Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile:
Saxenda was evaluated for safety in 5 double-blind, placebo controlled trials that enrolled 5,813 adult patients with overweight or obesity with at least one weight-related comorbidity. Overall, gastrointestinal reactions were the most frequently reported adverse reactions during treatment (67.9%) (see section ‘Description of selected adverse reactions’).


Tabulated list of adverse reactions
Table 3 lists adverse reactions reported in adults. Adverse reactions are listed by system organ class and frequency. Frequency categories are defined as: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.


Table 3 Adverse reactions reported in adults
MedDRA system       Very             Common                  Uncommon            Rare            Not known organ classes       common
Immune system                                                                    Anaphylactic disorders                                                                        reaction Metabolism and                       Hypoglycaemia*          Dehydration nutrition disorders
Psychiatric                          Insomnia** disorders
Nervous system      Headache         Dizziness disorders                            Dysgeusia
Cardiac disorders                                            Tachycardia Gastrointestinal    Nausea           Dry mouth               Pancreatitis***                     Intestinal disorders           Vomiting         Dyspepsia               Delayed gastric                     obstruction† Diarrhoea        Gastritis               emptying****
Constipation     Gastro- oesophageal reflux disease
Abdominal pain upper
Flatulence
Eructation
Abdominal distension
Hepatobiliary                        Cholelithiasis***       Cholecystitis*** disorders
Skin and                             Rash                    Urticaria subcutaneous tissue disorders
Renal and urinary                                                                Acute renal disorders                                                                        failure Renal impairment
General disorders                         Injection site       Malaise and administration                        reactions site conditions                           Asthenia
Fatigue
Investigations                            Increased lipase
Increased amylase
*Hypoglycaemia (based on self-reported symptoms by patients and not confirmed by blood glucose measurements) reported in patients without type 2 diabetes mellitus treated with Saxenda in combination with diet and exercise. Please see section ‘Description of selected adverse reactions’ for further information.
**Insomnia was mainly seen during the first 3 months of treatment.
***See section 4.4.
****From controlled phase 2, 3a and 3b clinical trials†ADR from post marketing sources.


Description of selected adverse reactions:

Hypoglycaemia in patients without type 2 diabetes mellitus
In clinical trials in overweight or obese patients without type 2 diabetes mellitus treated with Saxenda in combination with diet and exercise, no severe hypoglycaemic events (requiring third party assistance) were reported. Symptoms of hypoglycaemic events were reported by 1.6 % of patients treated with Saxenda and 1.1% of patients treated with placebo; however, these events were not confirmed by blood glucose measurements. The majority of events were mild.


Hypoglycaemia in patients with type 2 diabetes mellitus
In a clinical trial in overweight or obese patients with type 2 diabetes mellitus treated with Saxenda in combination with diet and exercise, severe hypoglycaemia (requiring third party assistance) was reported by 0.7% of patients treated with Saxenda and only in patients concomitantly treated with sulfonylurea. Also, in these patients documented symptomatic hypoglycaemia was reported by 43.6% of patients treated with Saxenda and in 27.3% of patients treated with placebo. Among patients not concomitantly treated with sulfonylurea, 15.7% of patients treated with Saxenda and 7.6% of patients treated with placebo reported documented symptomatic hypoglycaemic events (defined as plasma glucose ≤ 3.9 mmol/L accompanied by symptoms).


Hypoglycaemia in patients with type 2 diabetes mellitus treated with insulin In a clinical trial in overweight or obese patients with type 2 diabetes mellitus treated with insulin and liraglutide 3.0 mg/day in combination with diet and exercise and up to 2 OADs, severe hypoglycaemia (requiring third party assistance) was reported by 1.5% of patients treated with liraglutide 3.0 mg/day.
In this trial, documented symptomatic hypoglycaemia (defined as plasma glucose ≤ 3.9 mmol/L accompanied by symptoms) was reported by 47.2% of patients treated with liraglutide 3.0 mg/day and by 51.8% of patients treated with placebo. Among patients concomitantly treated with sulfonylurea, 60.9% of patients treated with liraglutide 3.0 mg/day and 60.0% of patients treated with placebo reported documented symptomatic hypoglycaemic events.

Gastrointestinal adverse reactions
Most episodes of gastrointestinal events were mild to moderate, transient and the majority did not lead to discontinuation of therapy. The reactions usually occurred during the first weeks of treatment and diminished within a few days or weeks on continued treatment.

Patients ≥ 65 years of age may experience more gastrointestinal effects when treated with Saxenda.

Patients with mild or moderate renal impairment (creatinine clearance ≥ 30 ml/min) may experience more gastrointestinal effects when treated with Saxenda.

Acute renal failure
In patients treated with GLP-1 receptor agonists, there have been reports of acute renal failure. A majority of the reported events occurred in patients who had experienced nausea, vomiting, or diarrhoea leading to volume depletion (see section 4.4).

Allergic reactions
Few cases of anaphylactic reactions with symptoms such as hypotension, palpitations, dyspnoea and oedema have been reported with marketed use of liraglutide. Anaphylactic reactions may potentially be life threatening. If an anaphylactic reaction is suspected, liraglutide should be discontinued and treatment should not be restarted (see section 4.3).

Injection site reactions
Injection site reactions have been reported in patients treated with Saxenda. These reactions were usually mild and transitory and the majority disappeared during continued treatment.


Tachycardia
In clinical trials, tachycardia was reported in 0.6% of patients treated with Saxenda and in 0.1% of patients treated with placebo. The majority of events were mild or moderate. Events were isolated and the majority resolved during continued treatment with Saxenda.

Paediatric population

In a clinical trial conducted in adolescents of 12 years to less than 18 years with obesity, 125 patients were exposed to Saxenda for 56 weeks.
Overall, the frequency, type and severity of adverse reactions in the adolescents with obesity were comparable to that observed in the adult population. Vomiting occurred with a 2-fold higher frequency in adolescents compared to adults.
The percentage of patients reporting at least one episode of clinically significant hypoglycaemia was higher with liraglutide (1.6%) compared to placebo (0.8%). No severe hypoglycaemic episodes occurred in the trial.


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