Trulicity solution d / n / k int. 1.5mg / 0.5ml, # 4 syringe-pen

Trulicity Щ is indicated in adult patients with type 2 diabetes mellitus to improve glycemic control in the form of:

Monotherapy

If diet and exercise do not provide the necessary glycemic control in patients who are not indicated for the use of metformin due to intolerance or contraindications.

Combination therapy

In combination with other hypoglycemic drugs, including insulin, if these drugs, together with diet and exercise, do not provide the necessary glycemic control.

Trulicity Щ should be injected subcutaneously into the abdomen, thigh or upper arm. The drug should not be administered intravenously or intramuscularly.

The drug can be administered at any time of the day, regardless of food intake.

Monotherapy The
recommended dose is 0.75 mg once a week.

Combination therapy The
recommended dose is 1.5 mg once a week.

In patients aged 75 years and older, the recommended initial dose of the drug is 0.75 mg once a week.

When dulaglutide is added to ongoing therapy with metformin and / or pioglitazone, metformin and / or pioglitazone can be continued at the same dose. When dulaglutide is added to current therapy with sulfonylurea derivatives or prandial insulin, it may be necessary to reduce the dose of the sulfonylurea derivative or prandial insulin to reduce the risk of hypoglycemia.

Additionally, glycemic control is not required to adjust the dose of dulaglutide. Additional glycemic control may be required to adjust the dose of sulfonylurea derivatives or prandial insulin.

Skipping a dose
If a dose of Trulicity Щ has been missed, it should be administered as soon as possible, if there are at least 3 days (72 hours) before the next scheduled dose. If less than 3 days (72 hours) remain before the next scheduled dose, you must skip the drug administration and enter the next dose according to the schedule. In each case, patients can resume their usual regimen of drug administration once a week.

The day of administration of the drug, if necessary, can be changed, provided that the last dose was administered at least 3 days (72 hours) ago.

Elderly patients (over 65 years of age)
No dose adjustment depending on age is required. However, the experience of therapy in patients ?75 years of age is very limited; in such patients, the recommended initial dose of the drug is 0.75 mg once a week.

Patients with impaired renal function
In patients with mild to moderate renal impairment, dose adjustment is not required. There is very limited experience with the use of dulaglutide in patients with severe renal impairment (estimated glomerular filtration rate (GFR) <30 ml / min / 1.73 m2) or end-stage renal disease, therefore the use of dulaglutide in this population is not recommended.

Patients with impaired liver function
In patients with impaired liver function, dose adjustment is not required.

Children The
safety and efficacy of dulaglutide in children under 18 years of age has not been established. No data available.

The solution for subcutaneous administration is transparent, colorless.

0.5 ml

dulaglutide 1.5 mg

Excipients: anhydrous citric acid - 0.07 mg, mannitol - 23.2 mg, polysorbate 80 (vegetable) - 0.10 mg, sodium citrate dihydrate - 1.37 mg, water d / i - qs up to 0.5 ml ..

• Hypersensitivity to the active or any of the excipients that make up the drug;

• type 1 diabetes mellitus;

• diabetic ketoacidosis;

• severe renal dysfunction;

• chronic heart failure;

• pregnancy;

• breastfeeding period;

• severe diseases of the gastrointestinal tract, incl. severe paresis of the stomach;

• acute pancreatitis;

• children under 18 years of age.

Carefully

In patients taking oral medications that require rapid absorption in the gastrointestinal tract; in patients aged 75 and over.

Pharmacological properties

Mechanism of action
Dulaglutide is a long-acting glucagon-like peptide 1 (GLP-1) receptor agonist. Its molecule consists of two identical chains linked by disulfide bonds, each of which contains an analogue of modified human GLP-1, covalently linked to a fragment of the heavy chain (Fc) of modified human immunoglobulin G4 (IgG4) using a small polypeptide chain. The GLP-1 analogue portion of dulaglutide has approximately 90% homology to native human GLP-1. The half-life (t1 / 2) of native human GLP-1 due to cleavage by dipeptidyl peptidase-4 (DPP-4) and renal clearance is 1.5-2 minutes. Unlike native GLP-1, dulaglutide is resistant to DPP-4 cleavage and has a large size, which slows down absorption and reduces renal clearance.These structural features provide a soluble form and a half-life of 4.7 days, making the drug suitable for subcutaneous administration once a week. In addition, the dulaglutide molecule was designed to reduce the Fcy receptor mediated immune response and reduce the immunogenic potential.

The hypoglycemic effect of dulaglutide is due to several mechanisms of GLP-1 action. With an increased concentration of glucose, dulaglutide increases the content of intracellular cyclic adenosine monophosphate (cAMP) in the beta cells of the pancreas, which leads to an increase in insulin secretion. Dulaglutide suppresses the excessive secretion of glucagon in patients with type 2 diabetes mellitus, which leads to a decrease in the release of glucose by the liver. In addition, dulaglutide slows down the rate of gastric emptying.

Pharmacodynamics
In patients with type 2 diabetes mellitus, starting from the first administration, dulaglutide improves glycemic control by sustaining a decrease in fasting blood glucose concentration, before meals and after meals, which is maintained for a week before the next dose.

A pharmacodynamic study of dulaglutide showed that in patients with type 2 diabetes mellitus there was a restoration of the first phase of insulin secretion to the value observed in healthy individuals receiving placebo, and an improvement in the second phase of insulin secretion in response to an intravenous bolus of glucose. In the same study, it was also shown that a single administration of dulaglutide at a dose of 1.5 mg increased the maximum insulin secretion by pancreatic P-cells and improved P-cell function in patients with type 2 diabetes mellitus compared with placebo.

The pharmacokinetic profile and the corresponding pharmacodynamic profile of dulaglutide allows the drug to be administered once a week.

Clinical efficacy and safety Glycemic
control The
safety and efficacy of dulaglutide was evaluated in 6 randomized, controlled phase III trials, in which 5171 patients with type 2 diabetes mellitus participated. Of these, 958 were over the age of 65, of which 93 were over the age of 75. These studies included 3136 patients who received dulaglutide, of which 1719 received dulaglutide at a dose of 1.5 mg once a week, and 1417 received dulaglutide at a dose of 0.75 mg once a week. In all studies, dulaglutide provided a clinically significant improvement in glycemic control as measured by glycated hemoglobin (HbA1c).

Monotherapy
The use of dulaglutide in monotherapy was studied in a clinical study with active control for 52 weeks in comparison with metformin. The efficacy of dulaglutide at doses of 1.5 mg or 0.75 mg once a week was superior to the efficacy of metformin at a dose of 1500-2000 mg / day in reducing HbA1c, and a significantly larger number of patients reached the target HbA1c <7.0% and? 6.5% when using dulaglutide in doses of 1.5 mg or 0.75 mg once a week than when using metformin after 26 weeks.

The frequency of documented cases of symptomatic hypoglycemia with the use of dulaglutide in doses of 1.5 mg or 0.75 mg once a week and with the use of metformin was 0.62; 0.15 and 0.09 episodes / patient / year, respectively. There were no cases of severe hypoglycemia with the use of dulaglutide.

Therapy in combination with metformin The
safety and efficacy of dulaglutide was evaluated in a placebo-controlled and actively-controlled clinical study (sitagliptin 100 mg / day) for 104 weeks, in which all drugs were used in combination with metformin. The use of dulaglutide at doses of 1.5 mg or 0.75 mg once a week after 52 weeks led to a greater decrease in HbA1c compared to the use of sitagliptin, while a significantly larger number of patients using dulaglutide achieved the target HbA1c <7.0% and ? 6.5%. These effects persisted until the end of the study (104 weeks).

The frequency of documented symptomatic hypoglycemia with the use of dulaglutide in doses of 1.5 mg or 0.75 mg once a week and with the use of sitagliptin was 0.19; 0.18 and 0.17 episodes / patient / year, respectively. There were no cases of severe hypoglycemia with the use of dulaglutide.

The safety and efficacy of dulaglutide was also evaluated in an active controlled study in comparison with the use of liraglutide at a dose of 1.8 mg / day (initial dose 0.6 mg / day; after 1 week, the dose was increased to 1.2 mg / day, and then by 2 week - up to 1.8 mg / day) lasting 26 weeks; both drugs were used in combination with metformin. The use of dulaglutide at a dose of 1.5 mg once a week led to a comparable decrease in HbA1c and the number of patients who achieved the target HbA1c <7.0% and? 6.5%, compared with liraglutide therapy.

The frequency of documented symptomatic hypoglycemia with the use of dulaglutide at a dose of 1.5 mg once a week was 0.12 episodes / patient / year, and with liraglutide - 0.29 episodes / patient / year. There were no cases of severe hypoglycemia.

Therapy in combination with metformin and sulfonylurea derivatives
In an active control study of 78 weeks duration, dulaglutide was compared with insulin glargine, both drugs were used in combination with metformin and sulfonylurea derivatives. After 52 weeks, the use of dulaglutide at a dose of 1.5 mg once a week led to a significantly greater decrease in HbA1c compared with the use of insulin glargine, which persisted after 78 weeks; whereas the decrease in HbA1c with the use of dulaglutide at a dose of 0.75 mg once a week was comparable to the decrease in HbA1c with the use of insulin glargine. In the group using dulaglutide at a dose of 1.5 mg, significantly more patients achieved the target HbA1c <7.0% or ?6.5% after 52 and 78 weeks compared with the group using insulin glargine.

The frequency of documented cases of symptomatic hypoglycemia with the use of dulaglutide in doses of 1.5 mg or 0.75 mg once a week and with the use of insulin glargine was 1.67; 1.67 and 3.02 episodes / patient / year, respectively. With the use of dulaglutide at a dose of 1.5 mg once a week and with the use of insulin glargine, the same number of cases of severe hypoglycemia was observed (2 cases each).

Therapy in combination with metformin and pioglitazone
In placebo-controlled studies and studies with active control (the dose of Exenatide was 5 ?g 2 times a day for the first 4 weeks and 10 ?g 2 times a day thereafter), when using both drugs in combination with metformin and pioglitazone, when dulaglutide was administered at doses of 1.5 mg or 0.75 mg once a week, a significantly more significant decrease in HbA1c was demonstrated compared with placebo and exenatide, which was accompanied by a significantly larger number of patients who achieved the target HbA1c <7.0% or? 6.5%.

The frequency of documented cases of symptomatic hypoglycemia with the use of dulaglutide in doses of 1.5 mg or 0.75 mg 1 time per week and with the use of Exenatide 2 times a day was 0.19; 0.14 and 0.75 episodes / patient / year, respectively. With the use of dulaglutide, no cases of severe hypoglycemia were observed, with the use of Exenatide, 2 cases of severe hypoglycemia were noted.

Therapy in combination with insulin, with or without metformin
In a clinical study, patients who received insulin 1 or 2 times a day before the start of the study discontinued the previous therapy and were randomized to the groups of dulaglutide 1 time per week or insulin glargine 1 time per day; both therapy regimens were carried out in combination with lispro prandial insulin given 3 times a day in combination with or without metformin. After 26 weeks, the efficacy of dulaglutide at doses of 1.5 mg or 0.75 mg once a week was superior to the efficacy of insulin glargine in reducing HbA1c, the same effect persisted by week 52 of the study. The average change in HbA1c for the groups using dulaglutide at a dose of 1.5 mg or 0.75 mg once a week and the group using insulin glargine once a day was: -1.64% [p <0.025], -1.59% [ p <0.025] and -1.41%, respectively,after 26 weeks; -1.48% [p <0.025], -1.42% [p <0.025] and -1.23%, respectively, after 52 weeks. More patients with dulaglutide achieved target HbA1c <7.0% or? 6.5% at 26 weeks and <7.0% at 52 weeks than with insulin glargine.

The frequency of documented cases of symptomatic hypoglycemia with the use of dulaglutide in doses of 1.5 mg or 0.75 mg once a week and with the use of insulin glargine was 31.06; 35.66 and 40.95 episodes / patient / year, respectively. 10 patients reported severe hypoglycemia with dulaglutide 1.5 mg once a week, 7 patients with dulaglutide 0.75 mg once a week, and 15 patients with insulin glargine.

Fasting blood glucose concentration
The use of dulaglutide led to a significantly greater decrease in fasting blood glucose concentration compared to the initial value. The main effect on fasting blood glucose concentration was observed after 2 weeks. The improvement in fasting blood glucose concentration persisted over the longest study period, 104 weeks.

Postprandial blood glucose concentration (postprandial glycemia) The use of dulaglutide resulted in a significant decrease in mean postprandial glycemia compared to baseline (the change in glycemia from baseline to the primary time point ranged from -1.95 mmol / L to -4.23 mmol / L) ...

Pancreatic beta cell function
Clinical studies have shown an improvement in pancreatic beta cell function with dulaglutide, as measured by a homeostatic assessment model (HOMA2-% B). The effect on beta cell function persisted over the longest study period of 104 weeks.

Body weight
With the use of dulaglutide at a dose of 1.5 mg once a week, there was a steady decrease in body weight throughout the study (the change in the mean from baseline to the final time point was from -0.35 kg to -2.90 kg). The change in body weight when using dulaglutide at a dose of 0.75 mg once a week ranged from 0.86 kg to -2.63 kg. A decrease in body weight was observed in patients who received dulaglutide, regardless of the occurrence of nausea, although the numerical reduction was greater in the group of patients who experienced nausea.

Results Based on Patient
Survey Dulaglutide significantly improved overall satisfaction with therapy compared with twice daily Exenatide therapy. In addition, the revealed frequency of hyperglycemia and hypoglycemia with the use of dulaglutide was significantly lower than with the use of Exenatide 2 times a day.

Blood pressure (BP)
The effect of dulaglutide on BP was assessed in a study involving 755 patients with type 2 diabetes mellitus using outpatient BP monitoring. Dulaglutide therapy was accompanied by a decrease in systolic blood pressure (difference - 2.8 mm Hg compared with placebo) after 16 weeks. There was no difference in diastolic blood pressure. Similar results for systolic and diastolic blood pressure were shown at the study endpoint of 26 weeks.

Risk for the cardiovascular system
According to the results of a meta-analysis of phase II and III studies, 51 patients (dulaglutide: 26 (N = 3885); all comparison drugs: 25 (N = 2125)) showed at least one cardiovascular event. system (death caused by disorders of the cardiovascular system; non-fatal myocardial infarction, non-fatal stroke, or hospitalization due to unstable angina). The results showed that with the use of dulaglutide, the risk of cardiovascular disorders did not increase compared with treatment with comparator drugs (hazard ratio: 0.57; confidence interval: (0.30; 1.10)).

Preclinical Safety
Preclinical studies of dulaglutide have not shown any particular risk to humans according to standardized safety pharmacology and repeated dose toxicity studies.

During a 6-month carcinogenicity study in transgenic mice, no oncogenic response was observed. In a 2-year carcinogenicity study in rats at a concentration of dulaglutide ?7 times higher than the therapeutic dose of dulaglutide in humans, which is 1.5 mg once a week, dulaglutide caused a significant dose-dependent increase in the incidence of C-cell thyroid tumors (adenomas and carcinomas ). The significance of such results for humans is currently not known.

In studies of fertility at doses associated with a decrease in food intake and weight gain in the mother, there was a decrease in the number of corpus luteum and an increase in the duration of the estrous cycle; however, no effect on fertility and conception rates or embryonic development was observed. In studies of reproductive toxicity in rats and rabbits, an effect on skeletal formation and a decrease in fetal growth was observed with exposure to dulaglutide, which was 11-44 times higher than the clinical one, but no congenital anomalies were observed. Administration of dulaglutide to rats during pregnancy and lactation caused a memory deficit in female offspring at exposure that was 16 times higher than the suggested clinical exposure.

Pharmacokinetics
Absorption
After subcutaneous administration to patients with type 2 diabetes mellitus, the maximum plasma concentration (Cmax) of dulaglutide is observed after 48 hours. After repeated subcutaneous administration of dulaglutide at a dose of 1.5 mg to patients with type 2 diabetes mellitus, the average 'time' (AUC) were approximately 114 ng / ml and 14000 ngh / ml, respectively. Equilibrium plasma concentration was observed after 2-4 weeks of dulaglutide administration at a dose of 1.5 mg once a week. Concentrations following subcutaneous administration of a single dose of dulaglutide (1.5 mg) to the abdomen, thigh, or upper arm were comparable. The average absolute bioavailability of dulaglutide after a single subcutaneous injection at a dose of 1.5 mg or 0.75 mg was 47% and 65%, respectively.

Distribution
After subcutaneous administration of dulaglutide at doses of 0.75 mg or 1.5 mg to patients with type 2 diabetes mellitus at steady state, the mean volume of distribution was approximately 19.2 L and 17.4 L, respectively.

Metabolism
Dulaglutide is believed to be broken down into its constituent amino acids via major pathways for protein catabolism.

Withdrawal The
average clearance of dulaglutide in humans in an equilibrium state after administration at doses of 0.75 mg or 1.5 mg was 0.073 l / h and 0.107 l / h, respectively, with a half-life of 4.5 and 4.7 days, respectively.

Special groups of patients
Elderly patients (over 65 years of age)
The patient's age did not have a clinically significant effect on the pharmacokinetic and pharmacodynamic properties of dulaglutide.

Gender and race
Gender and race did not have a clinically significant effect on the pharmacokinetics of dulaglutide.

Body mass or body mass index
Pharmacokinetic analysis showed a statistically significant inverse relationship between body mass or body mass index (BMI) and dulaglutide therapy, but there was no clinically significant effect of body weight or BMI on glycemic control.

Patients with impaired renal function The
pharmacokinetics of dulaglutide were assessed during a clinical pharmacological study; in general, it was similar in healthy participants and in patients with mild to severe renal impairment (creatinine clearance <30 ml / min), including end-stage renal failure (during hemodialysis). In clinical studies, the safety profile of dulaglutide in patients with moderate renal impairment was similar to the safety profile in the general population of patients with type 2 diabetes. These studies did not include patients with severe renal impairment or end-stage renal disease.

Patients with impaired liver function The
pharmacokinetics of dulaglutide was evaluated in a clinical and pharmacological study, in which patients with impaired liver function showed a statistically significant decrease in the mean values ??of Cmax and AUC by 30% and 33%, respectively, compared with healthy patients. With the deterioration of liver function, the time to reach Cmax (tmax) of dulaglutide increased. The pharmacokinetic parameters of dulaglutide did not depend on the degree of liver dysfunction. Such changes were not considered clinically significant.

Children
Pharmacokinetic studies of dulaglutide in children have not been conducted

Overdose

Symptoms of dulaglutide overdose in clinical trials included gastrointestinal disturbances and hypoglycemia.

Ћечение
¬ случае передозировки необходимо начать симптоматическую терапию в соответствии с клиническими признаками и симптомами.

¬заимодействие с другими лекарственными средствами

?улаглутид вызывает задержку скорости опорожнени¤ желудка, следовательно, обладает способностью воздействовать на всасывание пероральных препаратов при одновременном применении. ?улаглутид следует примен¤ть с осторожностью у пациентов, принимающих пероральные препараты, которые требуют быстрого всасывани¤ в желудочно-кишечном тракте. «адержка скорости опорожнени¤ желудка может незначительно увеличить экспозицию препаратов с замедленным высвобождением за счет увеличени¤ времени высвобождени¤ препарата.

ѕарацетамол
ѕосле введени¤ первой дозы дулаглутида в дозах 1 или 3 мг —mах парацетамола снижалась на 36 % и 50 % соответственно, а медиана tmах достигалась позднее (через 3 и 4 ч соответственно). ѕосле одновременного применени¤ с дулаглутидом в дозе до 3 мг в равновесном состо¤нии не наблюдалось статистически значимой разницы значений јU— (0-12) (площадь под кривой Ђконцентраци¤-врем¤ї от 0 до 12 ч), —mах или tmах парацетамола. ѕри применении с дулаглутидом коррекции дозы парацетамола не требуетс¤.

јторвастатин
ќдновременное применение дулаглутида с аторвастатином вызывало снижение —mах и јU—(о-?) аторвастатина и его основного метаболита о-гидроксиаторвастатина до 70 % и 21 % соответственно. —редний t1/2 аторвастатина и о-гидроксиаторвастатина после введени¤ дулаглутида увеличивалс¤ на 17 % и 41 % соответственно. “акие изменени¤ не считаютс¤ клинически значимыми. ѕри совместном применении с дулаглутидом коррекции дозы аторвастатина не требуетс¤.

?игоксин
ѕосле одновременного применени¤ дигоксина в равновесном состо¤нии с двум¤ последовательными дозами дулаглутида обща¤ экспозици¤ (јU—t) и tmах дигоксина не измен¤лись; —mах снижалась на 22 % максимально. —читаетс¤, что такое изменение не имеет клинических последствий. ѕри применении с дулаглутидом коррекции дозы дигоксина не требуетс¤.

vипотензивные препараты
ќдновременное применение многократных доз дулаглутида с лизиноприлом в равновесном состо¤нии не вызывало клинически значимых изменений јU— или —mах лизиноприла. —татистически значима¤ задержка tmах лизиноприла приблизительно на 1 ч наблюдалась в 3 и 24 дни исследовани¤. ѕри одновременном применении однократной дозы дулаглутида с метопрололом јU— или —mах метопролола увеличивались на 19 % и 32 % соответственно. Ќесмотр¤ на то, что tmах метопролола достигалось на 1 ч позже, такое изменение не было статистически значимым. ?анные изменени¤ не считались значимыми с клинической точки зрени¤; таким образом, коррекции дозы лизиноприла или метопролола при применении с дулаглутидом не требуетс¤.

¬арфарин
ѕосле одновременного применени¤ с дулаглутидом концентраци¤ S- и R-варфарина, а также —mах R-варфарина не измен¤лись, а —mах S-варфарина снижалась до 22 %. площадь под кривой Ђконцентраци¤-врем¤ї дл¤ международного нормализованного отношени¤ (јU—мно) увеличивалась на 2 %, что, веро¤тно, не имеет клинического значени¤, вли¤ни¤ на максимальное значение международного нормализованного отношени¤ (ћЌќmах) не наблюдалось. ¬рем¤ ответа по международному нормализованному отношению (tћЌќmах) удлин¤лось на 6 ч, что согласуетс¤ с задержкой tmах приблизительно на 4 и 6 ч дл¤ S- и R-варфарина соответственно. “акие изменени¤ не считаютс¤ клинически значимыми.  оррекции дозы варфарина при применении с дулаглутидом не требуетс¤.

ѕероральные контрацептивы
ќдновременное применение дулаглутида с пероральными контрацептивами (норгестимат 0,18 мг/этинилэстрадиол 0,025 мг) не оказывало вли¤ни¤ на общую экспозицию норэлгестромина и этинилэстрадиола. ?л¤ норэлгестромина и этинилэстрадиола наблюдалось статистически значимое снижение —mах на 26 % и 13 % и задержка на 2 и 0,30 ч соответственно. “акие наблюдени¤ не считаютс¤ клинически значимыми.  оррекции дозы пероральных контрацептивов при применении с дулаглутидом не требуетс¤.

ћетформин
ѕосле одновременного применени¤ многократных доз дулаглутида и метформина с обычным высвобождением в равновесном состо¤нии јU—t увеличивалась до 15 %, а —mах снижалась до 12 %, tmах не измен¤лось. “акие изменени¤ соответствуют задержке опорожнени¤ желудка, которую вызывает дулаглутид, и наход¤тс¤ в пределах вариабельности фармакокинетики метформина и поэтому не считаютс¤ клинически значимыми.  оррекции дозы метформина обычного высвобождени¤ при одновременном применении с дулаглутидом не требуетс¤.

—итаглиптин
ѕри одновременном применении с однократной дозой дулаглутида концентраци¤ ситаглиптина не измен¤лась. ѕосле одновременного применени¤ с двум¤ последовательными дозами дулаглутида јU—(0-t) и —mах ситаглиптина снижались приблизительно на 7,4 % и 23,1 % соответственно. tmах ситаглиптина увеличивалось приблизительно на 0,5 ч после одновременного применени¤ с дулаглутидом по сравнению с монотерапией ситаглиптином.

—итаглиптин может вызывать ингибирование на 80 % ?ѕѕ-4 в течение 24 ч. ѕри одновременном применении дулаглутида и ситаглиптина экспозици¤ и —mах дулаглутида увеличивались приблизительно на 38 % и 27 % соответственно, а медианное tmах увеличивалось примерно до 24 ч. “аким образом, дулаглутид обладает высокой степенью защиты от инактивации ?ѕѕ-4.

ќсобые указани¤

?улаглутид не рекомендуетс¤ примен¤ть у пациентов с сахарным диабетом 1 типа или дл¤ лечени¤ диабетического кетоацидоза.

Ќарушени¤ со стороны желудочно-кишечного тракта
ѕрименение агонистов рецепторов vѕѕ-1 может быть св¤зано с нежелательными реакци¤ми со стороны желудочно-кишечного тракта. Ёто следует учитывать при при применении дулаглутида у пациентов с нарушением функции почек, так как диспептические ¤влени¤ (тошнота, рвота и/или диаре¤) могут вызвать обезвоживание, которое может привести к ухудшению функции почек. ѕрименение дулаглутида у пациентов с т¤желыми заболевани¤ми желудочно-кишечного тракта, включа¤ т¤желый парез желудка, не изучалось, поэтому препарат не рекомендован данной группе пациентов.

ќстрый панкреатит
ѕрименение агонистов рецепторов vѕѕ-1 св¤зано с риском развити¤ острого панкреатита. ¬ клинических исследовани¤х отмечались случаи острого панкреатита, св¤занные с терапией дулаглутидом.

ѕациентов следует информировать о характерных симптомах острого панкреатита, включа¤ посто¤нные сильные боли в области живота. ѕри подозрении на панкреатит терапию дулаглутидом следует прекратить. ѕри подтверждении диагноза панкреатита дулаглутид следует отменить без возобновлени¤ терапии. ¬ отсутствие других признаков и характерных симптомов острого панкреатита повышение активности ферментов поджелудочной железы само по себе не ¤вл¤етс¤ прогностическим фактором дл¤ острого панкреатита.

vипогликеми¤
” пациентов, получающих дулаглутид одновременно с производными сульфонилмочевины или инсулином, может быть повышен риск гипогликемии. –иск гипогликемии можно снизить за счет уменьшени¤ дозы производных сульфонилмочевины или инсулина.

Ќеизученные группы пациентов
ќпыт применени¤ дулаглутида у пациентов с хронической сердечной недостаточностью ограничен.

—одержание натри¤
ѕрепарат содержит менее 1 ммоль натри¤ (23 мг) на дозу 1,5 мг, т.е. практически не содержит натри¤.

‘ертильность
?анные о вли¤нии дулаглутида на фертильность у человека отсутствуют. ” крыс не наблюдалось пр¤мого вли¤ни¤ на спаривание или фертильность после применени¤ дулаглутида.

¬ли¤ние на способность управл¤ть транспортными средствами и механизмами

Dulaglutide has minimal or no effect on the ability to drive vehicles and mechanisms. When using dulaglutide in combination with sulfonylurea derivatives or insulin, it is recommended to be careful to avoid the development of hypoglycemia when driving and operating machinery.