Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 28-Apr-2017

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4.2      Posology and method of administration

Flexibility in dosing time

Sentence added:

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

Patients with type 2 diabetes mellitus

Paragraph  and text added:

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

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

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

- transferring to Tresiba from twice-daily basal insulin

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

Patients with type 1 diabetes mellitus

Paragraph changed per bold.

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

Sentence deleted:

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

5.1      Pharmacodynamic properties

Section updated to include data from clinical trials.

10.      DATE OF REVISION OF THE TEXT

Revised 04/2017

Reasons for adding or updating:

• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 23-Apr-2015

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Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 30-Jan-2015

Legal Category:POM

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Tresiba new indication:

4.1      Therapeutic indications

Treatment of diabetes mellitus in adults,

Text added: adolescents and children from the age of 1 year.

4.2      Posology and method of administration

Paediatric population

Text deleted: The safety and efficacy of Tresiba in children and adolescents below 18 years of age have not been established. Currently available data are described in section 5.2, but no recommendation on a posology can be made

Text added: Tresiba can be used in adolescents and children from the age of 1 year (see section 5.1). When changing basal insulin to Tresiba, dose reduction of basal and bolus insulin needs to be considered on an individual basis, in order to minimise the risk of hypoglycaemia (see section 4.4)

Text deleted: glucose monitoring should be intensified and the insulin dose adjusted on an individual basis.

4.4      Special warnings and precautions for use

Hypoglycaemia

Text added: In children, care should be taken to match insulin doses (especially in basal-bolus regimens) with food intake and physical activities in order to minimise the risk of hypoglycaemia.

4.8      Undesirable effects

Paediatric population

Safety and efficacy have

Text added: 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).

Text deleted: not been investigated in children and adolescents.

Reporting of suspected adverse reactions

Text added:

Ireland

HPRA Pharmacovigilance

Earlsfort Terrace

IRL - Dublin 2

Tel: +353 1 6764971

Fax: +353 1 6762517

Website: www.hpra.ie

e-mail: medsafety@hpra.ie

United Kingdom

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

5.1      Pharmacodynamic properties

Paediatric population

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

Text deleted:

Children and adolescents from 10 to less than 18 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).

Text added:

The efficacy and safety of Tresiba has 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 HbA_1c 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.

10.      DATE OF REVISION OF THE TEXT

Date Added: 01/2015

Reasons for adding or updating:

• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 08-May-2014

Legal Category:POM

Black Triangle (CHM): YES

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4.8 Reporting of suspected adverse reactions

Via: The Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

10.      DATE OF REVISION OF THE TEXT

05/2014

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 28-Apr-2014

Legal Category:POM

Black Triangle (CHM): YES

Free-text change information supplied by the pharmaceutical company:

Additional text in bold

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

4.2 Posology and method of administration

Posology

Additional text in bold

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

Patients with type 1 diabetes mellitus

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

When adding Tresiba to GLP-1 receptor agonists, the recommended daily starting dose is 10 units followed by individual dosage adjustments.

When adding GLP-1 receptor agonists to Tresiba, it is recommended to reduce the dose of Tresiba by 20% to minimise the risk of hypoglycaemia. Subsequently, dosage should be adjusted individuallyfollowed by individual dosage adjustments.

Other special populations

Bold text added

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

4.8 Undesirable effects

Bold text added

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: Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard.

5.1 Pharmacodynamic properties

Bold text added.

Pharmacotherapeutic group: Drugs used in diabetes. Insulins and analogues for injection, long acting not yet assigned. ATC code: A10AE06 not yet assigned.

10. DATE OF REVISION OF THE TEXT

April 2014

Reasons for adding or updating:

• Change to section 8 - Marketing authorisation number(s)

Date of revision of text on the SPC: 06-May-2013

Legal Category:POM

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8. MARKETING AUTHORISATION NUMBERS

Additional presentations added

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/1/12/807/005

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/1/12/807/015

Tresiba▼ 100 units/mL solution for injection in cartridge

EU/1/12/807/008

Reasons for adding or updating:

• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 06-May-2013

Legal Category:POM

Black Triangle (CHM): YES

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The amended SmPC is version 2.0. The revision date is 05/2013 which can be found under Section 10 of the SmPC.

Reasons for adding or updating:

• New SPC for new product

Legal Category:POM

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