Janumet Long, 1000 mg+50 mg 56 pcs

The drug is a combination of two hypoglycemic drugs with a complementary mechanism of action, designed to improve glycemic control in patients with type 2 diabetes: sitagliptin, an enzyme inhibitor of dipeptidyl peptidase-4 (DPP-4), and metformin, a representative of biguanide class.

Indications

Active ingredient

How to take, the dosage

Interaction

Contraindications

Type 1 diabetes mellitus;

Renal disease or reduced renal function (with serum creatinine concentration >1.5 mg/dL and >1.4 mg/dL in men and women, respectively, or decreased CK (<60 ml/min), including Due to cardiovascular collapse (shock), acute myocardial infarction, or septicemia;

Acute conditions with risk of renal dysfunction, such as dehydration (in diarrhea, vomiting), fever, severe infectious diseases, conditions of hypoxia (shock, sepsis, renal infections, bronchopulmonary diseases);

Acute or chronic metabolic acidosis, including diabetic ketoacidosis (with or without coma);

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Clinically manifest acute and chronic conditions that can lead to tissue hypoxia (including.ч. cardiac or respiratory failure, acute myocardial infarction);

Extensive surgical procedures and trauma where insulin therapy is indicated;

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Hepatic failure, impaired liver function; chronic alcoholism, acute alcohol poisoning; pregnancy, lactation;

Lactacidosis (including.ч. history);

The use for at least 48 hours before and 48 hours after radioisotopic or radiology studies with iodine contrast agent;

Hypocaloric diet (less than 1000 kcal/d);

Before 18 years of age; hypersensitivity to sitagliptin, metformin, or any component of the drug.

With caution:

Because the primary route of excretion of sitagliptin and metformin is the kidneys, and sincebecause renal excretory function decreases with age, caution should be exercised when prescribing the drug in elderly patients. The dose should be carefully adjusted and renal function regularly monitored to prevent metformin-associated lactacidosis.

The efficacy and safety of sitagliptin in elderly (older than 65 years) patients has been compared to that in younger patients (younger than 65 years) according to clinical studies.

The number of elderly patients among participants in controlled trials of metformin was insufficient to draw a formal conclusion about age-related differences in efficacy and safety of the drug, although no such differences were observed on the available data. Because metformin is primarily excreted by the kidneys, and impaired kidney function increases the risk of serious adverse reactions, the drug should only be prescribed in patients with confirmed normal renal function.

Side effects

In studies, combined treatment with sitagliptin and metformin was generally well tolerated in patients with type 2 diabetes. The incidence of side effects when combined treatment with sitagliptin and metformin was comparable to the incidence when metformin was taken in combination with placebo.

Combination treatment with sitagliptin and metformin

Start therapy. In a 24-week placebo-controlled factorial study of starter therapy in a group of patients taking sitagliptin 50 mg 2 times/day in combination with metformin 500 mg or 1000 mg 2 times/day, the following drug-related adverse reactions were observed with a frequency of ≥1% and more frequent compared with the metformin 500 mg or 1000 mg 2 times/day monotherapy or sitagliptin 100 mg once/day or placebo groups: Diarrhea, 3.5% (3.3%. 0.0%. 1.1% in the metformin monotherapy, sitagliptin and placebo groups, respectively), nausea, 1.6% (2.5%, 0.0%, 0.6%), dyspepsia, 1.3% (1.1%, 0.0% and 0.0%), flatulence 1.3% (0.5%, 0.0% and 0.0%), vomiting 1.1% (0.3%, 0.0% and 0.0%), headache 1.3% (1.1%, 0.6% and 0.0%) and hypoglycemia 1.1% (0.5%, 0.6% and 0.0%).

The addition of sitagliptin to current metformin therapy. In a 24-week placebo-controlled study, sitagliptin was added to current metformin therapy: 464 patients took metformin with the addition of sitagliptin at a dose of 100 mg once daily, and 237 patients took placebo and metformin. The only adverse drug-related reaction in the sitagliptin and metformin treatment group observed with a frequency ≥1% higher than that in the placebo group was nausea (1.1% in the metformin and sitagliptin combination therapy group and 0.4% in the placebo and metformin group).

Hypoglycemia and adverse gastrointestinal reactions. In placebo-controlled studies of combination therapy with sitagliptin and metformin, the incidence of hypoglycemia (regardless of causality) in patients receiving a combination of sitagliptin and metformin was comparable to that in the group of patients receiving metformin in combination with placebo. In the study of starting therapy with sitagliptin and metformin, the incidence of hypoglycemia was 1.6% in the metformin and sitagliptin combination therapy group and 0.8% in the metformin therapy group. In the study of metformin therapy with sitagliptin addition, the incidence of hypoglycemia was 1.3% in the metformin-sitagliptin combination therapy group and 2.1% in the metformin therapy group. In the study of start therapy with sitagliptin and metformin, the incidence of monitored adverse GI reactions (regardless of causality) in patients receiving the combination of sitagliptin and metformin was comparable to the incidence in the group of patients receiving metformin with placebo: diarrhea (7.5% in the sitagliptin and metformin combination therapy group, 7.7% in the metformin group), nausea (4.8%, 5.5%), vomiting (2.1%, 0.5%), and abdominal pain (3.0%, 3.8%). In a study of metformin therapy with sitagliptin supplementation, the frequency of monitored adverse GI reactions (regardless of causality) in patients receiving the combination of sitagliptin and metformin was comparable to the frequency in the group of patients receiving metformin with placebo: diarrhea (2.4% in the sitagliptin and metformin combination therapy group, 2.5% in the metformin group), nausea (1.3%, 0.8%), vomiting (1.1%, 0.8%), and abdominal pain (2.2%, 3.8%).

In all studies, adverse reactions in the form of hypoglycemia were reported based on all reports of clinically significant symptoms of hypoglycemia. Additional measurement of blood glucose concentration was not required.

Combination treatment with sitagliptin, metformin, and a sulfonylurea derivative

. In a 24-week placebo-controlled study, when sitagliptin at a daily dose of 100 mg was added to current combination therapy with glimepiride at a daily dose ≥4 mg and metformin at a daily dose ≥1500 mg, the following drug-related adverse reactions were observed with a frequency of ≥1% in the sitagliptin treatment group and more frequently than in the placebo group Hypoglycemia (13.8% in the sitagliptin group and 0.9% in the placebo group) and constipation (1.7% and 0.0%).

Combination therapy with sitagliptin, metformin, and PPARγ agonist

. In a placebo-controlled study, when sitagliptin at a daily dose of 100 mg was added to current rosiglitazone and metformin combination therapy at 18 weeks of treatment, the following drug-related adverse reactions were observed with a frequency of ≥1% in the sitagliptin treatment group and more frequently than in the placebo group Headache (2.4% in the sitagliptin group. 0.0% in the placebo group), diarrhea (1.8%. 1.1%), nausea (1.2%. 1.1%), hypoglycemia (1.2%, 0.0%), vomiting (1.2%. 0.0%). At 54 weeks of therapy, the following drug-related adverse reactions were observed with a frequency of ≥1% in the sitagliptin treatment group and more frequently than in the placebo group: headache (2.4%, 0.0%), hypoglycemia (2.4%, 0.0%), upper respiratory tract infections (1.8%, 0.0%), nausea (1.2%, 1.1%), cough (1.2%, 0.0%), fungal skin infections (1.2%, 0.0%), peripheral edema (1.2%, 0.0%), vomiting (1.2%, 0.0%).

Combination therapy with sitagliptin, metformin, and insulin

. In a 24-week placebo-controlled study when sitagliptin at a daily dose of 100 mg was added to current combination therapy with metformin at a daily dose of ≥1500 mg and insulin at a constant dose, the only adverse drug-related reactions observed at a frequency of ≥1% in the sitagliptin treatment group and more frequently than in the placebo group were hypoglycemia (10.9% in the sitagliptin group, 5.2% in the placebo group). In another 24-week study in which patients received sitagliptin as adjunctive therapy during ongoing intensification of insulin therapy (with or without metformin), the only adverse drug-related reaction observed with a frequency of ≥1% in the sitagliptin and metformin therapy group and more frequently than in the placebo and metformin group was vomiting (1.1% in the sitagliptin and metformin therapy group and 0.4% in the placebo and metformin group.)

Pancreatitis

. According to a pooled analysis of the results of 19 double-blind randomized clinical trials that included data from patients receiving cigliptin at a daily dose of 100 mg or the corresponding control drug (active or placebo), the incidence of unconfirmed acute pancreatitis was 0.1 case per 100 patient-years of treatment in each group.

There were no clinically significant abnormalities in vital signs or ECG (including QTc interval length) on sitagliptin and metformin combination therapy.

Sitagliptin-induced adverse reactions

There have been no adverse reactions associated with sitagliptin administration in patients with an incidence of ≥1%.

Adverse reactions attributable to metformin administration

The adverse reactions (regardless of causality) observed with a frequency of >5% in patients in the sustained-release metformin therapy group and more frequently than in the placebo group are diarrhea, nausea/vomiting, flatulence, asthenia, dyspepsia, abdominal discomfort and headache.

Effects on the cardiovascular system (TECOS safety study)

The Clinical Trial to Assess the Effects of Sitagliptin on the Cardiovascular System (TECOS) included 7332 patients with type 2 diabetes who received sitagliptin at a daily dose of 100 mg (or 50 mg/day if baseline estimated glomerular filtration rate (pSCF) was ≥30 and <50 ml/min/173 m2), and 7339 placebo-treated patients among patients who received at least one dose of the study drug. The study drug (sitagliptin or placebo) was administered in addition to baseline treatment aimed at controlling cardiovascular risk factors and achieving target glycated hemoglobin (HbA1c) levels, according to local patient management standards. The study included 2004 patients aged ≥75 years, 970 of whom received sitagliptin and 1,034 of whom received placebo. Overall, the incidence of serious adverse events in the group of patients receiving sitagliptin was comparable to the incidence of adverse events in the placebo group. When predefined complications due to diabetes mellitus were evaluated, comparable rates of infections (18.4% in the sitagliptin therapy group, 17.7% in the placebo group) and renal failure (1.4% in the sitagliptin therapy group and 1.5% in the placebo group) were found between the groups. The adverse event profile in patients aged ≥75 years was generally comparable to that of the general population.

In the intention-to-treat patient population (patients who took at least one dose of the study drug) who were initially receiving insulin and/or sulfonylurea, the incidence of severe hypoglycemia was 2.7% in the sitagliptin therapy group and 2.5% in the placebo group. In patients not initially receiving insulin and/or sulfonylurea derivatives, the incidence of severe hypoglycemia was 1.0% in the sitagliptin therapy group and 0.7% in the placebo group. The incidence of confirmed pancreatitis was 0.3% in the sitagliptin-treated patients and 0.2% in the placebo group. The incidence of cases of confirmed malignancies in patients treated with sitagliptin was 3.7%; in the placebo group it was 4.0%.

Post-registration observations

In post-registration monitoring of the use of the combination metformin + sitagliptin or sitagliptin as part of its composition, in monotherapy and/or in combination therapy with other hypoglycemic agents, additional adverse reactions were identified. Because these data were obtained voluntarily from a population of uncertain size, it is generally not possible to reliably determine the frequency and causal relationship of these adverse reactions to therapy.

These include: hypersensitivity reactions, including Anaphylaxis, angioedema, skin rash, urticaria, cutaneous vasculitis and exfoliative skin diseases, including Stevens-Johnson syndrome, acute pancreatitis, including hemorrhagic and necrotic forms with or without lethal outcome, deterioration of renal function, including acute renal failure (sometimes dialysis is required), upper respiratory tract infections, nasopharyngitis, constipation, vomiting, headache, arthralgia, myalgia, pain in the extremities, back pain, skin itching, pemphigoid.

Changes in laboratory parameters

Sitagliptin. The incidence of abnormal laboratory parameters in the sitagliptin and metformin therapy groups was comparable to that in the placebo and metformin therapy groups. In most, but not all, clinical trials, a small increase in leukocyte counts (approximately 200/μL compared with placebo, mean count at the start of treatment was approximately 6600/μL) was noted, due to an increase in neutrophil counts. This change is not considered clinically significant.

Metformin. In controlled clinical trials of metformin lasting 29 weeks, a decrease in normal serum cyanocobalamin (vitamin B12) concentrations to subnormal values without clinical manifestations was observed in approximately 7% of patients. Such a decrease, probably due to selective impairment of vitamin B12 absorption (namely, impaired formation of a complex with intrinsic factor Kasl, the so-called complex internal complex necessary for vitamin B12 absorption), is very rarely accompanied by the development of anemia and is easily corrected by withdrawal of metformin or additional vitamin B12 intake.

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