Trulicity solution for subcutaneous injection 0.75mg/0.5ml syringe pen 0.5ml, 4pcs

Composition

0.5 ml of the drug contains:

Active ingredient: dulaglutide 0.75 mg;

Auxiliary substances: citric acid anhydrous 0.07 mg; mannitol 23.2 mg; polysorbate 80 (vegetable) 0.10 mg; sodium citrate dihydrate 1.37 mg; water for injection q. s. up to 0.5 ml

Pharmacological action

Hypoglycemic agent-an analog of glucagon-like peptide-1 (GLP-1).

ATX code: A 10 BJ 05

Pharmacological properties

Mechanism

of action Dulaglutide is a long-acting GLP-1 receptor agonist. Its molecule consists of two identical chains linked by disulfide bonds, each containing an analog of modified human GLP-1 covalently bound to a fragment of the heavy chain (Fc) of modified human immunoglobulin G4 (IgG4) by a small polypeptide chain. The part of dulaglutide that is analogous to GLP-1 is approximately 90% homologous to native human GLP-1. The half-life (t_1/2) 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. Such features of the structure provide a soluble form and a half-life of 4.7 days, so the drug is suitable for subcutaneous (subcutaneous) use 1 time per week. In addition, the dulaglutide molecule was designed to prevent the Fcy-receptor-mediated immune response and reduce the immunogenic potential.

The hypoglycemic effect of dulaglutide is due to several mechanisms of action of GLP-1. At elevated glucose concentrations, dulaglutide increases the content of intracellular cyclic adenosine monophosphate (cAMP) in pancreatic beta cells, which leads to an increase in insulin secretion. Dulaglutide suppresses excessive glucagon secretion in patients with type 2 diabetes mellitus (DM2), which leads to a decrease in glucose release by the liver. In addition, dulaglutide slows down the rate of gastric emptying.

Pharmacodynamics

In patients with DM2, starting from the first dose, dulaglutide improves glycemic control by steadily reducing fasting, pre-meal, and post-meal blood glucose concentrations, which is maintained for a week before the next dose is administered.

A pharmacodynamic study of dulaglutide showed that patients with DM2 showed a recovery of the first phase of insulin secretion to values higher than those in healthy volunteers receiving placebo, and an improvement in the second phase of insulin secretion in response to intravenous bolus use of dextrose (glucose) solution. The same study also showed that a single 1.5 mg dose of dulaglutide increased maximal insulin secretion by pancreatic beta cells, as well as improved beta cell function in patients with DM2 compared to placebo.

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

Clinical efficacy and safety

Glycemic control

The efficacy and safety of dulaglutide has been studied in clinical trials where dulaglutide was used in monotherapy, in combination therapy with metformin, in combination therapy with metformin and a sulfonylurea derivative, in combination therapy with a sulfonylurea derivative, in combination therapy with a sodium-dependent glucose transporter type 2 (SGLT2i) inhibitor with or without metformin, in combination therapy with metformin and pioglitazone, in combination therapy with titrated basal insulin with or without metformin, combination therapy with prandial insulin with or without metformin.

In all studies, dulaglutide provided clinically significant improvements in glycemic control, which was assessed by glycated hemoglobin (HbA1c).

Fasting blood glucose concentration

The use of dulaglutide resulted in a significant decrease in the fasting blood glucose concentration compared to the initial value. The main effect on fasting blood glucose concentration was observed after 2 weeks. Improvement in fasting blood glucose levels was maintained over the longest study period – 104 weeks.

Blood glucose concentration after meals (postprandial glycemia)

The use of dulaglutide resulted in a significant decrease in the average postprandial glycemia compared to the initial one (the change in glycemia from the initial value to the primary time point was from -1.95 mmol/l to-4.23 mmol/l).

Pancreatic beta cell function

The results of clinical studies showed an improvement in the function of pancreatic beta cells when using dulaglutide, determined using a homeostatic assessment model (HOMA2 index-%B). The effect on beta cell function was maintained for the longest study period – 104 weeks.

Body weight

When using dulaglutide at a dose of 1.5 mg once a week, a steady decrease in body weight was observed throughout the studies (the change from the initial value was from -0.35 kg to -2.90 kg at the final time point). The change in body weight when using dulaglutide at a dose of 0.75 mg once a week varied from 0.86 kg to -2.63 kg. A decrease in body weight was observed in patients who received dulaglutide, regardless of the onset of nausea, although the numerical decrease was greater in the group of patients who experienced nausea.

Results based on a patient survey

, Dulaglutide significantly improved overall treatment satisfaction.

Blood pressure (BP)

The effect of dulaglutide on blood pressure was evaluated in a study involving patients with DM2 using outpatient blood pressure monitoring. Dulaglutide therapy was associated with a decrease in systolic blood pressure (a difference of -2.8 mm Hg compared to placebo) after 16 weeks. There was no difference in diastolic blood pressure. Similar results for systolic and diastolic BP were shown at the end point of the study-26 weeks.

Assessment of the impact on the cardiovascular system

The results of a meta-analysis of phase II and III studies showed that the risk of cardiovascular disorders did not increase with dulaglutide compared to the treatment with reference drugs.

In a long-term study of cardiovascular outcomes, Trulicity significantly reduced the risk of serious cardiovascular events compared to placebo. In patients treated with dulaglutide, both those with cardiovascular diseases and those with risk factors but not diagnosed with cardiovascular disease, the incidence of serious cardiovascular complications (death due to cardiovascular pathology, non-fatal myocardial infarction, non-fatal stroke) was lower than in patients in the placebo group. The relative risk of major cardiovascular events was consistently below 1.00 for all three major cardiovascular events.

When using Trulicity® in addition to standard therapy compared to placebo, a significant and stable decrease in HbA1c was observed after 60 months compared to baseline. Trulicity® demonstrated stable efficacy in the main population subgroups and disease subgroups, including the previous stage of cardiovascular disease, baseline HbA1c, gender, duration of diabetes, age, and glomerular filtration rate (GFR).

Special patient groups

Patients with renal insufficiency

In a 52-week study, dulaglutide 1.5 mg and 0.75 mg were compared with insulin glargine as an adjunct to prandial insulin lispro to assess the effect on glycemic control and safety in patients with moderate or severe renal insufficiency (15 ml / min / 1.73 m2 < GFR

After 26 weeks of therapy, dulaglutide at a dose of 1.5 mg and 0.75 mg was not inferior to insulin glargine in reducing the HbA1c index, while the effect persisted for 52 weeks. Percentage of patients who achieved the HbA1c target

The safety profile of dulaglutide in patients with severe renal insufficiency was similar to that observed in other studies of dulaglutide.

Pharmacokinetics

Suction

After subcutaneous use to patients with type 2 diabetes, the maximum concentration (cmax) of dulaglutide in plasma is observed after 48 hours. After repeated subcutaneous use of dulaglutide at a dose of 1.5 mg to patients with DM2, the mean_cmax and area under the concentration-time curve (AUC) were approximately 114 ng/ml and 14,000 ngh/ml, respectively. Steady-state plasma concentrations were observed after 2-4 weeks of dulaglutide use at a dose of 1.5 mg once a week. Concentrations after subcutaneous use of a single dose of dulaglutide (1.5 mg) to the abdomen, hip, or shoulder were comparable. The mean absolute bioavailability of dulaglutide after a single subcutaneous injection of 1.5 mg or 0.75 mg was 47% and 65%, respectively.

Distribution

After subcutaneous use of dulaglutide in doses of 0.75 mg or 1.5 mg to patients with DM2 at steady state, the average volume of distribution was approximately 19.2 l and 17.4 L, respectively.

Metabolism

It is believed that dulaglutide is broken down into its constituent amino acids through the main pathways of protein catabolism.

Deduction

The mean clearance of dulaglutide in humans at steady state after use at

doses of 0.75 mg or 1.5 mg was 0.111 l / h and 0.107 l / h, respectively, with

a half-life of 4.5 and 4.7 days, respectively.

Pharmacokinetics of dulaglutide in special patient groups

In elderly patients

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 weight or body mass index

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

In patients with renal insufficiency

, the pharmacokinetics of dulaglutide were evaluated in a clinical and pharmacological study, generally similar in healthy participants and in patients with mild to severe renal insufficiency (creatinine clearance Additionally, in a 52-week clinical trial involving patients with DM2 and moderate or severe renal insufficiency (15 ml / min / 1.73 m2 < GFR This study did not include patients with end-stage renal failure.

In patients with hepatic insufficiency

, the pharmacokinetics of dulaglutide were evaluated in a clinical and pharmacological study, in which patients with hepatic insufficiency showed a statistically significant decrease in the average values of_cmax and AUC by 30% and 33%, respectively, compared with healthy volunteers. With worsening liver function, the time to reach_cmax (tmax) of dulaglutide increased. Dulaglutide exposure was independent of the degree of liver failure. These changes were not considered clinically significant.

For children and adolescents under 18 years of age

The pharmacokinetics of dulaglutide in children and adolescents under 18 years of age have not been studied.

Indications

Trulicity® is indicated for adult patients with type 2 diabetes mellitus with insufficient glycemic control against the background of diet and exercise in the form of:

• monotherapy

in patients who are not indicated for the use of metformin due to intolerance or contraindications;

• combination therapy

in combination with other medications for the treatment of diabetes mellitus.

Trulicity® is indicated for reducing the risk of developing serious cardiovascular complications (death due to cardiovascular pathology, non-fatal myocardial infarction, non-fatal stroke).

• in adult patients with type 2 diabetes mellitus and multiple risk factors for cardiovascular diseases without a diagnosed cardiovascular disease;
• in adult patients with type 2 diabetes mellitus and diagnosed cardiovascular disease as an adjunct to standard therapy for cardiovascular diseases.

Use during pregnancy and lactation

Pregnancy

Data on the use of dulaglutide in pregnant women are not available or their volume is limited. Animal studies have shown the presence of reproductive toxicity, so the use of dulaglutide is contraindicated during pregnancy.

Breast-feeding

There are no data on the penetration of dulaglutide into breast milk. The risk for newborns/children cannot be excluded. The use of dulaglutide during breastfeeding is contraindicated.

Contraindications

• hypersensitivity to dulapuri or any of the excipients included in the product;
• diabetes mellitus, type 1;
• diabetic ketoacidosis;
• end-stage renal failure (GFR < 15 ml/min/1.73 m 2);
• congestive heart failure (CHF) III or IV functional class (according to the classification of new York heart Association, NYHA);
• pregnancy;
• lactation;
• severe disease of the gastrointestinal tract (GIT), including severe paresis of the stomach;
• acute pancreatitis;
• in patients with a personal or family history of medullary thyroid cancer
• in patients with the syndrome of multiple endocrine neoplasia type 2;
• the age of 18 (due to the lack of data on the efficacy and safety of the use dellagloria in this age group).

With caution

In patients taking oral medications that require rapid absorption into the gastrointestinal tract; in patients with CHF of functional class I and II (according to the classification of the New York Heart Association, NYHA).

Side effects

Security Profile Overview

The safety of dulaglutide was studied in initial phase II and III clinical trials, where patients received dulaglutide alone or in combination with other hypoglycemic drugs. The most common adverse reactions in clinical trials were gastrointestinal reactions, including nausea, vomiting, and diarrhea. In general, these reactions were mild or moderate in severity and temporary in nature. The results of a long-term study of cardiovascular outcomes were similar.

HP identified during the evaluation of the results of phase II and III clinical trials, a long-term study of cardiovascular outcomes, and post-marketing experience are divided into systemic-organ classes, indicating the frequency of their occurrence according to WHO recommendations: very common: ≥1/10; often: ≥1/100 – <1/10; infrequently: ≥1/1000 – <1/100; rarely: ≥1/10000 – <1/1000; very rare:

Immune system disorders: infrequently-hypersensitivity, rarely-anaphylactic reaction#;

Metabolic and nutritionaldisorders: very often – hypoglycemia* when used in combination with insulin, glimepiride, metformin† or metformin and glimepiride; often-hypoglycemia* when used as monotherapy or in combination with metformin and pioglitazone; infrequently-dehydration;

Gastrointestinal disorders: very often – nausea, diarrhea, vomiting, abdominal pain; often – decreased appetite, dyspepsia, constipation, flatulence, bloating, gastroesophageal reflux disease, belching; rarely-acute pancreatitis; with unknown frequency-non-mechanical intestinal obstruction;

Liver and biliary tractdisorders: infrequently-cholelithiasis, cholecystitis;

Skin and subcutaneous tissue disorders: rarely-angioedema#;

General disorders and disorders at the injectionsite: often-weakness; infrequently – reactions at the injection site;

Laboratory and instrumental data: often-sinus tachycardia, atrioventricular block of the first degree.

# Post-registration application experience

* Documented symptomatic hypoglycemia with a blood glucose concentration < 3.9 mmol/l.

† Only for dulaglutide 1.5 mg. The frequency of HP for dulaglutide at a dose of 0.75 mg corresponds to a lower category.

Description of individual NRS

Hypoglycemia

When using dulaglutide at doses of 0.75 mg and 1.5 mg once a week as monotherapy or in combination with metformin or metformin and pioglitazone, the frequency of documented symptomatic hypoglycemia ranged from 5.9% to 10.9%, or from 0.14 to 0.62 events/patient / year, with no cases of severe hypoglycemia.

When using dulaglutide at doses of 0.75 mg and 1.5 mg once a week in combination with a sulfonylurea derivative and metformin, the frequency of documented symptomatic hypoglycemia was 39.0% and 40.3%, respectively, or 1.67 and 1.67 events/patient/year, respectively. The incidence of severe hypoglycemia was 0% and 0.7%, or 0.00 and 0.01 events / patient / year, for each dose, respectively. The frequency of documented cases of symptomatic hypoglycemia when using dulaglutide in doses of 1.5 mg with a sulfonylurea derivative was 11.3% and 0.90 episodes/patient / year. There were no cases of severe hypoglycemia.

The frequency of documented cases of symptomatic hypoglycemia when using dulaglutide at doses of 1.5 mg with insulin glargine was 35.3% and 3.38 episodes/patient / year. The incidence of severe hypoglycemia was 0.7% and 0.01 episodes / patient / year.

When using dulaglutide at doses of 0.75 mg and 1.5 mg once a week in combination with prandial insulin, the frequency of hypoglycemia was 85.3% and 80.0%, or 35.66 and 31.06 events/patient/year, respectively. The incidence of severe hypoglycemia was 2.4% and 3.4%, or 0.05 and 0.06 events/patient / year, respectively.

HP from the gastrointestinal tract

Cumulative reporting of gastrointestinal events for up to 104 weeks with dulaglutide 0.75 mg and 1.5 mg once a week, respectively, included nausea (12.9% and 21.2%), diarrhea (10.7% and 13.7%), and vomiting (6.9% and 11.5%). They were usually mild or moderate in severity, with their maximum frequency occurring during the first 2 weeks of therapy and rapidly decreasing over the next 4 weeks, after which the frequency remained relatively constant.

In clinical and pharmacological studies that were conducted in patients with DM2 and lasted up to 6 weeks, most gastrointestinal events were observed within the first 2-3 days after the first dose, their frequency decreased with the use of subsequent doses.

Acute pancreatitis

The incidence of acute pancreatitis in phase II and III clinical trials was 0.07% with dulaglutide compared to 0.14% with placebo and 0.19% with reference drugs, with or without additional basic hypoglycemic therapy.

Pancreatic enzymes

When using dulaglutide, the average increase in the activity of pancreatic enzymes (lipase and / or pancreatic amylase) is 11-21% compared to the initial indicators. In the absence of other signs and symptoms of acute pancreatitis, increased activity of pancreatic enzymes is not a prognostic factor for the development of acute pancreatitis.

Increased heart rate

When using dulaglutide at doses of 0.75 mg and 1.5 mg once a week, a small average increase in heart rate by 2-4 beats per minute (bpm) was observed, while the frequency of sinus tachycardia with an increase in heart rate compared to the initial indicator by ≥15 bpm was 1.3% and 1.4%, respectively.

Grade I atrioventricular block/increased PR interval

When using dulaglutide at doses of 0.75 mg and 1.5 mg once a week, there was a small average increase in the PR interval by 2-3 ms compared to baseline, while the frequency of grade I atrioventricular block was 1.5% and 2.4%, respectively.

Immunogenicity

In clinical studies, the use of dulaglutide was accompanied by the detection of antibodies to dulaglutide with a frequency of 1.6%, which indicates that structural changes in GLP-1 and modified IgG4 regions in the dulaglutide molecule, along with high homology to native GLP-1 and native IgG4, minimize the risk of developing an immune response during dulaglutide therapy. Patients who developed dulaglutide antibodies usually had a low antibody titer; however, despite the small number of patients who developed dulaglutide antibodies, evaluation of the results of phase III clinical trials did not reveal a clear effect of dulaglutide antibodies on the change in HbA1c. None of the patients with systemic hypersensitivity developed antibodies to dulaglutide.

Hypersensitivity

In phase II and III clinical trials, systemic hypersensitivity events (e. g., urticaria, edema) were observed in 0.5% of patients who received dulaglutide. In the post-marketing experience with dulaglutide, cases of anaphylactic reaction were rare.

Injection site reactions

Injection site reactions were observed in 1.9% of patients treated with dulaglutide. Potentially immuno-mediated injection site adverse events (e. g. rash, erythema) occurred in 0.7% of patients and were usually mild.

Early termination of participation in clinical trials due to an undesirable event

In 26-week studies, the incidence of early withdrawal due to adverse events was 2.6% (0.75 mg once a week) and 6.1% (1.5 mg once a week) with dulaglutide, compared with 3.7% with placebo. During the entire duration of the study (up to 104 weeks), the frequency of early termination of participation due to adverse events with dulaglutide was 5.1% (0.75 mg once a week) and 8.4% (1.5 mg once a week). The most frequent NRS that led to early termination of participation in the groups using dulaglutide at doses of 0.75 mg and 1.5 mg once a week were nausea (1.0% and 1.9%), diarrhea (0.5% and 0.6%) and vomiting (0.4% and 0.6%), mainly such reactions were observed during the first 4-6 weeks of therapy.

Interaction

Dulaglutide causes a delay in gastric emptying, therefore, it has the ability to affect the absorption of oral drugs when used simultaneously. Dulaglutide should be used with caution in patients taking oral medications that require rapid absorption in the gastrointestinal tract. Delayed gastric emptying may slightly increase exposure to delayed-release drugs by increasing the release time of the drug.

Paracetamol

After the first use of dulaglutide at doses of 1 and 3 mg_{, the cmax of} paracetamol decreased by 36% and 50%, respectively, and the median tmax was reached later (after 3 and 4 hours, respectively). No statistically significant difference in the AUC _(0-12) (area under the concentration-time curve from 0 to 12 hours), cmax, or tmax of paracetamol was observed after concomitant use with dulaglutide at a dose of up to 3 mg at steady state. When used with dulaglutide, no dose adjustment of paracetamol is required.

Atorvastatin

Concomitant use of dulaglutide with atorvastatin resulted in a decrease in the_cmax and

AUC_{(0 -∞)} of atorvastatin and its main metabolite o-hydroxyatorvastatin to 70% and 21%, respectively. The average t_1/2 of atorvastatin and o-hydroxyatorvastatin after dulaglutide use increased by 17% and 41%, respectively. Such changes are not considered clinically significant. When combined with dulaglutide, no dose adjustment of atorvastatin is required.

Digoxin

After simultaneous application of digoxin at steady state with two consecutive doses of dulaglutide, the total exposure (AUCt) and tmax of digoxin did not change; cmax decreased by a maximum of 22%. It is considered that such a change has no clinical consequences. When used with dulaglutide, no dose adjustment of digoxin is required.

Antihypertensive drugs

Concomitant use of multiple doses of dulaglutide with lisinopril at steady state did not cause clinically significant changes in the AUC or_cmax of lisinopril. A statistically significant delay of approximately 1 h in lisinopril tmax was observed on days 3 and 24 of the study. When a single dose of dulaglutide was co-administered with metoprolol, the AUC or_cmax of metoprolol increased by 19% and 32%, respectively. Despite the fact that the tmax of metoprolol was reached 1 h later, this change was not statistically significant. These changes were not considered clinically significant; therefore, dose adjustment of lisinopril or metoprolol when used with dulaglutide is not required.

Warfarin

After simultaneous use with dulaglutide, the concentration of S – and R-warfarin, as well as the_cmax of R-warfarin, did not change, and the_cmax of S-warfarin decreased by 22%. Area under the concentration-time curve for the international normalized ratio (AUC_INR) increased by 2%, which probably has no clinical significance; there was no effect on the maximum value of the international normalized ratio (INR_max). The international normalized ratio response time (_tmnax) was extended by 6 hours, which is consistent with a delay of tmax of approximately 4 and 6 hours for S – and R-warfarin, respectively. Such changes are not considered clinically significant. No dose adjustment of warfarin is required when used with dulaglutide.

Oral contraceptives

Concomitant use of dulaglutide with oral contraceptives (norgestimate 0.18 mg / ethinylestradiol 0.025 mg) did not affect the total exposure of norelgestromine and ethinylestradiol. For norelgestromine and ethinyl estradiol, there was a statistically significant decrease in_cmax by 26% and 13% and a delay in tmax by 2 and 0.30 hours, respectively. Such observations are not considered clinically significant. No dose adjustment of oral contraceptives is required when used with dulaglutide.

Metformin

After simultaneous use of multiple doses of dulaglutide and metformin with a normal steady-state release, AUCt increased to 15%, and_cmax decreased to 12%, and tmax did not change. These changes correspond to the delayed gastric emptying caused by dulaglutide and are within the range of metformin pharmacokinetic variability, so they are not considered clinically significant. There is no need to adjust the dose of normal-release metformin when used concomitantly with dulaglutide.

Sitagliptin

When used concomitantly with a single dose of dulaglutide, the concentration of sitagliptin did not change. After concomitant use with two consecutive doses of dulaglutide, the AUC_(0-t) and_cmax of sitagliptin decreased by approximately 7.4% and 23.1%, respectively. tmax of sitagliptin increased by approximately 0.5 h after concomitant use with dulaglutide compared to sitagliptin monotherapy.

Sitagliptin can cause up to 80% inhibition of DPP-4 activity within 24 hours.When dulaglutide and sitagliptin were co-administered, the exposure and_cmax of dulaglutide increased by approximately 38% and 27%, respectively, and the median tmax increased to approximately 24 hours. Thus, dulaglutide has a high degree of protection against DPP-4 inactivation. Increased exposure may increase the effect of dulaglutide on blood glucose concentrations.

How to take, course of use and dosage

Trulicity should be administered subcutaneously in the abdomen, hip, or shoulder.

The drug should not be administered intravenously or intramuscularly.

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

Monotherapy

The recommended dose is 0.75 mg once a week.

Combination therapy

The recommended dose is 1.5 mg once a week.

If dulaglutide is added to current metformin and/or pioglitazone therapy, metformin and/or pioglitazone can be continued at the same dose. If dulaglutide is added to current therapy with metformin and / or SGLT2i, metformin and SGLT2i can be continued at the same dose. When dulaglutide is added to current therapy with a sulfonylurea derivative or insulin, it may be necessary to reduce the dose of a sulfonylurea derivative or insulin to reduce the risk of hypoglycemia.

Additional self-monitoring of glycemia during dulaglutide therapy is not required. In the case of combination with sulfonylurea derivatives or insulin, especially when starting Trulicity® therapy, self-monitoring is required, as it may be necessary to adjust the dose of insulin or a sulfonylurea derivative. A step-by-step reduction of the insulin dose is recommended.

Skipping a dose

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

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

Use of the drug in special clinical groups of patients

In elderly patients

No age-dependent dose adjustment is required.

In patients with renal insufficiency

In patients with mild, moderate or severe renal insufficiency (15 ml / min / 1.73 m2 < GFR

There is very limited experience with dulaglutide in patients with end-stage renal failure (

In patients with hepatic insufficiency

No dose adjustment is required in patients with hepatic insufficiency.

For children and adolescents under 18 years of age

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

Overdose

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

Treatment

In case of overdose of dulaglutide, symptomatic therapy should be carried out in accordance with the clinical signs and symptoms.

Description

Transparent colorless solution.

Special instructions

Dulaglutide is contraindicated in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis. Dulaglutide is not a substitute for insulin. Diabetic ketoacidosis has been reported in insulin-dependent patients after rapid withdrawal or reduction of the insulin dose.

Dehydration

Cases of dehydration, sometimes leading to acute renal failure or deterioration of renal function, have been reported in patients treated with Trulicity, especially at the beginning of therapy. Many renal adverse events have been reported in patients who have previously experienced nausea, vomiting, diarrhea, or dehydration. Patients receiving Trulicity® therapy should be informed about the possible risk of dehydration, especially due to adverse reactions from the gastrointestinal tract, and precautions should be taken to avoid hypovolemia.

The use of dulaglutide in patients with severe gastrointestinal diseases, including severe gastric paresis, has not been studied, so the drug is contraindicated in this cohort of patients.

Acute pancreatitis

The use of GLP-1 receptor agonists is associated with the risk of acute pancreatitis. Cases of acute pancreatitis associated with dulaglutide therapy have been reported in clinical trials.

Patients should be informed about the characteristic symptoms of acute pancreatitis, including persistent severe abdominal pain. If pancreatitis is suspected, dulaglutide therapy should be discontinued. If the diagnosis of pancreatitis is confirmed, dulaglutide should be discontinued without resuming therapy. In the absence of other signs and characteristic symptoms of acute pancreatitis, increased activity of pancreatic enzymes is not in itself a prognostic factor for acute pancreatitis.

If the patient has a history of pancreatitis, treatment with other hypoglycemic drugs should be considered.

Hypoglycemia

Patients receiving dulaglutide concomitantly with a sulfonylurea derivative or insulin may have an increased risk of hypoglycemia. The risk of hypoglycemia can be reduced by reducing the dose of a sulfonylurea derivative or insulin.

CHF

Experience with dulaglutide in patients with CHF is limited.

Dulaglutide should be used with caution in patients with CHF of functional class I or II (according to NYHA classification).

Acute renal failure

In post-marketing experience with GLP-1 receptor agonists, including dulaglutide, cases of acute renal failure and exacerbation of chronic renal failure that required hemodialysis have been reported. Some of these events have been reported in patients without a diagnosed kidney disease. Most of the reported events occurred in patients experiencing nausea, vomiting, diarrhea, or dehydration. Since these reactions may impair renal function, caution should be exercised when prescribing therapy and increasing the dose of the drug in patients with renal insufficiency. Renal function should be monitored in patients with renal insufficiency who report severe gastrointestinal disorders.

Macrovascular complications

There are no data from clinical studies confirming a reduction in the risk of macrovascular complications in patients with DM2 when using Trulicity®.

Risk of medullary thyroid cancer

Patients should be informed about the potential risk of medullary thyroid cancer when using dulaglutide and the clinical symptoms of a thyroid tumor (increased tissue volume or nodules in the neck, shortness of breath, persistent hoarseness).

Sodium content

The drug contains less than 1 mmol of sodium (23 mg) for a dose of 1.5 mg, i. e. practically does not contain sodium.

Fertility

There are no data on the effect of dulaglutide on human fertility. In rats, there was no direct effect on mating or fertility after dulaglutide use.

Effect on the ability to drive vehicles and mechanisms

Dulaglutide has minimal or no effect on the ability to drive vehicles and mechanisms. When using dulaglutide in combination with a sulfonylurea derivative or insulin, caution is recommended to avoid the development of hypoglycemia when driving vehicles and mechanisms.

Form of production

Solution for subcutaneous use,0.75 mg/0.5 ml or 1.5 mg/0.5 ml.

0.5 ml of the drug in a 1 ml neutral glass type I syringe with a small rim, capped on one side with a rubber plunger, and on the other side equipped with a 29 G injection needle with a protective cap for injection needles. The syringe is embedded in the pen. 4 syringe pens each, together with instructions for using the drug, instructions for using the syringe pen in a cardboard pack.

Storage conditions

In a dark place at a temperature of 2 to 8 ° C. Do not freeze it. Do not use the drug if it has been frozen. The drug purchased at the pharmacy can be stored at a temperature of no more than 30 ° C for 14 days. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date indicated on the package.

Active ingredient

Dulaglutide

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection

Purpose

For adults

Indications

Type 2 Diabetes