Adverse reactions : תופעות לוואי

4.8      Undesirable effects

Summary of the safety profile
The most frequently reported adverse reaction during treatment is hypoglycaemia (see section ‘Description of selected adverse reactions’ below).

Tabulated list of adverse reactions
Adverse reactions listed below are based on clinical trial data and classified according to MedDRA System Organ Class. Frequency categories are defined according to the following convention: 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) and not known (cannot be estimated from the available data).

System organ class                                     Frequency        Adverse reaction Immune system disorders                                Rare             Hypersensitivity Urticaria
Metabolism and nutrition disorders                     Very common      Hypoglycaemia Skin and subcutaneous tissue disorders                 Uncommon         Lipodystrophy Not known        Cutaneous amyloidosis†
General disorders and administration site conditions   Common           Injection site reactions Uncommon         Peripheral oedema
†   ADR from postmarketing sources.

Description of selected adverse reactions
Immune system disorders
With insulin preparations, allergic reactions may occur. Immediate-type allergic reactions to either insulin itself or the excipients may potentially be life-threatening.

With Tregludec 100 units/mL, hypersensitivity (manifested with swelling of tongue and lips, diarrhoea, nausea, tiredness and itching) and urticaria were reported rarely.

Hypoglycaemia
Hypoglycaemia may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. The symptoms of hypoglycaemia usually occur suddenly. They may include cold sweats, cool pale skin, fatigue, nervousness or tremor, anxiousness, unusual tiredness or weakness, confusion, difficulty in concentration, drowsiness, excessive hunger, vision changes, headache, nausea and palpitation.

Skin and subcutaneous tissue disorders
Lipodystrophy (including lipohypertrophy, lipoatrophy) 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).

Injection site reactions
Injection site reactions (including injection site haematoma, pain, haemorrhage, erythema, nodules, swelling, discolouration, pruritus, warmth and injection site mass) occurred in patients treated with Tregludec 100 units/mL. These reactions are usually mild and transitory and they normally disappear during continued treatment.

Paediatric population
Tregludec 100 units/mL has been administered to children and adolescents up to 18 years of age for the investigation of pharmacokinetic properties (see section 5.2). Safety and efficacy have 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).

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

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 https://sideeffects.health.gov.il.