Toujeo 300 units/ml SoloStar solution for injection in a pre-filled pen

Label update requested by the PRAC during the insulin glargine PSUSA

Replace UK/Ireland PIL with Ireland only PIL

1.       NAME OF THE MEDICINAL PRODUCT

Toujeo 300 units/ml SoloStar, solution for injection in a pre-filled pen

Toujeo 300 units/ml DoubleStar, solution for injection in a pre-filled pen

2.       QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 300 units insulin glargine* (equivalent to 10.91 mg).

SoloStar pen

Each pen contains 1.5 ml of solution for injection, equivalent to 450 units.

DoubleStar pen

Each pen contains 3 ml of solution for injection, equivalent to 900 units.

* Insulin glargine is produced by recombinant DNA technology in Escherichia coli.

For the full list of excipients, see section 6.1.

Toujeo must not be administered intravenously. The prolonged duration of action of Toujeo is dependent on its injection into subcutaneous tissue. Intravenous administration of the usual subcutaneous dose could result in severe hypoglycaemia.

Toujeo must not be used in insulin infusion pumps.

Toujeo is available in two pre-filled pens. The dose window shows the number of units of Toujeo to be injected. The Toujeo SoloStar and Toujeo DoubleStar pre-filled pens have been specifically designed for Toujeo and no dose re-calculation is required for either pen.

Before using Toujeo SoloStar pre-filled pen or Toujeo DoubleStar pre-filled pen, the instructions for use included in the package leaflet must be read carefully (see section 6.6).

With Toujeo SoloStar pre-filled pen, a dose of 1-80 units per single injection, in steps of 1 unit, can be injected.

 The dose window shows the number of Toujeo units to be injected. The Toujeo SoloStar pre-filled pen has been specifically designed for Toujeo, therefore no dose re-calculation is required.

With Toujeo DoubleStar pre-filled pen a dose of 2-160 units per single injection, in steps of 2 units, can be injected.

When changing from Toujeo SoloStar to Toujeo DoubleStar, if the patient’s previous dose was an odd number (e.g. 23 units) then the dose must be increased or decreased by 1 unit (e.g. 24 or 22 units).

Toujeo DoubleStar prefilled pen is recommended for patients requiring at least 20 units per day. (see section 6.6)

Toujeo must not be drawn from the cartridge of the Toujeo SoloStar pre-filled pen or Toujeo DoubleStar pre-filled pen into a syringe or severe overdose can result (see section 4.4, 4.9 and 6.6).

Particular caution should be exercised, and intensified blood glucose monitoring is advisable in patients in whom hypoglycaemic episodes might be of particular clinical relevance, such as in patients with significant stenosis stenoses of the coronary arteries or of the blood vessels supplying the brain (risk of cardiac or cerebral complications of hypoglycaemia) as well as in patients with proliferative retinopathy, particularly if not treated with photocoagulation (risk of transient amaurosis following hypoglycaemia).

To avoid dosing errors and potential overdose, the patients must be instructed to never use a syringe to remove Toujeo (insulin glargine 300 units/ml) from the Toujeo SoloStar pre‑filled pen or Toujeo DoubleStar pre-filled pen (see section 4.9 and 6.6)

It is essential for patients with pre‑existing or gestational diabetes to maintain good metabolic control throughout pregnancy to prevent adverse outcomes associated with hyperglycaemiahyperglycemia. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin requirements decline rapidly (increased risk of hypoglycaemia). Careful monitoring of glucose control is essential.

As observed in euglycaemiceuglycemic clamp studies in patients with type 1 diabetes, the glucose lowering effect of Toujeo was more stable and prolonged in comparison with insulin glargine 100 units/ml  after subcutaneous injection. Figure 1 shows results from a cross-over study in 18 patients with type 1 diabetes conducted for a maximum of 36 hours after injection.The effect of Toujeo was beyond 24 hours (up to 36 hours) at clinically relevant doses.

The total therapeutic insulin concentration (insulin glargine and its metabolites) found in type 1 diabetic patients was markedly lower than what would be required for a half maximalhalfmaximal occupation of the IGF‑1 receptor and the subsequent activation of the mitogenic‑proliferative pathway initiated by the IGF‑1 receptor.

The superiority of Toujeo over insulin glargine 100 units/ml in lowering the risk of confirmed nocturnal hypoglycaemiahypoglycemia was shown in patients with type 2 diabetes treated with basal insulin in combination with either non‑insulin anti‑hyperglycaemic medicinal product (18% risk reduction) or mealtime insulin (21% risk reduction) during the period from week 9 to end of study period.

6.3     Shelf life

Toujeo SoloStar

30 months.

Toujeo DoubleStar

24 months.

Shelf life after first use of the pen

The medicinal product may be stored for a maximum of 6 weeks below 30°C and away from direct heat or direct light. Pens in use must not be stored in the refrigerator. The pen cap must be put back on the pen after each injection in order to protect from light.

6.5     Nature and contents of container

SoloStar penPre-filled pen

Cartridge (type 1 colourless glass) with a blackgrey plunger (bromobutyl rubber) and a flanged cap (aluminium) with a stopper (laminate of isoprene and bromobutyl rubber).The cartridge is sealed in a disposable pen injector. Each cartridge contains 1.5 ml solution.

DoubleStar pen

Cartridge (type 1 colourless glass) with a black plunger (bromobutyl rubber) and a flanged cap (aluminium) with a stopper (laminate of isoprene and bromobutyl rubber).The cartridge is sealed in a disposable pen injector. Each cartridge contains 3 ml solution.

Packs of 1, 3, 6 (2 packs of 3) and 9 (3 packs of 3) pens are available. Not all pack sizes may be marketed.

Needles are not included in the pack.

6.6     Special precautions for disposal and other handling

Before first use, the pen must be stored at room temperature at least 1 hour before use.

Before using Toujeo SoloStar or Toujeo DoubleStar pre-filled pen, the Instructions for Use included in the package leaflet must be read carefully. Toujeo SoloStar pre-filled pens havehas to be used as recommended in these Instructions for Use (see section 4.2). Instruct patients to perform a safety test as described in Step 3 of the Instructions for Use. If they don’t, the full dose might not be delivered. If this occurs, patients should increase the frequency of checking their blood glucose levels and might need to administer additional insulin.

Insulin label must always be checked before each injection to avoid medication errors between Toujeo and other insulins.The strengthstrengh“300” is highlighted in honey gold on the label (see section 4.4).

Patients should be informed that the dose counter of Toujeo SoloStar or Toujeo DoubleStar pre-filled pen shows the number of units of Toujeo to be injected. No dose re-calculation is required.

• The Toujeo SoloStar pen contains 450 units of Toujeo. It delivers doses of 1-80 units per injection, in steps of 1 unit.
• The Toujeo DoubleStar pen contains 900 units of Toujeo. It delivers doses of 2-160 units per injection, in steps of 2 units.
  • To reduce potential underdose, Toujeo DoubleStar is recommended for patients requiring at least 20 units per day.
• If safety tests are not performed before the first use of a new pen, insulin underdose can occur.

A syringe must never be used to withdraw Toujeo from the cartridge of the SoloStar pre‑filled pen or severe overdose can result (see section 4.2, 4.4 and 4.9).

8.       MARKETING AUTHORISATION NUMBER(S)

EU/1/00/133/033

EU/1/00/133/034

EU/1/00/133/035

EU/1/00/133/036

EU/1/00/133/037

EU/1/00/133/038

EU/1/00/133/039

EU/1/00/133/040

Section 4.2

Wording repositioned in Section

·         Before using Toujeo SoloStar pre-filled pen, the instructions for use included in the package leaflet must be read carefully (see section 6.6).

Added:-

·         4.4

Section 4.4 added:-

·         Medication errors have been reported in which other insulins, particularly rapid acting insulins, have been accidentally administered instead of long acting insulins. Insulin label must always be checked before each injection to avoid medication errors between Toujeo and other insulins (see section 6.6).

·         To avoid dosing errors and potential overdose, the patients must be instructed to never use a syringe to remove Toujeo (insulin glargine 300 units/ml) from the SoloStar pre filled pen (see section 4.9 and 6.6)

·         A new sterile needle must be attached before each injection. Patients must also be instructed to not re use needles. Re use of needles increases the risk of blocked needles which may cause underdosing or overdosing. In the event of blocked needle, the patients must follow the instructions described in Step  3 of the Instructions for Use accompanying the package leaflet (see section  6.6).

Section 5.1

Amendments to graph

Section 6.6 added:-

·         4.4 and 4.9

·         A new sterile needle must be attached before each injection.

·         Needles must not be re used

·         and 4.4).

Removed:-

·         A new sterile needle must be attached before each injection.

Type II-B.II.d.1.e)-To widen the specification limit for sum of related impurities/degradation products from ≤ 2.0% to ≤ 2.5%.
Type IB-B.II.f.1.d)-To change the storage conditions of the finished product to extend the in-use period after first opening from 4 to 6 weeks when stored below 30°C.