4.5 Interaction with other medicinal products and other forms of interaction

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

The following substances may reduce the insulin requirement

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

The following substances may increase the insulin requirement

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

Beta-blockers 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.

4.6 Fertility, pregnancy and lactation

Pregnancy

There is no clinical experience with the use of Tresiba in pregnant women.

Animal reproduction studies have not revealed any difference between insulin degludec and human insulin regarding embryotoxicity and teratogenicity.

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.

Breast-feeding

There is no clinical experience with Tresiba during breast-feeding. In rats, insulin degludec was secreted in milk; the concentration in milk was lower than in plasma.

It is unknown whether insulin degludec is excreted in human milk. No metabolic effects are anticipated in the breast-fed newborn/infant.

Fertility

Animal reproduction studies with insulin degludec have not revealed any adverse effects on fertility.

4.7 Effects on ability to drive and use machines

This medicinal product has no or negligible influence on the ability to drive and use machines. However, the patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or using machines).

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

4.8 Undesirable effects

Summary of the safety profile

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

Tabulated list of adverse reactions

Adverse reactions listed below are based on clinical trial data and classified according to MedDRA System Organ Class. Frequency categories are defined according to the following convention: Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1,000 to <1/100); rare (>1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from the available data).

" ADR from postmarketing sources.

Description of selected adverse reactions

Immune system disorders

With insulin preparations, allergic reactions may occur. Immediate-type allergic reactions to either insulin itself or the excipients may potentially be life-threatening.

With Tresiba, hypersensitivity (manifested with swelling of tongue and lips, diarrhoea, nausea, tiredness and itching) and urticaria were reported rarely.

Hypoglycaemia

Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. The symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.

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 given injection area may help to reduce or prevent these reactions (see section 4.4).

Injection site reactions

Injection site reactions (including injection site haematoma, pain, haemorrhage, erythema, nodules, swelling, discolouration, pruritus, warmth and injection site mass) occurred in patients treated with Tresiba. These reactions are usually mild and transitory and they normally disappear during continued treatment.

Paediatric population

Tresiba has been administered to children and adolescents up to 18 years of age for the investigation of pharmacokinetic properties (see section 5.2). Safety and efficacy have been demonstrated in a long term trial in children aged 1 to less than 18 years. The frequency, type and severity of adverse reactions in the paediatric population do not indicate differences to the experience in the general diabetes population (see section 5.1).

Other special populations

Based on results from clinical trials, the frequency, type and severity of adverse reactions observed in elderly and in patients with renal or hepatic impairment do not indicate any differences to the broader experience in the general population.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in

4.9 Overdose

A specific overdose for insulin cannot be defined. However, 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 products containing sugar. It is therefore recommended that the patient always carries glucose-containing products.
• Severe hypoglycaemic episodes, where the patient is not able to treat himself, 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 carbohydrates is recommended for the patient in order to prevent a relapse.

• 5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, long-acting. ATC code: A10AE06.

Mechanism of action

Insulin degludec binds specifically to the human insulin receptor and results in the same pharmacological effects as human insulin.

The blood glucose-lowering effect of insulin is due to the facilitated uptake of glucose following the binding of insulin to receptors on muscle and fat cells and to the simultaneous inhibition of glucose output from the liver.

Pharmacodynamic effects

Tresiba is a basal insulin that forms soluble multi-hexamers upon subcutaneous injection, resulting in a depot from which insulin degludec is continuously and slowly absorbed into the circulation leading to a flat and stable glucose-lowering effect of Tresiba (see figure 1). During a period of 24 hours with once-daily treatment, the glucose-lowering effect of Tresiba, in contrast to insulin glargine, was evenly distributed between the first and second 12 hours (AUCGIR,0–12h,SS/AUCGIR,to­tal,SS = 0.5).

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Treatment IDeg 0.6 units/kg

Figure 1 Glucose infusion rate profile, smoothed, steady state – Mean profile 0–24 hours – IDeg 100 units/mL 0.6 units/kg – Trial 1987

The duration of action of Tresiba is beyond 42 hours within the therapeutic dose range.

Steady state will occur after 2–3 days of dose administration.

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 (AUCgir,t,ss) and 2–24 hours (AUCoiR2–24h,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

AUCGIR,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).

The total glucose-lowering effect of Tresiba increases linearly with increasing doses.

The total glucose-lowering effect is comparable for Tresiba 100 units/mL and 200 units/mL after administration of the same doses of the two products.

There is no clinically relevant difference in the pharmacodynamics of this medicinal product between elderly and younger adult patients.

Clinical efficacy and safety

11 multinational clinical trials of 26 or 52 weeks’ duration were conducted as controlled, open-label, randomised, parallel, treat-to-target trials exposing 4,275 patients to Tresiba (1,102 in type 1 diabetes mellitus and 3,173 in type 2 diabetes mellitus).

In the open-label trials the effect of Tresiba was tested in patients with type 1 diabetes mellitus (Table 3), in insulin naive patients (insulin initiation in type 2 diabetes mellitus, Table 4) and in previous insulin users (insulin intensification in type 2 diabetes mellitus, Table 5) with fixed as well as flexible dosing time (Table 6), and the reduction in HbA1c from baseline to end of trial was confirmed to be non-inferior in all trials against all comparators (insulin detemir and insulin glargine (100 units/mL)). While improvements in HbA1c were non-inferior compared to other insulin products, against sitagliptin Tresiba was statistically significantly superior in reducing HbA1c (Table 5).

In a prospectively planned meta-analysis across seven open-label treat-to-target confirmatory trials in patients with type 1 and type 2 diabetes mellitus, Tresiba was superior in terms of a lower number of treatment-emergent confirmed hypoglycaemic episodes (driven by a benefit in type 2 diabetes mellitus, see Table 2) and nocturnal confirmed hypoglycaemic episodes compared to insulin glargine (100 units/ml) (administered according to label). The reduction in hypoglycaemia was achieved at a lower average FPG level with Tresiba than with insulin glargine.

Table 2 Hypoglycaemia meta-analysis outcomes

Statistically significant a Confirmed hypoglycaemia was defined as episodes confirmed by plasma glucose <3.1 mmol/L or by the patient needing third party assistance. Nocturnal confirmed hypoglycaemia was defined as episodes between midnight and 6 a.m. b Episodes from week 16.

There is no clinically relevant development of insulin antibodies after long-term treatment with Tresiba.

Table 3 Results from open-label clinical trials in type 1 diabetes mellitus

1 In a once-daily regimen + insulin aspart to cover mealtime insulin requirements

2 Confirmed hypoglycaemia was defined as episodes confirmed by plasma glucose <3.1 mmol/L or by the patient needing third party assistance. Nocturnal confirmed hypoglycaemia was defined as episodes between midnight and 6 a.m.

Table 4 Results from open-label clinical trials in insulin naive type 2 diabetes mellitus (insulin initiation)

1 Once-daily regimen + metformin ± DPP-IV inhibitor

2 Confirmed hypoglycaemia was defined as episodes confirmed by plasma glucose <3.1 mmol/L or by the patient needing third party assistance. Nocturnal confirmed hypoglycaemia was defined as episodes between midnight and 6 a.m.

Table 5 Results from open-label clinical trials in type 2 diabetes mellitus: left – prior basal insulin users, right – insulin naive

1 Once-daily regimen + insulin aspart to cover mealtime insulin requirements ± metformin ± pioglitazone

2 Once-daily regimen ± metformin SU/glinide ± pioglitazone

3 Confirmed hypoglycaemia was defined as episodes confirmed by plasma glucose <3.1 mmol/L or by the patient needing third party assistance. Nocturnal confirmed hypoglycaemia was defined as episodes between midnight and 6 a.m.

Table 6 Results from an open-label clinical trial with flexible dosing of Tresiba in type 2 diabetes mellitus

1 Once-daily regimen (with main evening meal) + one or two of the following oral antidiabetes agents: SU, metformin or DPP-4 inhibitor

2 Flexible once-daily regimen (intervals of approximately 8–40 hours between doses) + one or two of the following oral antidiabetes agents SU, metformin or DPP-4 inhibitor

3 Once-daily regimen + one or two of the following oral antidiabetes agents: SU, metformin or DPP-4 inhibitor

4 Confirmed hypoglycaemia was defined as episodes confirmed by plasma glucose <3.1 mmol/L or by the patient needing third party assistance. Nocturnal confirmed hypoglycaemia was defined as episodes between midnight and 6 a.m.

5 The difference is for Tresiba Flex – Tresiba 6 The ratio is for Tresiba Flex/Tresiba.

In a 104-week clinical trial, 57% of patients with type 2 diabetes treated with Tresiba (insulin degludec) in combination with metformin achieved a target HbA1c <7.0%, and the remaining patients continued in a 26-week open-label trial and were randomised to add liraglutide or a single dose of insulin aspart (with the largest meal). In the insulin degludec + liraglutide arm, the insulin dose was reduced by 20% in order to minimise the risk of hypoglycaemia. Addition of liraglutide resulted in a statistically significantly greater reduction of HbA1c (-0.73% for liraglutide vs –0.40% for comparator, estimated means) and body weight (-3.03 vs 0.72 kg, estimated means). The rate of hypoglycaemic episodes (per patient year of exposure) was statistically significantly lower when adding liraglutide compared to adding a single dose of insulin aspart (1.0 vs 8.15; ratio: 0.13; 95% CI: 0.08 to 0.21).

Furthermore, two 64-week controlled, double-blind, randomised, cross-over, treat-to-target trials were conducted in patients with at least one risk factor for hypoglycaemia and with type 1 diabetes mellitus (501 patients) or type 2 diabetes mellitus (721 patients). Patients were randomised to either Tresiba or insulin glargine (100 units/mL) followed by cross-over. The trials evaluated the rate of hypoglycaemia upon treatment with Tresiba compared to insulin glargine (100 units/mL) (see Table 7).

Table 7 Results from the double-blind, cross-over clinical trials in type 1 and type 2 diabetes mellitus

1 In a once-daily regimen + insulin aspart to cover mealtime insulin requirements

2 In a once-daily regimen ± OADs (any combination of metformin, dipeptidyl peptidase-4 inhibitor, alpha-glucosidase inhibitor, thiazolidinediones, and sodium glucose cotransporter-2 inhibitor)

3 Per patient year of exposure

4 Episodes from week 16 in each treatment period

5 Blood glucose (BG) confirmed symptomatic hypoglycaemia was defined as episodes confirmed by a plasma glucose value of less than 3.1 mmol/L, with symptoms consistent with hypoglycaemia. Nocturnal confirmed hypoglycaemia was defined as episodes between midnight and 6 a.m.

Cardiovascular evaluation

DEVOTE was a randomised, double-blind, and event-driven clinical trial with a median duration of 2 years comparing the cardiovascular safety of Tresiba versus insulin glargine (100 units/mL) in 7,637 patients with type 2 diabetes mellitus at high risk of cardiovascular events.

The primary analysis was time from randomisation to first occurrence of a 3-component major adverse cardiovascular event (MACE) defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. The trial was designed as a non-inferiority trial to exclude a pre-specified risk margin of 1.3 for the hazard ratio (HR) of MACE comparing Tresiba to insulin glargine. The cardiovascular safety of Tresiba as compared to insulin glargine was confirmed (HR 0.91 [0.78; 1.06]) (Figure 2). Results from subgroup analyses (e.g. sex, diabetes duration, CV risk group and previous insulin regimen) was aligned with the primary analysis.

N: Number of subjects with a first EAC confirmed event during trial. %: Percentage of subjects with a first EAC confirmed event relative to the number of randomised subjects. EAC: Event adjudication committee. CV: Cardiovascular. MI: Myocardial infarction. CI: 95% confidence interval.

Figure 2 Forest plot of analysis of the composite 3-point MACE and individual cardiovascular endpoints in DEVOTE

At baseline, HbA1c was 8.4% in both treatment groups and after 2 years HbA1c was 7.5% both with Tresiba and insulin glargine.

Tresiba was superior compared to insulin glargine in terms of a lower rate of severe hypoglycaemic events and a lower proportion of subjects experiencing severe hypoglycaemia. The rate of nocturnal severe hypoglycaemia was significantly lower for Tresiba compared to insulin glargine (Table 8).

Table 8 Results from DEVOTE

1 In addition to standard of care for diabetes and cardiovascular disease

2 Nocturnal severe hypoglycaemia was defined as episodes between midnight and 6 a.m.

Paediatric population

The European Medicines Agency has waived the obligation to submit the results of trials with Tresiba in:

• Neonates and infants from birth to less than 12 months of age with type 1 diabetes mellitus and

children from birth to less than 10 years of age with type 2 diabetes mellitus on the grounds that the disease or condition for which the specific medicinal product is intended does not occur in the specified paediatric subset (see section 4.2 for information on paediatric use).

The efficacy and safety of Tresiba have been studied in a 1:1 randomised controlled clinical trial in children and adolescents with type 1 diabetes mellitus for a period of 26 weeks (n=350), followed by a 26-week extension period (n=280). Patients in the Tresiba arm included 43 children aged 1–5 years, 70 children aged 6–11 years and 61 adolescents aged 12–17 years. Tresiba dosed once daily showed similar reduction in HbA1c at week 52 and greater reduction in FPG from baseline versus the comparator insulin detemir dosed once or twice daily. This was achieved with 30% lower daily doses of Tresiba compared to insulin detemir. The rates (events per patient-year of exposure) of severe hypoglycaemia (ISPAD definition; 0.51 vs 0.33), confirmed hypoglycaemia (57.71 vs 54.05) and nocturnal confirmed hypoglycaemia (6.03 vs 7.60) were comparable with Tresiba versus insulin detemir. In both treatment arms, children aged 6–11 years had a numerically higher rate of confirmed hypoglycaemia than in the other age groups. A numerically higher rate of severe hypoglycaemia in children aged 6–11 years in the Tresiba arm was observed. The rate of hyperglycaemic episodes with ketosis was significantly lower for Tresiba versus insulin detemir, 0.68 and 1.09, respectively. No safety issues were identified with Tresiba with respect to adverse events and standard safety parameters. Antibody development was sparse and had no clinical impact. Efficacy and safety data for adolescent patients with type 2 diabetes mellitus have been extrapolated from data for adolescent and adult patients with type 1 diabetes mellitus and adult patients with type 2 diabetes mellitus. Results support the use of Tresiba in adolescent patients with type 2 diabetes mellitus.

• 5.2 Pharmacoki­netic properties

Absorption

After subcutaneous injection, soluble and stable multi-hexamers are formed creating a depot of insulin in the subcutaneous tissue. Insulin degludec monomers gradually separate from the multi-hexamers thus resulting in a slow and continuous delivery of insulin degludec into the circulation.

Steady-state serum concentration is reached after 2–3 days of daily Tresiba administration.

During a period of 24 hours with once-daily treatment, the exposure of insulin degludec was evenly distributed between the first and second 12 hours. The ratio between AUCGiR,o-12h,ss and AUCgir,t,ss was 0.5.

Distribution

The affinity of insulin degludec to serum albumin corresponds to a plasma protein binding of >99% in human plasma.

Biotransformation

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

Elimination

The half-life after subcutaneous administration of Tresiba is determined by the rate of absorption from the subcutaneous tissue. The half-life of Tresiba is approximately 25 hours independent of dose.

Linearity

Dose proportionality in total exposure is observed after subcutaneous administration within the therapeutic dose range. In direct comparison, requirements for bioequivalence are met for Tresiba 100 units/mL and Tresiba 200 units/mL (based on AUCiDeg,T,ss and Cmax,iDeg,ss).

Gender

There is no gender difference in the pharmacokinetic properties of this medicinal product.

Elderly, race, renal and hepatic impairment

There is no difference in the pharmacokinetics of insulin degludec between elderly and younger adult patients, between races or between healthy subjects and patients with renal or hepatic impairment.

Paediatric population

Pharmacokinetic properties of insulin degludec in children (1–11 years) and adolescents (12–18 years) were at steady state comparable to those observed in adults with type 1 diabetes mellitus. Total exposure after a single dose was, however, higher in children and adolescents than in adults with type 1 diabetes mellitus.

5.3 Preclinical safety data

Non-clinical data reveal no safety concerns for humans based on studies of safety pharmacology, repeated dose toxicity, carcinogenic potential, and toxicity to reproduction.

The ratio of mitogenic relative to metabolic potency for insulin degludec is comparable to that of human insulin.

• 6. PHARMACEUTICAL PARTICULARS

• 6.1 List of excipients

Glycerol

Metacresol

Phenol

Zinc acetate

Hydrochloric acid (for pH adjustment)

Sodium hydroxide (for pH adjustment)

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with any other medicinal products.

Substances added to Tresiba may cause degradation of insulin degludec.

Tresiba must not be added to infusion fluids.

6.3 Shelf life

30 months.

Tresiba 100 units/mL solution for injection in pre-filled pen

After first opening or carried as a spare, the medicinal product may be stored for a maximum of 8 weeks. Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect from light.

Tresiba 200 units/mL solution for injection in pre-filled pen

After first opening or carried as a spare, the medicinal product may be stored for a maximum of 8 weeks. Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect from light.

Tresiba 100 units/mL solution for injection in cartridge

After first opening or carried as a spare, the medicinal product may be stored for a maximum of 8 weeks. Do not store above 30°C. Do not refrigerate. Keep cartridges in the outer carton in order to protect from light.

6.4 Special precautions for storage

Tresiba 100 units/mL solution for injection in pre-filled pen

Before first use:

Store in a refrigerator (2°C – 8°C). Do not freeze.

Keep away from the freezing element.

Keep the cap on the pen in order to protect it from light.

Tresiba 200 units/mL solution for injection in pre-filled pen

Before first use:

Store in a refrigerator (2°C – 8°C). Do not freeze.

Keep away from the freezing element.

Keep the cap on the pen in order to protect it from light.

Tresiba 100 units/mL solution for injection in cartridge

Before first use:

Store in a refrigerator (2°C – 8°C). Do not freeze.

Keep away from the freezing element.

Keep cartridges in the outer carton in order to protect them from light.

For storage conditions after first opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Tresiba 100 units/mL solution for injection in pre-filled pen

3 mL solution in a cartridge (type 1 glass) with a plunger (halobutyl) and a laminate rubber sheet (halobutyl/po­lyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene.

Pack sizes of 1 (with or without needles), 5 (without needles) and multipack containing 10 (2 packs of 5) (without needles) pre-filled pens.

Not all pack sizes may be marketed.

Tresiba 200 units/mL solution for injection in pre-filled pen

3 mL solution in a cartridge (type 1 glass) with a plunger (halobutyl) and a laminate rubber sheet

(halobutyl/po­lyisoprene) contained in a pre-filled multidose disposable pen made of polypropylene.

Pack sizes of 1 (with or without needles), 2 (without needles), 3 (without needles), 5 (without needles) and multipack containing 6 (2 packs of 3) (without needles) pre-filled pens.

Not all pack sizes may be marketed.

Tresiba 100 units/mL solution for injection in cartridge

3 mL solution in a cartridge (type 1 glass) with a plunger (halobutyl) and a laminate rubber sheet (halobutyl/po­lyisoprene) in a carton.

Pack sizes of 5 and 10 cartridges.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

This medicinal product is for use by one person only. It must not be refilled.

Tresiba must not be used if the solution does not appear clear and colourless.

Tresiba which has been frozen must not be used.

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.

Any waste material should be disposed of in accordance with local requirements.

For detailed instructions for use, see 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 solution for injection in pre-filled pen

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

The pre-filled pen (FlexTouch) is designed to be used with NovoFine/NovoTwist injection needles up to a length of 8 mm. It delivers 1–80 units in steps of 1 unit. Detailed instructions accompanying the pre-filled pen must be followed.

Tresiba 200 units/mL solution for injection in pre-filled pen

Tresiba 200 units/mL packaging and label are dark green with striping with a red box highlighting the formulation strength.

The pre-filled pen (FlexTouch) is designed to be used with NovoFine/NovoTwist injection needles up to a length of 8 mm. It delivers 2–160 units in steps of 2 units. Detailed instructions accompanying the pre-filled pen must be followed.

Tresiba 100 units/mL solution for injection in cartridge

The cartridge (Penfill) is designed to be used with Novo Nordisk delivery systems (durable devices for repeated use not included in the pack) and NovoFine/NovoTwist injection needles up to a length of 8 mm. Detailed instructions accompanying the delivery system must be followed.

• 7. MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsv^rd

Denmark

• 8. MARKETING AUTHORISATION NUMBERS

Tresiba 100 units/mL solution for injection in pre-filled pen

EU/1/12/807/001

EU/1/12/807/002

EU/1/12/807/003

EU/1/12/807/004

EU/1/12/807/005

Tresiba 200 units/mL solution for injection in pre-filled pen

EU/1/12/807/009

EU/1/12/807/006

EU/1/12/807/010

EU/1/12/807/012

EU/1/12/807/013

EU/1/12/807/015

EU/1/12/807/016

Tresiba 100 units/mL solution for injection in cartridge

EU/1/12/807/007

EU/1/12/807/008

• 9. DATE OF FIRST AUTHORISATION/RE­NEWAL OF THE AUTHORISATION

Date of first authorisation: 21 January 2013

Date of latest renewal: 21 September 2017

• 10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the web site of the European Medicines Agency

• ANNEX II

• A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

• B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

• C. OTHER CONDITIONS AND REQUIREMENTS OF THE

MARKETING AUTHORISATION

• D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE

SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT

• A. MANUFACTURERS OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers of the biological active substance

Novo Nordisk A/S

Hallas Alle

DK-4400 Kalundborg

Denmark

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsv^rd

Denmark

Name and address of the manufacturer responsible for batch release

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsv^rd

Denmark

• B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

• C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION

• Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any subsequent updates published on the European medicines web-portal.

• D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT

• Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities and interventions detailed in the agreed RMP presented in Module 1.8.2. of the marketing authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:

• – At the request of the European Medicines Agency;

• – Whenever the risk management system is modified, especially as the result of new information being received that may lead to a significant change to the benefit/risk profile or as the result of an important (pharmacovigilance or risk minimisation) milestone being reached.

• Additional risk minimisation measures

The MAH shall provide an educational pack prior to launch targeting all physicians and nurses who are expected to be involved in the treatment and management of diabetic patients and all pharmacists who are expected to dispense Tresiba.

The educational pack is aimed at increasing awareness about the introduction of a new strength of insulin in the European market and describing key differences in the design of the packages and the pre-filled pen devices to minimise the risk of medication errors and mix up between the two different strengths of Tresiba.

The educational pack should contain:

• – Direct Healthcare Professional Communication letter as described below;

• – Summary of Product Characteristics and Package Leaflet;

• – Poster for display in pharmacies/diabetic units;

• – Patient Brochures.

The MAH shall ensure that healthcare professionals are informed that all patients who have been prescribed Tresiba should be provided with a patient brochure and be trained on the correct use of the pre-filled pen before prescribing or dispensing Tresiba.

The Poster for pharmacies/diabetic units shall contain the following key elements:

• – That Tresiba is available in 2 strengths;

• – Key differences in the design of the packages and the pre-filled pen devices;

• – When prescribing to make sure that the correct strength is mentioned in the prescription slip;

• – Always check the insulin label before dispensing to make sure the correct strength is delivered

to the patient;

• – Always check the insulin label before each injection to avoid accidental mix-ups between the two different strengths of Tresiba;

• – Do not use outside of the pre-filled pen device (e.g. syringes);

• – Reporting of medication errors or any side effects.

The patient brochure shall contain the following key elements:

• – That Tresiba is available in 2 strengths;

• – Key differences in the design of the packages and the pre-filled pen devices;

• – Always check the insulin label before each injection to avoid accidental mix-ups between the two different strengths of Tresiba;

• – Patients who are blind or have poor vision must be instructed always to get help/assistance from another person who has good vision and is trained in using the insulin device;

• – Always use the dose recommended by your healthcare provider;

• – Always use the dose counter and the dose pointer to select the dose. Do not count the pen clicks to select the dose;

• – Check how many units were selected before injecting the insulin;

• – The dose counter shows the number of units regardless of strength and no dose conversion

should be done;

• – Reporting of medication errors or any side effects.

The MAH shall agree on the final text of the Direct Healthcare Professional Communication letter and the content of the patient brochure together with a communication plan, with the National Competent Authority in each Member State prior to distribution of the educational pack in the Member State.

ANNEX III

LABELLING AND PACKAGE LEAFLET

A. LABELLING

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON (100 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT

Tresiba 100 units/mL solution for injection in pre-filled pen insulin degludec

• 2. STATEMENT OF ACTIVE SUBSTANCE

One pre-filled pen contains 300 units of insulin degludec in 3 mL solution

1 mL solution contains 100 units of insulin degludec (equivalent to 3.66 mg)

• 3. LIST OF EXCIPIENTS

Glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection (FlexTouch) 1 × 3 mL

1 × 3 mL + 7 NovoFine needles

1 × 3 mL + 7 NovoTwist needles

5 × 3 mL

• 5. METHOD AND ROUTE OF ADMINISTRATION

Needles are not included

Read the package leaflet before use Subcutaneous use

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNINGS, IF NECESSARY

Use only clear, colourless solution Single patient use only

Do not withdraw solution from the pen

• 8. EXPIRY DATE

EXP

After first opening: Use within 8 weeks

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C)

Do not freeze

After first opening: Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect it from light

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Discard the needle safely after each injection

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle DK-2880 Bagsv^rd Denmark

• 12. MARKETING AUTHORISATION NUMBERS

EU/1/12/807/001 1 pen of 3 mL

EU/1/12/807/002 1 pen of 3 mL and 7 NovoFine needles

EU/1/12/807/003 1 pen of 3 mL and 7 NovoTwist needles

EU/1/12/807/004 5 pens of 3 mL

• 13. BATCH NUMBER

Batch

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Tresiba pre-filled pen 100 units/mL

• 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included.

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC SN NN

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PEN LABEL (100 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION

Tresiba 100 units/mL solution for injection

insulin degludec

FlexTouch

• 2. METHOD OF ADMINISTRATION

SC use

• 3. EXPIRY DATE

EXP

• 4. BATCH NUMBER

Batch

• 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

3 mL

• 6. OTHER

Novo Nordisk A/S

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

MULTIPACK LABEL (100 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT

Tresiba 100 units/mL solution for injection in pre-filled pen insulin degludec

• 2. STATEMENT OF ACTIVE SUBSTANCE

One pre-filled pen contains 300 units of insulin degludec in 3 mL solution

1 mL solution contains 100 units of insulin degludec (equivalent to 3.66 mg)

• 3. LIST OF EXCIPIENTS

Glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection (FlexTouch)

Multipack: 10 (2 packs of 5) 3 mL pre-filled pens

• 5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use Subcutaneous use

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNINGS, IF NECESSARY

Use only clear, colourless solution Single patient use only

Do not withdraw solution from the pen

• 8. EXPIRY DATE

EXP

After first opening: Use within 8 weeks

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C)

Do not freeze

After first opening: Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect it from light

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Discard the needle safely after each injection

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsverd

Denmark

• 12. MARKETING AUTHORISATION NUMBER

EU/1/12/807/005 10 pens of 3 mL

• 13. BATCH NUMBER

Batch

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Tresiba pre-filled pen 100 units/mL

• 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included.

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC SN NN

PARTICULARS TO APPEAR ON THE INNER PACKAGING

CARTON FOR MULTIPACK (100 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT

Tresiba 100 units/mL solution for injection in pre-filled pen insulin degludec

• 2. STATEMENT OF ACTIVE SUBSTANCE

One pre-filled pen contains 300 units of insulin degludec in 3 mL solution

1 mL solution contains 100 units of insulin degludec (equivalent to 3.66 mg)

• 3. LIST OF EXCIPIENTS

Glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection (FlexTouch)

• 5 × 3 mL. Component of a multipack, cannot be sold separately

• 5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use Subcutaneous use

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNINGS, IF NECESSARY

Use only clear, colourless solution Single patient use only

Do not withdraw solution from the pen

• 8. EXPIRY DATE

EXP

After first opening: Use within 8 weeks

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C)

Do not freeze

After first opening: Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect it from light

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Discard the needle safely after each injection

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsverd

Denmark

• 12. MARKETING AUTHORISATION NUMBER

EU/1/12/807/005 10 pens of 3 mL

• 13. BATCH NUMBER

Batch

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Tresiba pre-filled pen 100 units/mL

• 17. UNIQUE IDENTIFIER – 2D BARCODE

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON (200 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT

Tresiba 200 units/mL solution for injection in pre-filled pen insulin degludec

• 2. STATEMENT OF ACTIVE SUBSTANCE

One pre-filled pen contains 600 units of insulin degludec in 3 mL solution

1 mL solution contains 200 units of insulin degludec (equivalent to 7.32 mg)

• 3. LIST OF EXCIPIENTS

Glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection (FlexTouch) 1 × 3 mL

1 × 3 mL + 7 NovoFine needles

• 1 × 3 mL + 7 NovoTwist needles

• 2 × 3 mL

• 3 × 3 mL

• 5 × 3 mL

• 5. METHOD AND ROUTE OF ADMINISTRATION

Needles are not included

Read the package leaflet before use

Subcutaneous use

Caution: One step equals 2 units

• – the pen shows the dose

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNINGS, IF NECESSARY

Use only clear, colourless solution Single patient use only

Do not withdraw solution from the pen

• 8. EXPIRY DATE

EXP

After first opening: Use within 8 weeks

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C)

Do not freeze

After first opening: Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect it from light

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Discard the needle safely after each injection

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle DK-2880 Bagsv^rd Denmark

• 12. MARKETING AUTHORISATION NUMBERS

EU/1/12/807/009 1 pen of 3 mL

EU/1/12/807/006 1 pen of 3 mL and 7 NovoFine needles

EU/1/12/807/010 1 pen of 3 mL and 7 NovoTwist needles

EU/1/12/807/012 2 pens of 3 mL

EU/1/12/807/013 3 pens of 3 mL

EU/1/12/807/016 5 pens of 3 mL

• 13. BATCH NUMBER

Batch

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Tresiba pre-filled pen 200 units/mL

• 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included.

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC SN NN

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PEN LABEL (200 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION

Tresiba 200 units/mL solution for injection

insulin degludec

FlexTouch

• 2. METHOD OF ADMINISTRATION

SC use

• 3. EXPIRY DATE

EXP

• 4. BATCH NUMBER

Batch

• 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

3 mL

• 6. OTHER

Novo Nordisk A/S

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

MULTIPACK LABEL (200 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT

Tresiba 200 units/mL solution for injection in pre-filled pen insulin degludec

• 2. STATEMENT OF ACTIVE SUBSTANCE

One pre-filled pen contains 600 units of insulin degludec in 3 mL solution

1 mL solution contains 200 units of insulin degludec (equivalent to 7.32 mg)

• 3. LIST OF EXCIPIENTS

Glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection (FlexTouch)

Multipack: 6 (2 packs of 3) 3 mL pre-filled pens

• 5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use Subcutaneous use

Caution: One step equals 2 units

• – the pen shows the dose

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNINGS, IF NECESSARY

Use only clear, colourless solution Single patient use only

Do not withdraw solution from the pen

• 8. EXPIRY DATE

After first opening: Use within 8 weeks

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C)

Do not freeze

After first opening: Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect it from light

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Discard the needle safely after each injection

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle DK-2880 Bagsv^rd Denmark

• 12. MARKETING AUTHORISATION NUMBER

EU/1/12/807/015 6 pens of 3 mL

• 13. BATCH NUMBER

Batch

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Tresiba pre-filled pen 200 units/mL

• 17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

• 18. UNIQUE IDENTIFIER – HUMAN READABLE DATA

PC

PARTICULARS TO APPEAR ON THE INNER PACKAGING

CARTON FOR MULTIPACK (200 units/mL pre-filled pen (FlexTouch))

• 1. NAME OF THE MEDICINAL PRODUCT

Tresiba 200 units/mL solution for injection in pre-filled pen insulin degludec

• 2. STATEMENT OF ACTIVE SUBSTANCE

One pre-filled pen contains 600 units of insulin degludec in 3 mL solution

1 mL solution contains 200 units of insulin degludec (equivalent to 7.32 mg)

• 3. LIST OF EXCIPIENTS

Glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection (FlexTouch)

3 × 3 mL. Component of a multipack, cannot be sold separately

• 5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use Subcutaneous use

Caution: One step equals 2 units

• – the pen shows the dose

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNINGS, IF NECESSARY

Use only clear, colourless solution Single patient use only

Do not withdraw solution from the pen

• 8. EXPIRY DATE

After first opening: Use within 8 weeks

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C)

Do not freeze

After first opening: Do not store above 30°C. Can be stored in a refrigerator (2°C – 8°C). Keep the cap on the pen in order to protect it from light

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Discard the needle safely after each injection

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle DK-2880 Bagsv^rd Denmark

• 12. MARKETING AUTHORISATION NUMBER

EU/1/12/807/015 6 pens of 3 mL

• 13. BATCH NUMBER

Batch

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Tresiba pre-filled pen 200 units/mL

• 17. UNIQUE IDENTIFIER – 2D BARCODE

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER CARTON (100 units/mL cartridge (Penfill))

• 1. NAME OF THE MEDICINAL PRODUCT

Tresiba 100 units/mL solution for injection in cartridge insulin degludec

• 2. STATEMENT OF ACTIVE SUBSTANCE

One cartridge contains 300 units of insulin degludec in 3 mL solution

1 mL solution contains 100 units of insulin degludec (equivalent to 3.66 mg)

• 3. LIST OF EXCIPIENTS

Glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections

• 4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection (Penfill)

• 5 × 3 mL

10 × 3 mL

• 5. METHOD AND ROUTE OF ADMINISTRATION

Read the package leaflet before use Subcutaneous use

• 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children

• 7. OTHER SPECIAL WARNINGS, IF NECESSARY

Use only clear, colourless solution Single patient use only

• 8. EXPIRY DATE

EXP

After first opening: Use within 8 weeks

• 9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator (2°C – 8°C)

Do not freeze

After first opening: Do not refrigerate. Do not store above 30°C. Keep the cartridge in the outer carton in order to protect it from light

• 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

Discard the needle safely after each injection

• 11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Novo Nordisk A/S

Novo Alle DK-2880 Bagsv^rd Denmark

• 12. MARKETING AUTHORISATION NUMBERS

EU/1/12/807/007 5 cartridges of 3 mL

EU/1/12/807/008 10 cartridges of 3 mL

• 13. BATCH NUMBER

Batch

• 14. GENERAL CLASSIFICATION FOR SUPPLY

• 15. INSTRUCTIONS ON USE

• 16. INFORMATION IN BRAILLE

Tresiba cartridge 100

• 17. UNIQUE IDENTIFIER – 2D BARCODE 2D barcode carrying the unique identifier included.

PC

SN

NN

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

LABEL (100 units/mL cartridge (Penfill))

• 1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION

Tresiba 100 units/mL solution for injection

insulin degludec

Penfill

• 2. METHOD OF ADMINISTRATION

SC use

• 3. EXPIRY DATE

EXP

• 4. BATCH NUMBER

Batch

• 5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

3 mL

• 6. OTHER

Novo Nordisk A/S

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Tresiba 100 units/mL solution for injection in pre-filled pen insulin degludec

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. see section 4.

What is in this leaflet

• 1. What Tresiba is and what it is used for

• 2. What you need to know before you use Tresiba

• 3. How to use Tresiba

• 4. Possible side effects

• 5. How to store Tresiba

• 6. Contents of the pack and other information

1. what tresiba is and what it is used for

Tresiba is a long-acting basal insulin called insulin degludec. It is used to treat diabetes mellitus in adults, adolescents and children aged 1 year and above. Tresiba helps your body reduce your blood sugar level. It is used for once-daily dosing. On occasions when you cannot follow your regular dosing schedule, you can change the time of dosing because Tresiba has a long blood sugar-lowering effect (see section 3 for ‘Flexibility in dosing time’). Tresiba can be used with meal-related rapid-acting insulin products. In type 2 diabetes mellitus, Tresiba may be used in combination with tablets for diabetes or with injectable antidiabetic medicines, other than insulin.

In type 1 diabetes mellitus, Tresiba must always be used in combination with meal-related rapid-acting insulin medicines.

2. what you need to know before you use tresiba

Do not use Tresiba

• if you are allergic to insulin degludec or any of the other ingredients of this medicine (listed in

section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Tresiba. Be especially aware of the following:

• Low blood sugar (hypoglycaemia) – if your blood sugar is too low, follow the guidance for low

blood sugar in section 4.

• High blood sugar (hyperglycaemia) – if your blood sugar is too high, follow the guidance for high blood sugar in section 4.
• Switching from other insulin medicines – the insulin dose may need to be changed if you switch

from another type, brand or manufacturer of insulin. Talk to your doctor.

• Pioglitazone used together with insulin, see ‘Pioglitazone’ be­low.
• Eye disorder – fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disorder. If you experience eye problems, talk to your doctor.
• Ensuring you use the right type of insulin – always check the insulin label before each injection

to avoid accidental mix-ups between different strengths of Tresiba as well as other insulin products.

If you have poor eyesight, please see section 3.

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.

Children and adolescents

Tresiba can be used in adolescents and children aged 1 year and above. There is no experience with the use of Tresiba in children below the age of 1 year.

Other medicines and Tresiba

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. Some medicines affect your blood sugar level, this may mean your insulin dose has to be changed.

Listed below are the most common medicines which may affect your insulin treatment.

Your blood sugar level may fall (hypoglycaemia) if you take:

• other medicines for diabetes (oral and injectable)
• sulfonamides, for infections
• anabolic steroids, such as testosterone
• beta-blockers, for high blood pressure. They may make it harder to recognise the warning signs

of too low blood sugar (see section 4 ‘Warning signs of too low blood sugar’)

• acetylsalicylic acid (and other salicylates), for pain and mild fever
• monoamine oxidase (MAO) inhibitors, for depression
• angiotensin converting enzyme (ACE) inhibitors, for some heart problems or high blood pressure.

Y our blood sugar level may rise (hyperglycaemia) if you take:

• danazol, for endometriosis
• oral contraceptives (birth control pills)
• thyroid hormones, for thyroid problems
• growth hormone, for growth hormone deficiency
• glucocorticoids such as ‘cortisone’, for inflammation
• sympathomimetics such as epinephrine (adrenaline), salbutamol or terbutaline, for asthma thiazides, for high blood pressure or if your body keeps too much water (water retention).

Octreotide and lanreotide : used to treat a rare condition involving too much growth hormone (acromegaly). They may increase or decrease your blood sugar level.

Pioglitazone : oral antidiabetic medicine used to treat type 2 diabetes mellitus. Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).

If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist or nurse.

Tresiba with alcohol

If you drink alcohol, your need for insulin may change. Your blood sugar level may either rise or fall. You should therefore monitor your blood sugar level more often than usual.

Pregnancy and breast-feeding

It is not known if Tresiba affects the baby in pregnancy or during breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes is needed in pregnancy. Avoiding too low blood sugar (hypoglycaemia) is particularly important for the health of your baby.

Driving and using machines

Having too low or too high blood sugar can affect your ability to drive or use any tools or machines. If your blood sugar is too low or too high, your ability to concentrate or react might be affected. This could be dangerous to yourself or others. Ask your doctor whether you can drive if:

• you often get too low blood sugar
• you find it hard to recognise too low blood sugar.

Important information about some of the ingredients of Tresiba

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that the medicine is essentially ‘sodium-free’.

3. how to use tresiba

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the FlexTouch pre-filled pen.

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. In addition, Tresiba 100 units/mL packaging and label are light green, and Tresiba 200 units/mL packaging and label are dark green with striping with a red box highlighting the formulation strength.

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

The pre-filled pen 100 units/mL can provide a dose of 1–80 units in one injection in steps of 1 unit. The dose counter of the pre-filled pen shows the number of units of insulin to be injected. Do not make any dose re-calculation.

Your doctor will decide together with you:

• how much Tresiba you will need each day
• when to check your blood sugar level and if you need a higher or lower dose.

Flexibility in dosing time

• Always follow your doctor’s recom­mendation for dose.
• Use Tresiba once each day, preferably at the same time every day.
• On occasions when it is not possible to take Tresiba at the same time of the day, it can be taken

at a different time of day. Make sure to have a minimum of 8 hours between the doses. There is no experience with flexibility in dosing time of Tresiba in children and adolescents.

• If you want to change your usual diet, check with your doctor, pharmacist or nurse first as a change in diet may alter your need for insulin.

Based on your blood sugar level, your doctor may change your dose.

When using other medicines, ask your doctor if your treatment needs to be adjusted.

Use in elderly (>65 years old)

Tresiba can be used in elderly, but if you are elderly, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

If you have kidney or liver problems

If you have kidney or liver problems, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

Injecting your medicine

Before you use Tresiba for the first time, your doctor or nurse will show you how to use the pre-filled pen.

• Check the name and strength on the label of the pen to make sure it is Tresiba 100 units/mL.

Do not use Tresiba

• in insulin infusion pumps.
• if the pen is damaged or has not been stored correctly (see section 5).
• if the insulin does not appear clear and colourless.

How to inject

• Tresiba is given as an injection under the skin (subcutaneous injection). Do not inject it into a

vein or muscle.

• The best places to inject are the front of your thighs, upper arms or the front of your waist (abdomen).
• Change the place within the area where you inject each day to reduce the risk of developing

lumps and skin pitting (see section 4).

• Always use a new needle for each injection. Re-use of needles may increase the risk of blocked needles leading to inaccurate dosing. Dispose of the needle safely after each use.
• Do not use a syringe to remove the solution from the pen to avoid dosing errors and potential overdose.

Detailed instructions for use are provided on the other side of this leaflet.

If you use more Tresiba than you should

If you use too much insulin, your blood sugar may get too low (hypoglycaemia), see advice in section 4 ‘Too low blood sugar’.

If you forget to use Tresiba

If you forget a dose, inject the missed dose when discovering the mistake, ensuring a minimum of 8 hours between doses. If you discover that you missed your previous dose when it is time to take your next regular scheduled dose, do not inject a double dose, but resume your once-daily dosing schedule.

If you stop using Tresiba

Do not stop using your insulin without talking to your doctor. If you stop using your insulin, this could lead to a very high blood sugar level and ketoacidosis (a condition with too much acid in the blood), see advice in section 4 ‘Too high blood sugar’.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Hypoglycaemia (too low blood sugar) may occur very commonly with insulin treatment (may affect more than 1 in 10 people). It can be very serious. If your blood sugar level falls too much, you may become unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If you have symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See advice in ‘Too low blood sugar’ below.

If you have a serious allergic reaction (seen rarely) to the insulin or any of the ingredients in Tresiba, stop using this medicine and see a doctor straight away. The signs of a serious allergic reaction are:

• the local reactions spread to other parts of your body
• you suddenly feel unwell with sweating you start being sick (vomiting) you experience difficulty in breathing
• you experience rapid heartbeat or feeling dizzy.

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.

Other side effects include:

Common (may affect up to 1 in 10 people)

Local reactions: Local reactions at the place you inject yourself may occur. The signs may include: pain, redness, hives, swelling and itching. The reactions usually disappear after a few days. See your doctor if they do not disappear after a few weeks. Stop using Tresiba and see a doctor straight away if the reactions become serious. For more information, see ‘serious allergic reaction’ above.

Uncommon (may affect up to 1 in 100 people)

Swelling around your joints: When you first start using your medicine, your body may keep more water than it should. This causes swelling around your ankles and other joints. This is usually only short-lasting.

Rare (may affect up to 1 in 1,000 people)

This medicine can cause allergic reactions such as hives, swelling of the tongue and lips, diarrhoea, nausea, tiredness and itching.

General effects from diabetes treatment

• Too low blood sugar (hypoglycaemia)

Too low blood sugar may happen if you:

drink alcohol; use too much insulin; exercise more than usual; eat too little or miss a meal.

Warning signs of too low blood sugar – these may come on suddenly:

Headache; slurred speech; fast heartbeat; cold sweat, cool pale skin; feeling sick, feeling very hungry; tremor or feeling nervous or worried; feeling unusually tired, weak and sleepy; feeling confused, difficulty in concentrating; short-lasting changes in your sight.

What to do if you get too low blood sugar

• Eat glucose tablets or another high sugar snack, like sweets, biscuits or fruit juice (always carry glucose tablets or a high sugar snack, just in case).
• Measure your blood sugar if possible and rest. You may need to measure your blood sugar more than once, as with all basal insulin products improvement from the period of low blood sugar may be delayed.
• Wait until the signs of too low blood sugar have gone or when your blood sugar level has settled. Then carry on with your insulin as usual.

What others need to do if you pass out

Tell everyone you spend time with that you have diabetes. Tell them what could happen if your blood sugar gets too low, including the risk of passing out.

Let them know that if you pass out, they must:

• turn you on your side
• get medical help straight away
• not give you any food or drink because you may choke.

You may recover more quickly from passing out with an injection of glucagon. This can only be given by someone who knows how to use it.

• If you are given glucagon, you will need sugar or a sugary snack as soon as you come round.
• If you do not respond to a glucagon injection, you will have to be treated in a hospital.
• If severe low blood sugar is not treated over time, it can cause brain damage. This can be short or long-lasting. It may even cause death.

Talk to your doctor if:

• your blood sugar got so low that you passed out
• you have used an injection of glucagon
• you have had too low blood sugar a few times recently.

This is because the dosing or timing of your insulin injections, food or exercise may need to be changed.

• Too high blood sugar (hyperglycaemia)

Too high blood sugar may happen if you:

eat more or exercise less than usual; drink alcohol; get an infection or a fever; have not used enough insulin; keep using less insulin than you need; forget to use your insulin or stop using insulin without talking to your doctor.

Warning signs of too high blood sugar – these normally appear gradually:

Flushed, dry skin; feeling sleepy or tired; dry mouth, fruity (acetone) breath; urinating more often, feeling thirsty; losing your appetite, feeling or being sick (nausea or vomiting).

These may be signs of a very serious condition called ketoacidosis. This is a build-up of acid in the blood because the body is breaking down fat instead of sugar. If not treated, this could lead to diabetic coma and eventually death.

What to do if you get too high blood sugar

• Test your blood sugar level.
• Test your urine or blood for ketones.
• Get medical help straight away.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store tresiba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the pen label and carton, after ‘EXP’.

The expiry date refers to the last day of that month.

Before first use

Store in a refrigerator (2°C to 8°C). Do not freeze. Keep away from the freezing element. Keep the cap on the pen in order to protect it from light.

After first opening or if carried as a spare

You can carry your Tresiba pre-filled pen (FlexTouch) with you and keep it at room temperature (not above 30°C) or in a refrigerator (2°C to 8°C) for up to 8 weeks.

Always keep the cap on the pen when you are not using it in order to protect it from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Tresiba contains

• The active substance is insulin degludec. Each mL of solution contains 100 units of insulin degludec. Each pre-filled pen contains 300 units of insulin degludec in 3 mL solution.
• The other ingredients are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections (see section 2).

What Tresiba looks like and contents of the pack

Tresiba is presented as a clear and colourless solution for injection in a pre-filled pen (300 units per 3 mL).

Pack sizes of 1 (with or without needles), 5 (without needles) and multipack of 10 (2 × 5) (without needles) pre-filled pens of 3 mL. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsvsrd, Denmark

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

Instructions on how to use Tresiba 100 units/mL solution for injection in pre-filled pen (FlexTouch)

Please read these instructions carefully before using your FlexTouch pre-filled pen. If you do not follow the instructions carefully, you may get too little or too much insulin, which can lead to too high or too low blood sugar level.

Do not use the pen without proper training from your doctor or nurse.

Start by checking your pen to make sure that it contains Tresiba 100 units/mL, then look at the illustrations below to get to know the different parts of your pen and needle.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the FlexTouch pre-filled pen.

Your pen is a pre-filled dial-a-dose insulin pen containing 300 units of insulin. You can select a maximum of 80 units per dose, in steps of 1 unit. Your pen is designed to be used with NovoTwist or NovoFine single-use disposable needles up to a length of 8 mm.

△ Important information

Pay special attention to these notes as they are important for correct use of the pen.

Tresiba pre-filled pen and needle (example) (FlexTouch)

1 Prepare your pen

Check the name and strength on the label of your pen to make sure that it contains Tresiba 100 units/mL. This is especially important if you take more than one type of insulin. If you take a wrong type of insulin, your blood sugar level may get too high or too low.

Pull off the pen cap.

Check that the insulin in your pen is clear and colourless.

Look through the insulin window. If the insulin looks cloudy, do not use the pen.

Take a new needle and tear off the paper tab.

Push the needle straight onto the pen. Turn until it is on tight.

Pull off the outer needle cap and keep it for later. You will need it after the injection to correctly remove the needle from the pen.

Pull off the inner needle cap and throw it away. If you try to put it back on, you may accidentally stick yourself with the needle.

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

△ Always use a new needle for each injection.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

A Never use a bent or damaged needle.

2 Check the insulin flow

• Always check the insulin flow before you start.

This helps you to ensure that you get your full insulin dose.

• Turn the dose selector to select 2 units. Make sure the dose counter shows 2.

Hold the pen with the needle pointing up.

Tap the top of the pen gently a few times to let any air bubbles rise to the top.

Press and hold in the dose button until the dose counter returns to 0.

The 0 must line up 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 no drop appears, repeat steps 2A to 2C up to 6 times. If there is still no drop, change the needle and repeat steps 2A to 2C once more.

If a drop of insulin still does not appear, dispose of the pen and use a new one.

• △ Always make sure that a drop appears at the needle tip before you inject. This makes sure that the insulin flows.

If no drop appears, you will not inject any insulin, even though the dose counter may move. This may indicate a blocked or damaged needle.

• △ Always check the flow before you inject. If you do not check the flow, you may get too little insulin or no insulin at all. This may lead to too high blood sugar level.

• 3 Select your dose

• Make sure the dose counter shows 0 before you start.

The 0 must line up with the dose pointer.

• Turn the dose selector to select the dose you need, as directed by your doctor or nurse.

If you select a wrong dose, you can turn the dose selector forwards or backwards to the correct dose.

The pen can dial up to a maximum of 80 units.

The dose selector changes the number of units. Only the dose counter and dose pointer will show how many units you select per dose.

You can select up to 80 units per dose. When your pen contains less than 80 units, the dose counter stops at the number of units left.

The dose selector clicks differently when turned forwards, backwards or past the number of units left. Do not count the pen clicks.

• △ Always use the dose counter and the dose pointer to see how many units you have selected before injecting the insulin.

Do not count the pen clicks. If you select and inject the wrong dose, your blood sugar level may get too high or too low.

Do not use the insulin scale, it only shows approximately how much insulin is left in your pen.

• 4 Inject your dose

• Insert the needle into your skin as your doctor or nurse has shown you.
• Make sure you can see the dose counter.

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

• Press and hold down the dose button until the dose counter returns to 0.

The 0 must line up with the dose pointer.

You may then hear or feel a click.

• Leave the needle under the skin for at least 6 seconds to make sure you get your full dose.

Pull the needle and pen straight up from your skin.

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

You may see a drop of insulin at the needle tip after injecting. This is normal and does not affect your dose.

△ Always watch the dose counter to know how many units you inject.

The dose counter will show the exact number of units. Do not count the pen clicks. Hold the dose button down until the dose counter returns to 0 after the injection. If the dose counter stops before it returns to 0, the full dose has not been delivered, which may result in too high blood sugar level.

• 5 After your injection

• Lead the needle tip into the outer needle cap on a flat surface without touching the needle or the outer needle cap.

Once the needle is covered, carefully push the outer needle cap completely on.

Unscrew the needle and dispose of it carefully.

Put the pen cap on your pen after each use to protect the insulin from light.

Always dispose of the needle after each injection in an appropriate sharps container. This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing. If the needle is blocked, you will not inject any insulin.

When the pen is empty, throw it away without a needle on as instructed by your doctor, nurse, pharmacist or local authorities. Do not place the used needle in household waste.

A Never try to put the inner needle cap back on the needle. You may stick yourself with the needle.

A Always remove the needle after each injection and store your pen without the needle attached.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

• 6 How much insulin is left?

The insulin scale shows you approximately how much insulin is left in your pen.

Approx. how much insulin is left

To see precisely how much insulin is left, use the dose counter:

Turn the dose selector until the dose counter stops.

If it shows 80, at least 80 units are left in your pen.

If it shows less than 80, the number shown is the number of units left in your pen.

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

• If you need more insulin than the units left in your pen, you can split your dose between two pens.

• △ Be very careful to calculate correctly if splitting your dose.

If in doubt, take the full dose with a new pen. If you split the dose wrong, you will inject too little or too much insulin, which can lead to too high or too low blood sugar level.

• △ Further important information

• Always keep your pen with you.
• Always carry an extra pen and new needles with you in case of loss or damage.
• Always keep your pen and needles out of sight and reach of others, especially children.
• Never share your pen or your needles with other people. It might lead to cross-infection.
• Never share your pen with other people. Your medicine might be harmful to their health.
• Caregivers must be very careful when handling used needles to reduce the risk of needle

injury and cross-infection.

Caring for your pen

Treat your pen with care. Rough handling or misuse may cause inaccurate dosing, which can lead to too high or too low blood sugar level.

• Do not leave the pen in a car or other place where it can get too hot or too cold.
• Do not expose your pen to dust, dirt or liquid.
• Do not wash, soak or lubricate your pen. If necessary, clean it with mild detergent on a moistened cloth.

Do not drop your pen or knock it against hard surfaces.

If you drop it or suspect a problem, attach a new needle and check the insulin flow before you inject.

Do not try to refill your pen. Once empty, it must be disposed of.

Do not try to repair your pen or pull it apart.

Package leaflet: Information for the patient

Tresiba 200 units/mL solution for injection in pre-filled pen insulin degludec

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. see section 4.

What is in this leaflet

• 1. What Tresiba is and what it is used for

• 2. What you need to know before you use Tresiba

• 3. How to use Tresiba

• 4. Possible side effects

• 5. How to store Tresiba

• 6. Contents of the pack and other information

1. what tresiba is and what it is used for

Tresiba is a long-acting basal insulin called insulin degludec. It is used to treat diabetes mellitus in adults, adolescents and children aged 1 year and above. Tresiba helps your body reduce your blood sugar level. It is used for once-daily dosing. On occasions when you cannot follow your regular dosing schedule, you can change the time of dosing because Tresiba has a long blood sugar-lowering effect (see section 3 for ‘Flexibility in dosing time’). Tresiba can be used with meal-related rapid-acting insulin products. In type 2 diabetes mellitus, Tresiba may be used in combination with tablets for diabetes or with injectable antidiabetic medicines, other than insulin.

In type 1 diabetes mellitus, Tresiba must always be used in combination with meal-related rapid-acting insulin medicines.

2. what you need to know before you use tresiba

Do not use Tresiba

• if you are allergic to insulin degludec or any of the other ingredients of this medicine (listed in

section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Tresiba. Be especially aware of the following:

• Low blood sugar (hypoglycaemia) – if your blood sugar is too low, follow the guidance for low

blood sugar in section 4.

• High blood sugar (hyperglycaemia) – if your blood sugar is too high, follow the guidance for high blood sugar in section 4.
• Switching from other insulin medicines – the insulin dose may need to be changed if you switch from another type, brand or manufacturer of insulin. Talk to your doctor.
• Pioglitazone used together with insulin, see ‘Pioglitazone’ be­low.
• Eye disorder – fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disorder. If you experience eye problems, talk to your doctor.
• Ensuring you use the right type of insulin – always check the insulin label before each injection

to avoid accidental mix-ups between different strengths of Tresiba as well as other insulin products.

If you have poor eyesight, please see section 3.

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.

Children and adolescents

Tresiba can be used in adolescents and children aged 1 year and above. There is no experience with the use of Tresiba in children below the age of 1 year.

Other medicines and Tresiba

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. Some medicines affect your blood sugar level, this may mean your insulin dose has to be changed.

Listed below are the most common medicines which may affect your insulin treatment.

Your blood sugar level may fall (hypoglycaemia) if you take:

• other medicines for diabetes (oral and injectable)
• sulfonamides, for infections
• anabolic steroids, such as testosterone
• beta-blockers, for high blood pressure. They may make it harder to recognise the warning signs

of too low blood sugar (see section 4 ‘Warning signs of too low blood sugar’)

• acetylsalicylic acid (and other salicylates), for pain and mild fever
• monoamine oxidase (MAO) inhibitors, for depression
• angiotensin converting enzyme (ACE) inhibitors, for some heart problems or high blood pressure.

Y our blood sugar level may rise (hyperglycaemia) if you take:

• danazol, for endometriosis
• oral contraceptives (birth control pills)
• thyroid hormones, for thyroid problems
• growth hormone, for growth hormone deficiency
• glucocorticoids such as ‘cortisone’, for inflammation
• sympathomimetics such as epinephrine (adrenaline), salbutamol or terbutaline, for asthma thiazides, for high blood pressure or if your body keeps too much water (water retention).

Octreotide and lanreotide : used to treat a rare condition involving too much growth hormone (acromegaly). They may increase or decrease your blood sugar level.

Pioglitazone : oral antidiabetic medicine used to treat type 2 diabetes mellitus. Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).

If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist or nurse.

Tresiba with alcohol

If you drink alcohol, your need for insulin may change. Your blood sugar level may either rise or fall. You should therefore monitor your blood sugar level more often than usual.

Pregnancy and breast-feeding

It is not known if Tresiba affects the baby in pregnancy or during breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes is needed in pregnancy. Avoiding too low blood sugar (hypoglycaemia) is particularly important for the health of your baby.

Driving and using machines

Having too low or too high blood sugar can affect your ability to drive or use any tools or machines. If your blood sugar is too low or too high, your ability to concentrate or react might be affected. This could be dangerous to yourself or others. Ask your doctor whether you can drive if:

• you often get too low blood sugar
• you find it hard to recognise too low blood sugar.

Important information about some of the ingredients of Tresiba

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that the medicine is essentially ‘sodium-free’.

3. how to use tresiba

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the FlexTouch pre-filled pen.

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. In addition, Tresiba 100 units/mL packaging and label are light green, and Tresiba 200 units/mL packaging and label are dark green with striping with a red box highlighting the formulation strength.

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

The pre-filled pen 200 units/mL can provide a dose of 2–160 units in one injection in steps of 2 units. The dose counter of the pre-filled pen shows the number of units of insulin to be injected. Do not make any dose re-calculation.

Your doctor will decide together with you:

• how much Tresiba you will need each day
• when to check your blood sugar level and if you need a higher or lower dose.

Flexibility in dosing time

• Always follow your doctor’s recom­mendation for dose.
• Use Tresiba once each day, preferably at the same time every day.
• On occasions when it is not possible to take Tresiba at the same time of the day, it can be taken

at a different time of day. Make sure to have a minimum of 8 hours between the doses. There is no experience with flexibility in dosing time of Tresiba in children and adolescents.

• If you want to change your usual diet, check with your doctor, pharmacist or nurse first as a change in diet may alter your need for insulin.

Based on your blood sugar level, your doctor may change your dose.

When using other medicines, ask your doctor if your treatment needs to be adjusted.

Use in elderly (>65 years old)

Tresiba can be used in elderly, but if you are elderly, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

If you have kidney or liver problems

If you have kidney or liver problems, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

Injecting your medicine

Before you use Tresiba for the first time, your doctor or nurse will show you how to use the pre-filled pen.

• Check the name and strength on the label of the pen to make sure it is Tresiba 200 units/mL.
• The dose counter of your pen shows the exact number of insulin units. Do not make any dose

re-calculation.

Do not use Tresiba

• in insulin infusion pumps.
• if the pen is damaged or has not been stored correctly (see section 5 ‘How to store Tresiba’).
• if the insulin does not appear clear and colourless.

How to inject

• Tresiba is given as an injection under the skin (subcutaneous injection). Do not inject it into a vein or muscle.
• The best places to inject are the front of your thighs, upper arms or the front of your waist (abdomen).
• Change the place within the area where you inject each day to reduce the risk of developing lumps and skin pitting (see section 4).
• Always use a new needle for each injection. Re-use of needles may increase the risk of blocked needles leading to inaccurate dosing. Dispose of the needle safely after each use.
• Do not use a syringe to remove the solution from the pen to avoid dosing errors and potential overdose.

Detailed instructions for use are provided on the other side of this leaflet.

If you use more Tresiba than you should

If you use too much insulin, your blood sugar may get too low (hypoglycaemia), see advice in section 4 ‘Too low blood sugar’.

If you forget to use Tresiba

If you forget a dose, inject the missed dose when discovering the mistake, ensuring a minimum of

• 8 hours between doses. If you discover that you missed your previous dose when it is time to take your next regular scheduled dose, do not inject a double dose, but resume your once-daily dosing schedule.

If you stop using Tresiba

Do not stop using your insulin without talking to your doctor. If you stop using your insulin, this could lead to a very high blood sugar level and ketoacidosis (a condition with too much acid in the blood), see advice in section 4 ‘Too high blood sugar’.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Hypoglycaemia (too low blood sugar) may occur very commonly with insulin treatment (may affect more than 1 in 10 people). It can be very serious. If your blood sugar level falls too much, you may become unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If

you have symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See advice in ‘Too low blood sugar’ below.

• If you have a serious allergic reaction (seen rarely) to the insulin or any of the ingredients in Tresiba, stop using this medicine and see a doctor straight away. The signs of a serious allergic reaction are: the local reactions spread to other parts of your body
• you suddenly feel unwell with sweating
• you start being sick (vomiting)
• you experience difficulty in breathing
• you experience rapid heartbeat or feeling dizzy.

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.

Other side effects include:

Common (may affect up to 1 in 10 people)

Local reactions: Local reactions at the place you inject yourself may occur. The signs may include: pain, redness, hives, swelling and itching. The reactions usually disappear after a few days. See your doctor if they do not disappear after a few weeks. Stop using Tresiba and see a doctor straight away if the reactions become serious. For more information, see ‘serious allergic reaction’ above.

Uncommon (may affect up to 1 in 100 people)

Swelling around your joints: When you first start using your medicine, your body may keep more water than it should. This causes swelling around your ankles and other joints. This is usually only short-lasting.

Rare (may affect up to 1 in 1,000 people)

This medicine can cause allergic reactions such as hives, swelling of the tongue and lips, diarrhoea, nausea, tiredness and itching.

General effects from diabetes treatment

• Too low blood sugar (hypoglycaemia)

Too low blood sugar may happen if you:

drink alcohol; use too much insulin; exercise more than usual; eat too little or miss a meal.

Warning signs of too low blood sugar – these may come on suddenly:

Headache; slurred speech; fast heartbeat; cold sweat, cool pale skin; feeling sick, feeling very hungry; tremor or feeling nervous or worried; feeling unusually tired, weak and sleepy; feeling confused, difficulty in concentrating; short-lasting changes in your sight.

What to do if you get too low blood sugar

• Eat glucose tablets or another high sugar snack, like sweets, biscuits or fruit juice (always carry glucose tablets or a high sugar snack, just in case).
• Measure your blood sugar if possible and rest. You may need to measure your blood sugar more than once, as with all basal insulin products improvement from the period of low blood sugar may be delayed.
• Wait until the signs of too low blood sugar have gone or when your blood sugar level has settled. Then carry on with your insulin as usual.

What others need to do if you pass out

Tell everyone you spend time with that you have diabetes. Tell them what could happen if your blood sugar gets too low, including the risk of passing out.

Let them know that if you pass out, they must:

• turn you on your side
• get medical help straight away
• not give you any food or drink because you may choke.

You may recover more quickly from passing out with an injection of glucagon. This can only be given by someone who knows how to use it.

• If you are given glucagon, you will need sugar or a sugary snack as soon as you come round.
• If you do not respond to a glucagon injection, you will have to be treated in a hospital.
• If severe low blood sugar is not treated over time, it can cause brain damage. This can be short or long-lasting. It may even cause death.

Talk to your doctor if:

• your blood sugar got so low that you passed out
• you have used an injection of glucagon
• you have had too low blood sugar a few times recently.

This is because the dosing or timing of your insulin injections, food or exercise may need to be changed.

• Too high blood sugar (hyperglycaemia)

Too high blood sugar may happen if you:

eat more or exercise less than usual; drink alcohol; get an infection or a fever; have not used enough insulin; keep using less insulin than you need; forget to use your insulin or stop using insulin without talking to your doctor.

Warning signs of too high blood sugar – these normally appear gradually:

Flushed, dry skin; feeling sleepy or tired; dry mouth, fruity (acetone) breath; urinating more often, feeling thirsty; losing your appetite, feeling or being sick (nausea or vomiting).

These may be signs of a very serious condition called ketoacidosis. This is a build-up of acid in the blood because the body is breaking down fat instead of sugar. If not treated, this could lead to diabetic coma and eventually death.

What to do if you get too high blood sugar

• Test your blood sugar level.
• Test your urine or blood for ketones.
• Get medical help straight away.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store tresiba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the pen label and carton, after ‘EXP’.

The expiry date refers to the last day of that month.

Before first use

Store in a refrigerator (2°C to 8°C). Do not freeze. Keep away from the freezing element. Keep the cap on the pen in order to protect it from light.

After first opening or if carried as a spare

You can carry your Tresiba pre-filled pen (FlexTouch) with you and keep it at room temperature (not above 30°C) or in a refrigerator (2°C to 8°C) for up to 8 weeks.

Always keep the cap on the pen when you are not using it in order to protect it from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Tresiba contains

• The active substance is insulin degludec. Each mL of solution contains 200 units of insulin degludec. Each pre-filled pen contains 600 units of insulin degludec in 3 mL solution.
• The other ingredients are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections (see section 2).

What Tresiba looks like and contents of the pack

Tresiba is presented as a clear and colourless solution for injection in a pre-filled pen (600 units per

3 mL).

Pack sizes of 1 (with or without needles), 2 (without needles), 3 (without needles), 5 (without needles) and multipack of 6 (2 × 3) (without needles) pre-filled pens of 3 mL. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsvsrd, Denmark

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

Instructions on how to use Tresiba 200 units/mL solution for injection in pre-filled pen (FlexTouch)

Please read these instructions carefully before using your FlexTouch pre-filled pen. If you do not follow the instructions carefully, you may get too little or too much insulin, which can lead to too high or too low blood sugar level.

Do not use the pen without proper training from your doctor or nurse.

Start by checking your pen to make sure that it contains Tresiba 200 units/mL, then look at the illustrations below to get to know the different parts of your pen and needle.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the FlexTouch pre-filled pen.

Your pen is a pre-filled dial-a-dose insulin pen containing 600 units of insulin. You can select a maximum of 160 units per dose, in steps of 2 units. The dose counter of your pen shows the exact number of insulin units. Do not make any dose re-calculation. Your pen is designed to be used with NovoTwist or NovoFine single-use disposable needles up to a length of 8 mm.

△ Important information

Pay special attention to these notes as they are important for correct use of the pen.

Needle

Paper tab

Dose button

Dose selector

Tresiba pre-filled pen and needle (example) (FlexTouch)

Pen cap

Outer needle cap

Inner needle cap

Dose counter

Insulin scale

Insulin window

Pen label

Dose button with 2 dots indicates 2 units per step

Dose pointer

1 Prepare your pen

Check the name and strength on the label of your pen to make sure that it contains Tresiba 200 units/mL. This is especially important if you take more than one type of insulin. If you take a wrong type of insulin, your blood sugar level may get too high or too low.

Pull off the pen cap.

Check that the insulin in your pen is clear and colourless.

Look through the insulin window. If the insulin looks cloudy, do not use the pen.

Take a new needle and tear off the paper tab.

Push the needle straight onto the pen. Turn until it is on tight.

Pull off the outer needle cap and keep it for later. You will need it after the injection to correctly remove the needle from the pen.

Pull off the inner needle cap and throw it away. If you try to put it back on, you may accidentally stick yourself with the needle.

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

A Always use a new needle for each injection.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

A Never use a bent or damaged needle.

2 Check the insulin flow

Always check the insulin flow before you start.

This helps you to ensure that you get your full insulin dose.

Turn the dose selector to select 2 units. Make sure the dose counter shows 2.

Hold the pen with the needle pointing up.

Tap the top of the pen gently a few times to let any air bubbles rise to the top.

Press and hold in the dose button until the dose counter returns to 0.

The 0 must line up 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 no drop appears, repeat steps 2A to 2C up to 6 times. If there is still no drop, change the needle and repeat steps 2A to 2C once more.

If a drop of insulin still does not appear, dispose of the pen and use a new one.

• △ Always make sure that a drop appears at the needle tip before you inject. This makes sure that the insulin flows.

If no drop appears, you will not inject any insulin, even though the dose counter may move. This may indicate a blocked or damaged needle.

• △ Always check the flow before you inject. If you do not check the flow, you may get too little insulin or no insulin at all. This may lead to too high blood sugar level.

• 3 Select your dose

• Make sure the dose counter shows 0 before you start.

The 0 must line up with the dose pointer.

• Turn the dose selector to select the dose you need, as directed by your doctor or nurse.
• The dose counter shows the dose dialled in units. Do not make any dose re-calculation.

If you select a wrong dose, you can turn the dose selector forwards or backwards to the correct dose.

The pen can dial up to a maximum of 160 units.

The dose selector changes the number of units. Only the dose counter and dose pointer will show how many units you select per dose.

You can select up to 160 units per dose. When your pen contains less than 160 units, the dose counter stops at the number of units left.

The dose selector clicks differently when turned forwards, backwards or past the number of units left. Do not count the pen clicks.

• △ Always use the dose counter and the dose pointer to see how many units you have selected before injecting the insulin.

Do not count the pen clicks. If you select and inject the wrong dose, your blood sugar level may get too high or too low.

Do not use the insulin scale, it only shows approximately how much insulin is left in your pen.

• 4 Inject your dose

• Insert the needle into your skin as your doctor or nurse has shown you.
• Make sure you can see the dose counter.

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

• Press and hold down the dose button until the dose counter returns to 0.

The 0 must line up with the dose pointer.

You may then hear or feel a click.

• Leave the needle under the skin for at least 6 seconds to make sure you get your full dose.

Pull the needle and pen straight up from your skin.

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

You may see a drop of insulin at the needle tip after injecting. This is normal and does not affect your dose.

△ Always watch the dose counter to know how many units you inject.

The dose counter will show the exact number of units. Do not count the pen clicks. Hold the dose button down until the dose counter returns to 0 after the injection. If the dose counter stops before it returns to 0, the full dose has not been delivered, which may result in too high blood sugar level.

• 5 After your injection

Lead the needle tip into the outer needle cap on a flat surface without touching the needle or the outer needle cap.

Once the needle is covered, carefully push the outer needle cap completely on.

Unscrew the needle and dispose of it carefully.

Put the pen cap on your pen after each use to protect the insulin from light.

Always dispose of the needle after each injection in an appropriate sharps container. This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing. If the needle is blocked, you will not inject any insulin.

When the pen is empty, throw it away without a needle on as instructed by your doctor, nurse, pharmacist or local authorities. Do not place the used needle in household waste.

△ Never try to put the inner needle cap back on the needle. You may stick yourself with the needle.

△ Always remove the needle after each injection and store your pen without the needle attached.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

• 6 How much insulin is left?

The insulin scale shows you approximately how much insulin is left in your pen.

To see precisely how much insulin is left, use the dose counter:

Turn the dose selector until the dose counter stops.

If it shows 160, at least 160 units are left in your pen.

If it shows less than 160, the number shown is the number of units left in your pen.

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

• If you need more insulin than the units left in your pen, you can split your dose between two pens.

• △ Be very careful to calculate correctly if splitting your dose.

If in doubt, take the full dose with a new pen. If you split the dose wrong, you will inject too little or too much insulin, which can lead to too high or too low blood sugar level.

A Further important information

• Always keep your pen with you.
• Always carry an extra pen and new needles with you in case of loss or damage.
• Always keep your pen and needles out of sight and reach of others, especially children.
• Never share your pen or your needles with other people. It might lead to cross-infection.
• Never share your pen with other people. Your medicine might be harmful to their health.
• Caregivers must be very careful when handling used needles to reduce the risk of needle

injury and cross-infection.

Caring for your pen

Treat your pen with care. Rough handling or misuse may cause inaccurate dosing, which can lead to too high or too low blood sugar level.

• Do not leave the pen in a car or other place where it can get too hot or too cold.
• Do not expose your pen to dust, dirt or liquid.
• Do not wash, soak or lubricate your pen. If necessary, clean it with mild detergent on a moistened cloth.

Do not drop your pen or knock it against hard surfaces.

If you drop it or suspect a problem, attach a new needle and check the insulin flow before you inject.

Do not try to refill your pen. Once empty, it must be disposed of.

Do not try to repair your pen or pull it apart.

Package leaflet: Information for the patient

Tresiba 100 units/mL solution for injection in cartridge insulin degludec

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

- if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. see section 4.

What is in this leaflet

• 1. What Tresiba is and what it is used for

• 2. What you need to know before you use Tresiba

• 3. How to use Tresiba

• 4. Possible side effects

• 5. How to store Tresiba

• 6. Contents of the pack and other information

1. what tresiba is and what it is used for

Tresiba is a long-acting basal insulin called insulin degludec. It is used to treat diabetes mellitus in adults, adolescents and children aged 1 year and above. Tresiba helps your body reduce your blood sugar level. It is used for once-daily dosing. On occasions when you cannot follow your regular dosing schedule, you can change the time of dosing because Tresiba has a long blood sugar-lowering effect (see section 3 for ‘Flexibility in dosing time’). Tresiba can be used with meal-related rapid-acting insulin products. In type 2 diabetes mellitus, Tresiba may be used in combination with tablets for diabetes or with injectable antidiabetic medicines, other than insulin.

In type 1 diabetes mellitus, Tresiba must always be used in combination with meal-related rapid-acting insulin medicines.

2. what you need to know before you use tresiba

Do not use Tresiba

• if you are allergic to insulin degludec or any of the other ingredients of this medicine (listed in

section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Tresiba. Be especially aware of the following:

• Low blood sugar (hypoglycaemia) – if your blood sugar is too low, follow the guidance for low blood sugar in section 4.
• High blood sugar (hyperglycaemia) – if your blood sugar is too high, follow the guidance for high blood sugar in section 4.
• Switching from other insulin medicines – the insulin dose may need to be changed if you switch

from another type, brand or manufacturer of insulin. Talk to your doctor.

• Pioglitazone used together with insulin, see ‘Pioglitazone’ be­low.
• Eye disorder – fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disorder. If you experience eye problems, talk to your doctor.
• Ensuring you use the right type of insulin – always check the insulin label before each injection

to avoid accidental mix-ups between Tresiba and other insulin products.

If you have poor eyesight, please see section 3.

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.

Children and adolescents

Tresiba can be used in adolescents and children aged 1 year and above. There is no experience with the use of Tresiba in children below the age of 1 year.

Other medicines and Tresiba

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. Some medicines affect your blood sugar level, this may mean your insulin dose has to be changed.

Listed below are the most common medicines which may affect your insulin treatment.

Your blood sugar level may fall (hypoglycaemia) if you take:

• other medicines for diabetes (oral and injectable)
• sulfonamides, for infections
• anabolic steroids, such as testosterone
• beta-blockers, for high blood pressure. They may make it harder to recognise the warning signs

of too low blood sugar (see section 4 ‘Warning signs of too low blood sugar’)

• acetylsalicylic acid (and other salicylates), for pain and mild fever
• monoamine oxidase (MAO) inhibitors, for depression
• angiotensin converting enzyme (ACE) inhibitors, for some heart problems or high blood pressure.

Y our blood sugar level may rise (hyperglycaemia) if you take:

• danazol, for endometriosis
• oral contraceptives (birth control pills)
• thyroid hormones, for thyroid problems
• growth hormone, for growth hormone deficiency
• glucocorticoids such as ‘cortisone’, for inflammation
• sympathomimetics such as epinephrine (adrenaline), salbutamol or terbutaline, for asthma thiazides, for high blood pressure or if your body keeps too much water (water retention).

Octreotide and lanreotide : used to treat a rare condition involving too much growth hormone (acromegaly). They may increase or decrease your blood sugar level.

Pioglitazone : oral antidiabetic medicine used to treat type 2 diabetes mellitus. Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).

If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist or nurse.

Tresiba with alcohol

If you drink alcohol, your need for insulin may change. Your blood sugar level may either rise or fall. You should therefore monitor your blood sugar level more often than usual.

Pregnancy and breast-feeding

It is not known if Tresiba affects the baby in pregnancy or during breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes is needed in pregnancy. Avoiding too low blood sugar (hypoglycaemia) is particularly important for the health of your baby.

Driving and using machines

Having too low or too high blood sugar can affect your ability to drive or use any tools or machines. If your blood sugar is too low or too high, your ability to concentrate or react might be affected. This could be dangerous to yourself or others. Ask your doctor whether you can drive if:

• you often get too low blood sugar
• you find it hard to recognise too low blood sugar.

Important information about some of the ingredients of Tresiba

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that the medicine is essentially ‘sodium-free’.

3. how to use tresiba

if the cartridge is damaged or has not been stored correctly (see section 5 ‘how to store

Tresiba’).

• if the insulin does not appear clear and colourless.

How to inject

• Tresiba is given as an injection under the skin (subcutaneous injection). Do not inject it into a vein or muscle.
• The best places to inject are the front of your thighs, upper arms or the front of your waist (abdomen).
• Change the place within the area where you inject each day to reduce the risk of developing lumps and skin pitting (see section 4).
• Always use a new needle for each injection. Re-use of needles may increase the risk of blocked needles leading to inaccurate dosing. Dispose of the needle safely after each use.

If you use more Tresiba than you should

If you use too much insulin, your blood sugar may get too low (hypoglycaemia), see advice in section 4 ‘Too low blood sugar’.

If you forget to use Tresiba

If you forget a dose, inject the missed dose when discovering the mistake, ensuring a minimum of 8 hours between doses. If you discover that you missed your previous dose when it is time to take your next regular scheduled dose, do not inject a double dose, but resume your once-daily dosing schedule.

If you stop using Tresiba

Do not stop using your insulin without talking to your doctor. If you stop using your insulin, this could lead to a very high blood sugar level and ketoacidosis (a condition with too much acid in the blood), see advice in section 4 ‘Too high blood sugar’.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Hypoglycaemia (too low blood sugar) may occur very commonly with insulin treatment (may affect more than 1 in 10 people). It can be very serious. If your blood sugar level falls too much, you may become unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If you have symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See advice in ‘Too low blood sugar’ below.

• If you have a serious allergic reaction (seen rarely) to the insulin or any of the ingredients in Tresiba, stop using Tresiba and see a doctor straight away. The signs of a serious allergic reaction are: the local reactions spread to other parts of your body you suddenly feel unwell with sweating you start being sick (vomiting)
• you experience difficulty in breathing
• you experience rapid heartbeat or feeling dizzy.

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.

Other side effects include:

Common (may affect up to 1 in 10 people)

Local reactions: Local reactions at the place you inject yourself may occur. The signs may include: pain, redness, hives, swelling and itching. The reactions usually disappear after a few days. See your doctor if they do not disappear after a few weeks. Stop using Tresiba and see a doctor straight away if the reactions become serious. For more information, see ‘serious allergic reaction’ above.

Uncommon (may affect up to 1 in 100 people)

Swelling around your joints: When you first start using your medicine, your body may keep more water than it should. This causes swelling around your ankles and other joints. This is usually only short-lasting.

Rare (may affect up to 1 in 1,000 people)

This medicine can cause allergic reactions such as hives, swelling of the tongue and lips, diarrhoea, nausea, tiredness and itching.

General effects from diabetes treatment

• Too low blood sugar (hypoglycaemia)

Too low blood sugar may happen if you:

drink alcohol; use too much insulin; exercise more than usual; eat too little or miss a meal.

Warning signs of too low blood sugar – these may come on suddenly:

Headache; slurred speech; fast heartbeat; cold sweat, cool pale skin; feeling sick, feeling very hungry; tremor or feeling nervous or worried; feeling unusually tired, weak and sleepy; feeling confused, difficulty in concentrating; short-lasting changes in your sight.

What to do if you get too low blood sugar

• Eat glucose tablets or another high sugar snack, like sweets, biscuits or fruit juice (always carry

glucose tablets or a high sugar snack, just in case).

• Measure your blood sugar if possible and rest. You may need to measure your blood sugar more than once, as with all basal insulin products improvement from the period of low blood sugar may be delayed.
• Wait until the signs of too low blood sugar have gone or when your blood sugar level has settled. Then carry on with your insulin as usual.

What others need to do if you pass out

Tell everyone you spend time with that you have diabetes. Tell them what could happen if your blood sugar gets too low, including the risk of passing out.

Let them know that if you pass out, they must:

• turn you on your side
• get medical help straight away
• not give you any food or drink because you may choke.

You may recover more quickly from passing out with an injection of glucagon. This can only be given by someone who knows how to use it.

• If you are given glucagon, you will need sugar or a sugary snack as soon as you come round.
• If you do not respond to a glucagon injection, you will have to be treated in a hospital.
• If severe low blood sugar is not treated over time, it can cause brain damage. This can be short or long-lasting. It may even cause death.

Talk to your doctor if:

• your blood sugar got so low that you passed out
• you have used an injection of glucagon
• you have had too low blood sugar a few times recently.

This is because the dosing or timing of your insulin injections, food or exercise may need to be changed.

• Too high blood sugar (hyperglycaemia)

Too high blood sugar may happen if you:

eat more or exercise less than usual; drink alcohol; get an infection or a fever; have not used enough insulin; keep using less insulin than you need; forget to use your insulin or stop using insulin without talking to your doctor.

Warning signs of too high blood sugar – these normally appear gradually:

Flushed, dry skin; feeling sleepy or tired; dry mouth, fruity (acetone) breath; urinating more often, feeling thirsty; losing your appetite, feeling or being sick (nausea or vomiting).

These may be signs of a very serious condition called ketoacidosis. This is a build-up of acid in the blood because the body is breaking down fat instead of sugar. If not treated, this could lead to diabetic coma and eventually death.

What to do if you get too high blood sugar

• Test your blood sugar level.
• Test your urine or blood for ketones.
• Get medical help straight away.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store tresiba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the Penfill label and carton, after ‘EXP’. The expiry date refers to the last day of that month.

Before first use

Store in a refrigerator (2°C to 8°C). Do not freeze. Keep away from the freezing element.

After first opening or if carried as a spare

Do not refrigerate. You can carry your Tresiba cartridge (Penfill) with you and keep it at room temperature (not above 30°C) for up to 8 weeks.

Always keep Tresiba Penfill in the outer carton when you are not using it in order to protect it from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Tresiba contains

• The active substance is insulin degludec. Each mL of solution contains 100 units of insulin degludec. Each cartridge contains 300 units of insulin degludec of insulin in 3 ml solution.
• The other ingredients are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections (see section 2).

What Tresiba looks like and contents of the pack

Tresiba is presented as a clear and colourless solution for injection in a pre-filled pen (300 units per 3 mL).

Pack sizes of 1 (with or without needles), 5 (without needles) and multipack of 10 (2 × 5) (without needles) pre-filled pens of 3 mL. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsvsrd, Denmark

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

Instructions on how to use Tresiba 100 units/mL solution for injection in pre-filled pen (FlexTouch)

Please read these instructions carefully before using your FlexTouch pre-filled pen. If you do not follow the instructions carefully, you may get too little or too much insulin, which can lead to too high or too low blood sugar level.

Do not use the pen without proper training from your doctor or nurse.

Start by checking your pen to make sure that it contains Tresiba 100 units/mL, then look at the illustrations below to get to know the different parts of your pen and needle.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the FlexTouch pre-filled pen.

Your pen is a pre-filled dial-a-dose insulin pen containing 300 units of insulin. You can select a maximum of 80 units per dose, in steps of 1 unit. Your pen is designed to be used with NovoTwist or NovoFine single-use disposable needles up to a length of 8 mm.

△ Important information

Pay special attention to these notes as they are important for correct use of the pen.

Tresiba pre-filled pen and needle (example) (FlexTouch)

1 Prepare your pen

Check the name and strength on the label of your pen to make sure that it contains Tresiba 100 units/mL. This is especially important if you take more than one type of insulin. If you take a wrong type of insulin, your blood sugar level may get too high or too low.

Pull off the pen cap.

Check that the insulin in your pen is clear and colourless.

Look through the insulin window. If the insulin looks cloudy, do not use the pen.

Take a new needle and tear off the paper tab.

Push the needle straight onto the pen. Turn until it is on tight.

Pull off the outer needle cap and keep it for later. You will need it after the injection to correctly remove the needle from the pen.

Pull off the inner needle cap and throw it away. If you try to put it back on, you may accidentally stick yourself with the needle.

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

△ Always use a new needle for each injection.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

A Never use a bent or damaged needle.

2 Check the insulin flow

• Always check the insulin flow before you start.

This helps you to ensure that you get your full insulin dose.

• Turn the dose selector to select 2 units. Make sure the dose counter shows 2.

Hold the pen with the needle pointing up.

Tap the top of the pen gently a few times to let any air bubbles rise to the top.

Press and hold in the dose button until the dose counter returns to 0.

The 0 must line up 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 no drop appears, repeat steps 2A to 2C up to 6 times. If there is still no drop, change the needle and repeat steps 2A to 2C once more.

If a drop of insulin still does not appear, dispose of the pen and use a new one.

• △ Always make sure that a drop appears at the needle tip before you inject. This makes sure that the insulin flows.

If no drop appears, you will not inject any insulin, even though the dose counter may move. This may indicate a blocked or damaged needle.

• △ Always check the flow before you inject. If you do not check the flow, you may get too little insulin or no insulin at all. This may lead to too high blood sugar level.

• 3 Select your dose

• Make sure the dose counter shows 0 before you start.

The 0 must line up with the dose pointer.

• Turn the dose selector to select the dose you need, as directed by your doctor or nurse.

If you select a wrong dose, you can turn the dose selector forwards or backwards to the correct dose.

The pen can dial up to a maximum of 80 units.

The dose selector changes the number of units. Only the dose counter and dose pointer will show how many units you select per dose.

You can select up to 80 units per dose. When your pen contains less than 80 units, the dose counter stops at the number of units left.

The dose selector clicks differently when turned forwards, backwards or past the number of units left. Do not count the pen clicks.

• △ Always use the dose counter and the dose pointer to see how many units you have selected before injecting the insulin.

Do not count the pen clicks. If you select and inject the wrong dose, your blood sugar level may get too high or too low.

Do not use the insulin scale, it only shows approximately how much insulin is left in your pen.

• 4 Inject your dose

• Insert the needle into your skin as your doctor or nurse has shown you.
• Make sure you can see the dose counter.

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

• Press and hold down the dose button until the dose counter returns to 0.

The 0 must line up with the dose pointer.

You may then hear or feel a click.

• Leave the needle under the skin for at least 6 seconds to make sure you get your full dose.

Pull the needle and pen straight up from your skin.

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

You may see a drop of insulin at the needle tip after injecting. This is normal and does not affect your dose.

△ Always watch the dose counter to know how many units you inject.

The dose counter will show the exact number of units. Do not count the pen clicks. Hold the dose button down until the dose counter returns to 0 after the injection. If the dose counter stops before it returns to 0, the full dose has not been delivered, which may result in too high blood sugar level.

• 5 After your injection

• Lead the needle tip into the outer needle cap on a flat surface without touching the needle or the outer needle cap.

Once the needle is covered, carefully push the outer needle cap completely on.

Unscrew the needle and dispose of it carefully.

Put the pen cap on your pen after each use to protect the insulin from light.

Always dispose of the needle after each injection in an appropriate sharps container. This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing. If the needle is blocked, you will not inject any insulin.

When the pen is empty, throw it away without a needle on as instructed by your doctor, nurse, pharmacist or local authorities. Do not place the used needle in household waste.

A Never try to put the inner needle cap back on the needle. You may stick yourself with the needle.

A Always remove the needle after each injection and store your pen without the needle attached.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

• 6 How much insulin is left?

The insulin scale shows you approximately how much insulin is left in your pen.

Approx. how much insulin is left

To see precisely how much insulin is left, use the dose counter:

Turn the dose selector until the dose counter stops.

If it shows 80, at least 80 units are left in your pen.

If it shows less than 80, the number shown is the number of units left in your pen.

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

• If you need more insulin than the units left in your pen, you can split your dose between two pens.

• △ Be very careful to calculate correctly if splitting your dose.

If in doubt, take the full dose with a new pen. If you split the dose wrong, you will inject too little or too much insulin, which can lead to too high or too low blood sugar level.

• △ Further important information

• Always keep your pen with you.
• Always carry an extra pen and new needles with you in case of loss or damage.
• Always keep your pen and needles out of sight and reach of others, especially children.
• Never share your pen or your needles with other people. It might lead to cross-infection.
• Never share your pen with other people. Your medicine might be harmful to their health.
• Caregivers must be very careful when handling used needles to reduce the risk of needle

injury and cross-infection.

Caring for your pen

Treat your pen with care. Rough handling or misuse may cause inaccurate dosing, which can lead to too high or too low blood sugar level.

• Do not leave the pen in a car or other place where it can get too hot or too cold.
• Do not expose your pen to dust, dirt or liquid.
• Do not wash, soak or lubricate your pen. If necessary, clean it with mild detergent on a moistened cloth.

Do not drop your pen or knock it against hard surfaces.

If you drop it or suspect a problem, attach a new needle and check the insulin flow before you inject.

Do not try to refill your pen. Once empty, it must be disposed of.

Do not try to repair your pen or pull it apart.

Package leaflet: Information for the patient

Tresiba 200 units/mL solution for injection in pre-filled pen insulin degludec

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

– if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. see section 4.

What is in this leaflet

• 1. What Tresiba is and what it is used for

• 2. What you need to know before you use Tresiba

• 3. How to use Tresiba

• 4. Possible side effects

• 5. How to store Tresiba

• 6. Contents of the pack and other information

1. what tresiba is and what it is used for

Tresiba is a long-acting basal insulin called insulin degludec. It is used to treat diabetes mellitus in adults, adolescents and children aged 1 year and above. Tresiba helps your body reduce your blood sugar level. It is used for once-daily dosing. On occasions when you cannot follow your regular dosing schedule, you can change the time of dosing because Tresiba has a long blood sugar-lowering effect (see section 3 for ‘Flexibility in dosing time’). Tresiba can be used with meal-related rapid-acting insulin products. In type 2 diabetes mellitus, Tresiba may be used in combination with tablets for diabetes or with injectable antidiabetic medicines, other than insulin.

In type 1 diabetes mellitus, Tresiba must always be used in combination with meal-related rapid-acting insulin medicines.

2. what you need to know before you use tresiba

Do not use Tresiba

• if you are allergic to insulin degludec or any of the other ingredients of this medicine (listed in

section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Tresiba. Be especially aware of the following:

• Low blood sugar (hypoglycaemia) – if your blood sugar is too low, follow the guidance for low

blood sugar in section 4.

• High blood sugar (hyperglycaemia) – if your blood sugar is too high, follow the guidance for high blood sugar in section 4.
• Switching from other insulin medicines – the insulin dose may need to be changed if you switch from another type, brand or manufacturer of insulin. Talk to your doctor.
• Pioglitazone used together with insulin, see ‘Pioglitazone’ be­low.
• Eye disorder – fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disorder. If you experience eye problems, talk to your doctor.
• Ensuring you use the right type of insulin – always check the insulin label before each injection

to avoid accidental mix-ups between different strengths of Tresiba as well as other insulin products.

If you have poor eyesight, please see section 3.

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.

Children and adolescents

Tresiba can be used in adolescents and children aged 1 year and above. There is no experience with the use of Tresiba in children below the age of 1 year.

Other medicines and Tresiba

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. Some medicines affect your blood sugar level, this may mean your insulin dose has to be changed.

Listed below are the most common medicines which may affect your insulin treatment.

Your blood sugar level may fall (hypoglycaemia) if you take:

• other medicines for diabetes (oral and injectable)
• sulfonamides, for infections
• anabolic steroids, such as testosterone
• beta-blockers, for high blood pressure. They may make it harder to recognise the warning signs

of too low blood sugar (see section 4 ‘Warning signs of too low blood sugar’)

• acetylsalicylic acid (and other salicylates), for pain and mild fever
• monoamine oxidase (MAO) inhibitors, for depression
• angiotensin converting enzyme (ACE) inhibitors, for some heart problems or high blood pressure.

Y our blood sugar level may rise (hyperglycaemia) if you take:

• danazol, for endometriosis
• oral contraceptives (birth control pills)
• thyroid hormones, for thyroid problems
• growth hormone, for growth hormone deficiency
• glucocorticoids such as ‘cortisone’, for inflammation
• sympathomimetics such as epinephrine (adrenaline), salbutamol or terbutaline, for asthma thiazides, for high blood pressure or if your body keeps too much water (water retention).

Octreotide and lanreotide : used to treat a rare condition involving too much growth hormone (acromegaly). They may increase or decrease your blood sugar level.

Pioglitazone : oral antidiabetic medicine used to treat type 2 diabetes mellitus. Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).

If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist or nurse.

Tresiba with alcohol

If you drink alcohol, your need for insulin may change. Your blood sugar level may either rise or fall. You should therefore monitor your blood sugar level more often than usual.

Pregnancy and breast-feeding

It is not known if Tresiba affects the baby in pregnancy or during breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes is needed in pregnancy. Avoiding too low blood sugar (hypoglycaemia) is particularly important for the health of your baby.

Driving and using machines

Having too low or too high blood sugar can affect your ability to drive or use any tools or machines. If your blood sugar is too low or too high, your ability to concentrate or react might be affected. This could be dangerous to yourself or others. Ask your doctor whether you can drive if:

• you often get too low blood sugar
• you find it hard to recognise too low blood sugar.

Important information about some of the ingredients of Tresiba

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that the medicine is essentially ‘sodium-free’.

3. how to use tresiba

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the FlexTouch pre-filled pen.

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. In addition, Tresiba 100 units/mL packaging and label are light green, and Tresiba 200 units/mL packaging and label are dark green with striping with a red box highlighting the formulation strength.

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

The pre-filled pen 200 units/mL can provide a dose of 2–160 units in one injection in steps of 2 units. The dose counter of the pre-filled pen shows the number of units of insulin to be injected. Do not make any dose re-calculation.

Your doctor will decide together with you:

• how much Tresiba you will need each day
• when to check your blood sugar level and if you need a higher or lower dose.

Flexibility in dosing time

• Always follow your doctor’s recom­mendation for dose.
• Use Tresiba once each day, preferably at the same time every day.
• On occasions when it is not possible to take Tresiba at the same time of the day, it can be taken

at a different time of day. Make sure to have a minimum of 8 hours between the doses. There is no experience with flexibility in dosing time of Tresiba in children and adolescents.

• If you want to change your usual diet, check with your doctor, pharmacist or nurse first as a change in diet may alter your need for insulin.

Based on your blood sugar level, your doctor may change your dose.

When using other medicines, ask your doctor if your treatment needs to be adjusted.

Use in elderly (>65 years old)

Tresiba can be used in elderly, but if you are elderly, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

If you have kidney or liver problems

If you have kidney or liver problems, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

Injecting your medicine

Before you use Tresiba for the first time, your doctor or nurse will show you how to use the pre-filled pen.

• Check the name and strength on the label of the pen to make sure it is Tresiba 200 units/mL.
• The dose counter of your pen shows the exact number of insulin units. Do not make any dose

re-calculation.

Do not use Tresiba

• in insulin infusion pumps.
• if the pen is damaged or has not been stored correctly (see section 5 ‘How to store Tresiba’).
• if the insulin does not appear clear and colourless.

How to inject

• Tresiba is given as an injection under the skin (subcutaneous injection). Do not inject it into a vein or muscle.
• The best places to inject are the front of your thighs, upper arms or the front of your waist (abdomen).
• Change the place within the area where you inject each day to reduce the risk of developing lumps and skin pitting (see section 4).
• Always use a new needle for each injection. Re-use of needles may increase the risk of blocked needles leading to inaccurate dosing. Dispose of the needle safely after each use.
• Do not use a syringe to remove the solution from the pen to avoid dosing errors and potential overdose.

Detailed instructions for use are provided on the other side of this leaflet.

If you use more Tresiba than you should

If you use too much insulin, your blood sugar may get too low (hypoglycaemia), see advice in section 4 ‘Too low blood sugar’.

If you forget to use Tresiba

If you forget a dose, inject the missed dose when discovering the mistake, ensuring a minimum of

• 8 hours between doses. If you discover that you missed your previous dose when it is time to take your next regular scheduled dose, do not inject a double dose, but resume your once-daily dosing schedule.

If you stop using Tresiba

Do not stop using your insulin without talking to your doctor. If you stop using your insulin, this could lead to a very high blood sugar level and ketoacidosis (a condition with too much acid in the blood), see advice in section 4 ‘Too high blood sugar’.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Hypoglycaemia (too low blood sugar) may occur very commonly with insulin treatment (may affect more than 1 in 10 people). It can be very serious. If your blood sugar level falls too much, you may become unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If

you have symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See advice in ‘Too low blood sugar’ below.

• If you have a serious allergic reaction (seen rarely) to the insulin or any of the ingredients in Tresiba, stop using this medicine and see a doctor straight away. The signs of a serious allergic reaction are: the local reactions spread to other parts of your body
• you suddenly feel unwell with sweating
• you start being sick (vomiting)
• you experience difficulty in breathing
• you experience rapid heartbeat or feeling dizzy.

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.

Other side effects include:

Common (may affect up to 1 in 10 people)

Local reactions: Local reactions at the place you inject yourself may occur. The signs may include: pain, redness, hives, swelling and itching. The reactions usually disappear after a few days. See your doctor if they do not disappear after a few weeks. Stop using Tresiba and see a doctor straight away if the reactions become serious. For more information, see ‘serious allergic reaction’ above.

Uncommon (may affect up to 1 in 100 people)

Swelling around your joints: When you first start using your medicine, your body may keep more water than it should. This causes swelling around your ankles and other joints. This is usually only short-lasting.

Rare (may affect up to 1 in 1,000 people)

This medicine can cause allergic reactions such as hives, swelling of the tongue and lips, diarrhoea, nausea, tiredness and itching.

General effects from diabetes treatment

• Too low blood sugar (hypoglycaemia)

Too low blood sugar may happen if you:

drink alcohol; use too much insulin; exercise more than usual; eat too little or miss a meal.

Warning signs of too low blood sugar – these may come on suddenly:

Headache; slurred speech; fast heartbeat; cold sweat, cool pale skin; feeling sick, feeling very hungry; tremor or feeling nervous or worried; feeling unusually tired, weak and sleepy; feeling confused, difficulty in concentrating; short-lasting changes in your sight.

What to do if you get too low blood sugar

• Eat glucose tablets or another high sugar snack, like sweets, biscuits or fruit juice (always carry glucose tablets or a high sugar snack, just in case).
• Measure your blood sugar if possible and rest. You may need to measure your blood sugar more than once, as with all basal insulin products improvement from the period of low blood sugar may be delayed.
• Wait until the signs of too low blood sugar have gone or when your blood sugar level has settled. Then carry on with your insulin as usual.

What others need to do if you pass out

Tell everyone you spend time with that you have diabetes. Tell them what could happen if your blood sugar gets too low, including the risk of passing out.

Let them know that if you pass out, they must:

• turn you on your side
• get medical help straight away
• not give you any food or drink because you may choke.

You may recover more quickly from passing out with an injection of glucagon. This can only be given by someone who knows how to use it.

• If you are given glucagon, you will need sugar or a sugary snack as soon as you come round.
• If you do not respond to a glucagon injection, you will have to be treated in a hospital.
• If severe low blood sugar is not treated over time, it can cause brain damage. This can be short or long-lasting. It may even cause death.

Talk to your doctor if:

• your blood sugar got so low that you passed out
• you have used an injection of glucagon
• you have had too low blood sugar a few times recently.

This is because the dosing or timing of your insulin injections, food or exercise may need to be changed.

• Too high blood sugar (hyperglycaemia)

Too high blood sugar may happen if you:

eat more or exercise less than usual; drink alcohol; get an infection or a fever; have not used enough insulin; keep using less insulin than you need; forget to use your insulin or stop using insulin without talking to your doctor.

Warning signs of too high blood sugar – these normally appear gradually:

Flushed, dry skin; feeling sleepy or tired; dry mouth, fruity (acetone) breath; urinating more often, feeling thirsty; losing your appetite, feeling or being sick (nausea or vomiting).

These may be signs of a very serious condition called ketoacidosis. This is a build-up of acid in the blood because the body is breaking down fat instead of sugar. If not treated, this could lead to diabetic coma and eventually death.

What to do if you get too high blood sugar

• Test your blood sugar level.
• Test your urine or blood for ketones.
• Get medical help straight away.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store tresiba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the pen label and carton, after ‘EXP’.

The expiry date refers to the last day of that month.

Before first use

Store in a refrigerator (2°C to 8°C). Do not freeze. Keep away from the freezing element. Keep the cap on the pen in order to protect it from light.

After first opening or if carried as a spare

You can carry your Tresiba pre-filled pen (FlexTouch) with you and keep it at room temperature (not above 30°C) or in a refrigerator (2°C to 8°C) for up to 8 weeks.

Always keep the cap on the pen when you are not using it in order to protect it from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Tresiba contains

• The active substance is insulin degludec. Each mL of solution contains 200 units of insulin degludec. Each pre-filled pen contains 600 units of insulin degludec in 3 mL solution.
• The other ingredients are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections (see section 2).

What Tresiba looks like and contents of the pack

Tresiba is presented as a clear and colourless solution for injection in a pre-filled pen (600 units per

3 mL).

Pack sizes of 1 (with or without needles), 2 (without needles), 3 (without needles), 5 (without needles) and multipack of 6 (2 × 3) (without needles) pre-filled pens of 3 mL. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Novo Nordisk A/S

Novo Alle

DK-2880 Bagsvsrd, Denmark

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

Instructions on how to use Tresiba 200 units/mL solution for injection in pre-filled pen (FlexTouch)

Please read these instructions carefully before using your FlexTouch pre-filled pen. If you do not follow the instructions carefully, you may get too little or too much insulin, which can lead to too high or too low blood sugar level.

Do not use the pen without proper training from your doctor or nurse.

Start by checking your pen to make sure that it contains Tresiba 200 units/mL, then look at the illustrations below to get to know the different parts of your pen and needle.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this pen without help. Get help from a person with good eyesight who is trained to use the FlexTouch pre-filled pen.

Your pen is a pre-filled dial-a-dose insulin pen containing 600 units of insulin. You can select a maximum of 160 units per dose, in steps of 2 units. The dose counter of your pen shows the exact number of insulin units. Do not make any dose re-calculation. Your pen is designed to be used with NovoTwist or NovoFine single-use disposable needles up to a length of 8 mm.

△ Important information

Pay special attention to these notes as they are important for correct use of the pen.

Needle

Paper tab

Dose button

Dose selector

Tresiba pre-filled pen and needle (example) (FlexTouch)

Pen cap

Outer needle cap

Inner needle cap

Dose counter

Insulin scale

Insulin window

Pen label

Dose button with 2 dots indicates 2 units per step

Dose pointer

1 Prepare your pen

Check the name and strength on the label of your pen to make sure that it contains Tresiba 200 units/mL. This is especially important if you take more than one type of insulin. If you take a wrong type of insulin, your blood sugar level may get too high or too low.

Pull off the pen cap.

Check that the insulin in your pen is clear and colourless.

Look through the insulin window. If the insulin looks cloudy, do not use the pen.

Take a new needle and tear off the paper tab.

Push the needle straight onto the pen. Turn until it is on tight.

Pull off the outer needle cap and keep it for later. You will need it after the injection to correctly remove the needle from the pen.

Pull off the inner needle cap and throw it away. If you try to put it back on, you may accidentally stick yourself with the needle.

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

A Always use a new needle for each injection.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

A Never use a bent or damaged needle.

2 Check the insulin flow

Always check the insulin flow before you start.

This helps you to ensure that you get your full insulin dose.

Turn the dose selector to select 2 units. Make sure the dose counter shows 2.

Hold the pen with the needle pointing up.

Tap the top of the pen gently a few times to let any air bubbles rise to the top.

Press and hold in the dose button until the dose counter returns to 0.

The 0 must line up 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 no drop appears, repeat steps 2A to 2C up to 6 times. If there is still no drop, change the needle and repeat steps 2A to 2C once more.

If a drop of insulin still does not appear, dispose of the pen and use a new one.

• △ Always make sure that a drop appears at the needle tip before you inject. This makes sure that the insulin flows.

If no drop appears, you will not inject any insulin, even though the dose counter may move. This may indicate a blocked or damaged needle.

• △ Always check the flow before you inject. If you do not check the flow, you may get too little insulin or no insulin at all. This may lead to too high blood sugar level.

• 3 Select your dose

• Make sure the dose counter shows 0 before you start.

The 0 must line up with the dose pointer.

• Turn the dose selector to select the dose you need, as directed by your doctor or nurse.
• The dose counter shows the dose dialled in units. Do not make any dose re-calculation.

If you select a wrong dose, you can turn the dose selector forwards or backwards to the correct dose.

The pen can dial up to a maximum of 160 units.

The dose selector changes the number of units. Only the dose counter and dose pointer will show how many units you select per dose.

You can select up to 160 units per dose. When your pen contains less than 160 units, the dose counter stops at the number of units left.

The dose selector clicks differently when turned forwards, backwards or past the number of units left. Do not count the pen clicks.

• △ Always use the dose counter and the dose pointer to see how many units you have selected before injecting the insulin.

Do not count the pen clicks. If you select and inject the wrong dose, your blood sugar level may get too high or too low.

Do not use the insulin scale, it only shows approximately how much insulin is left in your pen.

• 4 Inject your dose

• Insert the needle into your skin as your doctor or nurse has shown you.
• Make sure you can see the dose counter.

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

• Press and hold down the dose button until the dose counter returns to 0.

The 0 must line up with the dose pointer.

You may then hear or feel a click.

• Leave the needle under the skin for at least 6 seconds to make sure you get your full dose.

Pull the needle and pen straight up from your skin.

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

You may see a drop of insulin at the needle tip after injecting. This is normal and does not affect your dose.

△ Always watch the dose counter to know how many units you inject.

The dose counter will show the exact number of units. Do not count the pen clicks. Hold the dose button down until the dose counter returns to 0 after the injection. If the dose counter stops before it returns to 0, the full dose has not been delivered, which may result in too high blood sugar level.

• 5 After your injection

Lead the needle tip into the outer needle cap on a flat surface without touching the needle or the outer needle cap.

Once the needle is covered, carefully push the outer needle cap completely on.

Unscrew the needle and dispose of it carefully.

Put the pen cap on your pen after each use to protect the insulin from light.

Always dispose of the needle after each injection in an appropriate sharps container. This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing. If the needle is blocked, you will not inject any insulin.

When the pen is empty, throw it away without a needle on as instructed by your doctor, nurse, pharmacist or local authorities. Do not place the used needle in household waste.

△ Never try to put the inner needle cap back on the needle. You may stick yourself with the needle.

△ Always remove the needle after each injection and store your pen without the needle attached.

This reduces the risk of contamination, infection, leakage of insulin, blocked needles and inaccurate dosing.

• 6 How much insulin is left?

The insulin scale shows you approximately how much insulin is left in your pen.

To see precisely how much insulin is left, use the dose counter:

Turn the dose selector until the dose counter stops.

If it shows 160, at least 160 units are left in your pen.

If it shows less than 160, the number shown is the number of units left in your pen.

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

• If you need more insulin than the units left in your pen, you can split your dose between two pens.

• △ Be very careful to calculate correctly if splitting your dose.

If in doubt, take the full dose with a new pen. If you split the dose wrong, you will inject too little or too much insulin, which can lead to too high or too low blood sugar level.

A Further important information

• Always keep your pen with you.
• Always carry an extra pen and new needles with you in case of loss or damage.
• Always keep your pen and needles out of sight and reach of others, especially children.
• Never share your pen or your needles with other people. It might lead to cross-infection.
• Never share your pen with other people. Your medicine might be harmful to their health.
• Caregivers must be very careful when handling used needles to reduce the risk of needle

injury and cross-infection.

Caring for your pen

Treat your pen with care. Rough handling or misuse may cause inaccurate dosing, which can lead to too high or too low blood sugar level.

• Do not leave the pen in a car or other place where it can get too hot or too cold.
• Do not expose your pen to dust, dirt or liquid.
• Do not wash, soak or lubricate your pen. If necessary, clean it with mild detergent on a moistened cloth.

Do not drop your pen or knock it against hard surfaces.

If you drop it or suspect a problem, attach a new needle and check the insulin flow before you inject.

Do not try to refill your pen. Once empty, it must be disposed of.

Do not try to repair your pen or pull it apart.

Package leaflet: Information for the patient

Tresiba 100 units/mL solution for injection in cartridge insulin degludec

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor, pharmacist or nurse.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

– if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. see section 4.

What is in this leaflet

• 1. What Tresiba is and what it is used for

• 2. What you need to know before you use Tresiba

• 3. How to use Tresiba

• 4. Possible side effects

• 5. How to store Tresiba

• 6. Contents of the pack and other information

1. what tresiba is and what it is used for

Tresiba is a long-acting basal insulin called insulin degludec. It is used to treat diabetes mellitus in adults, adolescents and children aged 1 year and above. Tresiba helps your body reduce your blood sugar level. It is used for once-daily dosing. On occasions when you cannot follow your regular dosing schedule, you can change the time of dosing because Tresiba has a long blood sugar-lowering effect (see section 3 for ‘Flexibility in dosing time’). Tresiba can be used with meal-related rapid-acting insulin products. In type 2 diabetes mellitus, Tresiba may be used in combination with tablets for diabetes or with injectable antidiabetic medicines, other than insulin.

In type 1 diabetes mellitus, Tresiba must always be used in combination with meal-related rapid-acting insulin medicines.

2. what you need to know before you use tresiba

Do not use Tresiba

• if you are allergic to insulin degludec or any of the other ingredients of this medicine (listed in

section 6).

Warnings and precautions

Talk to your doctor, pharmacist or nurse before using Tresiba. Be especially aware of the following:

• Low blood sugar (hypoglycaemia) – if your blood sugar is too low, follow the guidance for low blood sugar in section 4.
• High blood sugar (hyperglycaemia) – if your blood sugar is too high, follow the guidance for high blood sugar in section 4.
• Switching from other insulin medicines – the insulin dose may need to be changed if you switch

from another type, brand or manufacturer of insulin. Talk to your doctor.

• Pioglitazone used together with insulin, see ‘Pioglitazone’ be­low.
• Eye disorder – fast improvements in blood sugar control may lead to a temporary worsening of diabetic eye disorder. If you experience eye problems, talk to your doctor.
• Ensuring you use the right type of insulin – always check the insulin label before each injection

to avoid accidental mix-ups between Tresiba and other insulin products.

If you have poor eyesight, please see section 3.

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.

Children and adolescents

Tresiba can be used in adolescents and children aged 1 year and above. There is no experience with the use of Tresiba in children below the age of 1 year.

Other medicines and Tresiba

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines. Some medicines affect your blood sugar level, this may mean your insulin dose has to be changed.

Listed below are the most common medicines which may affect your insulin treatment.

Your blood sugar level may fall (hypoglycaemia) if you take:

• other medicines for diabetes (oral and injectable)
• sulfonamides, for infections
• anabolic steroids, such as testosterone
• beta-blockers, for high blood pressure. They may make it harder to recognise the warning signs

of too low blood sugar (see section 4 ‘Warning signs of too low blood sugar’)

• acetylsalicylic acid (and other salicylates), for pain and mild fever
• monoamine oxidase (MAO) inhibitors, for depression
• angiotensin converting enzyme (ACE) inhibitors, for some heart problems or high blood pressure.

Y our blood sugar level may rise (hyperglycaemia) if you take:

• danazol, for endometriosis
• oral contraceptives (birth control pills)
• thyroid hormones, for thyroid problems
• growth hormone, for growth hormone deficiency
• glucocorticoids such as ‘cortisone’, for inflammation
• sympathomimetics such as epinephrine (adrenaline), salbutamol or terbutaline, for asthma thiazides, for high blood pressure or if your body keeps too much water (water retention).

Octreotide and lanreotide : used to treat a rare condition involving too much growth hormone (acromegaly). They may increase or decrease your blood sugar level.

Pioglitazone : oral antidiabetic medicine used to treat type 2 diabetes mellitus. Some patients with long-standing type 2 diabetes mellitus and heart disease or previous stroke who were treated with pioglitazone and insulin experienced the development of heart failure. Inform your doctor immediately if you experience signs of heart failure such as unusual shortness of breath, rapid increase in weight or localised swelling (oedema).

If any of the above applies to you (or you are not sure), talk to your doctor, pharmacist or nurse.

Tresiba with alcohol

If you drink alcohol, your need for insulin may change. Your blood sugar level may either rise or fall. You should therefore monitor your blood sugar level more often than usual.

Pregnancy and breast-feeding

It is not known if Tresiba affects the baby in pregnancy or during breast-feeding. If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Your insulin dose may need to be changed during pregnancy and after delivery. Careful control of your diabetes is needed in pregnancy. Avoiding too low blood sugar (hypoglycaemia) is particularly important for the health of your baby.

Driving and using machines

Having too low or too high blood sugar can affect your ability to drive or use any tools or machines. If your blood sugar is too low or too high, your ability to concentrate or react might be affected. This could be dangerous to yourself or others. Ask your doctor whether you can drive if:

• you often get too low blood sugar
• you find it hard to recognise too low blood sugar.

Important information about some of the ingredients of Tresiba

This medicine contains less than 1 mmol sodium (23 mg) per dose. This means that the medicine is essentially ‘sodium-free’.

3. how to use tresiba

Always use this medicine exactly as your doctor has told you. Check with your doctor, pharmacist or nurse if you are not sure.

If you are blind or have poor eyesight and cannot read the dose counter on the pen, do not use this insulin product without help. Get help from a person with good eyesight who is trained to use the pen.

Your doctor will decide together with you:

• how much Tresiba you will need each day
• when to check your blood sugar level and if you need a higher or lower dose.

Flexibility in dosing time

• Always follow your doctor’s recom­mendation for dose.
• Use Tresiba once each day, preferably at the same time every day.
• On occasions when it is not possible to take Tresiba at the same time of the day, it can be taken at a different time of day. Make sure to have a minimum of 8 hours between the doses. There is no experience with flexibility in dosing time of Tresiba in children and adolescents.
• If you want to change your usual diet, check with your doctor, pharmacist or nurse first as a change in diet may alter your need for insulin.

Based on your blood sugar level, your doctor may change your dose.

When using other medicines, ask your doctor if your treatment needs to be adjusted.

Use in elderly (>65 years old)

Tresiba can be used in elderly, but if you are elderly, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

If you have kidney or liver problems

If you have kidney or liver problems, you may need to check your blood sugar level more often. Talk to your doctor about changes in your dose.

Injecting your medicine

Before you use Tresiba for the first time, your doctor or nurse will show you how to use it.

• Please also read the manual that comes with your insulin delivery system.
• Check the name and strength on the label to make sure it is Tresiba 100 units/mL.

Do not use Tresiba

• in insulin infusion pumps.
• if the cartridge or the delivery system you are using is damaged. Take it back to your supplier.

See your delivery system manual for further instructions.

if the cartridge is damaged or has not been stored correctly (see section 5 ‘how to store

Tresiba’).

• if the insulin does not appear clear and colourless.

How to inject

• Tresiba is given as an injection under the skin (subcutaneous injection). Do not inject it into a vein or muscle.
• The best places to inject are the front of your thighs, upper arms or the front of your waist (abdomen).
• Change the place within the area where you inject each day to reduce the risk of developing lumps and skin pitting (see section 4).
• Always use a new needle for each injection. Re-use of needles may increase the risk of blocked needles leading to inaccurate dosing. Dispose of the needle safely after each use.

If you use more Tresiba than you should

If you use too much insulin, your blood sugar may get too low (hypoglycaemia), see advice in section 4 ‘Too low blood sugar’.

If you forget to use Tresiba

If you forget a dose, inject the missed dose when discovering the mistake, ensuring a minimum of 8 hours between doses. If you discover that you missed your previous dose when it is time to take your next regular scheduled dose, do not inject a double dose, but resume your once-daily dosing schedule.

If you stop using Tresiba

Do not stop using your insulin without talking to your doctor. If you stop using your insulin, this could lead to a very high blood sugar level and ketoacidosis (a condition with too much acid in the blood), see advice in section 4 ‘Too high blood sugar’.

4. possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Hypoglycaemia (too low blood sugar) may occur very commonly with insulin treatment (may affect more than 1 in 10 people). It can be very serious. If your blood sugar level falls too much, you may become unconscious. Serious hypoglycaemia may cause brain damage and may be life-threatening. If you have symptoms of low blood sugar, take actions to increase your blood sugar level immediately. See advice in ‘Too low blood sugar’ below.

• If you have a serious allergic reaction (seen rarely) to the insulin or any of the ingredients in Tresiba, stop using Tresiba and see a doctor straight away. The signs of a serious allergic reaction are: the local reactions spread to other parts of your body you suddenly feel unwell with sweating you start being sick (vomiting)
• you experience difficulty in breathing
• you experience rapid heartbeat or feeling dizzy.

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.

Other side effects include:

Common (may affect up to 1 in 10 people)

Local reactions: Local reactions at the place you inject yourself may occur. The signs may include: pain, redness, hives, swelling and itching. The reactions usually disappear after a few days. See your doctor if they do not disappear after a few weeks. Stop using Tresiba and see a doctor straight away if the reactions become serious. For more information, see ‘serious allergic reaction’ above.

Uncommon (may affect up to 1 in 100 people)

Swelling around your joints: When you first start using your medicine, your body may keep more water than it should. This causes swelling around your ankles and other joints. This is usually only short-lasting.

Rare (may affect up to 1 in 1,000 people)

This medicine can cause allergic reactions such as hives, swelling of the tongue and lips, diarrhoea, nausea, tiredness and itching.

General effects from diabetes treatment

• Too low blood sugar (hypoglycaemia)

Too low blood sugar may happen if you:

drink alcohol; use too much insulin; exercise more than usual; eat too little or miss a meal.

Warning signs of too low blood sugar – these may come on suddenly:

Headache; slurred speech; fast heartbeat; cold sweat, cool pale skin; feeling sick, feeling very hungry; tremor or feeling nervous or worried; feeling unusually tired, weak and sleepy; feeling confused, difficulty in concentrating; short-lasting changes in your sight.

What to do if you get too low blood sugar

• Eat glucose tablets or another high sugar snack, like sweets, biscuits or fruit juice (always carry

glucose tablets or a high sugar snack, just in case).

• Measure your blood sugar if possible and rest. You may need to measure your blood sugar more than once, as with all basal insulin products improvement from the period of low blood sugar may be delayed.
• Wait until the signs of too low blood sugar have gone or when your blood sugar level has settled. Then carry on with your insulin as usual.

What others need to do if you pass out

Tell everyone you spend time with that you have diabetes. Tell them what could happen if your blood sugar gets too low, including the risk of passing out.

Let them know that if you pass out, they must:

• turn you on your side
• get medical help straight away
• not give you any food or drink because you may choke.

You may recover more quickly from passing out with an injection of glucagon. This can only be given by someone who knows how to use it.

• If you are given glucagon, you will need sugar or a sugary snack as soon as you come round.
• If you do not respond to a glucagon injection, you will have to be treated in a hospital.
• If severe low blood sugar is not treated over time, it can cause brain damage. This can be short or long-lasting. It may even cause death.

Talk to your doctor if:

• your blood sugar got so low that you passed out
• you have used an injection of glucagon
• you have had too low blood sugar a few times recently.

This is because the dosing or timing of your insulin injections, food or exercise may need to be changed.

• Too high blood sugar (hyperglycaemia)

Too high blood sugar may happen if you:

eat more or exercise less than usual; drink alcohol; get an infection or a fever; have not used enough insulin; keep using less insulin than you need; forget to use your insulin or stop using insulin without talking to your doctor.

Warning signs of too high blood sugar – these normally appear gradually:

Flushed, dry skin; feeling sleepy or tired; dry mouth, fruity (acetone) breath; urinating more often, feeling thirsty; losing your appetite, feeling or being sick (nausea or vomiting).

These may be signs of a very serious condition called ketoacidosis. This is a build-up of acid in the blood because the body is breaking down fat instead of sugar. If not treated, this could lead to diabetic coma and eventually death.

What to do if you get too high blood sugar

• Test your blood sugar level.
• Test your urine or blood for ketones.
• Get medical help straight away.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. how to store tresiba

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the Penfill label and carton, after ‘EXP’. The expiry date refers to the last day of that month.

Before first use

Store in a refrigerator (2°C to 8°C). Do not freeze. Keep away from the freezing element.

After first opening or if carried as a spare

Do not refrigerate. You can carry your Tresiba cartridge (Penfill) with you and keep it at room temperature (not above 30°C) for up to 8 weeks.

Always keep Tresiba Penfill in the outer carton when you are not using it in order to protect it from light.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. contents of the pack and other information

What Tresiba contains

• The active substance is insulin degludec. Each mL of solution contains 100 units of insulin degludec. Each cartridge contains 300 units of insulin degludec of insulin in 3 ml solution.
• The other ingredients are glycerol, metacresol, phenol, zinc acetate, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections (see section 2).