Sinjardi - Instructions For The Use Of Tablets, Price, Reviews, Analogues

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Sinjardi

Sinjardi: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Synjardy

ATX code: A10BD20

Active ingredient: metformin (Metformin) + empagliflozin (Empagliflozin)

Manufacturer: Boehringer Ingelheim Pharma (Germany)

Description and photo updated: 2018-29-11

Prices in pharmacies: from 2889 rubles.

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Sinjardi is a hypoglycemic agent.

Release form and composition

Sinjardi dosage form - film-coated tablets, oval, biconvex:

• dosage 500 mg + 5 mg: orange-yellow, engraved on one side with "500", on the other - "S5" and the Boehringer Ingelheim symbol;
• dosage 850 mg + 5 mg: yellowish-white color, engraved "850" on one side, on the other - "S5" and the symbol of the company Boehringer Ingelheim;
• dosage 1000 mg + 5 mg: brownish yellow, engraved on one side "1000", on the other - "S5" and the Boehringer Ingelheim symbol;
• dosage 500 mg + 12.5 mg: light brownish-purple, engraved on one side with "500", on the other - "S12" and the Boehringer Ingelheim symbol;
• dosage 850 mg + 12.5 mg: pinkish-white color, engraved on one side with "850", on the other - "S12" and the symbol of Boehringer Ingelheim;
• dosage 1000 mg + 12.5 mg: dark brownish purple, engraved on one side "1000", on the other - "S12" and the Boehringer Ingelheim symbol.

Packaging for the pharmacy chain: 10 pcs. in a blister, 3, 6 or 9 blisters and instructions for the use of Sinjardi in a cardboard box. Hospital packaging: 10 pcs. in a blister, 9 blisters in a cardboard box, 2 packs in plastic wrap with a label.

Composition of 1 film-coated tablet:

• active substances: metformin hydrochloride - 500, 850 or 1000 mg, empagliflozin - 5 or 12.5 mg;
• auxiliary components: anhydrous colloidal silicon dioxide, magnesium stearate, copovidone, corn starch;
• film shell: Opadry yellow (02B220011) (macrogol 400, talc, titanium dioxide, hypromellose 2910, iron oxide yellow oxide) - tablets containing 5 mg of empagliflozin; Opadry violet (02B200006) (talc, macrogol 400, titanium dioxide, hypromellose 2910, iron oxide red dye, iron oxide black dye) - tablets containing 12.5 mg of empagliflozin.

Pharmacological properties

Pharmacodynamics

Metformin hydrochloride

Metformin is a drug from the biguanide class. Its hypoglycemic effect is due to the ability to reduce the basal and postprandial blood glucose concentration. The substance does not stimulate insulin secretion, therefore it does not contribute to the development of hypoglycemia.

The drug has three mechanisms of action:

• inhibition of glycogenolysis and gluconeogenesis, which causes a decrease in glucose synthesis in the liver;
• slowing down the absorption of glucose in the intestine;
• increased utilization of glucose by cells and the sensitivity of peripheral receptors to insulin.

By acting on glycogen synthetase, metformin stimulates intracellular glycogen synthesis. Increases the transport capacity of all types of membrane glucose transporters currently known.

In therapeutic doses, metformin has a positive effect on lipid metabolism, lowers total cholesterol (CS), CS in triglycerides (TGD) and low density lipoproteins (LDL).

Empagliflozin

Empagliflozin is a reversible, highly active, competitive and selective inhibitor of type 2 sodium-dependent glucose transporter with a concentration value that is required to inhibit 50% of the enzyme activity (equal to 1.3 nmol).

The selectivity of empagliflozin is 5000 times that of the sodium-dependent type 1 glucose transporter, which is responsible for the absorption of glucose in the intestine.

It was also found that the drug has a high degree of selectivity against other glucose transporters, which are responsible for glucose homeostasis in various tissues.

Type 2 sodium-dependent glucose transporter is a major transporter protein responsible for the reabsorption of glucose from the glomeruli back into the bloodstream.

In patients with type 2 diabetes mellitus (DM 2), empagliflozin improves glycemic control by reducing renal glucose reabsorption. In this mechanism, the amount of glucose secreted by the kidneys depends on the level of glucose in the blood and the glomerular filtration rate (GFR).

Due to inhibition of the sodium-dependent type 2 glucose transporter in patients with type 2 diabetes and hyperglycemia, excess glucose is excreted by the kidneys.

In clinical studies, it was established: with diabetes mellitus 2, the excretion of glucose by the kidneys increased immediately after taking the first dose of empagliflozin, this effect continued for 24 hours, persisted until the end of the 4-week treatment period and was about 78 g / day (when taking empagliflozin in a daily dose of 25 mg). Due to the increased excretion, an immediate decrease in the plasma glucose concentration occurred.

The drug reduces blood glucose levels both when taken on an empty stomach and after meals.

The insulin-independent mechanism of action of empagliflozin is accompanied by a low risk of hypoglycemia. The effect of the drug does not depend on insulin metabolism and the state of the function of pancreatic P-cells. The beneficial effects of empagliflozin on surrogate markers of P-cell function have been noted, including the ratio of proinsulin to insulin and the model for assessing homeostasis-P (HOMA-P). In addition, due to the additional excretion of glucose by the kidneys, calories are lost, which leads to a decrease in the volume of adipose tissue and a decrease in body weight.

Glucosuria developing while taking empagliflozin is accompanied by a slight increase in urine output, which can cause a moderate decrease in blood pressure (BP).

Clinical trials investigated the effect of empagliflozin on the incidence of cardiovascular complications in patients with type 2 diabetes and a high risk of developing cardiovascular disease (one or more risk factors were taken into account, including peripheral arterial disease, coronary heart disease, and stroke or heart attack). myocardium in history). The patients received standard therapy: hypoglycemic agents and drugs for the treatment of concomitant cardiovascular disease. The primary endpoints of the assessment were cases of non-fatal stroke or myocardial infarction, as well as cases of cardiovascular death. Additional endpoints were chosen: hospitalization for heart failure, development of nephropathy or progressive worsening of nephropathy,general mortality and cardiovascular mortality. Empagliflozin showed a significant reduction in risk for the primary endpoint. The drug reduced the risk of hospitalization for heart failure and also improved overall survival by reducing the risk of cardiovascular death. Also, in the course of a clinical study, a decrease in the risks of developing nephropathy and a progressive deterioration of this disease was noted.

Patients with baseline macroalbuminuria receiving empagliflozin showed a significantly more frequent development of persistent normo- or microalbuminuria compared with placebo (hazard ratio, 1.82; 95% confidence interval, 1.4–2.37).

Pharmacokinetics

Metformin hydrochloride

Once in the gastrointestinal tract (GIT), metformin is absorbed in large volumes. Approximately 20-30% of the dose is not absorbed and is found in feces. The absorption process of the drug is characterized by saturation. The pharmacokinetics of its absorption, presumably, is non-linear.

The maximum plasma concentration (C _max) is approximately 2 μg / ml (15 μmol) and is achieved within 2.5 hours. When used in therapeutic doses, the equilibrium concentration (C _ss) in plasma usually does not exceed 1 μg / ml and is reached within 24-48 hours

In healthy volunteers, the absolute bioavailability is 50-60%. Simultaneous food intake reduces and slows down the absorption of metformin.

The substance is quickly distributed in tissues, almost does not bind to plasma proteins. C _max in blood is lower than in plasma, however, it is reached in about the same time. The drug penetrates into erythrocytes, which probably represent the secondary compartment of metformin distribution. The volume of distribution (V _d) averages 63–276 liters.

Metformin is metabolized to a very weak extent, no metabolites are found in the body. The substance is excreted mainly unchanged by the kidneys. In healthy volunteers, the clearance of metformin is more than 400 ml / min, which is 4 times more than the creatinine clearance (CC). This indicates the presence of active tubular secretion.

The half-life (T _½) is approximately 6.5 hours.

Pharmacokinetics in special cases:

• impaired renal function: the clearance of metformin decreases in proportion to CC, T _½ increases, the plasma concentration of the substance and the risk of its cumulation increase;
• children's age: with a single dose of 500 mg, the pharmacokinetic parameters in children and healthy adults are similar. With repeated administration of a dose of 500 mg 2 times a day for 7 days in children, C _max and AUC (area under the concentration-time curve) decreased by 33 and 40%, respectively, compared with adult patients with diabetes who received metformin 500 mg 2 times a day for 14 days. The clinical significance of these data is limited, since the dose of the drug is selected individually, depending on the parameters of glycemic control.

Empagliflozin

After oral administration, the substance is rapidly absorbed. C _max in blood plasma reaches within 1.5 hours. Further, there is a decrease in plasma concentration in two phases. When taking empagliflozin at a dose of 10 mg, the average AUC value during the period of stable plasma concentration is 1870 nmol · h / l, C _max - 259 nmol / l; at a dose of 25 mg - respectively 4740 nmol · h / l and 687 nmol / l.

The pharmacokinetic parameters of empagliflozin in patients with diabetes mellitus 2 and healthy volunteers are generally similar.

In healthy volunteers, the pharmacokinetics of the drug used at 5 mg 2 times a day and the drug used at a dose of 10 mg once a day are also comparable.

The overall effect of empagliflozin over a 24-hour period was similar when it was taken 5 mg twice a day and 10 mg once a day.

When using empagliflozin at a dose of 5 mg 2 times a day, C _{max is} lower, and the basal concentration of the substance in plasma (C _min) is higher than when taken at a dose of 10 mg 1 time a day.

There were no clinically significant changes in the pharmacokinetic parameters of the drug with simultaneous food intake.

V _d during the period of stable plasma concentration is approximately 73.8 liters.

Binding to erythrocytes of labeled empagliflozin [¹⁴ C] taken orally by healthy volunteers was approximately 36.8%, binding to plasma proteins - 86.2%.

Empagliflozin is metabolized mainly by glucuronidation with the participation of UDP-HT (UGT1A3, UGT1A8, UGT1A9, UGT2B7). The most frequently detected metabolites are three glucuronic conjugates - 2-O, 3-O and 6-O glucuronides, which have a slight systemic effect (no more than 10% of the total effect of empagliflozin).

When empagliflozin is taken 1 time per day, a stable plasma concentration is achieved, as a rule, after the fifth dose. T _½ is approximately 12.4 hours. In healthy volunteers who received orally labeled empagliflozin [¹⁴ C], approximately 95.6% of the dose was excreted: 41.2% through the intestine (mostly unchanged) and 54.4% - kidneys (unchanged - half).

Pharmacokinetics in special cases:

• race, age, sex, body mass index: no significant differences in pharmacokinetic parameters were found;
• liver dysfunction: with mild, moderate and severe liver failure (according to the Child-Pugh classification), the AUC value increases by about 23, 47 and 75%, respectively, and C _max also increases by about 4, 23 and 48%, respectively (compared with patients having normal liver function);
• impaired renal function: with mild (60 <GFR <90 ml / min / 1.73 m ²), moderate (30 <GFR <60 ml / min / 1.73 m ²), severe (GFR <30 ml / min / 1.73 m ²) of the degree and end-stage renal failure, there is an increase in AUC by about 18, 20, 66 and 48%, respectively (compared with patients with normal renal function). Plasma C _{max of} empagliflozin in middle and end-stage renal failure is similar to that in healthy volunteers. With mild and severe renal failure, plasma C _maxabout 20% more than in patients with normal renal function. According to population pharmacological analysis, the total clearance of empagliflozin decreases as the GFR decreases, as a result of which the effect of the drug increases;
• children's age: the pharmacokinetic parameters of empagliflozin in children have not been studied.

Indications for use

Sinjardi is prescribed for type 2 diabetes in adult patients in addition to dietary therapy and exercise to improve glycemic control. Taking the drug is recommended in the following cases:

• conducting previous combination therapy with metformin and empagliflozin in the form of separate drugs;
• unsatisfactory glycemic control of the disease against the background of monotherapy with metformin at the maximum tolerated dose;
• unsatisfactory glycemic control of the disease against the background of the use of metformin in combination with other hypoglycemic drugs (Sinjardi is prescribed as part of combination therapy with the indicated hypoglycemic agents).

Contraindications

Absolute:

• type 1 diabetes mellitus;
• diabetic ketoacidosis;
• diabetic precoma and coma;
• lactic acidosis;
• acute conditions, accompanied by the risk of developing functional impairment of the kidneys, in particular dehydration (with diarrhea or vomiting);
• severe renal failure (GFR <45 ml / min / 1.73 m ²);
• liver failure;
• chronic alcoholism, acute alcohol intoxication;
• adherence to a hypocaloric diet (less than 1000 kcal / day);
• acute and chronic diseases with clinically pronounced manifestations that can cause the development of tissue hypoxia (including respiratory failure, chronic heart failure with unstable hemodynamic parameters, acute heart failure, acute myocardial infarction);
• severe infectious diseases, shock;
• extensive trauma and surgery when insulin therapy is required;
• age under 18 and over 85;
• pregnancy and lactation;
• X-ray or radioisotope studies with the introduction of an iodine-containing contrast agent (period 48 hours before and 48 hours after);
• hypersensitivity to any of the active or auxiliary substances of Sinjardi.

Relative (Sinjardi tablets are used with extreme caution):

• a history of diabetic ketoacidosis;
• renal failure of moderate severity (GFR 45-59 ml / min / 1.73 m ²);
• chronic heart failure with stable hemodynamic parameters;
• diseases of the gastrointestinal tract, in which fluid loss is possible;
• low secretory activity of beta cells of the pancreas, a history of pancreatic disease (for example, pancreatitis, pancreatic surgery);
• alcohol abuse;
• a very low carbohydrate diet;
• urinary tract infections;
• age 75–85 years;
• concomitant use of insulin or sulfonylurea derivatives, diuretics, antihypertensive drugs, nonsteroidal anti-inflammatory drugs;
• the need to reduce the dose of insulin (in the case of combination therapy with insulin).

Sinjardi, instructions for use: method and dosage

Sinjardi tablets should be taken orally with meals.

Adults with normal renal function (GFR> 90 ml / min) are prescribed 1 tablet 2 times a day.

The doctor adjusts the specific dosages of active substances in the preparation and the dosage regimen individually, taking into account the nature of the current hypoglycemic therapy, its effectiveness and tolerance.

Sinjardi can be prescribed in a maximum daily dose containing 2000 mg of metformin and 25 mg of empagliflozin.

For patients who have unsatisfactory glycemic control with metformin monotherapy or the use of metformin in combination with other hypoglycemic agents, the Sinjardi dose is selected so that the metformin dose remains the same, and the empagliflozin dose is 5 mg 2 times a day. With good tolerance of empagliflozin in a daily dose of 10 mg and maintaining the need to improve the control of hypoglycemia, it is possible to increase the daily dose of empagliflozin to 25 mg.

For patients who have previously taken empagliflozin as monotherapy, the Sinjardi dose is determined so that the dose of this substance in its composition remains the same.

For patients who previously received a combination of empagliflozin + metformin in the form of separate drugs, Sinjardi is prescribed in such a dose that the same doses of the two active substances are preserved.

When Sinjardi is prescribed in combination with insulin and / or a sulfonylurea derivative, a lower dose of insulin and / or a sulfonylurea derivative may be used to reduce the risk of hypoglycemia.

In case of mild renal failure, there is no need to adjust the dose, however, before the appointment of Sinjardi and at least once a year during the entire period of treatment, it is necessary to monitor GFR. In elderly patients and if there is an increased risk of further progression of renal failure, it is recommended to monitor renal function more often, for example, every 3–6 months.

If one or more doses are missed, the patient should take the drug as soon as he remembers it, unless this means taking two doses at the same time. The use of a double dose in one day is prohibited.

If none of Sinjardi's dosages is suitable for the patient, it is necessary to stop taking the combined drug and continue therapy with empagliflozin and metformin as separate drugs.

The maximum daily doses of metformin and empagliflozin for patients with renal insufficiency, depending on the value of GFR:

• 60–89 ml / min: metformin - 3000 mg (with a decrease in renal function, a dose reduction is possible), empagliflozin - 25 mg;
• 45-59 ml / min: metformin - 2000 mg (with the initial dose not exceeding 1000 mg), empagliflozin - 10 mg;
• 30–44 ml / min: metformin - 1000 mg (with the initial dose not exceeding 500 mg), empagliflozin - use is not recommended;
• <30 ml / min: metformin - use is contraindicated, empagliflozin - use is not recommended.

Side effects

• from the side of the vessels: infrequently (from ≥ 1/1000 to <1/100) - hypovolemia ¹;
• on the part of metabolism and nutrition: very often (≥ 1/10) - hypoglycemia (when used together with sulfonylurea derivatives or insulin); often (from ≥ 1/100 to <1/10) - thirst ¹; rarely (from ≥ 1/10 000 to <1/1000) - DKA (diabetic ketoacidosis); very rarely (<1/10 000) - lactic acidosis ¹, decreased absorption of vitamin B ₁₂ (with prolonged use of metformin, in rare cases, a significant B ₁₂ deficiency may develop, for example, megaloblastic anemia) ²;
• on the part of the kidneys: often - an increase in urination ¹ and urinary tract; infrequently - dysuria ¹;
• from the liver and biliary tract: very rarely - deviation from the norm of indicators of liver function tests ², hepatitis ²;
• from the gastrointestinal tract: very often - abdominal pain ^{2, 3}, nausea ^{2, 3}, loss of appetite ^{2, 3}, vomiting ^{2, 3}, diarrhea ^{2, 3};
• from the nervous system: often - disturbances in taste ²;
• infectious and parasitic diseases: often - urinary tract infections (including pyelonephritis and urosepsis) ¹, balanitis, candidal vaginitis, vulvovaginitis and other genital infections ¹;
• on the part of the skin and subcutaneous tissue: often - skin rashes, itching ^{1, 2}; infrequently - urticaria; very rarely - erythema ²; frequency unknown - angioedema ¹;
• laboratory and instrumental data: often - an increase in the plasma concentration of lipids ¹; infrequently - an increase in hematocrit ¹, a decrease in GFR or an increase in the concentration of creatinine in the blood plasma.

¹ Reactions recorded with empagliflozin monotherapy.

² Reactions reported with metformin monotherapy.

³ Gastrointestinal symptoms, such as abdominal pain, nausea, diarrhea, decreased appetite and vomiting, most often appear at the initial stage of therapy and in most cases disappear spontaneously.

Description of selected adverse reactions:

• hypoglycemia: the incidence of this complication depended on the type of hypoglycemic therapy and was approximately the same for empagliflozin and placebo when used in combination with metformin, in combination with metformin and linagliptin, in a combination of empagliflozin with metformin in patients who had not previously received treatment, when compared with patients who received empagliflozin and metformin as separate drugs and in addition to standard therapy. The incidence of hypoglycemia compared with placebo was higher when empagliflozin was used in combination with sulfonylurea derivatives + metformin (empagliflozin at a dose of 10 mg - 16.1%, empagliflozin at a dose of 25 mg - 11.5%, placebo - 8.4%) or in combination with metformin + insulin (empagliflozin at a dose of 10 mg - 31.3%, empagliflozin at a dose of 25 mg - 36.2%, placebo - 34.7%);
• severe hypoglycemia (requiring medical intervention): severe hypoglycemia developed in no more than 1% of patients, its frequency is comparable to that of empagliflozin and placebo used in combination with metformin, and in the combination of empagliflozin + metformin in patients who had not previously received treatment (compared with patients taking empagliflozin and metformin as separate drugs and in addition to standard therapy). The incidence of severe hypoglycemia with the use of empagliflozin at a dose of 10 mg, empagliflozin at a dose of 25 mg and placebo in combination with metformin and insulin was 0.5, respectively; 0 and 0.5%. When empagliflozin was taken simultaneously with metformin + sulfonylureas, as well as simultaneously with metformin + linagliptin, not a single case of severe hypoglycemia was recorded;
• hypovolemia: the incidence of hypovolemia (manifested by dehydration, decreased blood pressure, orthostatic arterial hypertension, fainting) when using the combination of empagliflozin + metformin was low and comparable to that when taking placebo with metformin (empagliflozin 10 mg + metformin - 0.6%, empagliflozin 25 mg + metformin - 0.3%, placebo + metformin - 0.1%). The glucosuric effect of empagliflozin is accompanied by the development of osmotic diuresis, which can affect hydration in patients ≥ 75 years of age. One report was reported of a decrease in circulating blood volume as an adverse event in patients> 75 years of age (the patient received a combination of empagliflozin 25 mg + metformin);
• increased urination: the frequency of increased urination (symptoms such as polyuria, pollakiuria and nocturia were assessed) is higher with the combination of empagliflozin 10 mg + metformin (3%) and the combination of empagliflozin 25 mg + metformin (2.9%) than with the combination of placebo + metformin (1.4%). The incidence of nocturia is comparable in patients who received empagliflozin + metformin and patients who received placebo + metformin (<1%). The intensity of the increased urination was mild and moderate;
• urinary tract infections: the frequency of their development with the combination of empagliflozin 10 mg + metformin was higher (8.8%) than with the combination of empagliflozin 25 mg + metformin (6.6%) and the combination of placebo + metformin (7.8%) … As with placebo, urinary tract infections have usually been observed in patients with a history of chronic and recurrent urinary tract infections. The severity of infectious diseases is similar to that of patients treated with empagliflozin and placebo. According to the available data, infections were more common in women taking empagliflozin 10 mg + metformin than in women taking placebo. Infections were not observed with the use of empagliflozin 25 mg + metformin. In men, the frequency of infections was low, and the severity was similar in different treatment groups;
• genital infections (vulvovaginitis, candidal vaginitis, balanitis, etc.): the frequency of their development was higher when using a combination of empagliflozin 10 mg + metformin (4%) and a combination of empagliflozin 25 mg + metformin (3.9%) than when taking placebo or placebo + metformin (1.3%). These differences in frequency are less noticeable in men. The intensity of the infections was mild to moderate;
• a decrease in GFR and an increase in the concentration of creatinine in the blood: these indicators were similar when using empagliflozin with metformin and placebo with metformin (decrease in GFR: empagliflozin 10 mg - 0.1%, empagliflozin 25 mg - 0%, placebo - 0.2%; increase the level of creatinine in the blood: empagliflozin 10 mg - 0.5%, empagliflozin 25 mg - 0.1%, placebo - 0.4%). An initial temporary increase in the concentration of creatinine in the blood was noted. Compared to baseline, the mean change after 12 weeks was: empagliflozin 10 mg - 0.02 mg / dl, empagliflozin 25 mg - 0.02 mg / dl. There was also an initial transient decrease in the estimated GFR. Compared to baseline, the mean change after 12 weeks was: empagliflozin 10 mg - 1.46 ml / min / 1.73 m ², empagliflozin 25 mg - 2.05 ml / min / 1.73 m ²… In long-term studies, these changes were usually reversible with continued therapy or after discontinuation.

Overdose

In controlled clinical trials in healthy volunteers who took a single dose of 800 mg empagliflozin (which is 32 times the maximum recommended daily dose), the drug was well tolerated. There is no experience of using empagliflozin in higher doses.

In patients taking metformin at doses up to 85,000 mg, hypoglycemia did not occur, but in some cases this was the cause of the development of lactic acidosis. Thus, a significant overdose of metformin, as well as the presence of concomitant factors, is fraught with the development of lactic acidosis, a condition that requires urgent medical attention. Treatment is carried out in a hospital setting.

In case of taking an excessive dose of Sinjardi, vomiting should be induced (to remove the unabsorbed drug from the gastrointestinal tract). In the future, symptomatic treatment is carried out under the control of vital body functions. The most effective way to eliminate metformin and lactate is hemodialysis. Whether hemodialysis is effective in eliminating empagliflozin has not been established.

special instructions

Diabetic ketoacidosis (DKA)

Cases of DKA development have been reported in patients receiving empagliflozin. This condition is life-threatening and requires urgent hospitalization. In some patients, DKA did not show typical symptoms and was expressed only by a moderate increase in blood glucose levels - up to 14 mmol / L (250 mg / dL).

The likelihood of developing DKA should be taken into account when such nonspecific signs as unmotivated fatigue or drowsiness, disorientation, severe thirst, abdominal pain, nausea, anorexia, vomiting, and difficulty breathing appear. In the event of the occurrence of the described symptoms, regardless of the concentration of glucose in the blood, it is necessary to urgently examine the patient in order to exclude ketoacidosis. If DKA is suspected, Sinjardi is immediately discontinued and appropriate treatment is immediately prescribed.

The risk of developing DKA increases in the following cases: a history of ketoacidosis, severe dehydration, alcohol abuse, pancreatic disease with insulin deficiency (for example, type 1 diabetes mellitus, pancreatic surgery, pancreatitis in history), acute illness, adherence to a very low diet carbohydrate content, decreased insulin dose (including ineffective insulin pump operation). In all these cases, Sinjardi must be used with extreme caution.

In clinical situations that may lead to the development of DKA (for example, with prolonged fasting due to surgery or acute illness), consideration should be given to temporarily discontinuing Sinjardi and monitoring ketoacidosis.

It is not recommended to resume the use of SGLT2 inhibitors in the event that DKA developed against their background, unless an absolutely different causal factor for the development of this complication has not been established.

Lactic acidosis

Lactic acidosis is a very rare but serious metabolic complication that usually manifests itself as impairment of renal function, sepsis, and cardiorespiratory diseases. In acute functional impairment of the kidneys, the accumulation of metformin is noted, which increases the risk of developing lactic acidosis. If dehydration occurs (fever, decreased fluid intake and diarrhea / vomiting), stop taking Sinjardi and contact your doctor.

Along with metformin, it is necessary to use with caution drugs that can significantly impair renal function (for example, diuretics, antihypertensive and nonsteroidal anti-inflammatory drugs).

Other concomitant risk factors for lactic acidosis are: ketosis, poor glycemic control, liver failure, excessive alcohol consumption, prolonged fasting, any condition with hypoxia, and co-administration of drugs that can trigger the development of lactic acidosis.

When prescribing Sinjardi, the doctor must warn all patients about the risk of developing lactic acidosis and inform about its main symptoms: acidotic dyspnea, muscle cramps, abdominal pain, asthenia, hypothermia, and subsequently coma. With the development of any of these conditions, it is recommended to immediately consult a doctor.

When diagnosing, the following changes in laboratory parameters are taken into account: an increase in the concentration of lactate in plasma (> 5 mmol / l), a decrease in blood pH (<7.35), an increase in anion deficiency, an increase in the lactate / pyruvate ratio.

If lactic acidosis is suspected, Sinjardi is canceled and the patient is immediately hospitalized.

Effects on renal function

The effectiveness of empagliflozin depends on the functional state of the kidneys.

Before starting to take Sinjardi and regularly during the period of therapy, it is necessary to determine the GFR.

With the development of conditions that have a negative effect on kidney function, the drug should be canceled.

Effects on liver function

In clinical studies, cases of liver damage have been reported in patients taking empagliflozin. However, the causal relationship of the development of these lesions with the drug intake has not been reliably established.

Effects on heart function

The experience of using Sinjardi in patients with chronic heart failure (CHF) class I – II according to the NYHA (New York Heart Association) classification is limited. Empagliflozin has never been used in clinical trials involving patients with NYHA class III – IV CHF.

The study Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (studying the effect of empagliflozin on the outcomes of cardiovascular diseases and mortality from them in patients with type 2 diabetes mellitus) involved volunteers, among whom 10.1% suffered from heart failure. According to the results, the decrease in mortality due to acute cardiovascular disorders achieved among them was comparable to the same indicator in the general group of study participants.

Thus, Sinjardi can be prescribed to patients with CHF with stable hemodynamic parameters, subject to periodic monitoring of the function of the heart and kidneys.

In CHF with unstable hemodynamic parameters and acute heart failure, Sinjardi is contraindicated due to the content of metformin in its composition.

Risk of reduced circulating blood volume (BCC)

Empagliflozin, due to its mechanism of action, can moderately lower blood pressure. In this regard, Sinjardi should be used with caution in patients for whom a decrease in blood pressure is undesirable, for example, in old age, with cardiovascular diseases or the simultaneous use of antihypertensive drugs.

If, while taking Sinjardi, conditions develop that can lead to fluid loss (for example, gastrointestinal diseases), intensive monitoring of the patient's condition and blood pressure, control of electrolyte balance and hematocrit is required. If necessary, the drug is temporarily canceled until the water balance is restored.

Surgical interventions

If surgery is planned using general, epidural or spinal anesthesia, stop taking Sinjardi 48 hours later. Continuation of treatment is allowed no earlier than 48 hours after surgery or after resumption of oral nutrition and only if the results of re-assessment of renal function indicate no deterioration.

Increased frequency of lower limb amputations

In long-term studies of the use of another inhibitor SGLT2, an increase in the frequency of amputations of the lower extremities (mainly toes) was noted. Whether this effect is common to all members of the SGLT2 inhibitor class is unknown. As with anyone with diabetes, patients taking Sinjardi are advised to regularly take preventive foot care.

Results of laboratory tests of urine

In patients receiving Sinjardi, glucose is determined in urine analysis.

Influence on the ability to drive vehicles and complex mechanisms

Special studies on the influence of Sinjardi on human cognitive and psychophysical functions have not been conducted. However, it is necessary to take into account the risk of hypoglycemia, which may be accompanied by symptoms such as headache, drowsiness, dizziness, irritability, weakness, confusion, sweating, heart palpitations, panic attacks (especially with the simultaneous use of insulin and / or sulfonylurea derivatives). In this regard, during the period of therapy, the necessary precautions should be observed while driving a car and performing potentially dangerous types of work.

Application during pregnancy and lactation

Clinical experience with the use of Sinjardi and its active ingredients separately in pregnant women is limited. In this regard, the use of the drug is contraindicated both during pregnancy and during its planning.

Whether empagliflozin penetrates into breast milk in humans has not been established. In a study on animals, data were obtained on the penetration of the substance into the milk of a lactating female. It is also known that metformin in small amounts passes into breast milk. Sinjardi is prohibited for use during lactation.

Pediatric use

There is a lack of data confirming the safety and efficacy of Sinjardi in childhood and adolescence, so the drug is not used to treat patients under 18 years of age.

With impaired renal function

In mild renal failure, there is no need to adjust the dose, but GFR should be monitored.

With moderate renal impairment, the Sinjardi dose is determined depending on the GFR indicator.

In severe functional disorders (GFR <45 ml / min / 1.73 m ²), the drug is contraindicated.

For violations of liver function

Sinjardi is contraindicated in case of liver dysfunction.

Use in the elderly

The experience of using Sinjardi in patients over the age of 85 is limited, therefore, the drug is contraindicated in such patients.

In people over 75 years old, the drug is used with caution. Due to a possible age-related decrease in renal function, a dose adjustment of metformin may be required. Treatment should be carried out under regular (at least 2-4 times a year) monitoring of renal function (determination of the concentration of creatinine in the blood plasma). It is also necessary to take into account the risk of reducing the BCC.

Drug interactions

There have been no studies of possible drug interactions for Sinjardi. The data of pharmacokinetic studies on the interactions of the active components of the drug separately are described below.

Metformin

Metformin is contraindicated to use simultaneously with iodine-containing X-ray contrast agents. Radiological research with their use in patients with diabetes mellitus and functional liver failure can lead to the development of renal failure and lactic acidosis. Depending on the function of the kidneys, Sinjardi is canceled at least for the duration of the study or 48 hours before its start. Reception can be resumed not earlier than 48 hours after the study, but provided that the renal function during the study is recognized as normal.

It is not recommended to take alcoholic beverages during the period of therapy, since with acute alcohol intoxication the likelihood of developing lactic acidosis increases, especially in the case of liver failure, adherence to a low-calorie diet or malnutrition. You should also avoid taking ethanol-containing drugs.

The simultaneous use of inducers and inhibitors of substrates of the transporter of organic cations 1 and 2 (OCT1 and OCT2) should be avoided. When taking such combinations, it is possible to change the action of metformin:

• OCT1 inhibitors (eg verapamil), OCT1 and OCT2 inhibitors (olaparib, crizotinib) can reduce the hypoglycemic effect of metformin;
• OCT2 inhibitors (including trimethoprim, ranolazine, vandetanib, dolutegravir, isavuconazole, cimetidine) can reduce the excretion of metformin by the kidneys, as a result of which its concentration in blood plasma may increase;
• OCT1 inducers (for example, rifampicin) can enhance the absorption of metformin in the gastrointestinal tract and, as a result, increase its hypoglycemic effect.

Combinations requiring caution:

• loop diuretics: the risk of lactic acidosis increases with concomitant renal failure;
• glucocorticosteroids (GCS) of local and systemic action: glucose tolerance decreases, its concentration in the blood increases, which sometimes leads to the development of ketosis. With the simultaneous use of GCS and after their cancellation, it is necessary to control the level of glucose in the blood and adjust the dose of metformin;
• chlorpromazine in high doses (100 mg per day): the release of insulin decreases, as a result of which the concentration of glucose in the blood increases. When taking the drug and after its withdrawal, control of blood glucose levels and dose adjustment of metformin are required;
• β ₂ -adrenergic agonists, prescribed in the form of injections: β ₂ -adrenergic receptors are stimulated, which increases the level of glucose in the blood. Blood glucose control is necessary, in some cases insulin administration is required;
• danazol: blood glucose levels rise. With the simultaneous use of danazol and after its cancellation, it is necessary to control the level of glucose in the blood and adjust the dose of metformin;
• antihypertensive drugs (with the exception of angiotensin-converting enzyme inhibitors): a decrease in blood glucose levels is possible, which may require a dose adjustment of metformin;
• nifedipine: the absorption of metformin increases and its maximum concentration increases;
• insulin and insulin secretion stimulants (sulfonylurea derivatives): the risk of hypoglycemia may increase. A decrease in their dose is required;
• oral contraceptives, calcium channel blockers, estrogens, sympathomimetics, phenothiazides, phenytoin, isoniazid, glucagon, levothyroxine sodium, nicotinic acid: the hypoglycemic effect of metformin may decrease;
• cimetidine: the rate of elimination of metformin decreases, as a result of which the risk of developing lactic acidosis increases;
• indirect anticoagulants: their effect may be reduced.

In healthy volunteers who received metformin simultaneously with propranolol or ibuprofen, no changes in their pharmacokinetic parameters were observed.

Empagliflozin

Combinations requiring attention:

• thiazide and loop diuretics: it is possible to increase their action, which can lead to the development of arterial hypotension and dehydration;
• insulin and insulin secretion stimulants (sulfonylurea derivatives): the likelihood of developing hypoglycemia increases. A reduction in their doses is required.

According to the assessment of drug interactions in vitro, drug interactions are unlikely to occur with the simultaneous use of the following drugs: drugs that are substrates for CYP450 and UGT1A1 isoenzymes, substrates for P-gp, substrates for organic anionic carriers (OAT1 and OCT2).

The interaction of empagliflozin and inducers of enzymes of the UGT family has not been studied. Due to the potential for a decrease in the effect of empagliflozin, the use of such a combination is not recommended.

According to the assessment of drug interactions in vivo, in healthy volunteers, the pharmacokinetics of empagliflozin does not change with the simultaneous use of the following drugs: metformin, hydrochlorothiazide, warfarin, sitagliptin, pioglitazone, ramipril, linagliptin, torasemide, glimepiride, verapamilastatin. With the combined use of gemfibrozil, rifampicin and probenecid, an increase in the AUC of empagliflozin was observed by 59, 35 and 53%, respectively, but these changes are not considered clinically significant.

Empagliflozin has no significant effect on the pharmacokinetics of the following drugs: metformin, hydrochlorothiazide, warfarin, sitagliptin, glimepiride, simvastatin, linagliptin, pioglitazone, torasemide, ramipril, digoxin, oral contraceptives.

Analogs

Sinjardi's analogues are: Avandamet, Velmetia, Vipdomet, Galvus Met, Glibomet, Glibenfazh, Glukovans, Gluconorm, Metglib, Glimecomb, Amaryl M, Glykambi, Gentadueto, Reduxin Met, Yanumet and others.

Terms and conditions of storage

Store in original packaging at temperatures up to 25 ° C. Keep out of the reach of children.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Sinjardi

There are no reviews on Sinjardi on specialized sites and forums that would allow us to evaluate its effectiveness and portability.

Price for Sinjardi in pharmacies

The approximate price for Sinjardi for a pack of 60 tablets is 2908–3150 rubles.

Sinjardi: prices in online pharmacies

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Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!