Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
Safety data were obtained from a total of 5 451 patients exposed to vildagliptin at a daily dose of 100 mg (50 mg twice daily) in randomised double-blind placebo-controlled trials of at least 12 weeks duration. Of these patients, 4 622 patients received vildagliptin as monotherapy and 829 patients received placebo.
GAL API SEP22 V4                                        4                      EU SmPC 07.2022 The majority of adverse reactions in these trials were mild and transient, not requiring treatment discontinuations. No association was found between adverse reactions and age, ethnicity, duration of exposure or daily dose. Hypoglycaemia has been reported in patients receiving vildagliptin concomitantly with sulphonylurea and insulin. The risk of acute pancreatitis has been reported with the use of vildagliptin (see section 4.4).


Tabulated list of adverse reactions
Adverse reactions reported in patients who received Galvus in double-blind studies as monotherapy and add-on therapies are listed below for each indication by system organ class and absolute frequency. Frequencies 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), not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1    Adverse reactions reported in patients who received vildagliptin as monotherapy or as add-on therapy in controlled clinical studies and in post-marketing experience 
System organ class - adverse reaction                                Frequency Infections and infestations
Nasopharyngitis                                                      Very common Upper respiratory tract infection                                    Common Metabolism and nutrition disorders
Hypoglycaemia                                                        Uncommon Nervous system disorders
Dizziness                                                            Common Headache                                                             Common Tremor                                                               Common Eye disorders
Vision blurred                                                       Common Gastrointestinal disorders
Constipation                                                         Common Nausea                                                               Common Gastro-oesophageal reflux disease                                    Common Diarrhoea                                                            Common Abdominal pain, including upper                                      Common Vomiting                                                             Common Flatulence                                                           Uncommon Pancreatitis                                                         Rare Hepatobiliary disorders
Hepatitis                                                            Not known* Skin and subcutaneous tissue disorders
Hyperhidrosis                                                        Common Rash                                                                 Common Pruritis                                                             Common Dermatitis                                                           Common Urticaria                                                            Uncommon Exfoliative and bullous skin lesions, including bullous pemphigoid   Not known* Cutaneous vasculitis                                                 Not known* Musculoskeletal and connective tissue disorders
Arthralgia                                                           Common Myalgia                                                              Common Reproductive system and breast disorders
Erectile dysfunction                                                 Uncommon General disorders and administration site conditions
GAL API SEP22 V4                                        5                      EU SmPC 07.2022 Asthenia                                                            Common Oedema peripheral                                                   Common Fatigue                                                             Uncommon Chills                                                              Uncommon Investigations
Abnormal liver function tests                                       Uncommon Weight increase                                                     Uncommon *      Based on post-marketing experience.

Description of selected adverse reactions

Hepatic impairment
Rare cases of hepatic dysfunction (including hepatitis) have been reported. In these cases, the patients were generally asymptomatic without clinical sequelae and liver function returned to normal after discontinuation of treatment. In data from controlled monotherapy and add-on therapy trials of up to 24 weeks in duration, the incidence of ALT or AST elevations  3x ULN (classified as present on at least 2 consecutive measurements or at the final on-treatment visit) was 0.2%, 0.3% and 0.2% for vildagliptin 50 mg once daily, vildagliptin 50 mg twice daily and all comparators, respectively. These elevations in transaminases were generally asymptomatic, non-progressive in nature and not associated with cholestasis or jaundice.

Angioedema
Rare cases of angioedema have been reported on vildagliptin at a similar rate to controls. A greater proportion of cases were reported when vildagliptin was administered in combination with an angiotensin converting enzyme inhibitor (ACE-Inhibitor). The majority of events were mild in severity and resolved with ongoing vildagliptin treatment.

Hypoglycaemia
Hypoglycaemia was uncommon when vildagliptin (0.4%) was used as monotherapy in comparative controlled monotherapy studies with an active comparator or placebo (0.2%).
No severe or serious events of hypoglycaemia were reported. When used as add-on to metformin, hypoglycaemia occurred in 1% of vildagliptin-treated patients and in 0.4% of placebo-treated patients. When pioglitazone was added, hypoglycaemia occurred in 0.6% of vildagliptin-treated patients and in 1.9% of placebo-treated patients. When sulphonylurea was added, hypoglycaemia occurred in 1.2% of vildagliptin treated patients and in 0.6% of placebo-treated patients. When sulphonylurea and metformin were added, hypoglycaemia occurred in 5.1% of vildagliptin treated patients and in 1.9% of placebo treated patients. In patients taking vildagliptin in combination with insulin, the incidence of hypoglycaemia was 14% for vildagliptin and 16% for placebo.


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/