Stiglathra, 5 mg 28 pcs.

Pharmacotherapeutic group: oral hypoglycemic agent – inhibitor of sodium-dependent glucose transporter type 2.

CODATH: A10VCO4

PHARMACOLOGICAL PROPERTIES

Mechanism of action

The sodium-dependent glucose transporter type 2 (NGLT2) is the predominant transporter responsible for reabsorption of glucose from glomerular filtrate back into the bloodstream. Ertugliflozin is a potent, selective and reversible inhibitor of NGLT2. By inhibiting NGLT2, ertugliflozin reduces renal reabsorption of filtered glucose and decreases the renal threshold for glucose, thereby increasing glucose excretion by the kidneys.

Pharmacodynamics

Kidney glucose excretion and urine volume

Dose-dependent increases in glucose excretion by the kidneys were observed in healthy volunteers and in patients with type 2 diabetes after single and multiple doses of ertugliflozin. Modeling of the dose-response relationship showed that ertugliflozin at doses of 5 mg and 15 mg resulted in near maximal renal glucose excretion in patients with type 2 diabetes, providing 87% and 96% of maximal inhibition, respectively.

Pharmacokinetics

The pharmacokinetic parameters of ertugliflozin are similar in healthy volunteers and in patients with type 2 diabetes. Mean equilibrium values of area under the curve “concentration-time” (AUC) and maximum concentration (Cmax) in plasma were 398 ng/h/ml and 81 ng/ml, respectively, when using ertugliflozin 5 mg once daily, 1193 ng/h/ml and 268 ng/ml when using ertugliflozin 15 mg once daily. An equilibrium state is reached after 4-6 days of administration of once-daily ertugliflozin. Ertugliflozin has no time-dependent pharmacokinetic parameters and accumulates in plasma up to 10-40% after repeated administration.

Eabsorption

After single oral administration of ertugliflozin at doses of 5 mg and 15 mg, maximum ertugliflozin plasma concentration (median of time to reach maximum concentration Tmax) is reached 1 hour after drug intake on an empty stomach. Plasma concentrations and AUC of ertugliflozin increase dose-proportionally after a single dose of 0.5 mg to 300 mg and after multiple doses of 1 mg to 100 mg. After oral administration of ertugliflozin at a dose of 15 mg the absolute bioavailability is approximately 100%.

Entake of ertugliflozin with a high-fat, high-calorie diet decreases ertugliflozin Stache by 29% and increases Tmax by 1 hour, but has no effect on AUC compared to fasting food intake. The observed effect of food on the pharmacokinetic parameters of ertugliflozin is not considered clinically significant, and ertugliflozin can be taken regardless of food intake. In phase 3 clinical trials, ertugliflozin was administered regardless of food intake.

Ertugliflozin is a substrate of the p-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters.

Distribution

The mean volume of distribution of ertugliflozin in equilibrium after intravenous administration is 86 L. The degree of binding of ertugliflozin to plasma proteins is 93.6% and is independent of the plasma concentration of ertugliflozin. The degree of binding of ertugliflozin to plasma proteins does not change significantly in patients with renal impairment or hepatic impairment. The ratio of ertugliflozin concentrations in blood to plasma concentrations is 0.66.

Ertugliflozin is not a substrate of organic anion transporters (OATl, OATZ), organic cation transporters (OCTl, OCT2) or organic anion transporter polypeptides (OATl1B1, OATlBZ) in vitro.

Metabolism

Metabolism is the main clearance mechanism for ertugliflozin. The major metabolic pathway for ertugliflozin is UGT1A9- and UGT2B7-mediated O-glucuronidation to form two glucuronides, which are pharmacologically inactive at clinically relevant concentrations. SUR-mediated (oxidative) metabolism of ertugliflogin_m:1shimal,1:1( 12%).

Elevation

The mean systemic clearance of ertugliflozin from blood plasma after an intravenous dose of 100 mcg was 11 L/hour. Based on population pharmacokinetic analysis, the mean half-life in patients with type 2 diabetes mellitus with normal renal function was 17 hours.

After oral administration of [¹⁴C]-ertugliflozin solution by healthy volunteers, approximately 41% and 50% of the radioactive isotope bound to the drug were excreted through the gut and kidneys, respectively. Only 1.5% of the dose taken was excreted as unchanged ertugliflozin by the kidneys and 34% as unchanged ertugliflozin through the intestine, which is probably due to biliary excretion of the glucuronide metabolites and their subsequent hydrolysis to the parent substance.

Particular patient groups

Renal dysfunction

. In a phase 1 clinical pharmacology study in patients with type 2 diabetes mellitus and mild, moderate, or severe renal impairment (based on calculated glomerular filtration rate (rGFR)), the AUC of ertugliflozin was on average increased by :;;1.7-fold compared with patients with normal renal function.

These increases in the AUC of ertugliflozin are not considered clinically significant. No clinically significant differences in the Cmax values of ertugliflozin among groups of patients with different renal function have been reported. Daily renal glucose excretion decreased with increasing severity of renal function impairment. The degree of ertugliflozin binding to plasma proteins did not change in patients with impaired renal function.

Hepatic impairment

Moderate hepatic impairment (according to Child-Pugh classification) did not lead to increased exposure to ertugliflozin. The AUC value of ertugliflozin was reduced by approximately 13% and the Cmax value was reduced by approximately 21% compared to patients with normal liver function. This decrease in ertugliflozin exposure is not considered clinically significant.

There is no experience with the clinical use of ertugliflozin in patients with severe hepatic impairment (Child-Pugh class C). The degree of binding of ertugliflozin to plasma proteins did not change in patients with moderate hepatic impairment.

In children

The pharmacokinetics of ertugliflozin in children has not been studied.

The influence of age, body weight, sex and race

In a population pharmacokinetic analysis, there was no clinically significant effect of age, body weight, sex and race on the pharmacokinetics of ertugliflozin.

Drug interactions

In vitro evaluation of ertugliflozin

. In in vitro studies, ertugliflozin and ertugliflozin glucuronides neither inhibited nor inactivated 1A2, 2C9, 2C19, 2C8, 2Bb, 2D6, or ZA4 cytochrome 450 isoenzymes (CPR) nor induced 1A2, 2B6, or ZA4 CPR. Ertugliflozin and ertugliflozin glucuronides did not inhibit UDF-glucuronosyltransferase (UGT) ІAb, 1A9 or 2B7 activity in vitro.

Ertugliflozin was a weak inhibitor of UGT lAl and 1A4 in vitro at higher concentrations with no clinical significance. Ertugliflozin glucuronides had no effect on these isoforms. In general, the effect of ertugliflozin on the pharmacokinetics of concomitantly used drugs that are excreted by these enzymes seems unlikely.

Ertugliflozin and ertugliflozin glucuronides do not significantly inhibit P-gp, OAT2, OATl or OATZ transporters or OATPlBl and OATPlB transport polypeptides at clinically relevant concentrations in vitro. In general, the effect of ertugliflozin and ertugliflozin glucuronides on the pharmacokinetics of concomitantly used drugs that are substrates of these transporters seems unlikely.

Indications

Stiglathra is indicated for use in patients with type 2 diabetes mellitus aged 18 years and older in addition to diet and exercise to improve glycemic control:

Active ingredient

Composition

1 film-coated tablet contains:

Dosage 5 mg:

The active ingredient: ertugliflozin L-pyroglutamic acid 6.477 mg equivalent to 5.000 mg of ertugliflozin.

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

The film coating: Opadray II Pink 330150000.

The composition of Opadray II Pink ZZG150000: hypromellose 2910 / hypromellose bsR, lactose monohydrate, macrogol/PEG 3350, triacetin, titanium dioxide, iron oxide red dye.

How to take, the dosage

Orally.

How to use

Stigltra should be taken orally once daily in the morning, regardless of meals. If you have difficulty swallowing, the tablet may be broken or crushed because the drug is in immediate release dosage form.

Dosing regimen

The recommended starting dose of Stiglathra is 5 mg once daily in the morning, regardless of meals. In patients who tolerate Stiglathra 5 mg once daily, the dose may be increased to 15 mg once daily if glycemic control is required.

When using ertugliflozin in combination with insulin or insulin secretagogue preparation, lower doses of insulin or insulin secretagogue preparation may be required to reduce the risk of hypoglycemia.

In patients with decreased circulating blood volume (CBV), it is recommended that this condition be corrected before starting ertugliflozin.

If a dose is missed, it should be taken as soon as possible after the patient remembers it. Two doses of Stiglathra should not be taken on the same day.

Patient special groups

Kidney function impairment

It is recommended that renal function be assessed before starting therapy with Stiglathra and periodically during treatment.
Patients with a RRF less than 60 ml/min/1.73 m2 or with a creatinine clearance of less than 60 ml/min are not recommended to start therapy with Stiglathra.

Stiglathra should be discontinued if the rSKF is consistently less than 45 mL/min/1.73 m2 or the creatinine clearance is consistently less than 45 mL/min.

Stiglathra should not be used in patients with severe renal impairment, end-stage renal disease (ESRD), or patients on dialysis, since the drug is expected to be ineffective in these patients.

Hepatic impairment

Dose adjustment is not required for patients with mild to moderate hepatic impairment. The use of ertugliflozin has not been studied in patients with severe hepatic impairment and is not recommended in this group of patients.

Elderly patients P- 65 years)

Elderly patients do not require dose adjustment of ertugliflozin depending on age. Renal function and risk of decreased blood circulation should be taken into account. There is limited experience with Stiglathra in patients aged 75 years.

Children

The safety and efficacy of ertugliflozin in children under 18 years of age have not been studied. No data are available.

Interaction

Pharmacodynamic interaction

Diuretics

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

Insulin and insulin secretagogue preparations

Insulin and insulin secretagogue preparations (such as sulfonylurea preparations) are known to cause hypoglycemia. Ertugliflozin may increase the risk of hypoglycemia when used in combination with insulin and/or insulin secretagogue preparations. In this regard, it may be necessary to reduce the dose of insulin or insulin secretagogue preparations to reduce the risk of hypoglycemia when they are used in combination with ertugliflozin.

Pharmacokinetic interaction

The effect of other drugs on the pharmacokinetics of ertugliflozin Metabolism involving the UGTIA9 and UGT2B7 isoenzymes is the primary mechanism of ertugliflozin clearance.

The single-dose interaction studies with healthy volunteers suggest that sitagliptin, metformin, glimepiride or simvastatin do not alter the pharmacokinetics of ertugliflozin. Administration of multiple doses of rifampicin (an inducer of UGT and SAR) reduces the AUC and Stach of ertugliflozin by 39% and 15%, respectively. This reduction in exposure is not considered clinically significant and therefore no dose adjustment is recommended. Interactions with other inducers (e.g., carbamazepine, phenytoin, phenobarbital) are not expected to have a clinically significant effect.

The effect of UGT inhibitors on the pharmacokinetics of ertugliflozin has not been studied clinically, but a possible increase in ertugliflozin exposure due to UGT inhibition is not considered clinically significant.

Effects of ertugliflozin on the pharmacokinetics of other drugs Interaction studies with healthy volunteers suggest that ertugliflozin has no clinically significant effect on the pharmacokinetics of sitagliptin, metformin and glimepiride.

The co-administration of simvastatin and ertugliflozin resulted in a 24% and 19% increase in AUC and Stach of simvastatin, respectively, and a 30% and 16% increase in AUC and Stach of simvastatin, respectively. The mechanism of insignificant increase in simvastatin and simvastatinic acid parameters is unknown and is not the result of OATP inhibition by ertugliflozin. Such an increase is not considered to be clinically significant.

Special Instructions

Hypotension/reduction of O.UK

Ertugliflozin causes osmotic diuresis, which may lead to a reduction in intravascular volume. Because of this, symptomatic hypotension may occur after initiation of Stiglathra, especially in patients with impaired renal function

The rSCOF m,less-.bO-msmin/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. Before initiating therapy with Stiglathra, it is necessary to assess the state of blood pressure and, if necessary, perform its correction. Signs and symptoms should be monitored after initiation of therapy.

Owing to its mechanism of action, ertugliflozin induces osmotic diuresis, increases serum creatinine concentration and decreases rCP. Increase in serum creatinine concentration and decrease in rSKF were more pronounced in patients with mild to moderate renal dysfunction.

In the presence of conditions that may lead to fluid loss (e.g., gastrointestinal disease), close monitoring of CBC and electrolyte concentrations is recommended in patients receiving ertugliflozin (e.g., physical examination, blood pressure measurement, laboratory diagnosis, including hematocrit determination). Consideration should be given to temporarily discontinuing ertugliflozin therapy until fluid loss is corrected.

Diabetic ketoacidosis (DKA)

Rare cases of DKA, including life-threatening and fatal cases, have been reported in clinical trials and in the post-registration period in patients treated with NGLT2 inhibitors. Cases of DKA have been reported in clinical trials with ertugliflozin. Atypical development of the condition with only moderately elevated blood glucose concentrations (below 14 mmol/L (250 mg/dL)) has been observed in some cases.

It is unknown whether DKA may occur more frequently with higher doses of ertugliflozin.

The risk of diabetic ketoacidosis should be evaluated if nonspecific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue, or drowsiness occur. Patients should be immediately evaluated for ketoacidosis if these symptoms are present, regardless of blood glucose concentration.

In patients with suspected or diagnosed DKA, treatment with ertugliflozin should be discontinued immediately.

The treatment of patients hospitalized for extensive surgical procedures or due to serious acute illness should be interrupted. In both cases, treatment with ertugliflozin may be resumed after the patient’s condition has stabilized.

Before initiating therapy with ertugliflozin, consider factors in the patient’s history that may predispose to ketoacidosis.

. Patients at increased risk of developing DKA include those with low functional beta cell reserve (e.g., patients with type 2 diabetes with low C-peptide concentration or latent adult autoimmune diabetes (LADA) or patients with a history of pancreatitis), patients with conditions that result in restricted food intake or severe dehydration, patients who have had their insulin doses reduced, and patients who require increased insulin doses due to acute illness, surgery, or alcohol abuse.

HGLT2 inhibitors should be used with caution in this category of patients.

Resumption of NHLT2 inhibitor therapy in patients with a history of DKA on NHLT2 therapy is not recommended unless the other causative factor is clearly identified and resolved.

The safety and efficacy of ertugliflozin in patients with type 1 diabetes have not been established, and ertugliflozin should not be used to treat patients with type 1 diabetes. Limited data from clinical: studies suggest that DKA occurs frequently when treating patients with type 1 diabetes with NGLT2 inhibitors.

AMPU!SH!II of the lower extremities

In long-term clinical: studies with another NGLT2 inhibitor, there has been an increase in lower extremity (mainly toe) amputations. It is not known whether this is a class effect. As with all patients with diabetes mellitus, it is important to advise patients receiving ertugliflozin therapy on regular preventive foot care.

Renal dysfunction

As the efficacy of ertugliflozin depends on renal function, efficacy is reduced in patients with moderate renal dysfunction and probably absent in patients with severe renal dysfunction.

The drug Stiglathra should not be started in patients with a pSFR below 60 mL/min/1.73 m2 or a creatinine clearance below 60 mL/min. Stiglathra should be discontinued if rSKF is consistently less than 45 mL/min/1.73 m2 or creatinine clearance is consistently less than 45 mL/min, due to decreased efficacy.

It is recommended that renal function be monitored as follows:

Before starting ertugliflozin and periodically throughout treatment;

Frequently in patients with a pSFR below 60 mL/min/1.73 m2 or a creatinine clearance below 60 mL/min.

Hypoglycemia when concurrently using with/u> insulin or drugs secretagogues of insulin

Ertugliflozin may increase the risk of hypoglycemia when used in combination with insulin and/or insulin secretagogue drugs, which may cause hypoglycemia. Therefore, it may be necessary to reduce the dose of insulin or insulin secretagogue preparation to minimize the risk of hypoglycemia when used in combination with ertugliflozin.

Fungal genital infections

Ertugliflozin increases the risk of fungal genital infections. In studies with NGLT2 inhibitors, fungal genital infections were more likely to develop in patients with a history of fungal genital infections and in uncircumcised men. Patients should be closely monitored and treated appropriately.

Urinary tract infections

Glucose excretion by the kidneys may be accompanied by an increased risk of urinary tract infections. The incidence of urinary tract infections was not significantly different in the ertugliflozin 5 mg 15 mg groups (4.0% and 4.1%) and in the placebo group (3.9%). Most of the infections were of mild to moderate severity; there were no reports of severe cases. During treatment of pyelonephritis or urosepsis, temporary discontinuation of ertugliflozin should be considered.

Elderly patients

In elderly patients there may be an increased risk of decreased BOD. Patients aged 65 years and older who received ertugliflozin therapy had a higher incidence of adverse reactions associated with decreased RBC compared to younger patients. The efficacy of ertugliflozin in elderly patients with impaired renal function is expected to be reduced.

Heart failure

There is limited experience with New York Heart Association (NHA) class I-II heart failure; there is no clinical trial experience with NHA class III-IV heart failure.

Laboratory urinalysis

In accordance with the mechanism of action of the drug, the result of urinalysis for the presence of glucose in the urine in patients taking Stiglathra will be positive. Alternative methods should be used to monitor glycemic control. Effect on analysis for 1,5-anhydroglucitol{1,5-AH)

Monitoring of glycemic control using the l,5-AH assay is not recommended because measurement of 1,5-AH is not a reliable way to assess glycemic control in patients taking NGLT2 inhibitors. Alternative methods should be used to monitor glycemic control.

Impact on the ability to control TransportabilityMECHANISMS

. Ertugliflozin has no or negligible effect on the ability to drive vehicles and operate machinery. Patients should be cautioned about the risk of hypoglycemia when using Stiglathra in combination with insulin or insulin secretagogue drug and the increased risk of adverse reactions associated with decreased RBC, such as postural dizziness.

Synopsis

Pink biconvex triangular-shaped, film-coated tablets with “701” engraved on one side and smooth on the other.

Contraindications

WARNING

sup>2 or creatinine clearance less than 60 mL/min (for initiation of therapy). .

Side effects

Summary of p.Q.Q.f_il safety

Summarized data from placebo-controlled studies evaluating the safety of Stiglathra 5 mg and 15 mg.

The primary safety assessment was based on data from three 26-week placebo-controlled studies.

Ertugliflozin was used as monotherapy in one study and as adjunctive therapy in two studies. In these studies, 1,029 patients received ertugliflozin with a mean duration of therapy of about 25 weeks. Patients received ertugliflozin at a dose of 5 mg (N = 519), ertugliflozin at a dose of 15 mg

(N = 51O), or placebo (N = 515) once daily.

The most commonly reported adverse reactions during clinical trials were vulvovaginal fungal infections and other fungal infections of the female genitalia. Severe diabetic ketoacidosis has rarely been reported.

Table of adverse reactions

The adverse reactions listed below are classified according to frequency and systemic organ class. The frequency categories are defined as follows: very common( 1/10), common( 1/100 and< 1/10), infrequent ( 1/1000 and< 1/100), rare (::: 1/1OO and < 1/1OO), very rare (< 1/1OO), unknown (cannot be estimated from available data).

Very common Vulvovaginal fungal
infections and other fungal
genital infections in women,
Candida balanitis and other Frequent fungal genital infections
in men,

Frequent Hypoglycemia

Rarely Diabetic ketoacidosis

Frequent Decreased CPR

Often Increased frequency of urination
Infrequent Dysuria, increased blood
creatinine concentration/ decreased glomerular filtration rate

p> Often Vulvovaginal itching

Often Thirst

Often Changes in serum lipid concentration
increase in hemoglobin concentration.

Description of individual adverse reactions

Decreased CPR

The administration of ertugliflozin causes osmotic diuresis, which may lead to decreased intravascular volume and adverse reactions associated with decreased CPR. According to generalized data from placebo-controlled studies, the incidence of adverse events associated with decreased CPR (dehydration, postural dizziness, preconsciousness, syncope, hypotension and orthostatic hypotension) was low (< 2%) and was not significantly different in the ertugliflozin and placebo groups.

In a subgroup analysis of a larger volume of phase 3 studies, patients with rSFR < 60 mL/min/1.73 m2, patients aged 2′: 65 years, and patients taking diuretics had a higher rate of CPR reduction in the ertugliflozin groups than in the comparison drug groups. In patients with a pSCF,

< 60 mL/min/1.73 m2 the incidence was 5.1%, 2.6%, and 0.5% in the 5-mg dose ertugliflozin, 15-mg dose ertugliflozin, and comparison drug groups; In patients with a pSCF of 45 to

< 60 mL/min/1.73 m2 the incidence was 6.4%, 3.7%, and 0%, respectively.

Hypoglycemia

The incidence of reported hypoglycemia was higher in the 5 mg and 15 mg ertugliflozin groups (5.0% and 4.5%) compared with the placebo group (2.9%), according to summarized data from placebo-controlled studies. In this population, the incidence of severe hypoglycemia was 0.4% in each group.

The incidence of hypoglycemia was 2.6% in both ertugliflozin groups and 0.7% in the placebo group when receiving ertugliflozin as monotherapy. When receiving ertugliflozin in combination with metformin, the incidence of hypoglycemia was 7.2% in the 5-mg ertugliflozin group, 7.8% in the 15-mg ertugliflozin group, and 4.3% in the placebo group.

When comparing the combination of ertugliflozin and metformin with sulfonylurea drugs, the incidence of hypoglycemia was higher in patients taking sulfonylurea drugs (27%) compared with patients taking ertugliflozin (5.6% and 8.2% in the 5 mg and 15 mg ertugliflozin groups, respectively).

In patients with moderate renal dysfunction receiving insulins, sulfonylureas, or meglitinides as background therapy, the rates of reported hypoglycemia were 36%, 27%, and 36% in the 5 mg ertugliflozin, 15 mg ertugliflozin, and placebo groups, respectively.

Diabetic ketoacidosis

In the clinical program, ketoacidosis was detected in 3 of 3409 patients (0.1%) treated with ertugliflozin and in none of the patients (0.0%) treated with comparison drugs.

Elevated blood creatinine concentration/decreased glomerular filtration rate and renal function-related phenomena

In patients treated with ertugliflozin, there was generally a temporary initial increase in mean creatinine concentration and decrease in mean pGFR during continuous treatment. Patients with baseline renal dysfunction of moderate severity had large changes in mean values that did not return to baseline at week 26; these changes returned to baseline after discontinuation of treatment.

. Adverse reactions related to renal function (e.g., acute kidney injury, impaired renal function, acute prerenal renal failure) may occur in patients receiving ertugliflozin therapy, especially in patients with moderate renal dysfunction with rates of adverse reactions related to renal function of 2.5%, 1.3%, and 0.6% in patients in the ertugliflozin 5 mg, ertugliflozin 15 mg, and placebo groups, respectively.

Fungal genital infections

According to generalized data from three placebo-controlled studies, fungal genital infections in women (narI,i:> p, genital candidiasis, fungal genital infection, vaginal infection, vulvovaginal candidiasis, vulvovaginal fungal infection, and vulvovaginitis) were observed in 9.1%, 12%, and 3.0% of women receiving ertugliflozin at 5 mg, ertugliflozin at 15 mg, and placebo, respectively. Treatment interruption for fungal genital infections was required in 0.6% and 0% of women receiving ertugliflozin and placebo, respectively.

In the same data set, fungal genital infections in men (e.g., candida balanitis, balanopostitis, genital infection, fungal genital infection) occurred in 3.7%, 4.2%, and 0.4% of men receiving ertugliflozin at 5 mg, ertugliflozin at 15 mg, and placebo, respectively. Fungal genital infections occurred more frequently in uncircumcised men.

Treatment interruption for fungal genital infections was required in 0.2% and 0% of men receiving ertugliflozin and placebo, respectively. Phimosis was rarely reported, and in some cases circumcision was performed.

Overdose

Any oral administration of single doses up to 300 mg and multiple doses up to 100 mg daily for 2 weeks in healthy volunteers showed no evidence of ertugliflozin toxicity. No potential acute symptoms or signs of overdose were identified.

In the event of an overdose, the usual supportive measures (e.g., removal of unabsorbed substance from the gastrointestinal tract, clinical monitoring, and prescribing supportive treatment) should be applied based on the patient’s clinical condition. Removal of ertugliflozin by hemodialysis has not been studied.

Pregnancy use

Pregnancy

There are limited data on the use of ertugliflozin in pregnant women. Based on the results of studies in animals, ertugliflozin may affect renal development and maturation. Therefore, the use of Stiglitra during pregnancy is contraindicated.

Breastfeeding

There is no information about the presence of ertugliflozin in human breast milk, about the effect on the breastfed child or about the effect on breast milk production. Ertugliflozin was present in the milk of lactating rats and had effects on offspring, lactating rats. Pharmacologically mediated effects were observed in immature rats.

With human renal maturation occurring in utero and during the first 2 years of life, when exposure through breast milk is possible, risks to neonates and children cannot be excluded. The use of Stiglathra during breastfeeding is contraindicated.

Fertility

The effect of ertugliflozin on human fertility has not been studied. No effect on fertility has been observed in animal studies.