When using Galvus in monotherapy or in combination with other drugs, most of the adverse reactions were mild, temporary and did not require the withdrawal of therapy.Correlations between the incidence of adverse events (AEs) and age, gender, ethnicity, duration of administration, or dosing regimen were not identified.
The incidence of angioedema in the Galvus therapy was ≥1 / 10000, <1/1000 (gradation was "rare") and was similar to that in the control group. Most cases of angioedema have been observed with the drug in combination with angiotensin-converting enzyme inhibitors. In most cases, angioedema was of moderate severity and was resolved independently during the continuation of vildagliptin therapy.
Against the background of therapy with Galvus, there was rarely a violation of liver function (including hepatitis) of the asymptomatic course. In most cases, these abnormalities and abnormalities of liver function parameters from the norm were resolved independently without complications after discontinuation of therapy with the drug. When using Galvus in a dose of 50 mg 1 or 2 times a day, the frequency of increase in activity of "liver" enzymes (ALT or ACT ≥3 x HNG) was 0.2% or 0.3%, respectively (compared with 0.2% in the control group).The increase in activity of "liver" enzymes in most cases was asymptomatic, did not progress and was not accompanied by cholestasis or jaundice.
AEs are grouped according to the classification of organs and systems of organs MedDRA. Within each group of organ organs and organ systems, AEs are listed in order of decreasing incidence. Within each group, the incidence of AH is indicated in order of decreasing severity.
To assess the incidence of adverse events, the following criteria were used: very often (≥1 / 10), often (≥1 / 100, <1/10), infrequently (≥1 / 1,000, <1/100), rarely (≥1 / 10 000, <1/1 000), very rarely (<1/10 000), individual messages (the frequency is unknown).
When using Galvus in monotherapy
When using Galvus in a dose of 50 mg 1 or 2 times a day, the frequency of withdrawal of therapy due to the development of adverse reactions (0.2% or 0.1%, respectively) was no higher than in the placebo group (0.6%) or drug comparison (0.5%).
Against the backdrop of monotherapy with Galvus at a dose of 50 mg 1 or 2 times a day, the incidence of hypoglycemia without increasing the severity of the condition was 0.5% (2 patients out of 409) and 0.3% (4 of 1082), respectively, which is comparable to the drug comparison and placebo (0.2%).
Infectious and parasitic diseases: very rarely - infection of the upper respiratory tract, nasopharyngitis.
Disturbances from the nervous system: often - dizziness; infrequently - a headache.
Disorders from the gastrointestinal tract: infrequently - constipation.
Vascular disorders: infrequent - peripheral edema.
Long-term clinical trials of up to 2 years did not reveal any additional deviations in the safety profile or unforeseen risks when using vildagliptin in monotherapy.
When using Galvus in a dose of 50 mg 1 or 2 times a day in combination with metformin
When using Galvus in a dose of 50 mg / day in combination with metformin, the frequency of cancellation of therapy due to the development of undesired reactions was 0.4% (in groups vildagliptin (50 mg twice daily) + metformin and placebo + metformin There were no cases of cancellation of therapy due to the development of unwanted reactions).
When using Galvus in a dose of 50 mg 1 or 2 times a day in combination with metformin, hypoglycemia was noted in 0.9% and 0.5% of cases, respectively (in the placebo + metformin - 0.4%). In the group of the Galvus drug, there was no development of severe hypoglycemia.
Combination Therapy vildagliptin + metformin did not affect the body weight of patients.
Disturbances from the nervous system: often - tremor, dizziness, headache.
Disorders from the gastrointestinal tract: often - nausea.
Long-term clinical trials of up to 2 years did not reveal any additional deviations in the safety profile or unforeseen risks when using vildagliptin in combination with metformin.
The study of the use of combination vildagliptin and metformin as starting therapy for type 2 diabetes did not reveal any deviations in the safety profile or unforeseen risks.
When using Galvus in a dose of 50 mg / day in combination with sulfonylurea derivatives
With the use of Galvus in a dose of 50 mg / day in combination with glimepiride, the frequency of discontinuation of therapy due to the development of adverse reactions was 0.6% (compared to 0% in the group glimepiride + placebo).
The incidence of hypoglycemia in patients treated with Galvus at a dose of 50 mg / day along with glimepiride was 1.2% (compared with 0.6% in the placebo + glimepiride). In the group of the Galvus drug, there was no development of severe hypoglycemia.
When using Galvus in the recommended dose (50 mg / day) in combination with glimepiride, there was no increase in body weight.
Infectious and parasitic diseases: very rarely - nasopharyngitis.
Disorders from the gastrointestinal tract: infrequently - constipation.
Disturbances from the nervous system: often - tremor, dizziness, headache, asthenia.
When using Galvus in a dose of 50 mg 1 or 2 times a day in combination with thiazolidinedione derivatives
When using Galvus in a dose of 50 mg / day in combination with pioglitazone, the frequency of cancellation of therapy due to the development of adverse reactions was 0.7% (in groups vildagliptin 100 mg / day + pioglitazone and placebo + pioglitazone There were no cases of cancellation of therapy due to the development of unwanted reactions).
When using Galvus in a dose of 50 mg / day in combination with pioglitazone at a dose of 45 mg of hypoglycemia was not observed; in a group vildagliptin (in a dose of 50 mg twice a day) + pioglitazone (at a dose of 45 mg) there was a development of hypoglycemia in 0.6% of cases, and in patients receiving placebo + pioglitazone in a dose of 45 mg, in 1.9% of cases.
In the group of the Galvus drug, there was no development of severe hypoglycemia. The mean weight gain compared with placebo in patients treated with Galvus 50 mg once or twice daily with pioglitazone was +0.1 kg or +1.3 kg, respectively.
When Galvus was added at a dose of 50 mg 1 or 2 times a day to pioglitazone at a dose of 45 mg / day, the incidence of peripheral edema was 8.2% and 7%, respectively (compared to 2.5% with pioglitazone monotherapy). However, with initial combination therapy with vildagliptin 50 mg once or twice daily with pioglitazone at a dose of 45 mg / day, development of peripheral edema was observed in 3.5% or 6.1% of patients, respectively (compared with 9.3% for background of monotherapy with pioglitazone at a dose of 30 mg / day).
Vascular disorders: often - peripheral edema.
Disorders from the metabolism and nutrition: often - an increase in body weight.
When using Galvus in a dose of 50 mg twice a day in combination with insulin (with or without metformin)
When the drug was used in combination with insulin (in combination with metformin or without metformin), the frequency of discontinuation of therapy due to the development of side effects was 0.3%, in the group of therapy with vildagliptin, in the placebo group, there was no discontinuation of therapy.
In applying the drug in combination with insulin (in combination with metformin or without metformin) no increase in risk of hypoglycemia as compared to placebo + the combination of insulin (14% in the vildagliptin group and 16.4% in the placebo group). In 2 patients in the vildagliptin group and in 6 patients in the placebo group, severe hypoglycemia developed.
At the time of completion of the study drug had no effect on the average body weight (body weight increased by 0.6 kg as compared with the original in the vildagliptin group and remained unchanged in the placebo group).
Disturbances from the nervous system: often - headache, unknown - asthenia.
Disorders from the gastrointestinal tract: often - nausea, gastroesophageal reflux; infrequent - diarrhea, flatulence.
General disorders and disorders at the site of administration: often - chills.
Disorders from the metabolism and nutrition: often - hypoglycemia.
When using Galvus in a dose of 50 mg twice a day in combination with drugs of sulfonylurea and metformin
Cases, discontinuation of the drug-related adverse events in the combination therapy group, vildagliptin, metformin and glimepiride, have been reported. In the placebo, metformin and glimepiride combination therapy, the incidence of AH was 0,6%.
Hypoglycemia was noted frequently in both groups (5.1% in the combination group of vildagliptin, metformin and glimepiride and 1.9% in the placebo, metformin and glimepiride combination therapy group). In the vildagliptin group, one episode of severe hypoglycemia was noted.
At the time of completion of the study, no significant effect on body weight was detected (+0.6 kg in the vildagliptin group and -0.1 kg in the placebo group).
Disturbances from the nervous system: often - dizziness, tremor, asthenia.
Disorders from the metabolism and nutrition: often - hypoglycemia.
Disturbances from the skin and subcutaneous tissues: often - hyperhidrosis.
Post-marketing research
During post-registration studies, the following adverse reactions were identified (since reports were received voluntarily from a population of undetermined size, it is not possible to reliably determine the incidence of these AEs, and therefore they are classified as a frequency unknown): hepatitis (reversible upon discontinuation of therapy) , urticaria, pancreatitis, bullous and exfoliative skin lesions, arthralgia, rarely expressed, myalgia, increased activity of "hepatic" enzymes.
If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.