Stiglatra (Tablets) Instructions for Use

Marketing Authorization Holder

MSD Pharmaceuticals, LLC (Russia)

Manufactured By

Schering-Plough Labo N.V. (Belgium)

Or

Pfizer Manufacturing Deutschland, GmbH (Germany)

ATC Code

A10BK04 (Ertugliflozin)

Active Substance

Ertugliflozin (Rec.INN registered by WHO)

Dosage Forms

	Stiglatra	Film-coated tablets, 5 mg: 28 or 30 pcs.
		Film-coated tablets, 15 mg: 28 or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets pink, biconvex, triangular in shape, with an engraving “701” on one side, smooth on the other side.

Excipients: microcrystalline cellulose PH 102, lactose monohydrate, sodium carboxymethyl starch (type A), magnesium stearate.

Film coating: Opadry II Pink 33G150000 (hypromellose 2910/hypromellose 6cP, lactose monohydrate, macrogol/PEG 3350, triacetin, titanium dioxide, iron oxide red dye).

7 pcs. – blisters (4) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Film-coated tablets brownish-red, biconvex, triangular in shape, with an engraving “702” on one side, smooth on the other side.

Excipients: microcrystalline cellulose PH 102, lactose monohydrate, sodium carboxymethyl starch (type A), magnesium stearate.

Film coating: Opadry II Red 33G15398 (hypromellose 2910/hypromellose 6cP, lactose monohydrate, macrogol/PEG 3350, triacetin, titanium dioxide, iron oxide red dye).

7 pcs. – blisters (4) – cardboard packs.
10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Hypoglycemic agent for oral administration, sodium-dependent glucose transporter 2 inhibitor

Pharmacological Action

Hypoglycemic agent, inhibitor of sodium-dependent glucose transporter type 2 (SGLT2). It is a potent, selective, and reversible inhibitor of SGLT2. By inhibiting SGLT2, it reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion.

Pharmacokinetics

After a single oral dose of 5 mg and 15 mg, the C_max in plasma (median time to maximum concentration T_max) is reached 1 hour after administration in the fasting state. C_max and AUC in plasma increase dose-proportionally after a single dose from 0.5 mg to 300 mg and after multiple doses from 1 mg to 100 mg. After oral administration of a 15 mg dose, the absolute bioavailability is approximately 100%. The mean V_d at steady state after IV administration is 86 L. Plasma protein binding is 93.6% and is independent of plasma concentration. Metabolism is the primary clearance mechanism for ertugliflozin. The main metabolic pathway is UGT1A9- and UGT2B7-mediated O-glucuronidation to form two glucuronides, which are pharmacologically inactive at clinically significant concentrations. CYP-mediated (oxidative) metabolism of ertugliflozin is minimal (12%). The mean systemic plasma clearance after intravenous administration of a 100 mcg dose was 11 L/h. Based on population pharmacokinetic analysis, the mean T_1/2 in patients with type 2 diabetes mellitus with normal renal function was 17 hours.

Indications

Type 2 diabetes mellitus (as monotherapy in patients for whom metformin is not indicated due to intolerance or contraindications; as combination therapy with metformin, sulfonylurea derivatives, dipeptidyl peptidase-4 (DPP-4) inhibitors (including in combination with metformin) and insulin preparations when adequate glycemic control is not achieved with this therapy).

ICD codes

Dosage Regimen

Take orally once daily, in the morning, with or without food.

Swallow the tablet whole; do not split, crush, or chew.

The recommended starting dose is 5 mg once daily.

For patients requiring additional glycemic control, the dose may be increased to 15 mg once daily.

Assess renal function before initiation. Do not initiate if eGFR is below 60 ml/min/1.73 m².

Monitor renal function periodically during therapy. Discontinue if eGFR is persistently below 45 ml/min/1.73 m² due to loss of efficacy.

When used in combination with insulin or an insulin secretagogue (e.g., sulfonylurea), consider reducing the dose of these concomitant medications to lower the risk of hypoglycemia.

In patients with volume depletion, correct this condition before initiating therapy.

Interrupt therapy in patients hospitalized for major surgical procedures or acute serious illnesses.

Adverse Reactions

Urinary system disorders very common – vulvovaginal fungal infections and other genital fungal infections in women; common – vulvovaginal itching, candidal balanitis and other genital fungal infections in men. frequent urination (pollakiuria, urgent urge to urinate, polyuria, increased diuresis and nocturia); uncommon – dysuria, increased blood creatinine concentration/decreased glomerular filtration rate.

Metabolism and nutrition disorders common – hypoglycemia, thirst, polydipsia; rare – diabetic ketoacidosis.

Cardiovascular system disorders: common – decreased blood volume (arterial hypotension and orthostatic hypotension).

Nervous system disorders presyncope, syncope.

Laboratory parameters changes in serum lipid concentrations, increased hemoglobin concentration, increased blood urea nitrogen concentration.

Contraindications

Hypersensitivity; severe hepatic impairment; renal impairment with eGFR persistently below 45 ml/min/1.73 m² or with CrCl<45 ml/min or patients on dialysis; diabetic ketoacidosis; type 1 diabetes mellitus; children under 18 years of age; pregnancy and breastfeeding period.

With caution

Renal impairment with eGFR below 60 ml/min/1.73 m² or CrCl<60 ml/min.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation (breastfeeding).

Use in Hepatic Impairment

Contraindicated in severe hepatic impairment.

Use in Renal Impairment

Contraindicated in renal impairment with eGFR persistently below 45 ml/min/1.73 m² or with creatinine clearance less than 45 ml/min or patients on dialysis;

With caution: renal impairment with eGFR below 60 ml/min/1.73 m² or creatinine clearance less than 60 ml/min.

Pediatric Use

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

Geriatric Use

With caution in patients over 65 years of age, there may be an increased risk of decreased blood volume.

Special Precautions

Ertugliflozin causes osmotic diuresis, which can lead to a reduction in intravascular volume. In this regard, symptomatic hypotension may be observed after initiation of treatment, especially in patients with renal impairment (eGFR less than 60 ml/min/1.73 m² or creatinine clearance less than 60 ml/min), elderly patients (≥65 years), patients taking diuretics, or patients receiving antihypertensive therapy with a history of hypotension.

The risk of developing diabetic ketoacidosis (DKA) should be assessed in the presence of nonspecific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue, or drowsiness. If such symptoms are present, patients should be immediately examined for ketoacidosis, regardless of blood glucose concentration.
In patients with suspected or diagnosed DKA, treatment should be discontinued immediately.

Treatment of patients hospitalized for major surgical procedures or due to serious acute illnesses, treatment with ertugliflozin should be interrupted.

Safety and efficacy in patients with type 1 diabetes mellitus have not been established, and Ertugliflozin should not be used to treat patients with type 1 diabetes mellitus.

Since the efficacy of ertugliflozin depends on renal function, efficacy is reduced in patients with moderate renal impairment and is likely absent in patients with severe renal impairment; should not be initiated in patients with eGFR below 60 ml/min/1.73 m² or creatinine clearance below 60 ml/min. The drug should be discontinued if eGFR is persistently less than 45 ml/min/1.73 m² or creatinine clearance is persistently less than 45 ml/min, due to reduced efficacy.

Ertugliflozin may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue, which can cause hypoglycemia. Therefore, a reduction in the dose of insulin or the insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with ertugliflozin.

Ertugliflozin increases the risk of genital fungal infections.

Urinary glucose excretion may be associated with an increased risk of urinary tract infections. In most cases, infections were mild to moderate, and no reports of severe cases were received. During treatment of pyelonephritis or urosepsis, temporary discontinuation of ertugliflozin should be considered.

Elderly patients may have an increased risk of decreased blood volume. In patients aged 65 years and older who received ertugliflozin therapy, the frequency of adverse reactions associated with decreased blood volume was higher compared to younger patients.

According to the drug’s mechanism of action, the result of a urine test for glucose in patients taking this drug will be positive. Alternative methods should be used to monitor glycemic control.

Monitoring glycemic control using the 1,5-AG assay is not recommended, as measurement of 1,5-AG is not a reliable way to assess glycemic control in patients taking SGLT2 inhibitors. Alternative methods should be used to monitor glycemic control.

Effect on ability to drive vehicles and operate machinery

Has no effect on the ability to drive vehicles and operate machinery, or has a minor effect. Patients should be warned about the risk of hypoglycemia when using the drug in combination with insulin or an insulin secretagogue and about the increased risk of adverse reactions associated with decreased blood volume, such as postural dizziness.

Drug Interactions

Ertugliflozin may enhance the effect of diuretics and increase the risk of dehydration and arterial hypotension.

Ertugliflozin may increase the risk of hypoglycemia when used in combination with insulin and/or insulin secretagogues. Therefore, a reduction in the dose of insulin or the insulin secretagogue may be required to reduce the risk of hypoglycemia when used in combination with ertugliflozin.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.