Forxiga, 10 mg, film-coated tablets, 30 pieces, AstraZeneca UK Ltd. buy in Moscow at a low price

Forxiga, 30 pcs., 10 mg, film-coated tablets

Use in patients with impaired renal function

The effectiveness of dapagliflozin is dependent on renal function, and this effectiveness is reduced in patients with moderate renal impairment and is likely absent in patients with severe renal impairment. Among patients with moderate renal impairment (creatinine clearance <60 mL/min or estimated GFR <60 mL/min/1.73 m2), a greater proportion of patients receiving dapagliflozin experienced increased creatinine, phosphorus, PTH concentrations, and hypotension. patients receiving placebo. Forxiga™ is contraindicated in patients with moderate or severe renal impairment (creatinine clearance <60 mL/min or estimated GFR <60 mL/min/1.73 m2). Forxiga™ has not been studied in severe renal impairment (creatinine clearance <30 mL/min or estimated GFR <30 mL/min/1.73 m2) or end-stage renal disease.

It is recommended to monitor kidney function as follows:

- before starting therapy with dapagliflozin and at least once a year thereafter;

- before starting to take concomitant medications that may reduce renal function, and periodically thereafter;

- if kidney function is impaired, close to moderate severity, at least 2-4 times a year. If renal function decreases below a CK value <60 ml/min or an estimated GFR <60 ml/min/1.73 m2, it is necessary to stop taking dapagliflozin.

Use in patients with liver dysfunction

Clinical studies have provided limited data on the use of the drug in patients with impaired liver function. Exposure to dapagliflozin is increased in patients with severe hepatic impairment.

Use in patients at risk of reducing blood volume, developing arterial hypotension and/or electrolyte imbalance

In accordance with the mechanism of action, dapagliflozin increases diuresis, accompanied by a slight decrease in blood pressure. The diuretic effect may be more pronounced in patients with very high blood glucose concentrations.

Dapagliflozin is contraindicated in patients taking loop diuretics or in patients with decreased blood volume, for example due to acute illnesses (such as gastrointestinal diseases).

Caution should be exercised in patients for whom dapagliflozin-induced blood pressure reduction may pose a risk, such as patients with a history of cardiovascular disease, patients with a history of hypotension receiving antihypertensive therapy, or elderly patients.

When taking dapagliflozin, careful monitoring of blood volume and electrolyte concentrations (for example, physical examination, blood pressure measurement, laboratory tests, including hematocrit) is recommended against the background of concomitant conditions that may lead to a decrease in blood volume. If there is a decrease in blood volume, it is recommended to temporarily stop taking dapagliflozin until this condition is corrected.

Ketoacidosis

During post-marketing use of the drug, ketoacidosis has been reported, incl. diabetic ketoacidosis, in patients with type 1 and type 2 diabetes mellitus taking Forxiga™ and other SGLT2 inhibitors, although a cause-and-effect relationship has not been established. Forxiga™ is not indicated for the treatment of patients with type 1 diabetes mellitus.

Patients taking Forxiga™ with signs and symptoms suggestive of ketoacidosis, including nausea, vomiting, abdominal pain, malaise, and shortness of breath, should be monitored for ketoacidosis, even if blood glucose concentrations are below 14 mmol/L. If ketoacidosis is suspected, discontinuation or temporary discontinuation of Forxiga™ should be considered and the patient should be assessed immediately.

Factors predisposing to the development of ketoacidosis include low β-cell function due to impaired pancreatic function (eg, type 1 diabetes mellitus, pancreatitis, or history of pancreatic surgery), decreased insulin dosage, decreased calorie intake, or increased need for insulin due to infections, illness or surgery, or alcohol abuse. Forxiga® should be used with caution in such patients.

Urinary tract infections

In an analysis of pooled data from dapagliflozin use up to 24 weeks, urinary tract infections were reported more frequently with dapagliflozin 10 mg compared to placebo. The development of pyelonephritis was noted infrequently, with a similar frequency in the control group. Renal excretion of glucose may be accompanied by an increased risk of urinary tract infections, so temporary discontinuation of dapagliflozin therapy should be considered when treating pyelonephritis or urosepsis.

Urosepsis and pyelonephritis. Serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients taking Forxiga and other SGLT2 inhibitors have been reported during post-marketing use of the drug. Therapy with SGLT2 inhibitors increases the risk of developing urinary tract infections. Patients should be monitored for signs and symptoms of urinary tract infections and treated promptly if indicated.

Elderly patients

Elderly patients are more likely to have impaired renal function and/or use of antihypertensive drugs that may affect renal function, such as ACE inhibitors and angiotensin II type 1 receptor antagonists (ARAs). For elderly patients, the same recommendations for renal impairment apply as for all patient populations.

In patients aged ≥65 years, a higher proportion of patients receiving dapagliflozin experienced adverse reactions related to renal impairment or renal failure compared with placebo. The most common adverse reaction associated with renal impairment was an increase in serum creatinine concentration, most cases were transient and reversible.

In elderly patients, the risk of a decrease in blood volume may be higher, and the use of diuretics is more likely. A larger proportion of patients aged ≥65 years who received dapagliflozin experienced adverse reactions associated with a decrease in blood volume.

Experience with the drug in patients aged 75 years and older is limited. It is contraindicated to initiate dapagliflozin therapy in this population.

Chronic heart failure

Experience with the drug in patients with NYHA class I-II chronic heart failure is limited, and during clinical trials, dapagliflozin was not used in patients with NYHA class III-IV chronic heart failure.

Increased hematocrit value

An increase in hematocrit has been observed with the use of dapagliflozin, and therefore caution should be exercised in patients with elevated hematocrit values.

Urine test results estimates

Due to the drug's mechanism of action, urine glucose test results will be positive in patients taking Forxiga™.

Effect on the determination of 1,5-anhydroglucitol

Assessing glycemic control by measuring 1,5-anhydroglucitol is not recommended because measuring 1,5-anhydroglucitol is unreliable in patients taking SGLT2 inhibitors. Alternative methods should be used to assess glycemic control.

Impact on the ability to drive vehicles and operate machinery

No studies have been conducted to study the effect of dapagliflozin on the ability to drive vehicles and operate machinery.

Use of the drug Forxiga in patients with chronic heart failure

In 2021, The New England Journal of Medicine published an article on the use of Forxiga in patients with chronic heart failure.

Chronic heart failure is a serious, life-threatening, progressive disease with disabling, complex symptoms.

The antidiabetic drug Forxiga (dapagliflozin) has been shown to improve outcomes in patients with heart failure. This sodium-glucose cotransporter type 2 inhibitor may be the first in its class to break out of diabetes therapy alone.

Forxiga is now approved for the treatment of heart failure (class II - IV) with reduced ejection fraction in order to reduce the risk of death from cardiovascular complications or hospitalization due to heart failure. The drug can be used regardless of the presence or absence of type 2 diabetes mellitus. The corresponding approval was issued by the US Food and Drug Administration.

The phase III DAPA-HF clinical trial (randomized, placebo-controlled, multicenter, international) included patients (4744) with class II-IV heart failure with reduced left ventricular ejection fraction (≤40%) with both type 2 diabetes mellitus and not suffering.

Inclusion criteria: increased level of brain natriuretic peptide (NT-proBNP) to at least 600 pg/ml - or at least 400 pg/ml in case of hospitalization for heart failure in the last 12 months. In patients with atrial fibrillation or flutter, NT-proBNP levels were required to be at least 900 pg/ml, regardless of the presence or absence of a previous hospitalization.

Subjects were given daily dapagliflozin or placebo on top of standard drug therapy for heart failure.

In the dapagliflozin group, the study showed a 25% reduction in the likelihood of negative outcomes in patients with heart failure, regardless of the presence or absence of type 2 diabetes in the subjects.

A 30 percent reduction in the risk of a first episode of worsening heart failure and an 18 percent reduction in death from cardiovascular complications was found.

The specific mechanism of action of dapagliflozin in nondiabetic patients is unclear, but the drug is thought to have a protective effect on renal function and modify cardiometabolism.

Forxiga 10 mg No. 30 tablets

Content

Indications Dosage regimen Side effects Contraindications for use Use during pregnancy and lactation Use for impaired liver function Use for impaired renal function Use for children Use for elderly patients Special instructions Overdose Drug interactions Storage conditions Shelf life

Indications

Type 2 diabetes mellitus in addition to diet and exercise to improve glycemic control as:

monotherapy;
addition to therapy with metformin, sulfonylurea derivatives (including in combination with metformin), thiazolidinediones, dipeptidyl peptidase 4 (DPP-4) inhibitors (including in combination with metformin), insulin preparations (including in combinations with one or two oral hypoglycemic drugs) in the absence of adequate glycemic control on this therapy;
starting combination therapy with metformin, if this therapy is appropriate.

Dosage regimen

The drug is taken orally, regardless of food intake.

Monotherapy: the recommended dose of Forxiga™ is 10 mg 1 time/day.

Combination therapy: the recommended dose of Forxiga™ is 10 mg 1 time / day in combination with metformin, sulfonylurea derivatives (including in combination with metformin), thiazolidinediones, DPP-4 inhibitors (including in combination with metformin ), insulin preparations (including in combination with one or two hypoglycemic drugs for oral use).

In order to reduce the risk of hypoglycemia, when Forxiga™ is co-administered with insulin preparations or drugs that increase insulin secretion (for example, with a sulfonylurea derivative), it may be necessary to reduce the dose of insulin preparations or drugs that increase insulin secretion.

Initial combination therapy with metformin: the recommended dose of Forxiga™ is 10 mg 1 time/day, the dose of metformin is 500 mg 1 time/day. In case of inadequate glycemic control, the dose of metformin should be increased.

For mild or moderate liver dysfunction, there is no need to adjust the dose of the drug. For patients with severe liver dysfunction, an initial dose of 5 mg is recommended. If well tolerated, the dose can be increased to 10 mg.

The effectiveness of dapagliflozin depends on renal function. In patients with moderate renal impairment, the effectiveness of treatment is reduced, and in patients with severe impairment, it is most likely absent. Forxiga™ is contraindicated in patients with moderate to severe renal impairment (creatinine clearance <60 ml/min or GFR <60 ml/min/1.73 m2) or end-stage renal disease. For mild renal dysfunction, no dose adjustment is required.

The safety and effectiveness of dapagliflozin have not been studied in patients under 18 years of age.

In elderly patients, no dose adjustment is required. However, when choosing a dose, it should be taken into account that in this category of patients, renal dysfunction and the risk of a decrease in blood volume are more likely. Since clinical experience with the drug in patients aged 75 years and older is limited, initiation of dapagliflozin therapy in this age group is contraindicated.

Side effect

Infections and infestations: vulvovaginitis, balanitis and similar infections of the genital organs, urinary tract infection, vulvovaginal itching.
Metabolism: Hypoglycemia (when used in combination with a sulfonylurea derivative or insulin), decreased blood volume, thirst.
From the digestive system: constipation.
From the skin and subcutaneous tissues: increased sweating.
From the musculoskeletal system: back pain.
From the urinary system: dysuria, polyuria, nocturia.
Laboratory and instrumental data: dyslipidemia, increased hematocrit, increased creatinine concentration in the blood, increased urea concentration in the blood.

Contraindications for use

type 1 diabetes mellitus;
diabetic ketoacidosis;
moderate to severe renal failure (GFR <60 ml/min/1.73 m2) or end-stage renal failure;
hereditary lactose intolerance, lactase deficiency and glucose-galactose intolerance;
pregnancy;
breastfeeding period;
children and adolescents under 18 years of age (safety and effectiveness have not been studied);
patients taking loop diuretics, or with a reduced volume of blood volume, for example, due to acute diseases (such as gastrointestinal diseases);
elderly patients aged 75 years and older (to initiate therapy);
increased individual sensitivity to any component of the drug.

With caution: severe liver failure, urinary tract infections, risk of decreased blood volume, elderly patients, chronic heart failure, increased hematocrit.

Use during pregnancy and breastfeeding

Due to the fact that the use of dapagliflozin during pregnancy has not been studied, the drug is contraindicated in this category of patients. If pregnancy is diagnosed, dapagliflozin therapy should be discontinued.

It is unknown whether dapagliflozin and/or its inactive metabolites are excreted in breast milk. A risk to newborns/infants cannot be excluded. Dapagliflozin is contraindicated during breastfeeding.

Use for liver dysfunction

For mild or moderate liver dysfunction, there is no need to adjust the dose of the drug.

Use with caution in patients with severe liver failure; an initial dose of 5 mg is recommended. If well tolerated, the dose can be increased to 10 mg.

Use for renal impairment

For mild renal dysfunction, there is no need to adjust the dose of the drug.

Forxiga™ is contraindicated in patients with moderate to severe renal failure (creatinine clearance <60 ml/min or GFR <60 ml/min/1.73 m2) or end-stage renal disease.

Use in children

The use of the drug is contraindicated in children and adolescents under 18 years of age.

Use in elderly patients

In elderly patients there is no need to adjust the dose of the drug. However, when choosing a dose, it should be taken into account that in this category of patients, renal dysfunction and the risk of a decrease in blood volume are more likely.

Since clinical experience with the drug in patients 75 years of age and older is limited, initiation of dapagliflozin therapy in this age group is contraindicated.

special instructions

Use in patients with impaired renal function

The effectiveness of dapagliflozin is dependent on renal function, and this effectiveness is reduced in patients with moderate renal impairment and is likely absent in patients with severe renal impairment. Among patients with moderate renal impairment (creatinine clearance <60 mL/min or estimated GFR <60 mL/min/1.73 m2), a higher proportion of patients receiving dapagliflozin experienced increased creatinine, phosphorus, PTH concentrations, and hypotension. patients receiving placebo. Forxiga™ is contraindicated in patients with moderate or severe renal impairment (creatinine clearance <60 mL/min or estimated GFR <60 mL/min/1.73 m2). Forxiga™ has not been studied in severe renal impairment (creatinine clearance <30 mL/min or estimated GFR <30 mL/min/1.73 m2) or end-stage renal disease.

It is recommended to monitor kidney function as follows:

before starting dapagliflozin therapy and at least once a year thereafter;

before starting concomitant medications that may reduce renal function, and periodically thereafter;

for renal dysfunction close to moderate severity, at least 2-4 times a year. If renal function decreases below a CK value <60 ml/min or an estimated GFR <60 ml/min/1.73 m2, it is necessary to stop taking dapagliflozin.

Use in patients with liver dysfunction

Clinical studies have provided limited data on the use of the drug in patients with impaired liver function. Exposure to dapagliflozin is increased in patients with severe hepatic impairment.

Use in patients at risk of decreased blood volume, development of arterial hypotension and/or electrolyte imbalance

Dapagliflozin is contraindicated in patients taking loop diuretics or in patients with decreased blood volume, for example due to acute illnesses (such as gastrointestinal diseases).

Ketoacidosis

Urinary tract infections

Elderly patients

Experience with the drug in patients aged 75 years and older is limited. It is contraindicated to initiate dapagliflozin therapy in this population.

Chronic heart failure

Increased hematocrit value

An increase in hematocrit has been observed with the use of dapagliflozin, and therefore caution should be exercised in patients with elevated hematocrit values.

Urine test results estimates

Due to the drug's mechanism of action, urine glucose test results will be positive in patients taking Forxiga™.

Effect on the determination of 1,5-anhydroglucitol

Impact on the ability to drive vehicles and operate machinery

No studies have been conducted to study the effect of dapagliflozin on the ability to drive vehicles and operate machinery.

Overdose

Dapagliflozin is safe and well tolerated in healthy volunteers when administered in single doses up to 500 mg (50 times the recommended dose). Glucose was determined in urine after taking the drug (at least for 5 days after taking a dose of 500 mg), and no cases of dehydration, arterial hypotension, electrolyte imbalance, or clinically significant effect on the QTc interval were detected. The incidence of hypoglycemia was similar to that observed with placebo. In clinical studies in healthy volunteers and patients with T2DM who took the drug in single doses up to 100 mg (10 times the maximum recommended dose) for 2 weeks, the incidence of hypoglycemia was slightly higher than with placebo and was not dose dependent. . The incidence of adverse events, including dehydration or hypotension, was similar to the placebo group, and there were no clinically significant, dose-related changes in laboratory parameters, including serum concentrations of electrolytes and biomarkers of renal function.

Treatment: in case of overdose, maintenance therapy should be carried out, taking into account the patient's condition. Elimination of dapagliflozin by hemodialysis has not been studied.

Drug interactions

Pharmacodynamic interaction

Dapagliflozin may enhance the diuretic effect of thiazide and loop diuretics and increase the risk of dehydration and hypotension.

Hypoglycemia may occur during the use of insulin and drugs that increase insulin secretion. Therefore, in order to reduce the risk of hypoglycemia, when Forxiga™ is co-administered with an insulin drug or a drug that increases insulin secretion, it may be necessary to reduce the dose of the insulin drug or a drug that increases insulin secretion.

Pharmacokinetic interaction

Dapagliflozin is metabolized primarily through glucuronide conjugation by UGT1A9.

In in vitro studies, dapagliflozin did not inhibit the cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and did not induce CYP1A2, CYP2B6 or CYP3A4. Therefore, dapagliflozin is not expected to affect the metabolic clearance of concomitant medications that are metabolized by these isoenzymes.

Effect of other drugs on dapagliflozin

Interaction studies in healthy volunteers, mostly given a single dose of the drug, showed that metformin, pioglitazone, sitagliptin, glimepiride, voglibose, hydrochlorothiazide, bumetanide, valsartan or simvastatin did not affect the pharmacokinetics of dapagliflozin.

After combined use of dapagliflozin and rifampicin, an inducer of various active transporters and drug-metabolizing enzymes, a decrease in systemic exposure (AUC) of dapagliflozin by 22% was observed, with no clinically significant effect on daily renal glucose excretion. It is not recommended to adjust the dose of the drug. Clinically significant effects are not expected when used with other inducers (for example, carbamazepine, phenytoin, phenobarbital).

Following co-administration of dapagliflozin and mefenamic acid (a UGT1A9 inhibitor), a 55% increase in systemic exposure to dapagliflozin was observed, but without a clinically significant effect on 24-hour renal glucose excretion. It is not recommended to adjust the dose of the drug.

Effect of dapagliflozin on other drugs

In interaction studies in mostly single-dose healthy volunteers, dapagliflozin did not affect the pharmacokinetics of metformin, pioglitazone, sitagliptin, glimepiride, hydrochlorothiazide, bumetanide, valsartan, digoxin (P-gp substrate), or warfarin (S-warfarin, substrate isoenzyme CYP2C9), or on the anticoagulant effect assessed by MHO. The use of dapagliflozin in a single dose of 20 mg and simvastatin (a substrate of the CYP3A4 isoenzyme) led to an increase in AUC of simvastatin by 19% and AUC of simvastatin acid by 31%. Increased exposure to simvastatin and simvastatin acid is not considered clinically significant.

Other types of interaction

The effects of smoking, diet, herbal medications and alcohol consumption on the pharmacokinetic parameters of dapagliflozin have not been studied.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C.

Best before date

Shelf life: 3 years. Do not use after the expiration date shown on the packaging.