Ertoxa Tablet

Ertoxa tablet is a sodium glucose co-transporter 2 (SGLT2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Limitations of Use: Ertoxa tablet is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

SGLT2 is the predominant transporter responsible for reabsorption of glucose from the glomerular filtrate back into the circulation. Ertugliflozin is an inhibitor of SGLT2. By inhibiting SGLT2, ertugliflozin reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, and thereby increases urinary glucose excretion.

The recommended starting dose of Ertugliflozin is 5 mg once daily, taken in the morning, with or without food. In patients tolerating Ertugliflozin 5 mg once daily, the dose may be increased to a maximum recommended dose of 15 mg once daily if additional glycemic control is needed.

Patients with renal impairment-

• Assess renal function prior to initiation of Ertugliflozin and periodically thereafter
• Use of Ertugliflozin is contraindicated in patients with an eGFR less than 30 mL/minute/1.73 m2
• Initiation of Ertugliflozin is not recommended in patients with an eGFR of 30 mL/minute/1.73 m2 to less than 60 mL/minute/1.73 m2
• Continued use of Ertugliflozin is not recommended when eGFR is persistently between 30 and less than 60 mL/minute/1.73 m2.

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.

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

Ertugliflozin should be taken orally once daily in the morning, with or without food. All patients should continue their diet with an adequate distribution of carbohydrate intake during the day. Overweight patients should continue their energy restricted diet. If a dose is missed, advise patients to take it as soon as it is remembered unless it is almost time for the next dose, in which case patients should skip the missed dose and take the medicine at the next regularly scheduled time. Advise patients not to take two doses of Ertugliflozin at the same time.

Concomitant Use with Insulin And Insulin Secretogogues: Ertoxa may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretogogue. Therefore, a lower dose of insulin or insulin secretogogue may be required to minimize the risk of hypoglycemia when used in combination with Ertoxa.

Positive Urine Glucose Test: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors as SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Use alternative methods to monitor glycemic control.

Interference With 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.

Severe renal impairment, end-stage renal disease (ESRD), or dialysis. History of a serious hypersensitivity reaction to Ertugliflozin.

Side effects may include:

• cough (with or without phlegm),
• stuffy or runny nose,
• sore throat,
• mouth ulcers,
• diarrhea,
• nausea and vomiting,
• abdominal pain,
• constipation,
• weight loss,
• headache/dizziness,
• back pain
• joint pain,
• muscle pain,
• feeling weak,
• tremor etc.

Pregnancy: The limited available data with Ertugliflozin in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy. In animal studies, adverse renal changes were observed in rats when ertugliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy. Doses approximately 13 times the maximum clinical dose caused renal pelvic and tubule dilatations and renal mineralization that were not fully reversible. There was no evidence of feral harm in rats or rabbits at exposures of ertugliflozin approximately 300 times higher than the maximal clinical dose of 15 mg/day when administered during organogenesis. Based on animal data showing adverse renal effects, Ertugliflozin is not recommended during the second and third trimesters of pregnancy.

Lactation: There is no information regarding the presence of Ertugliflozin in human milk, the effects on the breastfed infant, or the effects on milk production. Ertugliflozin is present in the milk of lactating rats. Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. Because of the potential for serious adverse reactions in a breastfed infant, advise women that the use of Ertugliflozin is not recommended while breastfeeding.

Ketoacidosis: Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, have been identified in clinical trials and post marketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors and cases have been reported in Ertoxa treated patients in clinical trials. Across the clinical program, ketoacidosis was identified in 3 of 3,409 (0.1%) of Ertoxa treated patients and 0% of comparator-treated patients. Fatal cases of
ketoacidosis have been reported in patients taking SGLT2 inhibitors.

Patients treated with Ertoxa who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated with Ertoxa may be present even if blood glucose levels are less than 250 mg/dL. If ketoacidosis is suspected, Ertoxa should be discontinued, patient should be evaluated, and prompt treatment should be instituted. Treatment of ketoacidosis may require insulin, fluid and carbohydrate replacement.

General: Ertoxa is not indicated for the treatment of patients with type 1 diabetes mellitus.

Hypotension: Ertoxa causes intravascular volume contraction. Therefore, symptomatic hypotension may occur after initiating Ertoxa particularly in patients with impaired renal function (eGFR less than 60
mL/min/1.73 m2) [see Use In Specific Populations], elderly patients (>65 years), in patients with low systolic blood pressure, and in patients on diuretics. Before initiating Ertoxa, volume status should be assessed and corrected if indicated. Monitor for signs and symptoms of hypotension after initiating therapy.

Acute Kidney Injury And Impairment In Renal Function: Ertoxa causes intravascular volume contraction and can cause renal impairment. There have been post marketing reports of acute kidney injury some requiring hospitalization and dialysis in patients receiving SGLT2 inhibitors. Before initiating Ertoxa, consider factors that may predispose patients to acute kidney injury including hypovolemia, chronic renal insufficiency, congestive heart failure and concomitant medications (diuretics, ACE inhibitors, ARBs, NSAIDs). Consider temporarily discontinuing Ertoxa in any setting of reduced oral intake (such as acute illness or fasting) or fluid losses (such as gastrointestinal illness or excessive heat exposure); monitor patients for signs and symptoms of acute kidney injury. If acute kidney injury occurs, discontinue Ertoxa promptly and institute treatment. Ertoxa increases serum creatinine and decreases eGFR. Patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2) may be more susceptible to these changes. Renal function abnormalities can occur after initiating Ertoxa. Renal function should be evaluated prior to initiating Ertoxa and periodically thereafter. Use of Ertoxa is not recommended when eGFR is
persistently between 30 and less than 60 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 Hypoglycemia With Concomitant Use With Insulin And Insulin Secretogogues
Insulin and insulin secretogogues (e.g., sulfonylurea) are known to cause hypoglycemia. Ertoxa may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretogogue. Therefore, a lower dose of insulin or insulin secretogogue may be required to minimize the risk of hypoglycemia when used in combination with Ertoxa.

Increases In Low-Density Lipoprotein Cholesterol (LDL-C): Dose-related increases in LDL-C can occur with Ertoxa. Monitor and treat as appropriate.

Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with Ertoxa.

Pediatrics (<18 years of age): Safety and effectiveness of Ertoxa in pediatric patients under 18 years of age have not been established.

Geriatrics: No dosage adjustment of Ertoxa is recommended based on age. Across the clinical program, a total of 876 (25.7%) patients treated with Ertoxa were 65 years and older, and 152 (4.5%) patients treated with Ertoxa were 65 years and older had a higher incidence of adverse reactions related to volume depletion compared to younger patients; events were reported in 1.1%, 2.2% and 2.6% of patients treated with comparator, Ertoxa 5 mg, and Ertoxa 15 mg, respectively. Ertoxa is expected to have diminished efficacy in elderly patients with renal impairment.

In the event of an overdose with Ertoxa, contact the Poison Control Center. Employ the usual supportive measures as dictated by the atient's clinical status. Removal of Ertoxa by hemodialysis has not been studied.

Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors

To be taken as advised by the physician. To be dispensed only on the prescription of a registered physician. Store at 30°C or below in a dry place.