Onglyza 2.5 mg Film-Coated Tablets

2. What you need to know before you take Onglyza

Children and adolescents

Onglyza is not recommended for children and adolescents under 18 years. It is not known if this medicine is safe and effective when used in children and adolescents under 18 years of age.

Onglyza contains Ssodium content

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

6.Contents of the pack and other information

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This leaflet was last revised in 04/2023 04/2024.

Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu.

CV 23 0014 CV 24 0011

4.2 Posology and method of administration

Posology

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Special populations

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Paediatric population

The safety and efficacy of Onglyza in children aged birth10 to < 18 years hasve not yet been established. Therefore, treatment of children and adolescents with saxagliptin is not recommended. No data are available. Currently available data are described in sections 5.1 and 5.2. Onglyza has not been studied in children under 10 years of age.

5.1 Pharmacodynamic properties

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with Onglyza in one or more subsets of the paediatric population in the treatment of type 2 diabetes mellitus (see section 4.2 for information on paediatric use). In a paediatric study, patients aged 10 to < 18 years old with inadequately controlled type 2 diabetes mellitus were randomised to saxagliptin (88 patients) or placebo (76 patients) as add-on to metformin, insulin or a combination of metformin and insulin. In this 26-week, placebo-controlled, double-blind randomised clinical study with a 26 week safety extension, patients received 2.5 mg saxagliptin (with potential dose-increase to 5 mg) or placebo once daily following a lead-in period. The primary efficacy endpoint was the change in HbA1c from baseline to 26 weeks of treatment. The treatment difference from placebo was not statistically significant [-0.44% (95% CI: -0.93, 0.05)]. The safety profile was similar to that observed in the adult population treated with saxagliptin.

5.2 Pharmacokinetic properties

Paediatric population

The pharmacokinetics of saxagliptin and its major metabolite in paediatric patients aged 10 to < 18 years with type 2 diabetes mellitus were similar to that observed in adults with type 2 diabetes mellitus.

10.Date of revision of the text

26th November 2021 19th April 2024

Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.

CV 23 0028 CV 24 0010

Editorial and administrative changes:

Sodium statement moved from SmPC section 2 to section 4.4

Removal of Northern Ireland adverse reporting details.

Removal of Northern Ireland adverse reporting details.

Removal of Northern Ireland adverse reporting details.

Inserted text, Deleted text

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4. Possible side effects

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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 (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

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United Kingdom (Northern Ireland)

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

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6. Contents of the pack and other information

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Manufacturer:

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AstraZeneca GmbH

Tinsdaler Weg 183

22880 Wedel

Germany

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For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

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This leaflet was last revised in 02/2021 11/2021

Inserted text, Deleted text

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4.8         Undesirable effects

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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:

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United Kingdom (Northern Ireland)

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

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8.            MARKETING AUTHORISATION NUMBER(S)

Onglyza 2.5 mg film coated tablets

EU/1/09/545/011-015 14 film-coated tablets (calendar blister)

EU/1/09/545/012 28 film-coated tablets (calendar blister)

EU/1/09/545/013 98 film-coated tablets (calendar blister)

EU/1/09/545/014 30x1 (unit dose) film-coated tablets

EU/1/09/545/015 90x1 (unit dose) film-coated tablets

Onglyza 5 mg film coated tablets

EU/1/09/545/001-010 14 film-coated tablets

EU/1/09/545/002 28 film-coated tablets

EU/1/09/545/003 56 film-coated tablets

EU/1/09/545/004 98 film-coated tablets

EU/1/09/545/005 14 film-coated tablets (calendar blister)

EU/1/09/545/006 28 film-coated tablets (calendar blister)

EU/1/09/545/007 56 film-coated tablets (calendar blister)

EU/1/09/545/008 98 film-coated tablets (calendar blister)

EU/1/09/545/009 30x1 (unit dose) film-coated tablets

EU/1/09/545/010 90x1 (unit dose) film-coated tablets

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10.      DATE OF REVISION OF THE TEXT

12^th March 2020 26^th November 2021

Section 10 was 28^th June 2018 is now 2^nd August 2018

Sections 2 & 3  -  admin/editorial changes

Section 4.2 – Renal impairment dosing – no dose adjustment needed for GFR<45mL/min. Dose reduced to 2.5mg for patients with GFR<45mL/min.

Section 4.4 –In patients with GFR<45mL/min recommended dose is 2.5mg.

Section 4.8 – MHRA AE reporting updated

Section 5.2 – Study results for renal impairment patients updated

Sections 6.1, 6.5 & 8 – admin/editorial changes

Section 4.1 Indication text re-written to reflect new text in section 5.1.

Section 4.2 Minor editorial changes

Section 4.5 Minor editorial update.

Section 4.8 Minor editorial update including correction of spelling.

Section 5.1 information on ‘saxagliptin add on to dapagliflozin plus metformin therapy ‘added  and also information on ‘saxagliptin and dapagliflozin added on to metformin therapy’ added. Some text repositioned within this section.

Section 5.2 Minor editorial update.

Section 9 correction of date of first authorisation

Section 10- revision of date of update

Section 5.1 Savor all cause mortality data included.

Section 10 Revision date updated.

Section 4.4 –updated text on cardiac failure warnings.

Section 4.4 – addition of arthalgia warning.

Section 4.8 – addition of footnote referring to section 4.4 for arthalgia side effect.

Section 10 – date of revision updated.

Section 4.8 – Add constipation as unknown frequency a side effect. Update MT ADR reporting address in line with QRD Template.

Section 10 – Update to revision date.

- Section 1: data presented in line with QRD wording

- Section 4.2: Elderly populations and renal impairment wording updated in line with SAVOR study.

- Section 4.2: Method of administration section updated in line with Renewal changes.

- Section 4.4: Elderly populations, renal impairment, cardiac failure wording updated in line with SAVOR study.

- Section 4.5: Text reordered.

- Section 4.7: wording updated in line with QRD text during renewal.

- Section 4.8: Text updated in line with SAVOR study

- Section 4.8: AE reporting wording updated.

- Section 4.9: Overdose wording updated in line with Renewal changes.

- Section 5.1: updated in line with SAVOR study.
- Section 10 Updated date of revision

- Section 4.4 Acute Pancreatitis text added
- Section 10 updated date of revision

- Section 4.8 Additon of ‘Diarrhoea’ in Table 2 and associated footnote
- Section 4.8 Amended IMB address details for AE reporting

- Seciton 10 Revision date

- Section 4.1 – addition of monotherapy indication

-Section 4.2 – change of wording ‘elderly’ to ‘older people’

- Section 4.8 – change from 10.2% to 10.1% under the sub-heading Hypoglycaemia

                     – addition of Adverse event reporting wording as per Appendix 5

- Section 5.1 – addition of the following text: (see Table 3). The findings of these studies were confirmed with two subsequent 24‑week regional (Asian) monotherapy studies comparing saxagliptin 5 mg with placebo.

-Section 5.2 – change of wording ‘elderly’ to ‘older people’

- Section 10 – updated date of revision

- Section 4.8 – information provided in ‘Post marketing experience from clinical trials and spontaneous reports’ under Table 2; addition of ‘Abdominal pain’ and frequency ‘Unknown’

- Section 10 – updated date of revision

- Section 2 – administrative changes to comply with EU template

- Section 4.1 – addition of Triple Oral Therapy indication

- Section 4.2 – modified to include advice not to split of cut tablets and also when using Onglyza in combination with insulin or sulphonylurea

- Section 4.3 – cross reference to section 6.1 included

- Section 4.5 – combined oral contraceptive included in list of products that Onglyza does not meaningfully alter the pharmacokinetics of

- Section 4.6 – typographical change

- Section 4.7 – advice included to warn patients of the risk of hypoglycaemia when used in combination with other antidiabetic medicinal products known to cause hypoglycaemia (e.g. insulin, sulphonylureas)

- Section 4.8 – information provided in description of selected adverse reactions when Onglyza used as an add-on to metformin plus a sulphonylurea; additional information regarding hypoglycaemia

- Section 5.1 additional information regarding Onglyza add-on combination therapy with metformin and sulphonylurea; Additional study data included in Table 3

- Section 6.6 – minor update to comply with EU-template

- Section 10 – updated date of revision

Section 4.4

Additional Text

Pancreatitis

In post-marketing experience there have been spontaneously reported adverse reactions of acute pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of saxagliptin. If pancreatitis is suspected, Onglyza and other potentially suspect medicinal products should be discontinued.

Section 4.8

Table 2           Frequency of additional adverse reactions by system organ class

Addition of:

Gastrointestinal disorders

Nausea                                    Common

Pancreatitis                             Uncommon

Dermatitis                                Uncommon

Pruritus                                    Uncommon

Section 10

Date of revision changed to 22^nd December 2011

Section 4.1

New paragraph added

·         in combination with insulin (with or without metformin), when this regimen alone, with diet and exercise, does not provide adequate glycaemic control.

Section 4.2

Addition of word insulin to first paragraph.

Section 4.4

General

New paragraph added.

 Onglyza is not a substitute for insulin in insulin‑requiring patients.

Hepatic impairment

Text amended to:

Use with medicinal products known to cause hypoglycaemia

Sulphonylureas and insulin are known to cause hypoglycaemia. Therefore, a lower dose of sulphonylurea or insulin may be required to reduce the risk of hypoglycaemia when used in combination with Onglyza.  

Section 4.8

New Paragraph added before “Investigations” paragraph

When used as add‑on to insulin (with or without metformin), the overall incidence of reported hypoglycaemia was 18.4% for Onglyza 5 mg and 19.9% for placebo.

Section 5.1

New paragraph added after paragraph 10

Saxagliptin add‑on combination therapy with insulin (with or without metformin)

A total of 455 patients with type 2 diabetes participated in a 24‑week randomised, double‑blind, placebo‑controlled study to evaluate the efficacy and safety of saxagliptin in combination with a stable dose of insulin (baseline mean: 54.2 Units) in patients with inadequate glycaemic control (HbA1c ≥ 7.5% and ≤ 11%) on insulin alone (n=141) or on insulin in combination with a stable dose of metformin (n=314). Saxagliptin 5 mg add‑on to insulin with or without metformin provided significant improvements after 24 weeks in HbA1c and PPG compared with placebo add‑on to insulin with or without metformin. Similar HbA1c reductions versus placebo were achieved for patients receiving saxagliptin 5 mg add‑on to insulin regardless of metformin use (−0.4% for both subgroups). Improvements from baseline HbA1c were sustained in the saxagliptin add‑on to insulin group compared to the placebo add‑on to insulin group with or without metformin at Week 52. The HbA1c change for the saxagliptin group (n=244) compared to placebo (n=124) was ‑0.4% at Week 52.

Paragraph 12 Text amended to:

Patients with renal impairment

A 12 week, multi-centre, randomised, double-blind, placebo controlled study was conducted to evaluate the treatment effect of saxagliptin 2.5 mg once daily compared with placebo in 170 patients (85 patients on saxagliptin and 85 on placebo) with type 2 diabetes (HbA1c 7.0-11%) and renal impairment (moderate [n=90]; severe [n=41]; or ESRD [n=39]). In this study, 98.2% of the patients received other antihyperglycaemic treatments (75.3% on insulin and 31.2% on oral antihyperglycaemics; some received both). Saxagliptin significantly decreased HbA1c compared with placebo; the HbA1c change for saxagliptin was -0.9% at Week 12 (HbA1c change of -0.4% for placebo). Improvements in HbA1c following treatment with saxagliptin 2.5 mg were sustained up to Week 52, however the number of patients who completed 52 weeks without modification of other antihyperglycaemic treatments was low (26 subjects in the saxagliptin group versus 34 subjects in the placebo group). The incidence of confirmed hypoglycaemic events was somewhat higher in the saxagliptin group (9.4%) versus placebo group (4.7%) although the number of subjects with any hypoglycaemic event did not differ between the treatment groups. There was no adverse effect on renal function as determined by estimated glomerular filtration rate or CrCL at Week 12 and Week 52.

Table 3

Add-on Combination Studies updated.

New Paragraph at end of Section 5.1

Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with Onglyza in one or more subsets of the paediatric population in the treatment of type 2 diabetes mellitus (see section 4.2 for information on paediatric use).

Section 10

Date of revision changed to 22^nd November 2011

European Medicines Agency website address updated.

Section 4.3

 Additional text.