Forsiga
Forsiga: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Forxiga
ATX code: A10BX09
Active ingredient: Dapagliflozin (Dapagliflozin)
Producer: AstraZeneca Pharmaceuticals LP (USA), Bristol-Myers Squibb Manufacturing Company (Humacao) (Puerto Rico)
Description and photo update: 2018-27-07
Prices in pharmacies: from 2003 rubles.
Buy
Forsiga is an oral hypoglycemic drug.
Release form and composition
The dosage form of Forsiga is film-coated tablets: yellow, biconvex; 5 mg each - round, on one side engraved with "5", on the other - "1427"; 10 mg - diamond-shaped, on one side engraved with "10", on the other - "1428" (10 pcs. in blisters, in a cardboard box of 3 or 9 blisters; 14 pcs. in blisters, in a cardboard box 2 or 4 blister).
Composition of 1 tablet:
- active substance: dapagliflozin - 5 or 10 mg (dapagliflozin propanediol monohydrate - 6.15 or 12.3 mg, respectively);
- auxiliary components (5/10 mg): microcrystalline cellulose - 85.725 / 171.45 mg; anhydrous lactose - 25/50 mg; crospovidone - 5/10 mg; silicon dioxide - 1.875 / 3.75 mg; magnesium stearate - 1.25 / 2.5 mg;
- shell (5/10 mg): Opadry II yellow (partially hydrolyzed polyvinyl alcohol - 2/4 mg; titanium dioxide - 1.177 / 2.35 mg; macrogol 3350 - 1.01 / 2.02 mg; talc - 0.74 / 1.48 mg; dye iron oxide yellow - 0.073 / 0.15 mg) - 5/10 mg.
Pharmacological properties
Active substance Forsiga - dapagliflozin, is a powerful [inhibition constant (K i) - 0.55 nM] selective reversible inhibitor of the sodium glucose cotransporter type 2 (SGLT2), which is selectively expressed in the kidneys, and in more than 70 other body tissues (including liver, skeletal muscle, adipose tissue, mammary glands, bladder and brain) is not detectable.
SGLT2 is the main transporter involved in the reabsorption of glucose in the renal tubules. In type 2 diabetes mellitus (T2DM), reabsorption of glucose in the renal tubules continues, despite hyperglycemia. Dapagliflozin, inhibiting the renal transfer of glucose, reduces its reabsorption in the renal tubules, which leads to the excretion of glucose by the kidneys. As a result of the action of dapagliflozin in patients with T2DM, the concentration of glucose on an empty stomach and after a meal decreases, and the concentration of glycosylated hemoglobin also decreases.
The glucosuric effect (excretion of glucose) is observed after taking the first dose of Forsiga, the effect persists for the next 24 hours and continues throughout the entire period of use. The amount of glucose excreted by the kidneys through this mechanism depends on the glomerular filtration rate (GFR) and the concentration of glucose in the blood. Dapagliflozin does not disturb the normal production of endogenous glucose in response to hypoglycemia. The action of the substance does not depend on insulin secretion and sensitivity to it. In clinical studies, Forsiga noted an improvement in β-cell function.
Dapagliflozin-induced excretion of glucose by the kidneys is accompanied by loss of calories and weight loss. Inhibition of sodium-glucose cotransport occurs with weak transient natriuretic and diuretic effects.
Dapagliflozin has no effect on other glucose transporters that transport glucose to peripheral tissues. The substance shows more than 1400 times more selectivity for SGLT2 than for SGLT1, which is the main transporter in the intestine responsible for glucose absorption.
Pharmacodynamics
According to the data of clinical trials, with T2DM against the background of a long course (up to 2 years) in a daily dose of 10 mg, glucose excretion was maintained throughout the entire period of taking the drug.
The excretion of glucose by the kidneys also leads to osmotic diuresis and an increase in urine volume that persists for 12 weeks (375 ml / day). The increase in urine volume was accompanied by a transient and insignificant increase in sodium excretion by the kidneys, which did not lead to changes in serum sodium concentration in the blood.
Also, according to the research results, it was found that the use of the drug leads to a decrease in systolic and diastolic blood pressure (SBP and DBP) by 3.7 and 1.8 mm Hg. Art. (respectively) at 24 weeks of taking 10 mg of dapagliflozin per day in comparison with the placebo group (decrease in SBP and DBP by 0.5 mm Hg). A similar effect was observed during 104 weeks of treatment.
When using 10 mg of dapagliflozin per day in patients with type 2 diabetes with arterial hypertension and inadequate glycemic control, receiving angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, including in combination with other antihypertensive drugs, after 12 weeks of therapy compared with placebo a decrease in the glycosylated hemoglobin index by 3.1% and a decrease in SBP by 4.3 mm Hg were noted. Art.
Pharmacokinetics
Dapagliflozin after oral administration is completely and rapidly absorbed from the gastrointestinal tract. It is possible to take the drug both during meals and outside of it. C max (maximum concentration of the substance) dapagliflozin in blood plasma, as a rule, is achieved within 2 hours after taking on an empty stomach. The C max and AUC (area under the concentration-time curve) values increase in proportion to the dose received. The absolute bioavailability of the substance when taken orally at a dose of 10 mg is 78%. In healthy volunteers, food intake has a moderate effect on the pharmacokinetics of dapagliflozin. Eating a meal with a high fat content decreased the C max of dapagliflozin by 50%, lengthened the T max(time to reach maximum concentration) in plasma for about 1 hour, but had no effect on AUC compared to fasting. These changes are not clinically significant.
Plasma protein binding of dapagliflozin is approximately 91%. Renal / liver dysfunctions and other diseases do not affect this indicator.
Dapagliflozin is a C-linked glucoside, the aglycone of which is linked to glucose by a carbon-carbon bond. The substance is metabolized to predominantly form dapagliflozin-3-O-glucuronide (an inactive metabolite).
61% of the dose taken after oral administration of 50 mg of 14 C-dapagliflozin is metabolized to dapagliflozin-3-O-glucuronide (it accounts for 42% of the total plasma radioactivity). The share of the unchanged drug is 39% of the total plasma radioactivity, the rest of the metabolites individually - up to 5%. Dapagliflozin-3-O-glucuronide and other metabolites have no pharmacological effect.
The average T 1/2 (half-life) from plasma in healthy volunteers is 12.9 hours after a single dose of 10 mg of dapagliflozin. Excretion of the substance and its metabolites occurs mainly by the kidneys, less than 2% - unchanged. After taking 50 mg of 14 C-dapagliflozin, 96% of radioactivity is detected (in urine - 75%, in feces - 21%). Approximately 15% of the radioactivity found in feces is unchanged dapagliflozin.
At steady-state (mean AUC), the systemic exposure of dapagliflozin in patients with T2DM and mild, moderate or severe renal failure was 32%, 60% and 87% higher, respectively, than in normal renal function. The amount of glucose that is excreted by the kidneys within 24 hours when dapagliflozin is taken in an equilibrium state depends on the state of renal function. In patients with T2DM and normal renal function and mild, moderate or severe renal failure, 85, 52, 18 and 11 g of glucose are excreted per day, respectively. Differences in the binding of dapagliflozin to proteins in healthy volunteers and in patients with renal insufficiency of varying severity were not found. It is not known whether hemodialysis affects dapagliflozin exposure.
With mild or moderate hepatic impairment, the mean C max and AUC values of dapagliflozin were 12% and 36% (respectively) higher in comparison with healthy volunteers (they have no clinical significance). With severe liver failure, the average values of these indicators are 40% and 67% higher (respectively).
In patients over 65 years of age, an increase in exposure can be expected, which is associated with decreased renal function.
The average AUC at steady state in women is 22% higher than that in men.
With increased body weight, lower exposure values are noted (of no clinical significance).
Indications for use
Forsyga is prescribed for the treatment of type 2 diabetes as an adjunct to diet and exercise to improve glycemic control.
The drug can be used as follows:
- monotherapy;
- starting combination therapy with metformin (if this combination is appropriate);
- addition to treatment with metformin, thiazolidinediones, sulfonylurea derivatives (including in combination with metformin), dipeptidyl peptidase 4 (DPP-4) inhibitors (including in combination with metformin), insulin preparations (including in combined with one or two oral hypoglycemic drugs) in cases of lack of adequate glycemic control.
Contraindications
Absolute:
- hereditary glucose-galactose intolerance, lactose intolerance, lactase deficiency;
- type 1 diabetes mellitus;
- end-stage renal failure or moderate / severe renal failure (GFR <60 ml / min / 1.73 m 2);
- diabetic ketoacidosis;
- combination therapy with loop diuretics or reduced blood volume associated, for example, with acute illness (such as gastrointestinal disease);
- age up to 18 years;
- age from 75 years (to start using);
- pregnancy and the period of breastfeeding;
- individual intolerance to the components of the drug.
Relative (Forsiga is prescribed under medical supervision):
- increased hematocrit;
- chronic heart failure;
- severe liver failure;
- the risk of a decrease in the volume of circulating blood;
- urinary tract infections;
- elderly age.
Instructions for the use of Forsiga: method and dosage
Forsyga is taken orally. Food intake has no effect on the effectiveness of therapy.
The recommended dosage regimen is 10 mg once a day.
When carrying out combination therapy with insulin preparations or drugs that increase insulin secretion (in particular, with sulfonylurea derivatives), their dose may need to be reduced.
If Forsiga is used in the starting combination therapy with metformin, its daily dose is 500 mg in 1 dose. In case of inadequate glycemic control, the dose of metformin is increased.
The initial dose for severe hepatic impairment is 5 mg. With good tolerance, it is possible to use Forsiga 10 mg.
Side effects
Dizziness, urinary tract infections, nausea, rash, increased concentration of creatinine in the blood are among the most common adverse events leading to the cancellation of Forsiga. In one case, the development of an undesirable liver phenomenon (autoimmune and / or drug hepatitis) was noted. Most often, hypoglycemia occurred during therapy.
Possible adverse reactions (> 10% - very common;> 1% and 0.1% and <1% - infrequently):
- urinary system: often - dysuria, polyuria; infrequently - nocturia;
- digestive system: infrequently - constipation;
- musculoskeletal system: often - back pain;
- invasions / infections: often - balanitis, vulvovaginitis and similar infections of the genital organs, urinary tract infection; infrequently - vulvovaginal itching;
- instrumental / laboratory data: often - dyslipidemia, increased hematocrit; infrequently - an increase in the concentration of urea and creatinine in the blood;
- skin / subcutaneous tissue: infrequently - increased sweating;
- metabolism: very often - hypoglycemia (when used in combination with a sulfonylurea derivative or insulin); infrequently - thirst, a decrease in the volume of circulating blood.
Overdose
According to the instructions, Forsiga is a safe drug; when taken once in doses up to 500 mg by healthy volunteers, it is well tolerated. In case of overdose, the incidence of adverse events, including arterial hypotension or dehydration, is similar to that in the placebo group, with no clinically significant, dose-dependent changes in laboratory parameters.
In cases of overdose, supportive therapy should be carried out taking into account the patient's condition. The elimination of dapagliflozin by hemodialysis has not been studied.
special instructions
The effectiveness of Forsiga depends on renal function: in patients with moderate renal insufficiency, it is reduced, and in severe disease it is probably absent.
It is recommended to monitor the functional state of the kidneys as follows: before the start of taking Forsiga, subsequently - at least once a year; before you start taking concomitant medications that can affect renal function, then periodically; in patients with renal impairment close to moderate severity - at least 2-4 times a year, with a decrease in creatinine clearance <60 ml / min, or estimated GFR <60 ml / min / 1.73 m 2, the drug is canceled.
In severe liver dysfunctions, the exposure to dapagliflozin is increased.
At very high blood glucose concentrations, the diuretic effect may be more pronounced.
Patients for whom a decrease in blood pressure caused by dapagliflozin may be a risk, for example, with a burdened history of cardiovascular diseases, arterial hypotension, as well as during antihypertensive therapy and in elderly patients, care should be taken during therapy.
While taking Forsiga, it is recommended to carefully monitor the volume of circulating blood and electrolyte concentrations (in particular, physical examination, laboratory tests, including hematocrit, blood pressure measurement) against the background of concomitant conditions that can cause a decrease in this indicator. When it decreases until the correction of this condition, a temporary cessation of therapy is indicated.
If during the period of therapy symptoms such as abdominal pain, nausea, shortness of breath, malaise, vomiting appear, it is necessary to check the patient for ketoacidosis (even in cases of blood glucose concentration up to 14 mmol / l). If you suspect the development of this disorder, you should consider the possibility of cancellation / short-term cessation of the use of Forsiga and immediately conduct an examination.
The main factors predisposing to the development of ketoacidosis include a decrease in insulin dose, low functional activity of β-cells due to dysfunction of the pancreas, a decrease in calorie intake or an increased need for insulin due to infection, disease, alcohol abuse or surgery. The drug should be administered with caution to this group of patients.
When glucose is excreted by the kidneys, there may be an increased risk of urinary tract infections, and therefore, when treating urosepsis or pyelonephritis, the possibility of temporarily canceling Forsig should be considered.
With post-registration use, serious urinary tract infections have been reported, including the development of urosepsis and pyelonephritis, which required hospitalization of patients taking Forsyga and other SGLT2 inhibitors. Since the likelihood of urinary tract infections increases during therapy with SGLT2 inhibitors, the condition of patients should be monitored for the development of such infections. If the diagnosis is confirmed, immediate treatment is required.
The experience of using Forsyga in patients with chronic heart failure of I – II functional class according to NYHA classification is limited, during clinical trials the drug was not used in patients with chronic heart failure of III – IV class.
Due to the mechanism of action of Forsiga during therapy, the results of a urine glucose test will be positive.
It is not recommended to assess glycemic control using the determination of 1,5-anhydroglucitol, as the measurement of 1,5-anhydroglucitol is an unreliable method for patients taking SGLT2 inhibitors. For the purpose of assessing glycemic control, alternative methods should be used.
Application during pregnancy and lactation
The safety profile has not been studied; therefore, Forsiga is not prescribed to pregnant and breastfeeding women.
Pediatric use
The safety profile has not been studied, therefore, the drug is not prescribed to patients under 18 years of age.
With impaired renal function
Patients with end-stage renal failure or moderate / severe renal failure (with creatinine clearance <60 ml / min or GFR <60 ml / min / 1.73 m 2) are contraindicated to take Forsyga.
For violations of liver function
In severe hepatic impairment, therapy should be administered with caution.
Use in the elderly
The safety profile of Forsiga has not been studied; therefore, patients over 75 years of age are contraindicated to start therapy.
Drug interactions
Possible interactions:
- thiazide and loop diuretics: increasing their diuretic effect and increasing the likelihood of arterial hypotension and dehydration;
- insulin and drugs that increase insulin secretion: the development of hypoglycemia; the combination requires caution and, possibly, dose adjustment of these drugs.
Analogs
There is no information about Forsiga analogues.
Terms and conditions of storage
Store at temperatures up to 30 ° C. Keep out of the reach of children.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Forsyge
According to reviews, Forsiga is an effective drug used to remove glucose from the body. In some cases, therapy allows you to completely abandon insulin. However, many note the development of severe adverse reactions, including too frequent urination, exacerbation of inflammatory diseases of the genitourinary system, sleep disturbances, itching, fever, and shortness of breath.
Price for Forsyga in pharmacies
The approximate price for Forsyga 10 mg (30 tablets per pack) is 1470–2580 rubles.
Forsiga: prices in online pharmacies
|
Drug name Price Pharmacy |
|
Forsiga 10 mg film-coated tablets 30 pcs. 2003 RUB Buy |
|
Forsiga tab. p / o captivity. 10mg No. 30 2062 RUB Buy |
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!
