Pharmacy Diabetes

sglt-Steglatro

Ertugliflozin

  • Ertugliflozin tablets contain 6.48 or 19.43 mg of ertugliflozin pyroglutamic acid, which is equivalent to 5 and 15 mg of the active ingredient ertugliflozin.

  • STEGLATRO (ertugliflozin) is indicated as an adjunct to healthy eating and physical activity to improve. glycaemic management in adults with type 2 diabetes mellitus as:
    - monotherapy when metformin is considered inappropriate due to intolerance; or
    - in combination with other anti-hyperglycaemic agents
    For the latest PBS indications for STEGLATRO please see

https://www.pbs.gov.au/pbs/search?analyse=false&term=ERTUGLIFLOZIN&search-type=medicines

  • General - The recommended starting dose of STEGLATRO is 5 mg once daily, taken in the morning, with or without food. In those tolerating STEGLATRO 5 mg once daily the dose may be increased to 15 mg once daily if additional glycaemic management is needed.
  • Renal Impairment - Assessment of renal function is recommended prior to initiation of STEGLATRO and periodically thereafter. Initiation of STEGLATRO is not recommended in individuals with an eGFR less than 45 mL/min/1.73 m2. In those with an eGFR of 45 to less than 60 mL/min/1.73 m2, individually assess the risk benefit as HbA1c reduction was only demonstrated in a post hoc analysis for ertugliflozin 15 mg. Discontinue STEGLATRO if the eGFR falls persistently below 45 mL/min/1.73 m2.
  • Hepatic Impairment - No dose adjustment of STEGLATRO is necessary in those with mild or moderate hepatic impairment. STEGLATRO has not been studied in severe hepatic impairment and is therefore not recommended.

  • Safety and effectiveness of STEGLATRO in paediatric individuals under 18 years of age have not been established.

  • No dose adjustment of STEGLATRO is recommended based on age.

  • History of a serious hypersensitivity reaction to STEGLATRO or to any of the excipients.
  • Individuals with chronic kidney disease (CKD) receiving dialysis; eGFR < 30 mL/min/1.73 m2 or eGFR persistently < 45 mL/min/1.73m2 (CKD stage 3B, 4 and 5). The efficacy of STEGLATRO is dependent on renal function.

  • STEGLATRO should not be used in individuals with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
  • Hypotension - STEGLATRO causes an osmotic diuresis, which may lead to intravascular volume contraction. Therefore, symptomatic hypotension may occur after initiating STEGLATRO particularly in those with impaired renal function (eGFR less than 60 mL/min/1.73 m2), the elderly (≥ 65 years), or individuals on diuretics. Before initiating STEGLATRO, intravascular volume status should be assessed, and advised on the importance of adequate hydration The fast onset of action should be considered in individuals with delayed gastric emptying. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland may require changes in the insulin dose.
  • Ketoacidosis - STEGLATRO should not be used for the treatment of diabetic ketoacidosis. Reports of ketoacidosis, including diabetic ketoacidosis, a serious life-threatening condition requiring urgent hospitalisation, have been identified in clinical trials and post marketing surveillance in individuals receiving sodium glucose co-transporter-2 (SGLT2) inhibitors. Fatal cases of ketoacidosis have been reported in those taking SGLT2 inhibitors. STEGLATRO is not indicated for the treatment of type 1 diabetes mellitus. Individuals treated with STEGLATRO who present with signs and symptoms consistent with severe metabolic acidosis should be promptly assessed for ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated with SGLT2 inhibitors may be present even if blood glucose levels are less than 14 mmol/L. If ketoacidosis is suspected, STEGLATRO should be discontinued, the individual should be evaluated, and prompt treatment should be instituted. Treatment of ketoacidosis generally requires insulin, fluid, potassium, and carbohydrate replacement. Signs and symptoms of ketoacidosis may include excessive thirst, nausea, vomiting, abdominal pain, generalised malaise, and shortness of breath. Restarting SGLT2 inhibitor treatment with previous diabetic ketoacidosis while on SGLT2 inhibitor treatment is not recommended unless another clear precipitating factor is identified and resolved. Before initiating STEGLATRO, consider factors in the history that may predispose to ketoacidosis. Factors that predispose individuals to ketoacidosis include a low carbohydrate diet, dehydration, acute illness, surgery, a previous ketoacidosis, insulin dose reduction, malnourishment / reduced caloric intake or increased insulin requirements due to infections, insulin deficiency from any cause (including insulin pump failure, or history of pancreatitis or pancreatic surgery), and alcohol abuse. STEGLATRO should be used with caution in these individuals. Consider monitoring for ketoacidosis and temporarily discontinuing STEGLATRO in clinical situations known to predispose to ketoacidosis.
    Note: Diabetes MedsCheck with referral to health care team for education on side effect profile and preventive treatment.

  • STEGLATRO should not be used in individuals with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
  • Hypotension - STEGLATRO causes an osmotic diuresis, which may lead to intravascular volume contraction. Therefore, symptomatic hypotension may occur after initiating STEGLATRO particularly in those with impaired renal function (eGFR less than 60 mL/min/1.73 m2), the elderly (≥ 65 years), or individuals on diuretics. Before initiating STEGLATRO, intravascular volume status should be assessed, and advised on the importance of adequate hydration The fast onset of action should be considered in individuals with delayed gastric emptying. Concomitant diseases in the kidney, liver or affecting the adrenal, pituitary or thyroid gland may require changes in the insulin dose.
  • Ketoacidosis - STEGLATRO should not be used for the treatment of diabetic ketoacidosis. Reports of ketoacidosis, including diabetic ketoacidosis, a serious life-threatening condition requiring urgent hospitalisation, have been identified in clinical trials and post marketing surveillance in individuals receiving sodium glucose co-transporter-2 (SGLT2) inhibitors. Fatal cases of ketoacidosis have been reported in those taking SGLT2 inhibitors. STEGLATRO is not indicated for the treatment of type 1 diabetes mellitus. Individuals treated with STEGLATRO who present with signs and symptoms consistent with severe metabolic acidosis should be promptly assessed for ketoacidosis regardless of presenting blood glucose levels, as ketoacidosis associated with SGLT2 inhibitors may be present even if blood glucose levels are less than 14 mmol/L. If ketoacidosis is suspected, STEGLATRO should be discontinued, the individual should be evaluated, and prompt treatment should be instituted. Treatment of ketoacidosis generally requires insulin, fluid, potassium, and carbohydrate replacement. Signs and symptoms of ketoacidosis may include excessive thirst, nausea, vomiting, abdominal pain, generalised malaise, and shortness of breath. Restarting SGLT2 inhibitor treatment with previous diabetic ketoacidosis while on SGLT2 inhibitor treatment is not recommended unless another clear precipitating factor is identified and resolved. Before initiating STEGLATRO, consider factors in the history that may predispose to ketoacidosis. Factors that predispose individuals to ketoacidosis include a low carbohydrate diet, dehydration, acute illness, surgery, a previous ketoacidosis, insulin dose reduction, malnourishment / reduced caloric intake or increased insulin requirements due to infections, insulin deficiency from any cause (including insulin pump failure, or history of pancreatitis or pancreatic surgery), and alcohol abuse. STEGLATRO should be used with caution in these individuals. Consider monitoring for ketoacidosis and temporarily discontinuing STEGLATRO in clinical situations known to predispose to ketoacidosis.
    Note: Diabetes MedsCheck with referral to health care team for education on side effect profile and preventive treatment.

  • Treatment with STEGLATRO should be ceased prior to major surgery. An increase in other glucose lowering agents may be required during this time.
    Note: Diabetes MedsCheck with referral to health care team for education on side effect profile and preventive treatment.

  • Genital mycotic infections - STEGLATRO increases the risk of genital mycotic infections. In trials with SGLT2inhibitors, individuals with a history of genital mycotic infections and uncircumcised males were more likely to develop genital mycotic infections Monitor and treat appropriately.
    Note: Diabetes MedsCheck with referral to health care team for education on side effect profile and preventive treatment.
  • Necrotising Fasciitis of the Perineum - Post marketing cases of necrotising fasciitis of the perineum (also known as Fournier’s gangrene), a rare, but serious and life-threatening necrotising infection, have been reported in females and males with diabetes mellitus treated with SGLT2 inhibitors. Serious outcomes have included hospitalisation, multiple surgeries, and death. Individuals treated with STEGLATRO who present with pain or tenderness, erythema, swelling in the genital or perineal area, fever, and malaise should be evaluated for necrotising fasciitis. If suspected, STEGLATRO should be discontinued, and prompt treatment should be instituted (including broad-spectrum antibiotics and surgical debridement if necessary).
    Note: Diabetes MedsCheck with referral to health care team for education on side effect profile and preventive treatment.
  • Urosepsis and pyelonephritis - There have been post marketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalisation in patients receiving SGLT2 inhibitors. Evaluate Individuals for signs and symptoms of urinary tract infections and treat promptly, if indicated Discontinuation of STEGLATRO may be considered in cases of recurrent urinary tract infections.
    Note: Diabetes MedsCheck referral to health care team for education on for side effects and)
  • Lower limb amputations - David I don’t think we need any of this . An increase in cases of lower limb amputation (primarily of the toe) has also been observed in clinical trials with another SGLT2 inhibitor. It is important to counsel individuals on routine preventative foot-care for all indiiduals on a SGLT 2 inhibitor.
    Note: Diabetes MedsCheck with referral to health care team for education on for side effect profile.

Following single-dose oral administration of 5 mg and 15 mg of ertugliflozin, peak plasma concentrations (median Tmax) of ertugliflozin occur at 1 hour post dose under fasted conditions. Plasma Cmax and AUC of ertugliflozin increase in a dose-proportional manner following single doses from 0.5 mg to 300 mg and following multiple doses from 1 mg to 100 mg. The absolute oral bioavailability of ertugliflozin following administration of a 15-mg dose is approximately 100%. Administration of ertugliflozin with a high-fat and high-calorie meal decreases ertugliflozin Cmax by 29% and prolongs Tmax by 1 hour but does not alter AUC as compared with the fasted state. The observed effect of food on ertugliflozin pharmacokinetics is not considered clinically relevant, and ertugliflozin may be administered with or without food. In Phase 3 clinical trials, STEGLATRO was administered without regard to meals.

The mean steady-state volume of distribution of ertugliflozin following an intravenous dose is 85.5 L. Plasma protein binding of ertugliflozin is 93.6% and is independent of ertugliflozin plasma concentrations. Plasma protein binding is not meaningfully altered in patients with renal or hepatic impairment. The blood-to-plasma concentration ratio of ertugliflozin is 0.66.

Metabolism is the primary clearance mechanism for ertugliflozin. The major metabolic pathway for ertugliflozin is UGT1A9 and UGT2B7-mediated O-glucuronidation to two glucuronides.

The mean systemic plasma clearance following an intravenous 100 µg dose was 11.2 L/hr. The mean elimination half-life in those with type 2 diabetes with normal renal function was estimated to be 16.6 hours based on the population pharmacokinetic analysis. Following administration of an oral [14C]-ertugliflozin solution to healthy subjects, approximately 40.9% and 50.2% of the drug-related radioactivity was eliminated in faeces and urine, respectively. Only 1.5% of the administered dose was excreted as unchanged ertugliflozin in urine and 33.8% as unchanged ertugliflozin in faeces, which is likely due to biliary excretion of glucuronide metabolites and subsequent hydrolysis to parent.

For more information on STEGLATRO, please go to

https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2018-PI-01724-1&d=202106111016933