Special Warning : אזהרת שימוש

4.4    Special warnings and precautions for use

Traceability
In order to improve the traceability of biological medicinal products, the name of the administered product should be clearly recorded. It is recommended to record the batch number as well.

Toujeo is not the insulin of choice for the treatment of diabetic ketoacidosis. Instead, regular insulin administered intravenously is recommended in such cases.

In case of insufficient glucose control or a tendency to hyper- or hypoglycaemic episodes, the patient's adherence to the prescribed treatment regimen, injection sites and proper injection technique and all other relevant factors must be reviewed before dose adjustment is considered.

Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to an unaffected area has been reported to result in hypoglycaemia.
Blood glucose monitoring is recommended after the change in the injection site, and dose adjustment of antidiabetic medications may be considered.

Hypoglycaemia
The time of occurrence of hypoglycaemia depends on the action profile of the insulins used and may, therefore, change when the treatment regimen is changed.

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 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).

Patients should be aware of circumstances where warning symptoms of hypoglycaemia are diminished. The warning symptoms of hypoglycaemia may be changed, be less pronounced or be absent in certain risk groups. These include patients:
-     in whom glycaemic control is markedly improved,
-     in whom hypoglycaemia develops gradually,
-     who are elderly,
-     after transfer from animal insulin to human insulin,
-     in whom an autonomic neuropathy is present,
-     with a long history of diabetes,
-     suffering from a psychiatric illness,
-      receiving concurrent treatment with certain other medicinal products (see section 4.5).

Such situations may result in severe hypoglycaemia (and possibly loss of consciousness) prior to the patient's awareness of hypoglycaemia.

The prolonged effect of insulin glargine may delay recovery from hypoglycaemia.

If normal or decreased values for glycated haemoglobin are noted, the possibility of recurrent, unrecognised (especially nocturnal) episodes of hypoglycaemia must be considered.

Adherence of the patient to the dose and dietary regimen, correct insulin administration and awareness of hypoglycaemia symptoms are essential to reduce the risk of hypoglycaemia. Factors increasing the susceptibility to hypoglycaemia require particularly close monitoring and may necessitate dose adjustment. These factors include:
-     change in the injection area,
-     improved insulin sensitivity (e.g., by removal of stress factors), -     unaccustomed, increased or prolonged physical activity,
-     intercurrent illness (e.g.vomiting, diarrhoea),
-     inadequate food intake,
-     missed meals,
-     alcohol consumption,
-     certain uncompensated endocrine disorders, (e.g. in hypothyroidism and in anterior pituitary or adrenocortical insufficiency),
-     concomitant treatment with certain other medicinal products (see section 4.5).

Switch between insulin glargine 100 units/ml and Toujeo
Since insulin glargine 100 units/ml and Toujeo are not bioequivalent and are not interchangeable, switching may result in the need for a change in dose and should only be done under strict medical supervision (see section 4.2).

Switch between other insulins and Toujeo
Switching a patient between another type or brand of insulin and Toujeo should be done under strict medical supervision. Changes in strength, brand (manufacturer), type (regular, NPH, lente, long- acting, etc.), origin (animal, human, human insulin analogue) and/or method of manufacture may result in the need for a change in dose (see section 4.2).

Intercurrent illness
Intercurrent illness requires intensified metabolic monitoring. In many cases urine tests for ketones are indicated, and often it is necessary to adjust the insulin dose. The insulin requirement is often increased. Patients with type 1 diabetes must continue to consume at least a small amount of carbohydrates on a regular basis, even if they are able to eat only little or no food, or are vomiting etc.
and they must never omit insulin entirely.

Insulin antibodies
Insulin administration may cause insulin antibodies to form. In rare cases, the presence of such insulin antibodies may necessitate adjustment of the insulin dose in order to correct a tendency to hyper-or hypoglycaemia.

Combination of Toujeo with pioglitazone
Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin, especially in patients with risk factors for development of cardiac heart failure. This should be kept in mind if treatment with the combination of pioglitazone and Toujeo is considered. If the combination is used, patients should be observed for signs and symptoms of heart failure, weight gain and oedema.
Pioglitazone should be discontinued if any deterioration in cardiac symptoms occurs.


Medication errors prevention
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 Toujeo SoloStar pre-filled pen or Toujeo DoubleStar 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).

Patients must visually verify the number of selected units on the dose counter of the pen. Patients who are blind or have poor vision should be instructed to get help/assistance from another person who has good vision and is trained in using the insulin device.

See also section 4.2 under “Method of administration”.

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

Effects on Driving

4.7    Effects on ability to drive and use machines
The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia or hyperglycaemia or, for example, as a result of visual impairment. This may constitute a risk in situations where these abilities are of special importance (e.g.driving a car or using machines).

Patients should be advised to take precautions to avoid hypoglycaemia whilst driving. This is particularly important in those who have reduced or absent awareness of the warning symptoms of hypoglycaemia or have frequent episodes of hypoglycaemia. It should be considered whether it is advisable to drive or use machines in these circumstances.