Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile
The following adverse reactions were observed during clinical studies conducted with Toujeo (see section 5.1) and during clinical experience with insulin glargine 100 units/ml.
Hypoglycaemia, in general the most frequent adverse reaction of insulin therapy, may occur if the insulin dose is too high in relation to the insulin requirement.

Tabulated list of adverse reactions
The following related adverse reactions from clinical investigations are listed below by system organ class and in order of decreasing incidence (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; not known: cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

MedDRA                Very common     Common             Uncommon Rare                Very          Not known system organ                                                                          rare classes
Immune system                                                          Allergic disorders                                                              reactions Metabolism and        Hypoglycaemia nutrition disorders
Nervous system                                                                        Dysgeusia disorders


MedDRA                Very common     Common               Uncommon Rare               Very         Not known system organ                                                                           rare classes
Eyes disorders                                                         Visual impairment

Retinopathy
Skin and                              Lipohypertro- Lipoatrophy                                     Cutaneous subcutaneous                          phy                                                           amyloidosis tissue disorders
Musculoskeletal                                                                        Myalgia and connective tissue disorders
General                               Injection site                   Oedema disorders and                         reactions administration site conditions

Description of selected adverse reactions
Metabolism and nutrition disorders
Severe hypoglycaemic attacks, especially if recurrent, may lead to neurological damage. Prolonged or severe hypoglycaemic episodes may be life-threatening.

In many patients, the signs and symptoms of neuroglycopenia are preceded by signs of adrenergic counter-regulation. Generally, the greater and more rapid the decline in blood glucose, the more marked is the phenomenon of counter-regulation and its symptoms.

Immune system disorders
Immediate-type allergic reactions to insulin are rare. Such reactions to insulin (including insulin glargine) or the excipients may, for example, be associated with generalised skin reactions, angio-oedema, bronchospasm, hypotension and shock, and may be life-threatening. In Toujeo clinical studies in adult patients, the incidence of allergic reactions was similar in Toujeo-treated patients (5.3%) and insulin glargine 100 units/ml-treated patients (4.5%).

Eyes disorders
A marked change in glycaemic control may cause temporary visual impairment, due to temporary alteration in the turgidity and refractive index of the lens.

Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy.
However, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with temporary worsening of diabetic retinopathy. In patients with proliferative retinopathy, particularly if not treated with photocoagulation, severe hypoglycaemic episodes may result in transient amaurosis.

Skin and subcutaneous tissue disorders
Lipodystrophy 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).

General disorders and administration site conditions
Injection site reactions include redness, pain, itching, hives, swelling, or inflammation. Most minor reactions to insulins at the injection site usually resolve in a few days to a few weeks. In Toujeo clinical studies in adult patients, the incidence of injection site reactions was similar in Toujeo-treated patients (2.5%) and insulin glargine 100 units/ml-treated patients (2.8%).

Rarely, insulin may cause oedema particularly if previously poor metabolic control is improved by intensified insulin therapy.


Paediatric population
Safety and efficacy of Toujeo have been demonstrated in a study in children aged 6 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).
Clinical study safety data are not available for children under 6 years.

Other special populations
Based on the results from clinical studies, the safety profile of Toujeo in elderly patients and in patients with renal impairment was similar to that of the overall population (see section 5.1).

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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form at https://sideeffects.health.gov.il/.