The preparation of Yanuvia is generally well toleratedboth in monotherapy and in combination with other hypoglycemicth preparations. In a clinical trialthe total frequency of undesirableas well as the frequency of drug withdrawal because offor undesirable phenomena were similar to those when taking placebo.
According to 4 placebo-controlled trialsfollow-up (duration 18-24 weeks) drug Yanuvia "in a daily dose of 100-200 mg as mono- or combinedtreatment with metformin or pioglitezone there were no associated studiesunwanted reactionthe frequency of which exceeded 1% in the groupne patients taking the drug Yanuvia. Daily Security Profile 200 mg was comparable to the profile withoutrisk of a daily dose of 100 mg.
Analysis of data obtained during the indicatedth higher than clinical studies, showed that the overall incidence of hypoglycemia in patients taking the drug Januvia8, was similar to that of a placebo (Januvia 100 mg 1.2%, Yanuvia8 200 mg - 0.9%, placebo - 0.9%). Frequency measurable adverse effects on the gastrointestinal tract while taking the drug Janow "at both doses was similar to that when receiving placebo (except the more frequent occurrence of nausea while taking the drug Janow" at a dose of 200 mg per day): abdominal pain (Janow8 100 mg-2.3% Janow "200 mg-1.3%, 2.1% placebo), nausea (1.4%, 2.9%, 0.6%), vomiting (0.8% , 0.7%, 0.9%), diarrhea (3.0%, 2.6%, 2.3%).
In all studies, adverse reactions such as hypoglycemia were recorded based on all reports of symptomatic hypoglycemia symptoms; a parallel measurement of blood glucose concentration was not required. Start combination therapy with metformin
In a 24-week placebo-controlled factorial study of the starting combination therapy with Yanuvia8 in a daily dose of 100 mg and metformin at a daily dose of 1000 mg or 2000 mg (sitagliptin 50 mg + metformin 500 mg or 1000 mg x 2 times a day), the following adverse events were observed in the combination treatment group compared with the metformin monotherapy group:
associated with taking the drug nezhethe reactions observed with
frequency> 1% in the prep groupJanuvia "and more often than in the group
treatment with metformin in monotherapy: diarrhea (Yanuvia ® + metformin - 3.5%, metformin-3.3%), dyspepsia (1.3%, 1.1%), headache (1.3%, 1.1%), flatulence (1.3%, 0, 5%), hypoglycemia (1.1%, 0.5%), vomiting (1.1%, 0.3%). Combination with derivatives of sulfonylurea or derivatives of sulfonylureas and metformin In a 24-week placebo-controlled study of combined therapy with Yanuvia8 (daily dose of 100 mg) and glimepiride or glimepiride and metmormin in the study drug group compared to the placebo group and glimepiride or glimepiride and metformin, the following undesirable phenomena were observed:
associated with taking the drug nezhelspecific reactions observed with
frequency> 1% in the prep groupJanuvia and more often than in the group
combination therapy with placebo: ghypoglycaemia (Januvia8 - 9.5%, placebo - 0.9%).
Start combination therapy with agonists PPAR-y
In a 24-week study of starting combined therapy with Yanuvia "at a daily dose of 100 mg and pioglitazone at a daily dose of 30 mg in a group combined treatment compared with monotherapy with pioglitazone were observed the following undesirable phenomena: associated with taking the drug nezhe the reactions observed with frequency> 1% in the prep groupJanuvia "and more often than in the group treatment with pioglitazone in monotherapy:
asymptomatic decrease in concentrationof blood glucose (Yanuvia +
pioglitazone - 1.1%, pioglitazone -0.0%), symptomatic hypoglycaemia
(0,4%, 0,8%).
Combination with agonists PPAR-y and metformin
According to the placebo-controlled dataadherence to drug treatment
Yanuvia (daily dose of 100 mg) in a combinationwith rosiglitazone and metformin in group of study drug in comparisonwith a group of patients taking placebo with rosiglitazone and metformin, the following undesirable phenomena:
At week 18 of observation: associated with taking the drug nezhethe reactions observed with frequency> 1% in the prep grouprat Yanuvia " and more often than in the group combination therapy with placebo:
headache (Yanuvia - 2.4%, a placebof-0,0%), diarrhea (1,8%, 1,1%), tachycardia,
ta (1.2%, 1.1%), hypoglycemia (1.2%,0.0%), vomiting (1.2%, 0.0%).
At the 54th week of follow-up:
fromknitted with the drugthe reactions observed with
frequency> 1% in the prep groupJanuvia and more often than in the group
combination therapy with placebo: headache (Januvia® 2.4%, placebo 0.0%), hypoglycemia (2.4%, 0.0%), upper respiratory tract infection (1.8%, 0.0%), nausea 1,2%, 1,1%), cough (1,2%, 0,0%), fungal infection of the skin (1,2%, 0,0%), peripheral edema (1,2%, 0,0 %), vomiting (1.2%, 0.0%). Combination with insulin B A 24-week placebo-controlled study of combined therapy with Yanuvia8 (in a daily dose of 100 mg) and constant dose of insulin (with or without metformin), the following adverse events were observed in the study drug group compared to the placebo-insulin group (with or without metformin):
associated with taking the drug nezhelspecific reactions observed with
frequency> 1% in the prep groupJanuvia and more often than in the group
insulin treatment (with or without metforminmin): hypoglycemia (Januvia® + insulin (with or without metformin) -9.6%, placebo + insulin (with or without metformin) -5.3%), influenza (1.2%, 0.3% ), headache (1.2%, 0.0%).
In another 24-week study in which patients received the drug Januvia as an additional therapyand with insulin therapy (with or without metformin), there were no undesirable reactions associated with taking the drug at a frequency of> 1% in the Januvia treatment group (100 mg dose), and more often than in the placebo group.
Pancreatitis
In a generalized analysis of 19 double-blind, randomized clinical trials of the use of sitagliptin in a daily dose of 100 mg or a corresponding control drug (active or placebo), the incidence of acute pancreatitis was 0.1 cases per 100 patient-years of treatment in each group (see section "C pancreatitis "),
Clinically significant deviations in vital signs or ECG (including the duration of the interval QTc) on the background of treatment with Yanuvia "was not observed.
Post-market observations
During post-registration monitoringthe use of Yanuvia in monotherapy and / or combined therapy with other hypoglycemic agents revealed additional adverse events, since these data were obtained voluntarily from a population of uncertain size, the frequency and cause-and-effect relationship with the treatment of these undesirable phenomena can not be determined. :
hypersensitivity reactions, including anaphylaxis, angioedemarash, rash, urticaria, cutaneous vasculitis, exfoliative skin diseases, including Stevens-Johnson syndrome; acute pancreatitis, including hemorrhagic and necrotic forms with lethal and without lethal outcome; impairment of kidney function, including acute renal failure (sometimes dialysis is required); upper respiratory tract infection; nasopharyngitis; constipation; vomiting; headache; arthralgia; myalgia; pain in the limb; backache.
Changes in laboratory indicators
The frequency of laboratory deviations in the Januvia '' treatment groups (at a daily dose of 100 mg) was comparable to the frequency in the placebo groups.Most, but not all, of the clinical studies showed a slight increase in leukocyte count (approximately 200 / μL compared with placebo, with an average content of 6600 / μL at the beginning of treatment), due to an increase in the number of neutrophils.
Analysis of the clinical trial data showed a slight increase in the concentration of uric acid (approximately 0.2 mg / dL versus placebo, the mean concentration before treatment was 5-5 mg / dl) in patients receiving the drug Januvia "at a dose of 100 and 200 mg / day There were no cases of gout development.
A slight decrease in the concentrationof total alkaline phosphatase (approximately 5 IU / L compared to placebo, mean pre-treatment 56-62 IU / L), partially associated with a small decrease in the bone fraction of alkaline phosphatase.
The listed changes in laboratory indicators are not considered clinically significant.