Included in the formulation
Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):VED
АТХ:A.10.B.X Other hypoglycemic drugs
A.10.B.X.09 Dapaglyflozin
Pharmacodynamics:Dapagliflozin is a selective reversible inhibitor of the sodium-glucose cotransporter of the second type (SGLT2). SGLT2 is selectively expressed in the kidneys and is responsible for more than 90% of the glucose reabsorption in the kidneys. The block of this transporter leads to the release of glucose in the urine. The effect of dapagliflozin is to reduce fasting and post-prandial glucose and reduce the concentration of glycosylated hemoglobin in patients with type 2 diabetes mellitus. The effect of dapagliflozin is independent of insulin secretion and insulin sensitivity.
Pharmacokinetics:After oral administration dapagliflozin quickly and completely absorbed in the gastrointestinal tract and can be taken both during meals and outside it. The maximum concentration of dapagliflozin in blood plasma (Cmax) is usually achieved within 2 hours after taking an empty stomach. Absolute bioavailability of dapagliflozin when administered in a dose of 10 mg is 78%. Eating high in fat reduced Cmax dapagliflozin by 50%, lengthened Tmax (time to reach the maximum concentration in the plasma) for about 1 hour.
Dapagliflozin is approximately 91% bound to proteins. The mean half-life from blood plasma was 12.9 hours after a single dose of dapagliflozin inside at a dose of 10 mg. After ingestion, 61% of the dose taken is metabolized in the liver. Dapaglyflozin and its metabolites are excreted mainly by the kidneys, and only less than 2% is excreted unchanged.
Indications:Diabetes mellitus type 2 in addition to diet and exercise to improve glycemic control as:
- monotherapy;
- addition to metformin therapy in the absence of adequate glycemic control in this therapy;
- starting combination therapy with metformin, if this therapy is appropriate.
IV.E10-E14.E11 Non-insulin-dependent diabetes mellitus
Contraindications:- increased individual sensitivity to any component of the drug;
- Type 1 diabetes mellitus;
- diabetic ketoacidosis;
- renal failure of moderate and severe severity or terminal stage of renal failure;
- hereditary lactose intolerance, lactase insufficiency and glucose-galactose intolerance;
- pregnancy and the period of breastfeeding;
- Children under 18 years of age (safety and efficacy not studied);
- patients taking "looped" diuretics, or with a reduced volume of circulating blood (eg, due to acute gastrointestinal diseases);
- elderly patients aged 75 years and older (for initiation of therapy).
Carefully:Severe hepatic failure, urinary tract infection, risk of circulating blood loss, elderly patients, chronic heart failure, increased hematocrit, arterial hypotension; Patients, receiving antihypertensive therapy, diabetic ketoacidosis.
Pregnancy and lactation:Category FDA - FROM.
Due to the fact that the use of dapagliflozin during pregnancy has not been studied, the drug is contraindicated during pregnancy. In case of pregnancy diagnosis, dapagliflozin therapy should be discontinued.
It is not known whether the dapagliflozin and / or its inactive metabolites into breast milk. It is impossible to exclude the risk for newborns / infants. Dapaglyflozin contraindicated during breastfeeding.
Dosing and Administration:Inside, regardless of food intake.
Monotherapy: the recommended dose of the drug is 10 mg once a day.
Combination therapy: the recommended dose of the drug is 10 mg once a day in combination with metformin.
Start combination therapy with metformin: the recommended dose of the drug is 10 mg once a day, the dose of metformin is 500 mg once a day. In case of inadequate glycemic control, the dose of metformin should be increased.
Side effects:Disorders from the kidneys and urinary tract: urinary tract infections, dysuria, polyuria.
Disorders from the digestive tract: nausea, constipation.
Disorders from the cardiovascular system: hypotension.
Metabolic and nutritional disorders: hypoglycemia (when used in combination with sulfonylureas or insulin derivatives).
Laboratory and instrumental data: an increase in the concentration of creatinine in the blood, dyslipidemia, an increase in the value of hematocrit, an increase in the concentration of urea in the blood.
Other: dizziness, rash, weight loss.
Overdose:Dapagliflozin is safe and well tolerated. Cases of overdose are not clinically described. In case of an overdose it is necessary to carry out maintenance therapy, taking into account the condition of the patient.
Interaction:Dapagliflozin can enhance the diuretic effect of thiazide and "loop" diuretics and increase the risk of dehydration and arterial hypotension.
After the combined use of dapagliflozin and rifampicin, inducer of various active transporters and enzymes metabolizing drugs, a decrease in the systemic concentration of dapagliflozin by 22% was noted.
Special instructions:It is recommended to monitor kidney function as follows:
- before the start of dapagliflozin therapy and at least once a year afterwards;
- if the kidney function is violated, close to the average severity, at least 2-4 times a year.
With a decrease in the volume of circulating blood, a temporary discontinuation of dapagliflozin before the correction of this condition is recommended.
Impact on the ability to drive vehicles and manage mechanisms
Studies to study the effect of dapagliflozin on the ability to drive vehicles and mechanisms were not conducted.