Tresiba^® (Solution) Instructions for Use

Marketing Authorization Holder

Novo Nordisk A/S (Denmark)

Manufactured By

Novo Nordisk A/S (Denmark)

Or

Novo Nordisk Production S.A.S. (France)

Quality Control Release

NOVO NORDISK A/S (Denmark)

Or

NOVO NORDISK LLC (Russia)

Contact Information

NOVO NORDISK LLC (Russia)

ATC Code

A10AE06 (Insulin degludec)

Active Substance

Insulin degludec (Rec.INN registered by WHO)

Dosage Forms

	Tresiba®	Solution for subcutaneous administration 100 U/ml: cartridge in FlexTouch®/FlexPen® pen-injector 3 ml 5 pcs.
		Solution for subcutaneous administration 200 U/ml: cartridge in FlexTouch® pen-injector 3 ml 3 pcs.

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration transparent, colorless.

Each FlexTouch^® or FlexPen^® pen-injector contains 3 ml of solution, equivalent to 300 U of insulin degludec.

Excipients: glycerol, metacresol, phenol, zinc (as zinc acetate), hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.

3 ml (300 U) – glass cartridges (1) – disposable multidose pen-injectors for multiple injections FlexTouch^® (5) – cardboard packs.
3 ml (300 U) – glass cartridges (1) – disposable multidose pen-injectors for multiple injections FlexPen^® (5) – cardboard packs.

Solution for subcutaneous administration transparent, colorless.

Each FlexTouch^® pen-injector contains 3 ml of solution, equivalent to 600 U of insulin degludec.

Excipients: glycerol, metacresol, phenol, zinc (as zinc acetate), hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), water for injections.

3 ml (600 U) – glass cartridges (1) – disposable multidose pen-injectors for multiple injections FlexTouch^® (3) – cardboard packs.

* Insulin degludec is produced by recombinant DNA biotechnology using a strain of Saccharomyces cerevisiae.

Clinical-Pharmacological Group

Long-acting human insulin analogue

Pharmacotherapeutic Group

Drugs for the treatment of diabetes mellitus; insulins and their analogues; long-acting insulins and their analogues for injectable administration

Pharmacological Action

Mechanism of action

Insulin degludec specifically binds to the receptor of human endogenous insulin and, by interacting with it, realizes its pharmacological effect similarly to that of human insulin.

The hypoglycemic effect of insulin degludec is due to increased glucose utilization by tissues after insulin binds to receptors on muscle and fat cells and a simultaneous decrease in the rate of glucose production by the liver.

Pharmacodynamic effects

The drug Tresiba^® is a long-acting basal human insulin analogue; after subcutaneous injection, it forms soluble multihexamers in the subcutaneous depot, from which continuous and prolonged absorption of insulin degludec into the bloodstream occurs, providing a long, flat profile of action and a stable hypoglycemic effect of the drug (see figure 1). During a 24-hour monitoring period of the hypoglycemic effect of the drug in patients receiving a once-daily dose of insulin degludec, the drug Tresiba^®, unlike insulin glargine 100 U/ml, demonstrated an even distribution of action between the first and second 12-hour periods (AUC_GIR,0-12h,SS/AUC_GIR,total,SS = 0.5).

Figure 1. 24-hour average glucose infusion rate profile – steady-state concentration of insulin degludec 100 U/ml 0.6 U/kg (study 1987)

The duration of action of the drug Tresiba^® is more than 42 hours within the therapeutic dose range. The steady-state plasma concentration of the drug is reached after 2-3 days of administration.

The variability of daily hypoglycemic effect profiles, expressed as the coefficient of variation value, for the study of the hypoglycemic effect of the drug during one dosing interval of 0-24 hours at steady state (AUC_GIR,t,SS) for insulin degludec is 20%, which is significantly lower than for insulin glargine 100 U/ml.

A linear relationship has been demonstrated between the increase in the dose of the drug Tresiba^® and its overall hypoglycemic effect.

Both dosages of the drug Tresiba^® – 100 U/ml and 200 U/ml – demonstrate a comparable overall hypoglycemic effect when each of the two drug dosages is administered in the same total dose.

No clinically significant difference in the pharmacodynamics of the drug Tresiba^® was found between elderly patients and young adult patients.

Clinical efficacy and safety

The results of clinical studies demonstrated the same reduction in HbA_1c from baseline at the end of the study during therapy with Tresiba^® and insulin glargine 100 U/ml. In patients with T1DM, therapy with Tresiba^® was associated with a significantly lower incidence of severe hypoglycemia and severe or confirmed symptomatic hypoglycemia (overall hypoglycemia and nocturnal hypoglycemia) compared with insulin glargine 100 U/ml, both during the maintenance dose period and throughout the entire treatment period. In patients with T2DM, therapy with Tresiba^® was associated with a significant reduction in the incidence of severe or confirmed symptomatic hypoglycemia (overall hypoglycemia and nocturnal hypoglycemia) compared with insulin glargine 100 U/ml, both during the maintenance dose period and throughout the entire treatment period, as well as a reduction in the incidence of severe hypoglycemia episodes throughout the entire treatment period.

Clinical studies have proven the absence of superiority of comparator drugs (insulin detemir and insulin glargine 100 U/ml) over Tresiba^® in terms of reducing HbA_1c from baseline at the end of the study. The exception was sitagliptin, in comparison with which Tresiba^® demonstrated its statistically significant superiority in reducing HbA_1c.

The results of a meta-analysis of seven studies demonstrated the benefits of therapy with Tresiba^® in terms of a lower incidence of confirmed hypoglycemia episodes in patients compared with therapy with insulin glargine 100 U/ml (Table 1) and episodes of confirmed nocturnal hypoglycemia. The reduction in the frequency of hypoglycemia episodes during therapy with Tresiba^® was achieved with a lower mean fasting plasma glucose compared with insulin glargine 100 U/ml.

Table 1. Results of a meta-analysis of hypoglycemia episode data

* Statistically significant.
^a Confirmed symptomatic hypoglycemia is defined as an episode confirmed by a plasma glucose measurement of less than 3.1 mmol/L and accompanied by characteristic symptoms. Nocturnal confirmed hypoglycemia is hypoglycemia that occurred during the time of day between midnight and six o’clock in the morning.
^b Hypoglycemia episodes after the 16th week of therapy.

No clinically significant formation of antibodies to insulin was detected after long-term treatment with Tresiba^®.

In a clinical study in patients with T2DM treated with Tresiba^® in combination with metformin, the addition of liraglutide resulted in a statistically significantly greater reduction in HbA_1c and body weight. The frequency of hypoglycemia episodes was statistically significantly lower with the addition of liraglutide compared with the addition of a single dose of insulin aspart.

Assessment of cardiovascular effects

To compare the cardiovascular safety of Tresiba^® and insulin glargine 100 U/ml, the DEVOTE study was conducted involving 7637 patients with T2DM and high risk of cardiovascular events.

The cardiovascular safety of Tresiba^® compared with insulin glargine 100 U/ml was confirmed (Figure 2).

N: Number of patients with a first event, confirmed by EAC during the study.

%: Proportion of patients with a first event, confirmed by EAC, relative to the number of randomized patients.

EAC: Expert Committee for Adverse Event Assessment.

CI: 95% confidence interval.

Figure 2. Forest plot reflecting the analysis of the composite 3-point major adverse cardiovascular events and individual cardiovascular endpoints in the DEVOTE study

Similar improvement in HbA_1c levels and greater reduction in fasting plasma glucose with Tresiba^® were achieved with insulin glargine and Tresiba^® (Table 2).

Tresiba^® demonstrated an advantage over insulin glargine 100 U/ml in terms of a lower incidence of severe hypoglycemia episodes and a lower proportion of patients who developed severe hypoglycemia. The frequency of severe nocturnal hypoglycemia episodes was significantly lower with Tresiba^® compared with insulin glargine 100 U/ml (Table 2).

Table 2. Results of the DEVOTE study

¹ In addition to the standard of care for diabetes and cardiovascular disease.
² Nocturnal severe hypoglycemia is hypoglycemia that occurred during the time of day between 0 h and 6 h in the morning.

Pregnancy

Tresiba^® was studied in an open-label, randomized, active-controlled clinical trial in which pregnant women with T1DM were treated with a basal-bolus regimen with Tresiba^® (92 women) or insulin detemir (96 women) as basal insulin, both in combination with insulin aspart as prandial insulin (EXPECT study).

Tresiba^® was comparable to insulin detemir in terms of HbA_1c at the last scheduled visit before delivery after the 16th week of gestation. Furthermore, there were no differences between treatment groups in glycemic control (changes in HbA_1c, fasting plasma glucose, and postprandial glucose levels) during pregnancy.

There were no clinically significant differences between Tresiba^® and insulin detemir regarding maternal safety endpoints: hypoglycemia, preterm delivery, and adverse reactions during pregnancy. Preeclampsia was reported in 12 patients (13.2%) receiving Tresiba^® and in 7 patients (7.4%) receiving insulin detemir. Unplanned cesarean section was reported in 23 patients (25.3%) receiving Tresiba^® therapy and in 15 patients (16.0%) receiving insulin detemir therapy. Most of the adverse reactions reported in both groups were non-serious, mild in severity, unlikely related to Tresiba^® use, and had an outcome of “cured/resolved”. There were no deaths among patients randomized into the study.

No perinatal or neonatal deaths were reported. There were no clinically significant differences between Tresiba^® and insulin detemir regarding pregnancy endpoints (early fetal death, presence of serious anomalies, neonatal hypoglycemia, perinatal mortality, neonatal mortality, fetal macrosomia, large for gestational age, and adverse reactions in the newborn within 30 days after birth).

Children and adolescents

In a clinical study in children and adolescents with T1DM, once-daily administration of Tresiba^® showed a similar reduction in HbA_1c at week 52 and a more pronounced reduction in fasting plasma glucose from baseline compared with the comparator drug (insulin detemir once or twice daily). This result was achieved with Tresiba^® at a daily dose 30% lower than that of insulin detemir. The frequency (events per patient-year of exposure) of severe hypoglycemia (International Society for Pediatric and Adolescent Diabetes (ISPAD) definition) (0.51 compared with 0.33), confirmed hypoglycemia (57.71 compared with 54.05) and nocturnal confirmed hypoglycemia (6.03 compared with 7.60) was comparable with Tresiba^® and insulin detemir. In both treatment groups, children aged 6 to 11 years had a higher frequency of confirmed hypoglycemia episodes than other age groups. A higher frequency of severe hypoglycemia episodes was observed in children aged 6 to 11 years in the Tresiba^® group. The frequency of hyperglycemia with ketosis episodes was significantly lower with Tresiba^® compared with insulin detemir treatment, 0.68 and 1.09, respectively. The incidence, type, and severity of adverse reactions in the pediatric patient population do not differ from those in the general patient population with diabetes. Antibody formation was rare and had no clinical significance. Efficacy and safety data in adolescents with T2DM were extrapolated from data obtained in adolescents and adults with T1DM and adults with T2DM. The results obtained allow recommending Tresiba^® for the treatment of adolescents with T2DM.

Preclinical safety data

Preclinical data based on studies of pharmacological safety, repeated dose toxicity, carcinogenic potential, and reproductive toxicity did not reveal any specific hazard of insulin degludec for humans.

The ratio of metabolic and mitogenic activities of insulin degludec is similar to that of human insulin.

Pharmacokinetics

Absorption

The long-acting effect of insulin degludec is due to its specially designed molecular structure. After subcutaneous injection, soluble stable multihexamers are formed, which create an insulin depot in the subcutaneous adipose tissue. The multihexamers gradually dissociate, releasing insulin degludec monomers, resulting in slow and prolonged entry of the drug into the bloodstream.

The steady-state plasma concentration of insulin degludec is reached after 2-3 days of daily administration of the drug.

The action of insulin degludec over 24 hours with its once-daily administration is evenly distributed between the first and second 12-hour intervals (AUC_{IDeg,0-12h,SS}/AUC_IDeg,t,SS = 0.5).

Distribution

The binding of insulin degludec to plasma proteins (albumin) is >99%.

Metabolism

The degradation of insulin degludec is similar to that of human insulin; all metabolites formed are inactive.

Elimination

T_1/2 after subcutaneous injection of insulin degludec is determined by the rate of its absorption from the subcutaneous tissue. The T_1/2 of insulin degludec is approximately 25 hours and is independent of the dose.

Linearity

Upon subcutaneous administration, total plasma concentrations were proportional to the administered dose within the therapeutic dose range. In a direct comparison of both dosages of the drug Tresiba^® – 100 U/ml and 200 U/ml – data on their bioequivalence compliance with established requirements were obtained (based on data on AUC_IDeg,t,SS and C_max,IDeg,SS).

Pharmacokinetics in special patient groups

Gender. No differences in the pharmacokinetic properties of Tresiba^® were found depending on the gender of the patients.

Elderly patients, patients of different ethnic groups, patients with impaired renal and hepatic function. No differences in the pharmacokinetics of insulin degludec were found between elderly patients and young adult patients, between patients of different ethnic groups, between patients with impaired renal or hepatic function and healthy volunteers.

Children and adolescents. The pharmacokinetic properties of insulin degludec in children (from 1 to 11 years old) and adolescents (from 12 to 18 years old) at steady state were comparable to those observed in adult patients with type 1 diabetes mellitus. However, after a single dose, the total exposure in children and adolescents was higher than in adult patients with type 1 diabetes mellitus.

Indications

Adults, adolescents, and children aged 1 year and older

• Treatment of diabetes mellitus.

ICD codes

Dosage Regimen

The drug Tresiba^® is a long-acting insulin analog.

The drug is administered subcutaneously once daily at any time of the day, but it is preferable to administer the drug at the same time every day.

The activity of insulin analogs, including insulin degludec, is expressed in units (U). One unit (U) of insulin degludec corresponds to one international unit (IU) of human insulin, one unit (U) of insulin glargine 100 U/ml, or one unit (U) of insulin detemir.

In patients with type 2 diabetes mellitus, the drug Tresiba^® can be used both as monotherapy and in combination with oral hypoglycemic drugs, glucagon-like peptide-1 receptor agonists, and with bolus insulin (see the “Pharmacological Action” section).

Patients with type 1 diabetes mellitus are prescribed Tresiba^® in combination with short/ultra-short-acting insulin to cover prandial insulin requirements.

The dose of Tresiba^® should be determined individually according to the patient’s needs. To optimize glycemic control, it is recommended to adjust the drug dose based on fasting plasma glucose levels.

As with the use of any insulin drugs, dose adjustment of Tresiba^® may also be necessary with increased physical activity, changes in the patient’s usual diet, or concomitant illness.

Tresiba^® 100 U/ml and Tresiba^® 200 U/ml

Tresiba^® is available in two strengths. For both strengths, the required drug dose is set in units. However, the dose step differs between the two Tresiba^® strengths.

• The FlexTouch^® pen, pre-filled with Tresiba^® 100 U/ml, allows doses from 1 to 80 U to be administered in 1 U increments per injection.

• The FlexPen^® pen, pre-filled with Tresiba^® 100 U/ml, allows doses from 1 to 60 U to be administered in 1 U increments per injection.

• The FlexTouch^® pen, pre-filled with Tresiba^® 200 U/ml, allows doses from 2 to 160 U to be administered in 2 U increments per injection. The insulin dose is contained in half the volume of solution compared to 100 U/ml basal insulin products.

The dose counter shows the number of units regardless of the strength; it is not necessary to recalculate the dose when switching patients to a new strength.

Flexible dosing regimen

In cases where administration at the same time is not possible, Tresiba^® allows for a change in the time of its administration (see the “Pharmacological Action” section). In this case, the interval between injections should be at least 8 hours. There is no clinical experience with the flexible dosing regimen of Tresiba^® in children and adolescents.

Patients who forget to administer their insulin dose on time are advised to administer the dose as soon as they remember it, and then return to their usual time of once-daily administration.

Initial dose of Tresiba^®

Patients with type 2 diabetes mellitus

The recommended initial daily dose of Tresiba^® is 10 U, followed by individual dose titration.

Patients with type 1 diabetes mellitus

Tresiba^® is prescribed once daily in combination with prandial insulin administered with meals, followed by individual dose titration.

Switching from other insulin drugs

Careful monitoring of blood glucose concentration is recommended during the switch and in the first weeks of therapy with Tresiba^®. Adjustment of concomitant hypoglycemic therapy (dose and timing of short-acting and ultra-short-acting insulin drugs or other concurrently used hypoglycemic drugs) may be required.

Patients with type 2 diabetes mellitus

When switching patients with type 2 diabetes mellitus to Tresiba^® who are on a basal or basal-bolus insulin therapy regimen, or on a regimen of premixed insulin/self-mixed insulin therapy, the dose of Tresiba^® should be calculated based on the basal insulin dose the patient was receiving prior to the switch to the new insulin type, on a “unit-for-unit” basis, and then adjusted according to the patient’s individual needs.

A dose reduction of 20% from the previous basal insulin dose should be considered, followed by adjustment according to the patient’s individual needs in the following cases

• Switching from a basal insulin that was administered twice daily to Tresiba^®;
• Switching from insulin glargine 300 U/ml to Tresiba^®.

Patients with type 1 diabetes mellitus

When switching patients with type 1 diabetes mellitus to Tresiba^®, a dose reduction of 20% from the previous basal insulin dose or the basal component of continuous subcutaneous insulin infusions should be considered. The dose is then adjusted according to the patient’s individual needs based on glycemic readings.

Use of Tresiba^® in combination with GLP-1 receptor agonists in patients with type 2 diabetes mellitus

When adding Tresiba^® to treatment with GLP-1 receptor agonists, the recommended initial daily dose is 10 U with subsequent individual dose adjustment.

When adding GLP-1 receptor agonists to treatment with Tresiba^®, it is recommended to reduce the dose of Tresiba^® by 20% to minimize the risk of hypoglycemia. The dose should then be adjusted.

Special patient groups

Elderly patients (over 65 years)

Tresiba^® can be used in elderly patients. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually (see the “Pharmacokinetics” section).

Patients with renal and hepatic impairment

Tresiba^® can be used in patients with renal and hepatic impairment. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually (see the “Pharmacokinetics” section).

Children and adolescents

Tresiba^® can be used to treat adolescents and children aged 1 year and older (see the “Pharmacological Action” section). When switching from basal insulin to Tresiba^®, the need to reduce the dose of basal and bolus insulin should be considered in each individual case to minimize the risk of hypoglycemia (see the “Special Instructions” section).

Method of administration

Tresiba^® is for subcutaneous use only.

Tresiba^® must not be administered intravenously, as this may lead to severe hypoglycemia.

Tresiba^® must not be administered intramuscularly, as this alters the absorption of the drug.

Tresiba^® must not be used in insulin pumps.

It is not permitted to extract Tresiba^® with a syringe from the cartridge of a pre-filled pen (see the “Special Instructions” section).

Tresiba^® is administered subcutaneously into the thigh, upper arm, or abdominal wall. Injection sites should be rotated within the same anatomical area to reduce the risk of lipodystrophy and cutaneous amyloidosis (see the “Special Instructions” and “Adverse Reactions” sections).

Patients should be advised to always use a new needle. Reusing pen needles increases the risk of needle blockage, which may lead to underdosing or overdosing. In case of needle blockage, the patient should follow the instructions in the Patient Information Leaflet supplied with the pen (see below).

FlexTouch^® or FlexPen^® pens pre-filled with Tresiba^® are designed for use with Novofine^® injection needles.

Patient Information Leaflet for Tresiba^®, solution for subcutaneous injection 100 U/ml in FlexPen^® pen

Read this leaflet carefully before using Tresiba^® in the pre-filled FlexPen^® pen.

If you do not follow the instructions carefully, you may administer too little or too much insulin, which can lead to blood sugar levels that are too high or too low.

FlexPen^® is a pre-filled insulin pen with a dose selector. You can select doses from 1 to 60 units in 1-unit steps. The FlexPen^® pen is designed for use with disposable Novofine^® needles up to 8 mm in length. As a precaution, always carry a spare insulin delivery system in case your Tresiba^® FlexPen^® is lost or damaged.

Pen care

The FlexPen^® pen requires careful handling.

If dropped, subjected to strong mechanical impact, or damaged, the pen may leak insulin. This can cause incorrect dosing, which may lead to blood sugar levels that are too high or too low.

The surface of the FlexPen^® pen can be cleaned with a cotton swab moistened with alcohol. Do not immerse the pen in liquid, do not wash or lubricate it, as this may damage the mechanism.

Do not leave the pen in a car or any other place where it may be exposed to very high or very low temperatures.

The FlexPen^® pen must not be refilled.

Do not attempt to repair the pen or take it apart yourself.

1. Preparing the FlexPen^® pen

Check the name and color of the pen label to ensure it contains the correct type of insulin. This is especially important if you use different types of insulin. If you mistakenly administer the wrong type of insulin, your blood sugar may become too high or too low.

1A. Remove the cap from the pen.

1B. Remove the protective tab from a new disposable needle.

Screw the needle tightly onto the FlexPen^® pen.

1C. Pull off the large outer needle cap, but do not discard it.

1D. Pull off and discard the inner needle cap.

Never try to put the inner cap back on the needle. You may prick yourself.

Important! Use a new needle for each injection. This reduces the risk of contamination, infection, insulin leakage, needle blockage, and incorrect dosing.

Important! Be careful not to bend or damage the needle before use.

2. Checking insulin flow

Even with proper use, a small amount of air may collect in the cartridge. To avoid injecting an air bubble and ensure the correct dose is administered

2E. Dial 2 units by turning the dose selector.

2F. Holding the FlexPen^® pen with the needle pointing upwards, tap the cartridge gently with your fingertip a few times so that any air bubbles rise to the top of the cartridge.

2G. Holding the pen with the needle pointing upwards, press the push-button all the way in. The dose selector will return to zero.

A drop of insulin should appear at the needle tip. If it does not, replace the needle and repeat the procedure, but no more than 6 times.

If a drop of insulin still does not appear at the needle tip, this indicates that the pen is faulty. Use a new pen.

Important! Before each injection, make sure a drop of insulin appears at the needle tip. This guarantees insulin flow. If a drop does not appear, the dose will not be administered, even if the dose selector moves. This may indicate a blocked or damaged needle.

Important! Check insulin flow before each injection. If you do not check insulin flow, you may administer too little or no insulin, which can lead to blood sugar levels that are too high.

3. Setting the dose

Before starting the injection, make sure the dose selector is set at “0”.

3H. Dial the number of units you need for your injection by turning the dose selector.

The dose can be adjusted by turning the dose selector in either direction until the correct dose is aligned with the dose pointer. Be careful when turning the dose selector not to press the push-button accidentally, to avoid expelling insulin.

It is not possible to set a dose larger than the number of units remaining in the cartridge.

If the dose you need is larger than the number of units remaining in the cartridge, administer it using a new pen.

Important! Before injection, always check how many units of insulin you have dialed using the dose selector and dose pointer.

Important! Do not count the pen clicks. If you set and administer the wrong dose, your blood sugar may become too high or too low. The insulin scale shows the approximate amount of insulin left in the pen, so it must not be used for measuring the insulin dose.

4. Injecting insulin

Insert the needle under your skin using the injection technique recommended by your doctor or nurse.

4I. To inject, press the push-button all the way in until “0” appears aligned with the dose pointer. Be careful: only the push-button should be pressed when injecting.

Turning the dose selector will not inject insulin.

4J. After injection, leave the needle under the skin for at least 6 seconds, keeping the push-button fully depressed. This ensures the full dose of insulin is administered.

Pull the needle out of the skin and release the push-button.

Make sure the dose selector returns to zero after injection. If the dose selector stops before it shows “0”, the full insulin dose was not administered, which may lead to blood sugar levels that are too high.

4K. Point the needle into the large outer needle cap without touching the cap. When the needle is covered, push the cap on completely and unscrew the needle.

Discard the needle safely and put the cap back on the pen.

Important! Remove the needle after each injection and store the FlexPen^® pen with the needle removed. This reduces the risk of contamination, infection, insulin leakage, needle blockage, and incorrect dosing.

Important information

• Caregivers should handle used needles with special care to reduce the risk of accidental needle sticks and cross-infection.
• Discard the used FlexPen^® pen with the needle removed.
• Never share your pen and needles with others. This can lead to cross-infection.
• Never share your pen with others. Your medication may harm their health.
• Always keep the pen and needles out of reach of everyone, especially children.

Patient Information Leaflet for Tresiba^®, solution for subcutaneous injection 100 U/ml in FlexTouch^® pen

Read this leaflet carefully before using Tresiba^® in the pre-filled FlexTouch^® pen.

If you do not follow the instructions carefully, you may administer too little or too much insulin, which can lead to blood sugar levels that are too high or too low.

Only use the pen after you have been trained in its use by your doctor or nurse. First, check the labeling on the pen to make sure it contains Tresiba^® 100 U/ml, and then study the illustrations below showing the details of the pen and needle.

If you cannot see the numbers in the dose counter because you are blind or have serious vision problems, do not use the pen without assistance. A sighted person trained in the correct use of the pre-filled FlexTouch^® pen can assist you.

The pre-filled FlexTouch^® pen with Tresiba^® 100 U/ml contains 300 U of insulin degludec. The maximum dose you can set is 80 units in 1-unit steps. The pen is designed for use with disposable Novofine^® needles up to 8 mm in length. Needles are not included in the package.

1. Preparing the pen for use

Check the name and strength on the label of the pen to ensure it contains Tresiba^® 100 U/ml. This is especially important if you use different types of insulin. If you mistakenly administer the wrong type of insulin, your blood sugar may become too high or too low.

1A. Remove the cap from the pen.

1B. Make sure the insulin in the pen is clear and colorless. Look through the insulin scale window. If the product is cloudy, the pen must not be used.

1C. Take a new disposable needle and remove the protective tab.

1D. Place the needle on the pen and turn it to secure the needle firmly on the pen.

1E. Pull off the outer needle cap, but do not discard it. You will need it after the injection to remove the needle from the pen correctly.

1F. Remove and discard the inner needle cap. If you try to put the inner cap back on the needle, you may accidentally prick yourself.

A drop of insulin may appear at the needle tip. This is normal, however, you should still check the insulin flow.

Important! Always use a new needle for each injection.

This reduces the risk of contamination, infection, insulin leakage, needle blockage, and administration of an incorrect dose.

Important! Never use a needle if it is bent or damaged.

2. Checking insulin flow

Before each injection, check the insulin flow. This will help you ensure that the insulin dose is delivered completely.

2A. Dial 2 units of the medication by turning the dose selector. Make sure the dose counter shows “2”.

2B. Holding the pen with the needle pointing upwards, gently tap the top of the pen several times with your fingertip so that any air bubbles collect at the top.

2C. Press and hold the release button until the dose counter returns to “0”.

The “0” must be aligned with the dose pointer.

A drop of insulin should appear at the needle tip.

A small air bubble may remain at the needle tip, but it will not be injected.

If a drop of insulin does not appear at the needle tip, repeat steps 2A – 2C, but no more than 6 times. If a drop of insulin still does not appear, change the needle and repeat steps 2A – 2C again.

If a drop of insulin still does not appear at the needle tip, do not use this pen. Use a new pen.

Important! Before each injection, make sure that a drop of insulin appears at the needle tip. This guarantees insulin flow.

If a drop of insulin does not appear, the dose will not be delivered, even if the dose counter moves. This may indicate that the needle is blocked or damaged.

Important! Always check the insulin flow before each injection. If you do not check the insulin flow, you may deliver an insufficient dose of insulin or no insulin at all, which may lead to excessively high blood sugar.

3. Setting the dose

Before starting the injection, make sure the dose counter is set to “0”.

The “0” must be aligned with the dose pointer.

3A. Set the dose you need by turning the dose selector, as prescribed by your doctor.

If you have set the wrong dose, you can turn the dose selector forwards or backwards until you set the correct dose.

The maximum dose you can set is 80 units.

The dose selector allows you to set the number of units. Only the dose counter and dose pointer show the number of units of insulin in the dose you have dialed.

The maximum dose you can set is 80 units. If the remaining insulin in the pen is less than 80 units, the dose counter will stop at the number of insulin units left in the pen.

Clicks are heard each time the dose selector is turned; the sound of the clicks depends on the direction the dose selector is turned (forwards, backwards, or if the dialed dose exceeds the number of insulin units remaining in the pen). Do not count these clicks.

Important! Before each injection, check how many units of insulin you have dialed using the dose counter and dose pointer.

Do not count the pen clicks. If you set and deliver an incorrect dose, your blood sugar may become too high or too low.

The insulin scale shows the approximate amount of insulin remaining in the pen, so it cannot be used for measuring the insulin dose.

4. Injecting insulin

Insert the needle under your skin, using the injection technique recommended by your doctor or nurse.

Make sure the dose counter is in your field of vision. Do not touch the dose counter with your fingers. This may interrupt the injection.

Press the release button all the way down and hold it in this position until the dose counter returns to “0”.

The “0” must be exactly aligned with the dose pointer.

You may hear or feel a click during this.

4A. After the injection, leave the needle under the skin for at least 6 seconds, to ensure that the full insulin dose has been delivered.

4B. Remove the needle from under the skin by pulling the pen straight up.

If blood appears at the injection site, press lightly with a cotton swab. Do not rub the injection site.

After the injection is complete, you may see a drop of insulin at the needle tip. This is normal and does not affect the dose you have injected.

Important! Always check the dose counter reading to know how many units of insulin you have delivered.

The dose counter will show the exact number of units. Do not count the number of pen clicks. After injection, hold the release button until the dose counter returns to “0”. If the dose counter stopped before showing “0”, the full insulin dose was not delivered, which may lead to excessively high blood sugar.

5. After completing the injection

5A. Place the outer needle cap on a flat surface and, without touching the cap or the needle, insert the needle into the cap.

When the needle is inside the cap, carefully push the cap onto the needle.

5B. Unscrew the needle and discard it, taking safety precautions.

5C. After each injection, put the cap back on the pen to protect the insulin inside from light.

Always discard the needle after each injection. This reduces the risk of contamination, infection, insulin leakage, needle blockage, and administration of an incorrect dose. If the needle is blocked, you will not be able to inject insulin.

Discard the used pen with the needle removed, according to the recommendations given by your doctor, nurse, pharmacist, or according to local requirements.

Important! Never try to put the inner needle cap back on the needle. You may prick yourself.

Important! After each injection, always remove the needle and store the pen with the needle removed.

This reduces the risk of contamination, infection, insulin leakage, needle blockage, and administration of an incorrect dose.

6. How much insulin is left?

6A. The insulin scale shows the approximate amount of insulin remaining in the pen.

6B. To find out exactly how much insulin is left in your pen, use the dose counter.

Turn the dose selector until the dose counter stops.

• If the dose counter shows the number 80, this means there are at least 80 units of insulin left in your pen.
• If the dose counter shows less than 80, this means the amount of insulin units left in your pen is exactly the number displayed on the dose counter.

Turn the dose selector back until the dose counter shows “0”.

If there is not enough insulin left in the pen for a full dose, you can inject the dose you need in two injections using two pens.

Important! Be very careful when calculating the remaining dose of insulin you need.

If you are in doubt, it is better to inject the full dose of insulin using a new pen. If you miscalculate, you may deliver an insufficient or too high dose of insulin, which may cause your blood sugar to become too high or too low.

Important information

– Always carry the pen with you.

– Always carry a spare pen and new needles with you in case they are lost or damaged.

– Always store the pen and needles in a place out of reach of everyone, and especially children.

– Never share your pen and its needles with other people. This can lead to cross-infection.

– Never share your pen with other people. Your medication may be harmful to their health.

– Persons caring for the patient must handle used needles with special care to reduce the risk of needle sticks and cross-infection.

Pen care

Handle the pen with care. Careless or improper handling may cause incorrect dosing, which can lead to excessively high or low blood sugar.

– Do not leave the pen in a car or any other place where it may be exposed to very high or very low temperatures.

– Protect the pen from dust, dirt, and all kinds of liquids.

– Do not wash the pen, do not immerse it in liquid, and do not lubricate it. If necessary, the pen can be cleaned with a damp cloth moistened with a mild detergent.

– Do not drop or bang the pen on a hard surface.

If you drop the pen or are unsure if it is working properly, attach a new needle and check the insulin flow before making an injection.

– Do not attempt to refill the pen. An empty pen must be discarded.

– Do not attempt to repair the pen or take it apart yourself.

Instructions for patients on the use of Tresiba^®, solution for subcutaneous injection 200 units/ml in the FlexTouch^® pen

Read these instructions carefully before using Tresiba^® in the pre-filled FlexTouch^® pen. If you do not follow the instructions carefully, you may deliver an insufficient or too high dose of insulin, which may lead to excessively high or low blood sugar.

Use the pen only after you have learned how to use it under the guidance of a doctor or nurse. First, check the label on the pen to make sure it contains Tresiba^® 200 units/ml, and then study the illustrations below, which show the details of the pen and needle.

If you cannot see the numbers on the pen’s dose counter because you are blind or have serious vision problems, do not use the pen without assistance. You can be assisted by a sighted person trained in the correct use of the pre-filled FlexTouch^® pen.

The pre-filled FlexTouch^® pen with Tresiba^® 200 units/ml contains 600 units of insulin degludec. The maximum dose you can set is 160 units in steps of 2 units. The dose counter shows the exact number of insulin units. Recalculation of the dose is not necessary. The pen is designed for use with disposable NovoFine^® needles up to 8 mm in length. Needles are not included in the package.

1. Preparing the pen for use

Check the name and dosage on the pen label to make sure it contains Tresiba^® 200 units/ml. This is especially important if you use different types of insulin. If you accidentally inject the wrong type of insulin, your blood sugar may become too high or too low.

1A. Remove the cap from the pen.

1B. Make sure the insulin medication in the pen is clear and colorless.

Look through the insulin scale window. If the medication is cloudy, the pen must not be used.

1C. Take a new disposable needle and remove the protective sticker.

1D. Place the needle on the pen and turn it to secure the needle firmly on the pen.

1E. Remove the outer needle cap, but do not discard it. You will need it after completing the injection to remove the needle from the pen correctly.

1F. Remove and discard the inner needle cap. If you try to put the inner cap back on the needle, you may accidentally prick yourself.

A drop of insulin may appear at the needle tip. This is normal, however, you should still check the insulin flow.

Important! Always use a new needle for each injection.

This reduces the risk of contamination, infection, insulin leakage, needle blockage, and administration of an incorrect dose.

Important! Never use a needle if it is bent or damaged.

2. Checking insulin flow

Before each injection, check the insulin flow.

This will help you ensure that the insulin dose is delivered completely.

2A. Dial 2 units of the medication by turning the dose selector. Make sure the dose counter shows “2”.

2B. Holding the pen with the needle pointing upwards, gently tap the top of the pen several times with your fingertip so that any air bubbles collect at the top.

2C. Press and hold the release button until the dose counter returns to “0”.

The “0” must be aligned with the dose pointer.

A drop of insulin should appear at the needle tip.

A small air bubble may remain at the needle tip, but it will not be injected.

If a drop of insulin does not appear at the needle tip, repeat steps 2A – 2C, but no more than 6 times. If a drop of insulin still does not appear, change the needle and repeat steps 2A – 2C again.

If a drop of insulin still does not appear at the needle tip, do not use this pen. Use a new pen.

Important! Before each injection, make sure that a drop of insulin appears at the needle tip. This guarantees insulin flow.

If a drop of insulin does not appear, the dose will not be delivered, even if the dose counter moves. This may indicate that the needle is blocked or damaged.

Important! Always check the insulin flow before each injection. If you do not check the insulin flow, you may deliver an insufficient dose of insulin or no insulin at all, which may lead to excessively high blood sugar.

3. Setting the dose

Before starting the injection, make sure the dose counter is set to “0”.

The “0” must be aligned with the dose pointer.

3A. Set the dose you need by turning the dose selector, as prescribed by your doctor.

The dose counter shows the dialed dose in units. Recalculation of the dose is not necessary.

If you have set the wrong dose, you can turn the dose selector forwards or backwards until you set the correct dose.

The maximum dose you can set is 160 units.

The dose selector allows you to set the number of units. Only the dose counter and dose pointer show the number of units of insulin in the dose you have dialed.

The maximum dose you can set is 160 units. If the remaining insulin in the pen is less than 160 units, the dose counter will stop at the number of insulin units left in the pen.

Clicks are heard each time the dose selector is turned; the sound of the clicks depends on the direction the dose selector is turned (forwards, backwards, or if the dialed dose exceeds the number of insulin units remaining in the pen). Do not count these clicks.

Important! Before each injection, check how many units of insulin you have dialed using the dose counter and dose pointer.

Do not count the pen clicks. If you set and deliver an incorrect dose, your blood sugar may become too high or too low.

The insulin scale shows the approximate amount of insulin remaining in the pen, so it cannot be used for measuring the insulin dose.

4. Injecting insulin

Insert the needle under your skin, using the injection technique recommended by your doctor or nurse.

Make sure the dose counter is in your field of vision.

Do not touch the dose counter with your fingers. This may interrupt the injection.

Press the release button all the way down and hold it in this position until the dose counter returns to “0”.

The “0” must be exactly aligned with the dose pointer.

You may hear or feel a click during this.

4A. After the injection, leave the needle under the skin for at least 6 seconds, to ensure that the full insulin dose has been delivered.

4B. Remove the needle from under the skin by pulling the pen straight up.

If blood appears at the injection site, press lightly with a cotton swab. Do not rub the injection site.

After the injection is complete, you may see a drop of insulin at the needle tip.

This is normal and does not affect the dose you have injected.

Important! Always check the dose counter reading to know how many units of insulin you have delivered.

The dose counter will show the exact number of units. Do not count the number of pen clicks. After injection, hold the release button until the dose counter returns to “0”. If the dose counter stopped before showing “0”, the full insulin dose was not delivered, which may lead to excessively high blood sugar.

5. After completing the injection

5A. Place the outer needle cap on a flat surface and, without touching the cap or the needle, insert the needle into the cap.

When the needle is inside the cap, carefully push the cap onto the needle.

5B. Unscrew the needle and discard it, taking safety precautions.

5C. After each injection, put the cap back on the pen to protect the insulin inside from light.

Discard the needle after each injection. This reduces the risk of contamination, infection, insulin leakage, needle blockage, and administration of an incorrect dose. If the needle is blocked, you will not be able to inject insulin.

Discard the used pen with the needle removed, according to the recommendations given by your doctor, nurse, pharmacist, or according to local requirements.

Important! Never try to put the inner needle cap back on the needle. You may prick yourself.

Important! After each injection, always remove the needle and store the pen with the needle removed.

This reduces the risk of contamination, infection, insulin leakage, needle blockage, and administration of an incorrect dose.

6. How much insulin is left?

6A. The insulin scale shows the approximate amount of insulin remaining in the pen.

6B. To find out exactly how much insulin is left in your pen, use the dose counter.

• Turn the dose selector until the dose counter stops.
• If the dose counter shows the number 160, this means there are at least 160 units of insulin left in your pen.
• If the dose counter shows less than 160, this means the amount of insulin units left in your pen is exactly the number displayed on the dose counter.

Rotate the dose selector in the reverse direction until the dose counter shows “0”.

If the remaining insulin in the pen is not sufficient for a full dose, you can administer your required dose in two injections using two pens.

Important! Be very careful when calculating the remaining dose of insulin you need.

Important! If you are in doubt, it is better to administer a full dose of insulin using a new pen. If you make a mistake in your calculations, you could administer an insufficient or too large dose of insulin, which may cause your blood sugar level to become too high or too low.

Important information

– Always carry your pen with you.

– Always carry a spare pen and new needles in case of loss or damage.

– Always store the pen and needles in a place inaccessible to others, especially children.

– Never share your pen and its needles with other people. This can lead to cross-contamination.

– Never share your pen with other people. Your medication could be harmful to their health.

– Persons caring for the patient must handle used needles with special care to reduce the risk of needle sticks and cross-infection.

Pen care

Handle the pen with care. Careless or improper handling can cause incorrect dosing, which may lead to blood sugar levels that are too high or too low.

– Do not leave the pen in a car or any other place where it may be exposed to excessively high or low temperatures.

– Protect the pen from dust, dirt, and all types of liquids.

– Do not wash the pen, do not immerse it in liquid, and do not lubricate it. If necessary, the pen can be cleaned with a damp cloth moistened with a mild detergent.

– Do not drop or hit the pen on a hard surface.

If you drop the pen or are unsure of its condition, attach a new needle and check the insulin flow before making an injection.

– Do not attempt to refill the pen. An empty pen must be discarded.

– Do not attempt to repair the pen or disassemble it.

Special precautions for the disposal of used medicinal product or waste generated from the use of the medicinal product, and other handling of the product

The drug Tresiba^® is for individual use only. Refilling the pen cartridge is not permitted.

Do not use the drug if the solution is no longer clear and colorless.

Do not use the drug if it has been frozen.

A new needle must be used for each injection. Reuse of needles is not permitted. The patient should discard the needle after each injection.

In case of needle blockage, the patient should follow the instructions in the package leaflet provided with the pen.

All remaining medicinal product and waste should be disposed of in accordance with national legal requirements.

Tresiba^® in the pre-filled FlexTouch^® pen is supplied in two dosages. The pen label and carton clearly state “Tresiba^® FlexTouch^® 100 U/mL” or “Tresiba^® FlexTouch^® 200 U/mL”.

The FlexTouch^® 100 U/mL pen is a pre-filled pen designed for use with NovoFine^® needles up to 8 mm in length. It allows doses from 1 to 80 U to be administered in 1 U increments.

For detailed instructions for use, see the package leaflet provided with the FlexTouch^® 100 U/mL pen.

The FlexPen^® 100 U/mL pen is a pre-filled pen designed for use with NovoFine^® needles up to 8 mm in length. It allows doses from 1 to 60 U to be administered in 1 U increments.

For detailed instructions for use, see the package leaflet provided with the FlexPen^®.

The FlexTouch^® 200 U/mL pen is a pre-filled pen designed for use with NovoFine^® needles up to 8 mm in length. It allows doses from 2 to 160 U to be administered in 2 U increments.

For detailed instructions for use, see the package leaflet provided with the FlexTouch^® 200 U/mL pen.

Adverse Reactions

Summary of the safety profile

The most frequent adverse reaction reported during treatment with insulin degludec is hypoglycemia.

Tabulated list of adverse reactions

All adverse reactions presented below, based on data from clinical trials, are grouped by MedDRA system organ class. Frequency is defined as: 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), frequency not known (cannot be estimated from the available data).

* Adverse reaction from post-marketing sources.

Description of selected adverse reactions

Immune system disorders

Allergic reactions may occur with insulin products. Immediate-type allergic reactions to the insulin itself or to its excipients can be potentially life-threatening.

When using Tresiba^®, hypersensitivity reactions (manifesting as swelling of the tongue and lips, diarrhea, nausea, feeling tired, and skin itching) and urticaria have been reported rarely.

Hypoglycemia

Hypoglycemia may occur if the insulin dose is too high relative to the patient’s insulin requirement. Severe hypoglycemia may lead to unconsciousness and/or convulsions, temporary or permanent impairment of brain function, and may be fatal. Symptoms of hypoglycemia usually occur suddenly. They include “cold sweats,” pale skin, increased fatigue, nervousness or tremor, anxiety, unusual tiredness or weakness, disorientation, decreased concentration, drowsiness, severe hunger, visual disturbances, headache, nausea, palpitations.

Skin and subcutaneous tissue disorders

Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay insulin absorption. Regularly rotating the injection site within the same anatomical area helps reduce or prevent these reactions (see section “Special Precautions”).

Injection site reactions

Patients treated with Tresiba^® have experienced injection site reactions (including hematoma, pain, local hemorrhage, erythema, connective tissue nodules, swelling, skin discoloration, itching, irritation, and induration at the injection site). Most injection site reactions are mild and temporary and usually disappear with continued treatment.

Children and adolescents

Tresiba^® has been used in children and adolescents under 18 years of age to study its pharmacokinetic properties (see section “Pharmacokinetics”).

Safety and efficacy have been demonstrated in a long-term study in children aged 1 to 18 years. The frequency, type, and severity of adverse reactions in the pediatric population do not differ from those in the general population of patients with diabetes mellitus (see section “Pharmacodynamics”).

Other special populations

Clinical trials have revealed no differences in the frequency, type, or severity of adverse reactions between elderly patients and patients with renal or hepatic impairment and the general patient population.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration to ensure continuous monitoring of the benefit-risk balance of the drug. Healthcare professionals are encouraged to report any suspected adverse drug reactions through the national adverse reaction reporting system of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to insulin degludec or to any of the excipients.

Use in Pregnancy and Lactation

Pregnancy

The use of Tresiba^® in pregnant women with diabetes was studied in an interventional trial (see section “Pharmacodynamics”). Available data from clinical trials and post-marketing use in pregnant women (more than 400 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity. Animal reproduction studies revealed no differences between insulin degludec and human insulin in terms of embryotoxicity and teratogenicity.

The use of Tresiba^® during pregnancy is possible if the expected benefit to the mother outweighs the potential risk to the fetus.

In general, careful monitoring of blood glucose concentration and monitoring of pregnant women with diabetes throughout pregnancy and during possible conception is recommended. Insulin requirements usually decrease in the first trimester and gradually increase during the second and third trimesters of pregnancy. Shortly after delivery, insulin requirements quickly return to pre-pregnancy levels. Careful monitoring of blood glucose control and individual adjustment of insulin dose are recommended.

Breastfeeding period

There is no clinical experience with Tresiba^® in breastfeeding women. Animal studies have shown that insulin degludec is excreted in rat milk, with concentrations in milk lower than in plasma.

It is unknown whether insulin degludec is excreted in human breast milk. No metabolic effects are expected in newborns and breastfed infants.

Fertility

Animal studies have shown no adverse effects of insulin degludec on fertility.

Use in Hepatic Impairment

Tresiba^® can be used in patients with hepatic impairment. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually.

Use in Renal Impairment

Tresiba^® can be used in patients with renal impairment. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually.

Pediatric Use

Tresiba^® can be used for the treatment of adolescents and children aged 1 year and older.

Geriatric Use

Tresiba^® can be used in elderly patients. Blood glucose concentration should be carefully monitored and the insulin dose adjusted individually.

Special Precautions

Tresiba^® should be used with caution during pregnancy.

Hypoglycemia

Missing a meal or unplanned strenuous physical exercise can lead to hypoglycemia.

Hypoglycemia can occur if a dose of insulin too high for the patient’s requirement is administered (see sections “Adverse Reactions”, “Overdose”, and “Drug Interactions”).

In children, caution should be exercised when selecting insulin doses (especially with a basal-bolus regimen), taking into account food intake and physical activity to minimize the risk of hypoglycemia.

After compensation of carbohydrate metabolism (e.g., during intensive insulin therapy), the patient’s typical warning symptoms of hypoglycemia may change, and patients should be informed about this. Typical warning symptoms may disappear with long-standing diabetes.

Concomitant illnesses, especially infectious ones accompanied by fever, usually increase the body’s need for insulin. Dose adjustment may also be necessary in patients with concomitant kidney or liver diseases, or impaired adrenal, pituitary, or thyroid function.

As with other basal insulin products, recovery from hypoglycemia may be delayed with Tresiba^®.

Hyperglycemia

Rapid-acting insulin is recommended for the treatment of severe hyperglycemia.

Insufficient dosage and/or discontinuation of treatment in patients who require insulin can lead to hyperglycemia and diabetic ketoacidosis. In addition, concomitant illnesses, especially infections, can contribute to hyperglycemic conditions and, accordingly, increase the body’s need for insulin.

Typically, the first symptoms of hyperglycemia appear gradually over several hours or days. These symptoms include thirst, frequent urination, nausea, vomiting, drowsiness, flushed and dry skin, dry mouth, loss of appetite, and acetone breath odor. In type 1 diabetes, without appropriate treatment, hyperglycemia leads to diabetic ketoacidosis and can be fatal.

Transfer from other insulin products

Transferring a patient to another type or brand of insulin or from a different manufacturer should be done under strict medical supervision. Dose adjustment may be required upon transfer.

Skin and subcutaneous tissue disorders

Patients should be informed about the need to constantly rotate injection sites within the same anatomical area to reduce the risk of lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsening of glycemic control if insulin is injected into an area of lipodystrophy or amyloidosis. Reports have been received of hypoglycemia occurring after a sudden change of injection site from an affected area to normal tissue. After changing the injection site, monitoring of blood glucose is recommended, and adjustment of the dose of hypoglycemic drugs may be necessary.

Concomitant use of thiazolidinediones and insulin products

Cases of chronic heart failure have been reported when treating patients with thiazolidinediones in combination with insulin products, especially in patients with risk factors for chronic heart failure. This should be considered when prescribing combination therapy with thiazolidinediones and Tresiba^® to patients. When such combination therapy is prescribed, patients should be medically examined for signs and symptoms of chronic heart failure, weight gain, and the presence of peripheral edema. If symptoms of heart failure worsen in patients, treatment with thiazolidinediones should be discontinued.

Eye disorders

Intensification of insulin therapy with a rapid improvement in glycemic control may lead to a temporary worsening of diabetic retinopathy, while long-term improvement in glycemic control reduces the risk of progression of diabetic retinopathy.

Preventing accidental administration of the wrong insulin

The patient should be instructed to check the label on the pen before each injection to avoid accidental administration of the wrong dose or wrong insulin.

Before each injection, patients should check the dose counter to see the number of units in the dialed dose. Thus, only patients who can clearly distinguish the numbers on the dose counter can self-administer insulin.

Blind patients or people with impaired vision must be informed that they always need the assistance of a person with normal vision who is trained in using the pen.

To avoid incorrect dosing and possible overdose, patients and healthcare professionals should not withdraw the drug from the cartridge of the pre-filled pen using a syringe.

In case of needle blockage, the patient should follow the instructions in the patient information leaflet provided with the pen (see section “Dosage and Administration”).

Insulin antibodies

Antibody formation may occur with insulin use. In rare cases, antibody formation may necessitate an adjustment of the insulin dose to prevent hyperglycemia or hypoglycemia.

Sodium content

This medicinal product contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is essentially sodium-free.

Traceability

For biological medicinal products, the name and batch number of the administered product must be clearly recorded.

Effects on ability to drive and use machines

Patients’ ability to concentrate and react may be impaired during hypoglycemia, which may be dangerous in situations where these abilities are especially needed (e.g., when driving or operating machinery).

Patients should be advised to take measures to prevent hypoglycemia while driving. This is particularly important for patients with absent or reduced warning symptoms of developing hypoglycemia or with frequent episodes of hypoglycemia. In these cases, the advisability of driving should be considered.

Overdose

No specific dose for insulin overdose has been established; however, hypoglycemia may develop gradually if a dose too high for the patient’s requirement is administered.

• A patient can correct mild hypoglycemia by taking glucose or sugar-containing products orally. Therefore, patients with diabetes are recommended to always carry sugar-containing products with them;
• In case of severe hypoglycemia where the patient is unconscious, glucagon (0.5 to 1 mg) should be administered intramuscularly or subcutaneously (can be administered by a trained person), or intravenous glucose solution should be administered (can only be administered by a healthcare professional). Intravenous glucose should also be administered if the patient does not regain consciousness within 10-15 minutes after glucagon administration. After regaining consciousness, the patient is advised to eat a carbohydrate-rich meal to prevent recurrence of hypoglycemia.

Drug Interactions

There are a number of medicinal products that affect glucose metabolism.

The need for insulin can be reduced by GLP-1 receptor agonists, MAO inhibitors, non-selective beta-blockers, ACE inhibitors, salicylates, anabolic steroids, and sulfonamides.

The need for insulin can be increased by oral hormonal contraceptives, thiazide diuretics, glucocorticosteroids, thyroid hormones, sympathomimetics, somatropin, and danazol.

Beta-blockers may mask the symptoms of hypoglycemia.

Octreotide/lanreotide can either increase or decrease the body’s need for insulin.

Ethanol (alcohol) can either enhance or reduce the hypoglycemic effect of insulin.

Incompatibility

Certain medicinal substances, when added to Tresiba^®, may cause its degradation.

Tresiba^® must not be added to infusion solutions.

Tresiba^® must not be mixed with other medicinal products.

Storage Conditions

Before first use

Store in a refrigerator at a temperature between 2°C (35.6°F) and 8°C (46.4°F), but not near the freezer. Do not freeze. To protect from light, store the pen with the cap on.

Shelf Life

Shelf life is 30 months.

After first use or for a pen carried as a spare

Do not store for more than 8 weeks at a temperature not exceeding 30°C (86°F). It can be stored in a refrigerator (between 2°C (35.6°F) and 8°C (46.4°F)). To protect from light, store the pen with the cap on.

Dispensing Status

The product is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.