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.

Type 1 diabetes mellitus

Suliqua should not be used in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

Rotation of the injection site

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 medicinal product may be considered.

Hypoglycaemia

Hypoglycaemia was the most frequently reported observed adverse reaction during treatment with Suliqua (see section 4.8). Hypoglycaemia may occur if the dose of Suliqua is higher than required.

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).
- lixisenatide and/or insulin in combination with a sulfonylurea may result in an increased risk of hypoglycaemia. Therefore, Suliqua should not be given in combination with a sulfonylurea.

The dose of Suliqua must be individualised based on clinical response and is titrated based on the patient’s need for insulin (see section 4.2).
 Acute pancreatitis

Use of GLP-1 receptor agonists has been associated with a risk of developing acute pancreatitis.
There have been few reported events of acute pancreatitis with lixisenatide although a causal relationship has not been established. Patients should be informed of the characteristic symptoms of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis is suspected, Suliqua should be discontinued; if acute pancreatitis is confirmed, lixisenatide should not be restarted. Caution should be exercised in patients with a history of pancreatitis.

Severe gastrointestinal disease

Use of GLP-1 receptor agonists may be associated with gastrointestinal adverse reactions (see section 4.8). Suliqua has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis and therefore, the use of Suliqua is not recommended in these patients.

Severe renal impairment

There is no therapeutic experience in patients with severe renal impairment (creatinine clearance less than 30 ml/min) or end-stage renal disease. Use is not recommended in patients with severe renal impairment or end-stage renal disease (see sections 4.2 and 5.2).

Concomitant medicinal products
The delay of gastric emptying with lixisenatide may reduce the rate of absorption of orally administered medicinal products. Suliqua should be used with caution in patients receiving oral medicinal products that require rapid gastrointestinal absorption, require careful clinical monitoring or have a narrow therapeutic ratio. Specific recommendations regarding intake of such medicinal products are given in section 4.5.

Aspiration in association with general anaesthesia or deep sedation

Cases of pulmonary aspiration have been reported in patients receiving GLP-1 receptor agonists undergoing general anaesthesia or deep sedation. Therefore, the increased risk of residual gastric content due to delayed gastric emptying (see section 4.8) should be considered prior to performing procedures with general anaesthesia or deep sedation.

Dehydration

Patients treated with Suliqua should be advised of the potential risk of dehydration in relation to gastrointestinal adverse reactions and take precautions to avoid fluid depletion.

Antibody formation

Administration of Suliqua may cause formation of antibodies against insulin glargine and/or lixisenatide. In rare cases, the presence of such antibodies may necessitate adjustment of the Suliqua dose in order to correct a tendency for hyperglycaemia or hypoglycaemia.

Avoidance of medication errors

Patients must be instructed to always check the pen label before each injection to avoid accidental mix-ups between the two different strengths of Suliqua and mix-ups with other injectable diabetes medicinal products.
To avoid dosing errors and potential overdose, neither the patients nor healthcare professionals should ever use a syringe to draw the medicinal product from the cartridge in the pre-filled pen into a syringe.


Antidiabetic medicinal products not studied in combination with Suliqua 
Suliqua has not been studied in combination with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulfonylureas, glinides, and pioglitazone.

Travel

To avoid dosing errors and potential overdoses with changing to different time zones, the patient should seek the doctor’s advice before travelling.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.
This medicinal product contains metacresol, which may cause allergic reactions.

Effects on Driving

4.7      Effects on ability to drive and use machines

Suliqua has no or negligible influence on the ability to drive or use machines. However, 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 while driving and using machines. 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.