary of adverse reactions Side effects from clinical trials Side effects listed below are based on data from 6 completed therapeutic confirmatory trials in adults. In five of the trials Fiasp u00ae was compared to comparator insulin and in one trial compared to basal insulin only. In the six trials, 2163 patients were treated with Fiasp u00ae ; 1707 with type 1 diabetes mellitus of which 261 were using CSII, and 456 with type 2 diabetes mellitus. The side effects are classified according to MedDRA System Organ Class. Frequency categories are defined according to the following convention: Very common (u2265 1/10); common (u2265 1/100 to < 1/10); uncommon (u2265 1/1 000 to < 1/100).

Table 2 Side effects from clinical trials MedDRA System Organ Class Very common Common Uncommon Immune system disorders Hypersensitivity Metabolism and nutrition disorders Hypoglycaemia Allergic skin manifestations Lipodystrophy Skin and subcutaneous tissue disorders General disorders and administration site conditions Injection/infusion site reactions Other possible side effects Based on clinical trial data from other insulin aspart products: System organ class Side effect and frequency Immune system disorders Uncommon : Eruptions Very rare Anaphylactic reactions Eye disorders Uncommon Refraction (blurred vision) Uncommon Diabetic retinopathy: General disorders and administration site conditions Uncommon Oedema: Nervous system disorders Rare Peripheral neuropathy (painful neuropathy) Side effects from post-marketing sources The side effect listed below is based on post-marketing source data and is classified according to MedDRA System Organ Class.

MEDRA System organ class side effect and frequency Skin and subcutaneous tissue disorders Frequency: Unknown Cutaneous amyloidosis

Hypoglycaemia may develop over sequential stages if a patient is dosed with more insulin than required:

• Mild hypoglycaemic episodes can be treated by oral administration of glucose or other medicines containing sugar. It is therefore recommended that the diabetic patient always carries glucose-containing medicines.
• Severe hypoglycaemic episodes, where the patient is not able to treat him/herself, can be treated with glucagon (0.5 to 1 mg) given intramuscularly or subcutaneously by a trained person, or with glucose given intravenously by a healthcare professional. Glucose must be given intravenously if the patient does not respond to glucagon within 10 to 15 minutes. Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in order to prevent a relapse.