4.1. Therapeutic indications

Steglatro is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise:

• as monotherapy when metformin is considered inappropriate due to intolerance or contraindications.

• in addition to other medicinal products for the treatment of diabetes.

For study results with respect to combinations of therapies, effects on glycaemic control, cardiovascular events, and the populations studied, see sections 4.4, 4.5, and 5.1.

4.2. Posology and method of administration

Posology

The recommended starting dose of ertugliflozin is 5 mg once daily. In patients tolerating ertugliflozin 5 mg once daily, the dose can be increased to 15 mg once daily if additional glycaemic control is needed.

When ertugliflozin is used in combination with insulin or an insulin secretagogue, a lower dose of insulin or the insulin secretagogue may be required to reduce the risk of hypoglycaemia (see sections 4.4, 4.5, and 4.8).

In patients with volume depletion, correcting this condition prior to initiation of ertugliflozin is recommended (see section 4.4).

Missed dose

If a dose is missed, it should be taken as soon as the patient remembers. Patients should not take two doses of Steglatro on the same day.

Special populations

Renal impairment

Assessment of renal function is recommended prior to initiation of Steglatro and periodically thereafter (see section 4.4).

Initiation of this medicinal product is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m2 or creatinine clearance (CrCl) less than 45 mL/min (see section 4.4).

In patients with an eGFR ≥ 45 to < 60 mL/min/1.73 m2, Steglatro should be initiated at 5 mg and up-titrated to 15 mg as needed for glycaemic control.

Because the glycaemic lowering efficacy of ertugliflozin is reduced in patients with moderate renal impairment and likely absent in patients with severe renal impairment, if further glycaemic control is needed, the addition of other anti-hyperglycaemic agents should be considered (see section 4.4).

Steglatro should be discontinued when eGFR is persistently less than 30 mL/min/1.73 m2 or CrCl is persistently less than 30 mL/min.

Steglatro should not be used in patients with severe renal impairment, with end-stage renal disease (ESRD), or receiving dialysis, as there is no clinical data to support effectiveness in these patients.

Hepatic impairment

No dose adjustment of ertugliflozin is necessary in patients with mild or moderate hepatic impairment. Ertugliflozin has not been studied in patients with severe hepatic impairment and is not recommended for use in these patients (see section 5.2).

Elderly

No dose adjustment of ertugliflozin is recommended based on age. Renal function and risk of volume depletion should be taken into account (see sections 4.4 and 4.8).

Paediatric population

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

Method of administration

Steglatro should be taken orally once daily in the morning, with or without food. In case of swallowing difficulties, the tablet could be broken or crushed as it is an immediate-release dosage form.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

General

Steglatro should not be used in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis (DKA) in these patients.

Hypotension/Volume depletion

Ertugliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction. Therefore, symptomatic hypotension may occur after initiating Steglatro (see section 4.8), particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2 or CrCl less than 60 mL/min), elderly patients (≥ 65 years), patients on diuretics, or patients on anti-hypertensive therapy with a history of hypotension. Before initiating Steglatro, volume status should be assessed and corrected if indicated. Monitor for signs and symptoms after initiating therapy.

Due to its mechanism of action, ertugliflozin induces an osmotic diuresis and increases serum creatinine and decreases eGFR. Increases in serum creatinine and decreases in eGFR were greater in patients with moderate renal impairment (see section 4.8).

In case of conditions that may lead to fluid loss (e.g., gastrointestinal illness), careful monitoring of volume status (e.g., physical examination, blood pressure measurements, laboratory tests including haematocrit) and electrolytes is recommended for patients receiving ertugliflozin. Temporary interruption of treatment with ertugliflozin should be considered until the fluid loss is corrected.

Diabetic ketoacidosis

Rare cases of DKA, including life-threatening and fatal cases, have been reported in clinical trials and post-marketing in patients treated with sodium glucose co-transporter-2 (SGLT2) inhibitors, including ertugliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/L (250 mg/dL). It is not known if DKA is more likely to occur with higher doses of ertugliflozin.

The risk of DKA must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level.

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

Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with ertugliflozin may be restarted when the ketone values are normal and the patient's condition has stabilised.

Before initiating ertugliflozin, factors in the patient history that may predispose to ketoacidosis should be considered.

Patients who may be at higher risk of DKA include patients with a low beta-cell function reserve (e.g., type 2 diabetes patients with low C-peptide or latent autoimmune diabetes in adults (LADA) or patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery, or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients.

Restarting SGLT2 inhibitor treatment in patients with previous DKA while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is 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 for treatment of patients with type 1 diabetes. Limited data from clinical trials suggest that DKA occurs with common frequency when patients with type 1 diabetes are treated with SGLT2 inhibitors.

Lower limb amputations

In a long-term cardiovascular outcomes study VERTIS CV (eValuation of ERTugliflozin effIcacy and Safety, CardioVascular), a study in patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease, non-traumatic lower limb amputations (primarily of the toe) were reported with an incidence of 2% (0.57 subjects with event per 100 patient-years), 2.1% (0.60 subjects with event per 100 patient-years) and 1.6% (0.47 subjects with event per 100 patient-years) for ertugliflozin 5 mg, ertugliflozin 15 mg and placebo groups. The event rates of lower limb amputations were 0.75 and 0.96 versus 0.74 events per 100 patient-years for ertugliflozin 5 mg and ertugliflozin 15 mg versus placebo, respectively. An increase in cases of lower limb amputation (primarily of the toe) has been observed in long-term clinical studies in type 2 diabetes mellitus with SGLT2 inhibitors. It is not known whether this constitutes a class effect. It is important to counsel patients with diabetes on routine preventative foot care.

Renal impairment

The efficacy of ertugliflozin for glycaemic control is dependent on renal function, and glycaemic efficacy is reduced in patients who have moderate renal impairment and likely absent in patients with severe renal impairment (see section 4.2).

Steglatro should not be initiated in patients with an eGFR below 45 mL/min/1.73 m2 or CrCl below 45 mL/min. Steglatro should be discontinued when eGFR is persistently below 30 mL/min/1.73 m2 or CrCl is persistently below 30 mL/min due to a reduction of efficacy.

Monitoring of renal function is recommended as follows:

- Prior to ertugliflozin initiation and periodically during treatment (see section 4.2).

- More frequently in patients with an eGFR below 60 mL/min/1.73 m2 or a CrCl below 60 mL/min.

Hypoglycaemia with concomitant use with insulin and insulin secretagogues

Ertugliflozin may increase the risk of hypoglycaemia when used in combination with insulin and/or an insulin secretagogue, which are known to cause hypoglycaemia (see section 4.8). Therefore, a lower dose of insulin or insulin secretagogue may be required to minimise the risk of hypoglycaemia when used in combination with ertugliflozin (see sections 4.2 and 4.5).

Genital mycotic infections

Ertugliflozin increases the risk of genital mycotic infections. In trials with SGLT2 inhibitors, patients with a history of genital mycotic infections and uncircumcised males were more likely to develop genital mycotic infections (see section 4.8). Patients should be monitored and treated appropriately.

Urinary tract infections

Urinary glucose excretion may be associated with an increased risk of urinary tract infections (see section 4.8). Temporary interruption of ertugliflozin should be considered when treating pyelonephritis or urosepsis.

Necrotising fasciitis of the perineum (Fournier's gangrene)

Post-marketing cases of necrotising fasciitis of the perineum, (also known as Fournier's gangrene), have been reported in female and male patients taking SGLT2 inhibitors. This is a rare but serious and potentially life-threatening event that requires urgent surgical intervention and antibiotic treatment.

Patients should be advised to seek medical attention if they experience a combination of symptoms of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Be aware that either urogenital infection or perineal abscess may precede necrotising fasciitis. If Fournier's gangrene is suspected, Steglatro should be discontinued and prompt treatment (including antibiotics and surgical debridement) should be instituted.

Elderly patients

Elderly patients may be at an increased risk of volume depletion and renal impairment. Patients 65 years and older treated with ertugliflozin had a higher incidence of adverse reactions related to volume depletion compared to younger patients. In a long-term cardiovascular outcomes study VERTIS CV, safety and efficacy were similar for patients age 65 years and older compared to patients younger than 65 (see sections 4.2 and 4.8).

Cardiac failure

There is no experience in clinical studies with ertugliflozin in New York Heart Association (NYHA) class IV.

Urine laboratory assessments

Due to its mechanism of action, patients taking Steglatro will test positive for glucose in their urine. Alternative methods should be used to monitor glycaemic control.

Interference with 1,5-anhydroglucitol (1,5-AG) assay

Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors. Alternative methods should be used to monitor glycaemic control.

Lactose

Steglatro contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially 'sodium-free'.

4.5. Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions

Diuretics

Ertugliflozin may add to the diuretic effect of diuretics and may increase the risk of dehydration and hypotension (see section 4.4).

Insulin and insulin secretagogues

Insulin and insulin secretagogues, such as sulphonylureas, cause hypoglycaemia. Ertugliflozin may increase the risk of hypoglycaemia when used in combination with insulin and/or an insulin secretagogue. Therefore, a lower dose of insulin or an insulin secretagogue may be required to reduce the risk of hypoglycaemia when used in combination with ertugliflozin (see sections 4.2, 4.4, and 4.8).

Pharmacokinetic interactions

Effects of other medicinal products on the pharmacokinetics of ertugliflozin

Metabolism by UGT1A9 and UGT2B7 is the primary clearance mechanism for ertugliflozin.

Interaction studies conducted in healthy subjects, using a single dose design, suggest that the pharmacokinetics of ertugliflozin are not altered by sitagliptin, metformin, glimepiride, or simvastatin.

Multiple-dose administration of rifampicin (a uridine 5'-diphospho-glucuronosyltransferase [UGT] and cytochrome P450 [CYP] inducer) decreases ertugliflozin area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax) by 39% and 15%, respectively. This decrease in exposure is not considered clinically relevant and therefore, no dose adjustment is recommended. A clinically relevant effect with other inducers (e.g., carbamazepine, phenytoin, phenobarbital) is not expected.

The impact of UGT inhibitors on the pharmacokinetics of ertugliflozin has not been studied clinically, but potential increase in ertugliflozin exposure due to UGT inhibition is not considered to be clinically relevant.

Effects of ertugliflozin on the pharmacokinetics of other medicinal products

Interaction studies conducted in healthy volunteers suggest that ertugliflozin had no clinically relevant effect on the pharmacokinetics of sitagliptin, metformin, and glimepiride.

Coadministration of simvastatin with ertugliflozin resulted in a 24% and 19% increase in AUC and Cmax of simvastatin, respectively, and 30% and 16% increase in AUC and Cmax of simvastatin acid, respectively. The mechanism for the small increases in simvastatin and simvastatin acid is unknown and is not perpetrated through organic anion transporting polypeptide (OATP) inhibition by ertugliflozin. These increases are not considered to be clinically meaningful.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of ertugliflozin in pregnant women. Based on results from animal studies, ertugliflozin may affect renal development and maturation (see section 5.3). Therefore, Steglatro should not be used during pregnancy.

Breast-feeding

There is no information regarding the presence of ertugliflozin in human milk, the effects on the breast-fed infant, or the effects on milk production. Ertugliflozin is present in the milk of lactating rats and caused effects in the offspring of lactating rats. Pharmacologically-mediated effects were observed in juvenile rats (see section 5.3). Since human kidney maturation occurs in utero and during the first 2 years of life when exposure from breast-feeding may occur, a risk to newborns/infants cannot be excluded. Steglatro should not be used during breast-feeding.

Fertility

The effect of ertugliflozin on fertility in humans has not been studied. No effects on fertility were observed in animal studies (see section 5.3).

4.7. Effects on ability to drive and use machines

Ertugliflozin has no or negligible influence on the ability to drive and use machines. Patients should be alerted to the risk of hypoglycaemia when Steglatro is used in combination with insulin or an insulin secretagogue and to the elevated risk of adverse reactions related to volume depletion, such as postural dizziness (see sections 4.2, 4.4, and 4.8).

4.8. Undesirable effects

Summary of the safety profile

The safety and tolerability of ertugliflozin were assessed in 7 placebo- or active comparator-controlled studies with a total of 3 409 patients with type 2 diabetes mellitus treated with ertugliflozin 5 mg or 15 mg. In addition, the safety and tolerability of ertugliflozin in patients with type 2 diabetes and established atherosclerotic cardiovascular disease were assessed in VERTIS CV (see section 5.1) with a total of 5 493 patients treated with ertugliflozin 5 mg or 15 mg and a mean duration of exposure of 2.9 years.

Pool of placebo-controlled trials evaluating Steglatro 5 mg and 15 mg

The primary assessment of safety was conducted in a pool of three 26-week, placebo-controlled trials. Ertugliflozin was used as monotherapy in one trial and as add-on therapy in two trials (see section 5.1). These data reflect exposure of 1 029 patients to ertugliflozin with a mean exposure duration of approximately 25 weeks. Patients received ertugliflozin 5 mg (N=519), ertugliflozin 15 mg (N=510), or placebo (N=515) once daily.

The most commonly reported adverse reactions across the clinical program were urinary tract infections, vulvovaginal mycotic infection and other female genital mycotic infections. Serious DKA occurred rarely (see section 4.4).

Tabulated list of adverse reactions

Adverse reactions listed below are classified according to frequency and system organ class (SOC), within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Frequency categories are defined according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), not known (cannot be estimated from the available data).

Table 1: Adverse reactions from placebo- and active comparator-controlled clinical trials and post-marketing experience

System organ class

Frequency

Adverse reaction

Infections and infestations

Very common

Common

Not known

Urinary tract infections†

Vulvovaginal mycotic infection and other female genital mycotic infections*,†

Balanitis candida and other male genital mycotic infections*,†

Necrotising fasciitis of the perineum (Fournier's gangrene)*,a

Metabolism and nutrition disorders

Common

Rare

Hypoglycaemia*,†

DKA*,†

Vascular disorders

Common

Volume depletion*,†

Skin and subcutaneous tissue disorders

Not known

Rasha

Renal and urinary disorders

Common

Uncommon

Increased urination‡

Dysuria, Blood creatinine increased/Glomerular filtration rate decreased†

Reproductive system and breast disorders

Common

Vulvovaginal pruritus

General disorders and administration site conditions

Common

Thirst§

Investigations

Common

Serum lipids changed¶, Haemoglobin increased**, BUN increased¶¶

* See section 4.4.

† See subsections below for additional information.

‡ Includes: pollakiuria, micturition urgency, polyuria, urine output increased, and nocturia.

§ Includes: thirst and polydipsia.

¶ Mean percent changes from baseline for ertugliflozin 5 mg and 15 mg versus placebo, respectively, were low-density lipoprotein cholesterol (LDL-C) 5.8% and 8.4% versus 3.2%; total cholesterol 2.8% and 5.7% versus 1.1%; however, high-density lipoprotein cholesterol (HDL-C) 6.2% and 7.6% versus 1.9%. Median percent changes from baseline for ertugliflozin 5 mg and 15 mg versus placebo, respectively, were triglycerides -3.9% and -1.7% versus 4.5%.

** The proportion of subjects having at least 1 increase in haemoglobin > 2.0 g/dL was higher in the ertugliflozin 5 mg and 15 mg groups (4.7% and 4.1%, respectively) compared to the placebo group (0.6%).

¶¶ The proportion of subjects having any occurrence of blood urea nitrogen (BUN) values ≥ 50% increase and value >upper limit of normal (ULN) was numerically higher in the ertugliflozin 5 mg group and higher in the 15 mg group (7.9% and 9.8%, respectively) relative to the placebo group (5.1%).

a Adverse reactions were identified through post-marketing surveillance.

Description of selected adverse reactions

Volume depletion

Ertugliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion. In the pool of placebo-controlled studies, the incidence of adverse events related to volume depletion (dehydration, dizziness postural, presyncope, syncope, hypotension, and orthostatic hypotension) was low (< 2%) and not notably different across the ertugliflozin and placebo groups. In the subgroup analyses in the broader pool of phase 3 studies, subjects with eGFR < 60 mL/min/1.73 m2, subjects ≥ 65 years of age and subjects on diuretics had a higher incidence of volume depletion in the ertugliflozin groups relative to the comparator group (see sections 4.2 and 4.4). In subjects with eGFR < 60 mL/min/1.73 m2, the incidence was 5.1%, 2.6%, and 0.5% for ertugliflozin 5 mg, ertugliflozin 15 mg, and the comparator group and for subjects with eGFR 45 to < 60 mL/min/1.73 m2, the incidence was 6.4%, 3.7%, and 0% respectively.

Hypoglycaemia

In the pool of placebo-controlled studies, the incidence of documented hypoglycaemia was increased for ertugliflozin 5 mg and 15 mg (5% and 4.5%) compared to placebo (2.9%). In this population, the incidence of severe hypoglycaemia was 0.4% in each group. When ertugliflozin was used as monotherapy, the incidence of hypoglycaemic events in the ertugliflozin groups was 2.6% in both groups and 0.7% in the placebo group. When used as add-on to metformin, the incidence of hypoglycaemic events was 7.2% in the ertugliflozin 5 mg group, 7.8% in the ertugliflozin 15 mg group and 4.3% in the placebo group.

When ertugliflozin was added to metformin and compared to sulphonylurea, the incidence of hypoglycaemia was higher for the sulphonylurea (27%) compared to ertugliflozin (5.6% and 8.2% for ertugliflozin 5 mg and 15 mg, respectively).

In the VERTIS CV sub-studies, when ertugliflozin was added to insulin with or without metformin, the incidences of documented hypoglycaemia were 39.4%, 38.9% and 37.5% for ertugliflozin 5 mg, ertugliflozin 15 mg and placebo, respectively. When ertugliflozin was added to a sulphonylurea, the incidences of hypoglycaemia were 7.3%, 9.3% and 4.2% for ertugliflozin 5 mg, ertugliflozin 15 mg and placebo, respectively. When ertugliflozin was added to metformin and a sulphonylurea, the incidences of hypoglycaemia were 20%, 26.5% and 14.5% for ertugliflozin 5 mg, ertugliflozin 15 mg and placebo, respectively.

In patients with moderate renal impairment taking insulins, sulphonylurea, or meglitinides as background medicinal products, documented hypoglycaemia was 36%, 27% and 36% for ertugliflozin 5 mg, ertugliflozin 15 mg, and placebo, respectively (see sections 4.2, 4.4, and 4.5).

Diabetic ketoacidosis

In VERTIS CV, ketoacidosis was identified in 19 (0.3%) ertugliflozin-treated patients and in 2 (0.1%) placebo-treated patients. Across 7 other phase 3 clinical trials in the ertugliflozin development program, ketoacidosis was identified in 3 (0.1%) ertugliflozin-treated patients and 0 (0%) of comparator-treated patients (see section 4.4).

Blood creatinine increased/Glomerular filtration rate decreased and renal-related events

Initial increases in mean creatinine and decreases in mean eGFR in patients treated with ertugliflozin were generally transient during continuous treatment. Patients with moderate renal impairment at baseline had larger mean changes that did not return to baseline at Week 26; these changes reversed after treatment discontinuation.

In VERTIS CV, treatment with ertugliflozin was associated with an initial decrease in mean eGFR (at Week 6, -2.7, -3.8 and -0.4 mL/min/1.73 m2 in the ertugliflozin 5 mg, ertugliflozin 15 mg and placebo groups, respectively) followed by a return toward baseline. Long-term, continued treatment with ertugliflozin was associated with a slower decline in eGFR compared to placebo (up to week 260).

In VERTIS CV, the incidences of renal-related adverse reactions (e.g., acute kidney injury, renal impairment, acute prerenal failure) were 4.2%, 4.3% and 4.7% in patients treated with ertugliflozin 5 mg, ertugliflozin 15 mg and placebo respectively in the overall population; and were 9.7%, 10% and 10.2% in patients treated with ertugliflozin 5 mg, ertugliflozin 15 mg and placebo respectively in patients with an eGFR from 30 to less than 60 mL/min/1.73 m2.

Genital mycotic infections

In the pool of three placebo-controlled clinical trials, female genital mycotic infections (e.g., genital candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginitis) occurred in 9.1%, 12%, and 3% of females treated with ertugliflozin 5 mg, ertugliflozin 15 mg, and placebo, respectively. In females, discontinuation due to genital mycotic infections occurred in 0.6% and 0% of patients treated with ertugliflozin and placebo, respectively (see section 4.4).

In the same pool, male genital mycotic infections (e.g., balanitis candida, balanoposthitis, genital infection, genital infection fungal) occurred in 3.7%, 4.2%, and 0.4% of males treated with ertugliflozin 5 mg, ertugliflozin 15 mg, and placebo, respectively. Male genital mycotic infections occurred more commonly in uncircumcised males. In males, discontinuations due to genital mycotic infections occurred in 0.2% and 0% of patients treated with ertugliflozin and placebo, respectively. In rare instances, phimosis was reported and sometimes circumcision was performed (see section 4.4).

Urinary tract infections

In VERTIS CV, urinary tract infections occurred in 12.2%, 12% and 10.2% of patients treated with ertugliflozin 5 mg, ertugliflozin 15 mg and placebo, respectively. The incidences of serious urinary tract infections were 0.9%, 0.4%, and 0.8% with ertugliflozin 5 mg, ertugliflozin 15 mg and placebo, respectively.

Across 7 other phase 3 clinical trials in the ertugliflozin development program, the incidences of urinary tract infections were 4% and 4.1% for ertugliflozin 5 mg and 15 mg groups and 3.9% for placebo. Most of the events were mild or moderate, and no serious cases were reported.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Ertugliflozin did not show any toxicity in healthy subjects at single oral doses up to 300 mg and multiple doses up to 100 mg daily for 2 weeks. No potential acute symptoms and signs of overdose were identified.

In the event of an overdose, employ the usual supportive measures (e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring, and institute supportive treatment) as dictated by the patient's clinical status. Removal of ertugliflozin by haemodialysis has not been studied.