Tresiba 100 units/ml solution for injection in pre-filled pen (FlexTouch)

Throughout: Reference to the new Tresiba 100 units/mL FlexPen solution for injection in pre filled pen presentation has been included

Section 4.9: Reference to method of administration for glucagon has been removed. 

Reference to method of administration for glucagon has been removed

Section 2, Pregnancy and breast-feeding 

Text removed: It is not known if Tresiba affects the baby in pregnancy or during breast-feeding.

Revision date updated

This leaflet was last revised in: 01/2022

SECTION 4.6, updated

Pregnancy

There is no clinical experience with the use of Tresiba in pregnant women.The use of Tresiba in pregnant women with diabetes has been investigated in an interventional trial (see section 5.1). A moderate amount of clinical trial and post-marketing data in pregnant women (more than 400 pregnancy outcomes) indicate no malformative or feto/neonatal toxicity. Animal reproduction studies have not revealed any difference between insulin degludec and human insulin regarding embryotoxicity and teratogenicity.

The treatment with Tresiba may be considered during pregnancy, if clinically needed.

In general, intensified blood glucose control and monitoring of pregnant women with diabetes are recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually decrease in the first trimester and increase subsequently during the second and third trimesters. After delivery, insulin requirements usually return rapidly to pre-pregnancy values. Careful monitoring of glucose control is recommended and the insulin dose adjusted on an individual basis.

SECTION 5.1, new text added

Pregnancy

Tresiba has been studied in an open-label, randomised, active controlled clinical trial, in which pregnant women with type 1 diabetes mellitus were treated within a basal-bolus treatment regimen with Tresiba (92 women) or insulin detemir (96 women) as basal insulin, both in combination with insulin aspart as meal time insulin (EXPECT).

Tresiba was non-inferior to insulin detemir as measured by HbA_1c at last planned HbA_1c visit prior to delivery after gestational week 16. Moreover, no difference between treatment groups was observed for glycaemic control (change in HbA_1c, FPG and PPG) during pregnancy.

No clinically relevant differences were observed between Tresiba and insulin detemir for the maternal safety endpoints: hypoglycaemia, pre-term delivery and adverse events during the pregnancy. Pre-eclampsia was reported in 12 subjects treated with Tresiba (13.2%) and in 7 subjects (7.4%) who were treated with insulin detemir. Non-planned caesarean section was reported in 23 subjects (25.3%) treated with Tresiba and in 15 subjects (16.0%) treated with insulin detemir. The majority of the adverse events reported in both groups were non-serious, mild in severity, unlikely related to the trial product and had the outcome “recovered/resolved”. No deaths were reported in the subjects who were randomised in the trial.

No perinatal or neonatal death was reported. No clinically relevant differences were observed between Tresiba and insulin detemir for the pregnancy endpoints (early foetal death, presence of major abnormalities, neonatal hypoglycaemia, perinatal mortality, neonatal mortality, foetal macrosomia, large for gestational age, and adverse events in the infant during the 30 days after birth).

SECTION 10

Date revised to: 01/2022

Section 10: 

Revision date updated to 08/2021

Section 6 (Manufacturer):

Manufacturer text updated from 'Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark.' to 

Manufacturer

The manufacturer can be identified by the batch number printed on the slip of the carton and on the

label:

 –  If the second and third characters are P5, ZF or FG, the manufacturer is Novo Nordisk A/S, Novo Allé, DK-2880 Bagsværd, Denmark. 

–   If the second and third characters are T6, the manufacturer is Novo Nordisk Production SAS, 45 Avenue d’Orléans, 28000 Chartres, France.

Section 6 (Revision date): 

Date of revision updated to: 08/2021

Section 5.1

New text:

The day-to-day variability, expressed as the coefficient of variation, in glucose-lowering effect during one dosing interval of 0-24 hours at steady state (AUC_GIR,τ,SS) is 20% for insulin degludec, which is significantly lower than for insulin glargine (100 units/mL).

Text deleted:

The insulin degludec glucose-lowering action at steady state shows four times lower day‑to‑day variability in terms of Coefficients of Variation (CV) for the glucose-lowering effect during 0‑24 hours (AUC_GIR,τ,SS) and 2–24 hours (AUC_GIR2-24h,SS) as compared to insulin glargine, see Table 1.

Table 1 Day-to-day variability within-patients in glucose-lowering-effect of Tresiba and insulin glargine at steady state in patients with type 1 diabetes mellitus

CV: within-patient coefficient of variation in %

SS: Steady State

AUC_GIR,2-24h: metabolic effect in last 22 hours of dosing interval (i.e., not influenced by i.v. insulin during the clamp run-in period).

Section 2 – what you need to know - warnings and precautions

New text:

Skin changes at the injection site

The injection site should be rotated to help prevent changes to the fatty tissue under the skin, such as skin thickening, skin shrinking or lumps under the skin. The insulin may not work very well if you inject into a lumpy, shrunken or thickened area (see section 3 ‘How to use Tresiba^®’). Tell your doctor if you notice any skin changes at the injection site. Tell your doctor if you are currently injecting into these affected areas before you start injecting in a different area. Your doctor may tell you to check your blood sugar more closely, and to adjust your insulin or your other antidiabetic medications dose.

Section 4 – possible side effects

New text:

Skin changes at the injection site If you inject insulin at the same place, the fatty tissue may shrink (lipoatrophy) or thicken (lipohypertrophy) (may affect up to 1 in 100 people). Lumps under the skin may also be caused by build-up of a protein called amyloid (cutaneous amyloidosis; how often this occurs is not known). The insulin may not work very well if you inject into a lumpy, shrunken or thickened area. Change the injection site with each injection to help prevent these skin changes.

Deleted text:

Uncommon (may affect up to 1 in 100 people)

Changes under the skin where you use the injection (lipodystrophy): Fatty tissue under the skin may shrink (lipoatrophy) or get thicker (lipohypertrophy). Changing where you inject each time may reduce the risk of developing these skin changes. If you notice these skin changes, tell your doctor or nurse. If you keep injecting in the same place, these reactions can become more severe and affect the amount of medicine your body gets.

Section 4 – how to report a side effect

HPRA contact details updated to short version

Section 4.2 - method of administration

Updated text:

Injection sites should are always to be rotated within the same region in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections 4.4 and 4.8).

Section 4.4

New text:

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 medications may be considered.

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.

Section 4.8

Addition to adverse reaction list, skin and subcutaneous tissue disorders:

Not known – cutaneous amyloidosis†

† ADR from postmarketing sources.

Skin and subcutaneous tissue disorders

Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Continuous rotation of the injection site within the particular given injection area may help to reduce or prevent the risk of developing these reactions (see section 4.4).

Addition of joint SmPC covering all presentations

Additional presentations added as per the authorised EMA-approved SmPC (NovoRapid InnoLet, FlexTouch, PumpCart). These presentations are added to the local SmPC only, i.e. no change to marketing status. 

update to: section 6.5: word "stopper" was replaced with "laminate rubber sheet"

update to section 10: date of revision of the text changed to 11/2018.

section 8: Addition of a new license number 

section 9: revision date change

Tresiba must not be drawn from the cartridge of the pre-filled pen into a syringe (see section 4.4).

Patients should be instructed to always use a new needle. The re-use of insulin pen needles increases the risk of blocked needles, which may cause under- or overdosing. In the event of blocked needles, patients must follow the instructions described in the instructions for use accompanying the package leaflet (see section 6.6).

section 4.4
addition of:

To avoid dosing errors and potential overdose, patients and healthcare professionals should never use a syringe to draw the medicinal product from the cartridge in the pre-filled pen.

In the event of blocked needles, patients must follow the instructions described in the instructions for use accompanying the package leaflet (see section 6.6).

section 5.1
addition of Cardiovascular evaluation sub-section.

section 6.6
addition of:A  new needle must always be attached before each use. Needles must not be re-used. The patient should discard the needle after each injection.

In the event of blocked needles, patients must follow the instructions described in the instructions for use accompanying the package leaflet.

Tresiba in a pre-filled pen is available in two strengths. “Tresiba 100 units/mL” or “Tresiba 200 units/mL” is clearly marked on the pen label and packaging.

Tresiba 100 units/mL packaging and label are light green.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

4.2     Posology and method of administration

Posology

This medicinal product medicine resiba i is a basal insulin for once-daily subcutaneous administration at any time of the day, preferably at the same time every day.

The potency of insulin analogues, including insulin degludec, is expressed in units (U). One (1) unit (U) of insulin degludec corresponds to 1 international unit (IU) of human insulin, 1 unit of insulin glargine (100 units/mL), or 1 unit of insulin detemir.

In patients with type 2 diabetes mellitus, Tresiba this medicinal product medicine can be administered alone or in any combination with oral antidiabetic medicinal products, GLP-1 receptor agonists and bolus insulin (see section 5.1).

As with all insulin products, aAdjustment of dose may be necessary if patients undertake increased physical activity, change their usual diet or during concomitant illness.

Tresiba 100 units/mL and Tresiba 200 units/mL solution for injection in a pre‑filled pen

Tresiba is available in two strengths. For both, the needed dose is dialled in units. The dose steps, however, differ between the two strengths of the medicinal productmedicineTresiba.

Paediatric population

There is no clinical experience with the use of this medicinal product medicine in children below the age of 1 year. This medicinal product medicineresiba can be used in adolescents and children from the age of 1 year (see section 5.1).

Method of administration

Tresiba is for sSubcutaneous use only.

Tresiba  i must not be administered intravenously as it may result in severe hypoglycaemia.

This medicinal productresiba must not be administered intramuscularly as it may change the absorption.

This medicinal productresiba must not be used in insulin infusion pumps.

4.4       Special warnings and precautions for use

Sodium

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

4.5     Interaction with other medicinal products and other forms of interaction

Oral antidiabetic medicinal products, GLP‑1 receptor agonists, monoamine oxidase inhibitors (MAOI), beta‑blockers, angiotensin converting enzyme (ACE) inhibitors, salicylates, anabolic steroids and sulphfonamides.

4.7     Effects on ability to drive and use machines

This medicinal product medicine has no or negligible influence on the ability to drive and use machines.,

10.     DATE OF REVISION OF THE TEXT

09/2017

3. How to use Tresiba

Under Flexibility in dosing time.

Sentence has been added:

There is no experience with flexibility in dosing time of Tresiba in children and adolescents.

5.1 Clinical data included to include data from SWITCH trials.

10. This leaflet was last revised in: 04/2017

4.2      Posology and method of administration

Flexibility in dosing time

Sentence and text added:

“There is no clinical experience with flexibility in dosing time of Tresiba in children and adolescents.”

Patients with type 2 diabetes mellitus

Paragraph/text in bold added:

During transfer from other insulins; in type 2 diabetes (text added)

taking once-daily basal, basal-bolus, premix or self-mixed insulin therapy changing the basal insulin to Tresiba^® can be done unit-to-unit, based on the previous basal insulin component;

“A dose reduction of 20% based on the previous basal insulin dose followed by individual dosage adjustments should be considered when

- transferring to Tresiba from twice-daily basal insulin

- transferring to Tresiba from insulin glargine (300 units/mL)”

Patients with type 1 diabetes mellitus

Paragraph changed per bold.

For patients with type 1 diabetes a dose reduction of 20% based on the previous basal insulin dose or basal component of a continuous subcutaneous insulin infusion regimen should be considered with subsequent individual dosage adjustments based on the glycaemic response.

Sentence deleted:

For patients with type 1 diabetes transferring from twice-daily basal insulin or having HbA_1c < 8.0% at the time of transfer, the dose of Tresiba needs to be determined on an individual basis. Dose reduction needs to be considered followed by individual dosage adjustment based on the glycaemic response.

5.1      Pharmacodynamic properties

Section updated to include data from clinical trials.

10.      DATE OF REVISION OF THE TEXT

Revised 04/2017