Saterex^® (Tablets) Instructions for Use

Marketing Authorization Holder

Saterex LLC (Russia)

Manufactured By

Pharmasintez-Tyumen, LLC (Russia)

ATC Code

A10BH (Dipeptidyl peptidase-4 (DPP-4) inhibitors)

Active Substance

Gosogliptin (Rec.INN registered by WHO)

Dosage Forms

	Saterex®	Film-coated tablets, 20 mg: 28, 30, 56, 60, 70, 84, 90, 98, 112 or 120 pcs.
		Film-coated tablets, 30 mg: 28, 30, 56, 60, 70, 84, 90, 98, 112 or 120 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex; the core of the tablet on the cross-section is white or almost white.

Excipients : microcrystalline cellulose – 173.784 mg, calcium hydrogen phosphate – 86.892 mg, sodium carboxymethyl starch – 9 mg, magnesium stearate – 3 mg, polyvinyl alcohol – 4.8 mg, titanium dioxide – 3 mg, macrogol 4000 – 2.424 mg, talc – 1.776 mg.

7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
7 pcs. – contour cell packs (10) – cardboard packs.
7 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
10 pcs. – contour cell packs (7) – cardboard packs.
10 pcs. – contour cell packs (9) – cardboard packs.
10 pcs. – contour cell packs (12) – cardboard packs.
14 pcs. – contour cell packs (2) – cardboard packs.
14 pcs. – contour cell packs (4) – cardboard packs.
14 pcs. – contour cell packs (5) – cardboard packs.
14 pcs. – contour cell packs (6) – cardboard packs.
14 pcs. – contour cell packs (7) – cardboard packs.
14 pcs. – contour cell packs (8) – cardboard packs.
28 pcs. – jars^x (1) – cardboard packs.
30 pcs. – jars^x (1) – cardboard packs.
60 pcs. – jars^x (1) – cardboard packs.
70 pcs. – jars^x (1) – cardboard packs.
90 pcs. – jars^x (1) – cardboard packs.
120 pcs. – jars^x (1) – cardboard packs.

^x with first opening control

Film-coated tablets white, round, biconvex; the core of the tablet on the cross-section is white or almost white.

Excipients : microcrystalline cellulose – 260.676 mg, calcium hydrogen phosphate – 130.338 mg, sodium carboxymethyl starch – 13.5 mg, magnesium stearate – 4.5 mg, polyvinyl alcohol – 7.2 mg, titanium dioxide – 4.5 mg, macrogol 4000 – 3.636 mg, talc – 2.664 mg.

7 pcs. – contour cell packs (4) – cardboard packs.
7 pcs. – contour cell packs (8) – cardboard packs.
7 pcs. – contour cell packs (10) – cardboard packs.
7 pcs. – contour cell packs (12) – cardboard packs.
10 pcs. – contour cell packs (3) – cardboard packs.
10 pcs. – contour cell packs (6) – cardboard packs.
10 pcs. – contour cell packs (7) – cardboard packs.
10 pcs. – contour cell packs (9) – cardboard packs.
10 pcs. – contour cell packs (12) – cardboard packs.
14 pcs. – contour cell packs (2) – cardboard packs.
14 pcs. – contour cell packs (4) – cardboard packs.
14 pcs. – contour cell packs (5) – cardboard packs.
14 pcs. – contour cell packs (6) – cardboard packs.
14 pcs. – contour cell packs (7) – cardboard packs.
14 pcs. – contour cell packs (8) – cardboard packs.
28 pcs. – jars^x (1) – cardboard packs.
30 pcs. – jars^x (1) – cardboard packs.
60 pcs. – jars^x (1) – cardboard packs.
70 pcs. – jars^x (1) – cardboard packs.
90 pcs. – jars^x (1) – cardboard packs.
120 pcs. – jars^x (1) – cardboard packs.

^x with first opening control

Clinical-Pharmacological Group

Hypoglycemic drug – dipeptidyl peptidase-4 inhibitor

Pharmacotherapeutic Group

Hypoglycemic agent – dipeptidyl peptidase-4 inhibitor

Pharmacological Action

Hypoglycemic agent.

Gosogliptin is an active, highly selective inhibitor of the dipeptidyl peptidase-4 enzyme intended for the treatment of type 2 diabetes mellitus. By inhibiting DPP-4 activity, Gosogliptin increases the concentration of incretin family hormones synthesized in the intestine: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

The increase in GLP-1 and GIP concentrations causes an increase in the sensitivity of pancreatic beta-cells to glucose, leading to increased synthesis and secretion of insulin. The increase in GLP-1 concentration causes an increase in the sensitivity of pancreatic alpha-cells to glucose, leading to improved glucose-dependent regulation of glucagon secretion.

The reduction of elevated glucagon secretion during meals causes a decrease in insulin resistance. The decrease in glucagon concentration against the background of an increase in insulin concentration, due to the increase in GLP-1 and GIP concentrations, causes a decrease in hepatic glucose production, leading to a reduction in blood glucose levels.

In patients with type 2 diabetes mellitus with hyperglycemia, these changes in insulin and glucagon secretion lead to a decrease in glycated hemoglobin HbA1c concentration and a reduction in plasma glucose concentration both fasting and postprandial.

In more than 750 patients with type 2 diabetes mellitus treated with gosogliptin for 12 to 36 weeks as monotherapy or in combination with metformin, a significant long-term reduction in HbA1c, fasting blood glucose, and 2-hour postprandial glucose concentrations was observed.

No significant change in body weight was noted during treatment with gosogliptin; the frequency of hypoglycemic episodes was minimal.

Pharmacokinetics

Gosogliptin is rapidly absorbed after oral administration with an absolute bioavailability of more than 99%. C_max in plasma is reached within 1 hour after administration. Mean plasma concentrations increase proportionally with increasing dose.

The decrease in gosogliptin plasma concentration after reaching C_max is biphasic. After administration of gosogliptin at a dose of 30 mg, the AUC is, on average, 4800-5200 ng×h/ml, with an inter-individual variability coefficient for AUC of 11.5-27.2%.

Food intake increases the absorption rate up to 2 hours, but does not significantly affect the extent of absorption and AUC. Concomitant administration of gosogliptin with metformin does not affect the dynamics of their absorption.

The extent of gosogliptin binding to plasma proteins is 11.5%.

The main metabolic pathway of gosogliptin in humans involves hydroxylation of the pyrimidine group. Other metabolites are associated with amide hydrolysis, carbamoyl glucuronidation, formamide conjugation, glucose conjugation, and creatinine conjugation.

In in vitro studies using human liver microsomal enzymes, low binding constants and inhibition of cytochromes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 by gosogliptin were observed.

Gosogliptin is eliminated from the body primarily by the kidneys. After oral administration, about 77% of the gosogliptin dose is excreted by the kidneys, with 48.5% excreted unchanged.

10.5% of the dose is excreted via the intestine, with a significant portion accounted for by gosogliptin metabolites. T_1/2 after oral administration is about 20 hours.

The renal clearance of the free fraction of gosogliptin with normal renal function is about 45 ml/min after a single 20 mg dose.

Indications

Type 2 diabetes mellitus (in combination with diet therapy and physical exercise): as monotherapy in case of inefficacy of diet therapy and physical exercise in patients with contraindications to the use of metformin; in combination with metformin as initial therapy, or when diet and physical exercise in combination with monotherapy with one of the listed drugs do not lead to adequate glycemic control.

ICD codes

Dosage Regimen

Administer orally once daily in the morning or evening, regardless of meals.

Individualize the dosage regimen based on efficacy and tolerability.

For monotherapy or initial two-component combination therapy with metformin, the recommended starting dose is 20 mg/day.

For patients with mild chronic renal failure (CrCl ≥60 mL/min), no dose adjustment is required.

Use with caution in patients with moderate chronic renal failure (CrCl 30-59 mL/min) due to potential for increased plasma concentration.

Contraindicated in patients with severe chronic renal failure (CrCl <30 mL/min).

No dose adjustment is required for elderly patients or for patients with mild to moderate hepatic impairment.

Contraindicated in patients with severe liver dysfunction (ALT or AST >2.5 times ULN).

Swallow the tablet whole with water; do not split or chew.

If a dose is missed, take it as soon as remembered on the same day; do not double the dose the next day.

Regularly monitor blood glucose and glycated hemoglobin (HbA1c) levels.

Assess renal function before initiation and periodically during treatment.

Adverse Reactions

Immune system disorders uncommon – allergic dermatitis.

Nervous system disorders uncommon – dizziness, headache, drowsiness.

Gastrointestinal disorders uncommon – constipation, diarrhea, dyspepsia, pancreatitis.

Hepatobiliary disorders uncommon – increased activity of liver enzymes (ALT, AST), cholecystitis, steatosis, increased bilirubin, gallbladder polyp.

Renal and urinary disorders uncommon – urinary tract infections.

General disorders uncommon – asthenia, feeling of tiredness, peripheral edema, back pain.

Contraindications

Type 1 diabetes mellitus; diabetic ketoacidosis; severe liver dysfunction; severe chronic renal failure; age under 18 years; pregnancy and breastfeeding period

With caution

In patients with a history of pancreatitis, in patients with moderate chronic renal failure.

Use in Pregnancy and Lactation

Use is contraindicated during pregnancy and breastfeeding.

Use in Hepatic Impairment

Use is contraindicated in severe liver dysfunction.

Use in Renal Impairment

Use is contraindicated in severe chronic renal failure.

Pediatric Use

Use is contraindicated in children under 18 years of age.

Geriatric Use

No dose adjustment is required in elderly patients.

Special Precautions

Use in patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis is contraindicated.

In patients with mild chronic renal failure, dose reduction is not required. Due to the possibility of increased gosogliptin plasma concentration in patients with moderate renal failure, it is recommended to use with caution in these patients.

Use in patients with severe renal failure is not recommended due to limited experience of use in this patient group.

Use in patients with severe liver dysfunction (ALT or AST >2.5 times ULN) is not recommended due to limited experience of use in this category of patients.

Effect on ability to drive vehicles and operate machinery

During medication use, the risk of hypoglycemia development must be taken into account. If dizziness develops during treatment, patients should not drive vehicles or operate machinery.

Drug Interactions

Since Gosogliptin is not a substrate of liver microsomal enzymes, and does not inhibit or induce these enzymes, interaction of gosogliptin with drugs that are substrates, inhibitors, or inducers of liver microsomal enzymes is unlikely.

No clinically significant interaction of gosogliptin with drugs most commonly used in the treatment of type 2 diabetes mellitus has been established.

Concomitant use of gosogliptin with insulin, sulfonylurea derivatives, thiazolidinediones and other hypoglycemic drugs, except metformin, has not been studied.

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.