Januvia instructions for use

Composition

One tablet, film coated, contains: sitagliptin (in the form of phosphate monohydrate) 25, 50 and 100 mg.

Excipients: microcrystalline cellulose, calcium phosphate, sodium croscarmellose, magnesium stearate, sodium stearyl fumarate.

Shell composition: Opadry II beige 85 F17438, polyvinyl alcohol, titanium dioxide, macrogol (polyethylene glycol) 3350, talc, iron yellow oxide, iron red oxide.

Packaging

In the blister 14 tablets. In packing 2 blisters.

Pharmachologic effect

Januvia is an oral hypoglycemic drug, a highly selective inhibitor of dipeptidyl peptidase 4 (DPP-4).

Sitagliptin differs in chemical structure and pharmacological action from analogues of glucagon-like peptide-1 (GLP-1), insulin, sulfonylurea derivatives, biguanides, γ-peroxisome-activated proliferator-receptor agonists, alpha glycosidase inhibitors, amylin analogues. Inhibiting DPP-4, sitagliptin increases the concentration of 2 known hormones of the incretin family: GLP-1 and the glucose-dependent insulinotropic peptide (HIP). Hormones of the family of incretins are secreted in the intestine during the day, their level rises in response to food intake. Incretins are part of the internal physiological system for regulating glucose homeostasis. At normal or elevated blood glucose levels, hormones of the incretin family contribute to an increase in insulin synthesis, as well as its secretion by β-cells of the pancreas due to signaling intracellular mechanisms associated with cyclic AMP.

GLP-1 also contributes to the suppression of increased glucagon secretion by pancreatic α-cells. A decrease in glucagon concentration on the background of an increase in insulin levels contributes to a decrease in glucose production by the liver, which ultimately leads to a decrease in glycemia.

At low blood glucose concentrations, the listed effects of incretins on insulin release and a decrease in glucagon secretion are not observed. GLP-1 and HIP do not affect the release of glucagon in response to hypoglycemia. Under physiological conditions, the activity of incretins is limited by the enzyme DPP-4, which quickly hydrolyzes the incretins to form inactive products.

Sitagliptin prevents hydrolysis of the incretins by the DPP-4 enzyme, thereby increasing the plasma concentrations of the active forms of GLP-1 and HIP. By increasing the level of incretins, sitagliptin increases glucose-dependent insulin release and helps to reduce glucagon secretion. In patients with type 2 diabetes mellitus with hyperglycemia, these changes in insulin and glucagon secretion lead to a decrease in glycated hemoglobin НbА1С and a decrease in plasma glucose concentration, determined on an empty stomach and after a stress test.

In patients with type 2 diabetes, taking a single dose of Januvia drug leads to inhibition of the activity of the enzyme DPP-4 for 24 hours, which leads to an increase in the level of circulating GLP-1 and HIP incretin by a factor of 2-3, increasing the plasma concentration of insulin and C- peptide, reducing the concentration of glucagon in the blood plasma, reducing fasting glucose, as well as reducing glycemia after loading glucose or food load.

Indications

Januvia, indications for use

• Monotherapy: as a supplement to diet and physical exertion to improve glycemic control in type 2 diabetes.
• Combination therapy: type 2 diabetes mellitus to improve glycemic control in combination with metformin or PPAR agonists (for example, thiazolidinedione) when diet and exercise combined with monotherapy with the above agents do not lead to adequate glycemic control.

Contraindications

• Type 1 diabetes.
• Diabetic ketoacidosis.
• Pregnancy.
• Lactation period (breastfeeding).
• Hypersensitivity to the drug. It is not recommended to prescribe the drug Januvia to children and adolescents under the age of 18 years (data on the use of the drug in pediatric practice is not available). Use with caution in patients with renal insufficiency. In case of moderate and severe renal failure, as well as in patients with end-stage renal failure requiring hemodialysis, correction of the dosing regimen is required.

Dosage and administration

When used as monotherapy or in combination with metformin or a PPAR-γ agonist (for example, thiazolidinedione), the recommended dose of Januvia is 100 mg 1 time / day.

Yanuvia can be taken regardless of the meal. If the patient missed taking Januvia, the drug should be taken as soon as possible. Do not take a double dose of the drug Januvia.

In case of mild renal failure (CC ≥50 ml / min, approximately corresponding to serum creatinine ≤ 1.7 mg / dL in men, ≤ 1.5 mg / dL in women), no dose adjustment is required.

In moderately severe renal failure (CC ≥30 ml / min, but 1.7 mg / dL, but ≤ 3 mg / dL in men,> 1.5 mg / dL, but ≤ 2.5 mg / dL in women), the dose of Januvia is 50 mg 1 times / day

In severe renal failure (KK3 mg / dl in men,> 2.5 mg / dl in women), for patients with end-stage renal failure and the need for hemodialysis, the dose of the drug Januvia is 25 mg 1 time / day. hemodialysis procedures.

Use during pregnancy and lactation

Adequate and strictly controlled clinical studies of the safety of the drug Januvia in pregnant women was not conducted. The use of the drug during pregnancy is contraindicated. It is not known whether sitagliptin is excreted in human breast milk. If necessary, the use of the drug during lactation should decide on the termination of breastfeeding.

Side effects

On the part of the digestive system: abdominal pain, nausea, vomiting, diarrhea. Laboratory indicators: hyperuricemia, decrease in the activity of total and partially bone fraction of alkaline phosphatase, leukocytosis, due to an increase in the number of neutrophils.

Others (causal relationship with taking the drug has not been established): upper respiratory tract infections, nasopharyngitis, headache, arthralgia. The incidence of hypoglycemia is similar to that when taking placebo.

Special instructions

In clinical studies of the drug Januvia as monotherapy or as part of a combination therapy with metformin or pioglitazone, the incidence of hypoglycemia with the use of the drug Januvia was similar to the incidence of hypoglycemia with placebo. The combined use of the drug Januvia in combination with drugs that can cause hypoglycemia, such as insulin, sulfonylurea derivatives, has not been studied.

Patients with mild and moderate hepatic insufficiency do not require dose adjustment of the drug Januvia.

In clinical studies, the efficacy and safety of the drug Januvia in elderly patients (≥65 years, 409 patients) were comparable with these indicators in patients younger than 65 years. Dose adjustment for age is not required. Elderly patients are more likely to develop renal failure. Accordingly, as in other age groups, dose adjustment is necessary in patients with severe renal insufficiency.

Interaction

In studies of the interaction with other drugs, sitagliptin had no clinically significant effect on the pharmacokinetics of the following drugs: metformin, rosiglitazone, glibenclamide, simvastatin, warfarin, oral contraceptives. Based on these data, sitagliptin does not inhibit CYP3A4, 2C8 or 2C9 isoenzymes. Based on in vitro data, sitagliptin probably does not inhibit CYP2D6, 1A2, 2C19 or 2B6, nor does it induce CYP3A4. There was a slight increase in AUC (11%), as well as an average C max (18%) of digoxin when used together with sitagliptin. This increase is not considered clinically significant. It is not recommended to change the dose of either digoxin or Januvia when used simultaneously. An increase in AUC and С max of sitagliptin was noted by 29% and 68%, respectively, in patients with a joint use of Januvia in a single dose of 100 mg and cyclosporine (a p-glycoprotein potent inhibitor) in a single dose of 600 mg. These changes in the pharmacokinetic parameters of sitagliptin are not considered clinically significant. It is not recommended to change the dose of the drug Januvia when used together with cyclosporine and other inhibitors of p-glycoprotein (for example, ketoconazole). A population pharmacokinetic analysis in patients and healthy volunteers (n = 858) who received a wide range of concomitant medications (n ​​= 83, about half of which are excreted by the kidneys), did not reveal any clinically significant effect of drugs on the pharmacokinetics of sitagliptin.

Overdose

Symptoms: During clinical studies on healthy volunteers, good tolerability was observed when taking Januvia in a single dose of 800 mg. Minimal changes in the QTc interval, not considered clinically significant, were noted in one of the studies of the drug at the indicated dose. Clinical studies of the drug in a dose of more than 800 mg / day was not conducted.

Treatment: removal of an unabsorbed drug from the gastrointestinal tract, monitoring of vital signs, including an ECG, and, if necessary, symptomatic and supportive therapy. Sitagliptin is poorly dialyzed. In clinical studies, only 13.5% of the dose was removed from the body during the 3-4 hour dialysis session. Prolonged dialysis can be prescribed with in case of clinical need. There is no data on the effectiveness of peritoneal dialysis of sitagliptin.

Storage conditions

The drug should be stored at a temperature not higher than 30 °C.

Shelf life

2 years

Type 2 diabetes mellitus (non-insulin dependent)

In people with type 2 diabetes, the pancreas may produce an insufficient amount of insulin or the body is not able to adequately use it.

General information

All forms of diabetes are caused by the inability to adequately utilize glucose, the main source of energy in the body. This is due to the violation of the production or use of insulin hormone in the body, which is formed in the cells of the pancreas and which is necessary for the conversion of sugar, starches and other food components into energy.

In people with type 2 diabetes, the pancreas may produce an insufficient amount of insulin or the body is not able to adequately use it. As a result, the content of glucose in the blood rises, which leads to damage to blood vessels and other organs.

This form of diabetes occurs in people of middle age and older. The diagnosis of type 2 diabetes mellitus is made on the basis of high blood glucose, as well as urine glucose.

The reasons

It is believed that the occurrence of type 2 diabetes plays a role in genetic predisposition to the disease; a combination of risk factors such as age and overweight. With age, pancreatic function decreases. The most important predisposing factor, however, was obesity. It is established that more than 80% with type 2 diabetes are overweight. It is believed that excess fat violates the body's ability to dispose of insulin.

Symptoms of type 2 diabetes

Great thirst, frequent urination, rapid loss of body weight, weakness and fatigue, irritability, nausea and vomiting.

Complications

In the case of inadequate control of type 2 diabetes, the risk of myocardial infarction, stroke, kidney disease, neurological disorders, impotence, visual disturbances (including blindness), and gangrene increases. Dangerous diabetes mellitus type 2 diabetes. In the absence of effective therapy, death is possible, which is associated with complications due to high blood glucose or pathological changes on the part of organs and systems.

What can you do

For any symptoms of diabetes, you should immediately undergo a medical examination. Even if the symptoms of diabetes mellitus are absent, the blood sugar and urine should be monitored, especially for people with an indication of diabetes in the family history, people over 40 and / or overweight.

Once diagnosed with diabetes mellitus, regular medical monitoring and monitoring of blood glucose is necessary to avoid complications.

For effective treatment of diabetes, you should carefully monitor your condition.

People with type 2 diabetes should:

• control glucose and cholesterol, as well as body weight, including in your diet low-calorie foods that are low in sugar, fat and high in complex carbohydrates and plant fibers;
• exercise regularly in order to reduce the need for insulin and increase the loss of body weight;
• to determine the content of glucose in the blood at home with the help of simple devices, which helps a person to correct his diet and exercise and prevent the development of complications of diabetes. Self-monitoring of glucose also allows you to observe how the level of glucose in the blood decreases with decreasing body weight.

People suffering from diabetes should take preventive measures to avoid colds, it is recommended to observe hygiene of the feet.

The course of type 2 diabetes mellitus is largely dependent on self-control. In most cases, type 2 diabetes can be controlled through diet and exercise. However, not all people with type 2 diabetes are overweight. This category of patients requires the appointment of insulin and hypoglycemic drugs for oral administration.

What can your doctor do

If diabetes is suspected, the doctor should prescribe appropriate blood tests to diagnose the disease. If the diagnosis is made, the doctor must prescribe a special diet or refer the patient for consultation with a nutritionist. Diet and exercise are the basis for the treatment of type 2 diabetes. A number of studies have found that in 80% or more of cases of type 2 diabetes can be controlled by weight loss and exercise. If these methods are not effective and the level of glucose in the blood is not normalized, then the doctor should prescribe oral hypoglycemic drugs. Depending on the sugar content in the blood and the reaction to diet therapy, the doctor may prescribe medications that increase the body’s ability to effectively use its own insulin or increase its production.

Subsequently, the doctor determines the frequency of visits, depending on the need for various tests, the general condition of the patient and the risk of complications requiring special additional treatment.

In some cases, insulin injections may be required.

Preventive measures

To avoid type 2 diabetes, a balanced diet with a high fiber content should be used; exercise regularly; avoid overweight and its sharp decline; regularly monitor blood glucose, especially in the presence of diabetes mellitus in family history or with overweight.

All the main symptoms of diabetes

The causes of type 2 diabetes mellitus (non-insulin-dependent) are: genetic predisposition; obesity, often associated with overeating (80 to 90% of people with this disease are overweight), as well as diseases of the endocrine system: pathology of the pituitary, thyroid gland (hypo- and hyperfunction), adrenal cortex. Diabetes mellitus can occur as a complication of viral diseases (influenza, viral hepatitis, herpes virus, etc.), pancreatitis, pancreatic tumors.

In some cases, diabetes for the time being does not make itself felt. The symptoms of diabetes are different in diabetes I and diabetes II. Sometimes, there may be no signs at all, and diabetes is determined, for example, by referring to an optometrist while examining the fundus. But there is a complex of symptoms characteristic of both types of diabetes. The severity of symptoms depends on the degree of reduction of insulin secretion, the duration of the disease and the individual characteristics of the patient.

Diabetes mellitus - major signs:

• Increased thirst and frequent urination at night.
• Dry skin.
• Weight loss.
• Cramps gastrocnemius muscles.
• Blurred vision
• Itching of the skin and mucous genitals

Symptoms of diabetes 1 type

Symptoms of type 1 diabetes include frequent urination, excessive thirst, nausea, vomiting, weakness and increased fatigue, weight loss (despite normal or even increased food intake), persistent hunger, irritability. In children, bedwetting is one of the signs of diabetes, especially in cases where the child had not urinated into bed before. In type I diabetes, there are situations where the level of glucose in the blood becomes either very high or very low. Each of these conditions requires emergency medical care.

Symptoms of diabetes 1 type

Symptoms of type 1 diabetes include frequent urination, excessive thirst, nausea, vomiting, weakness and increased fatigue, weight loss (despite normal or even increased food intake), persistent hunger, irritability. In children, bedwetting is one of the signs of diabetes, especially in cases where the child had not urinated into bed before. In type I diabetes, there are situations where the level of glucose in the blood becomes either very high or very low. Each of these conditions requires emergency medical care.

Symptoms of diabetes diabetes type 2

Symptoms of type 2 diabetes include itching, blurred vision, unusual thirst, drowsiness, fatigue, skin infections, slow healing of wounds, numbness and paresthesias of the legs. This disease begins in adulthood and is usually associated with malnutrition. In diabetes, flu-like symptoms, hair loss on the legs, increased growth of hair on the face, small yellow growths on the body, called xanthomas, also occur. Balanoposthitis (inflammation of the foreskin) is sometimes the first sign of diabetes and is associated with frequent urination.

In order to establish the diagnosis of diabetes, it is necessary to determine two indicators:

• Blood sugar level
• Level of sugar in urine

Blood Sugar Level	Norm	Excess
Fasting	120 mg% (6.6 mmol / l)	more than 120 mg%
After eating	140mg% (7.7mmol / l)	more than 160-180 mg%

An increase in blood sugar on an empty stomach of more than 120 mg% indicates the development of diabetes in a patient. Normally, sugar in the urine is not detected, as the kidney filter retains all glucose. And when the level of sugar in the blood is more than 160-180 mg% (8.8-9.9 mmol / l), the kidney filter begins to pass sugar into the urine. Therefore, more or less significant amounts of glucose are excreted in the urine. Its presence in the urine can be determined using special test strips. The minimum blood sugar level at which it begins to be detected in the urine is called the "kidney threshold". Since the figures given in the table are interpreted differently by various medical institutions and authors, to obtain an accurate result, it is recommended to conduct the following test:

• On an empty stomach to determine the level of sugar in the blood.
• Drink 75 grams of grape sugar, diluted in 300 ml of boiled water.
• After 60 minutes to determine the level of sugar in the blood.
• After 120 minutes, determine the blood sugar level.

The test is considered negative, i.e. not confirming the diagnosis of diabetes, if in the blood taken on an empty stomach the sugar level is below 120 mg%, and in the blood taken after 120 minutes it is below 140%. If at the first measurement the sugar level is higher than 129 mg%, and when measured after 2 hours it is higher than 200 mg (11.1 mmol / l), then this result confirms that the patient has diabetes. This means that you should immediately consult a doctor!