Dosing & Uses
Dosage Forms & Strengths
tablet
- 5mg
- 15mg
Type 2 Diabetes Mellitus
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
Recommended starting dose is 5 mg PO qDay in the morning
If starting dose tolerated and additional glycemic control is needed, increase dose to maximum of 15 mg qDay
Dosage Modifications
Concomitant use with insulin and insulin secretagogues may increase the risk of hypoglycemia; lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with ertugliflozin
Renal impairment
- eGFR ≥45 mL/min/1.73 m2: No dosage adjustment necessary
- eGFR <45 mL/min/1.73 m2: Not recommended
- Hemodialysis: Contraindicated
Hepatic impairment
- Mild-to-moderate: No dosage adjustment necessary
- Severe: Not recommended
Dosing Considerations
Assess renal function before initiating and as clinically indicated
In patients with volume depletion, correct this condition before initiating
Limitations of use
- Not recommended in patients with type 1 diabetes mellitus; may increase risk of diabetic ketoacidosis in these patients
<18 years: Safety and efficacy not established
≥65 years: No dosage adjustment necessary
Patients aged ≥65 years had a higher incidence of adverse reactions related to volume depletion compared with younger patients
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (26)
- chlorpropamide
ertugliflozin, chlorpropamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- glimepiride
ertugliflozin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- glipizide
ertugliflozin, glipizide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- glyburide
ertugliflozin, glyburide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- ifosfamide
ifosfamide, ertugliflozin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Use Caution/Monitor. Monitor renal function in patients with severe renal impairment, severe intestinal inflammation, or prolonged use >2 gm/day.
- insulin aspart
ertugliflozin, insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin aspart protamine/insulin aspart
ertugliflozin, insulin aspart protamine/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin degludec
ertugliflozin, insulin degludec. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin detemir
ertugliflozin, insulin detemir. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin glargine
ertugliflozin, insulin glargine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin glulisine
ertugliflozin, insulin glulisine. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin inhaled
ertugliflozin, insulin inhaled. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin isophane human/insulin regular human
ertugliflozin, insulin isophane human/insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin lispro
ertugliflozin, insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin lispro protamine/insulin lispro
ertugliflozin, insulin lispro protamine/insulin lispro. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin NPH
ertugliflozin, insulin NPH. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- insulin regular human
ertugliflozin, insulin regular human. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- lithium
ertugliflozin decreases levels of lithium by Other (see comment). Use Caution/Monitor. Comment: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.
- lonapegsomatropin
lonapegsomatropin decreases effects of ertugliflozin by Other (see comment). Use Caution/Monitor. Comment: Closely monitor blood glucose when treated with antidiabetic agents. Lonapegsomatropin may decrease insulin sensitivity, particularly at higher doses. Patients with diabetes mellitus may require adjustment of their doses of insulin and/or other antihyperglycemic agents.
lonapegsomatropin decreases effects of ertugliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone. - nateglinide
ertugliflozin, nateglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- repaglinide
ertugliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- somapacitan
somapacitan decreases effects of ertugliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatrogon
somatrogon decreases effects of ertugliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatropin
somatropin decreases effects of ertugliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone (GH) analogs may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- tolazamide
ertugliflozin, tolazamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
- tolbutamide
ertugliflozin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin or insulin secretagogue to avoid hypoglycemia when coadministered with ertugliflozin.
Minor (0)
Adverse Effects
>10%
Female genital mycotic infections (9.1-12.2%)
1-10%
Volume depletion adverse effects (1.9-4.4%)
Male genital mycotic infections (3.7-4.2%)
Urinary tract infections (4-4.1%)
Headache (2.9-3.5%)
Vaginal pruritus (2.4-2.8%)
Increased urination (2.4-2.7%)
Nasopharyngitis (2-2.5%)
Back pain (1.7-2.5%)
Renal adverse effects (1.3-2.5%)
Weight decreased (1.2-2.4%)
Thirst (1.4-2.7%)
Adverse Effects
Postmarketing Reports
Necrotizing fasciitis of the perineum (Fournier’s Gangrene)
Angioedema
Diabetic ketoacidosis in patients with type 1 diabetes mellitus and other ketoacidosis
Warnings
Contraindications
Hypersensitivity to ertugliflozin or any excipient; reactions such as angioedema have occurred
Patients on dialysis
Cautions
Causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment, with low systolic blood pressure, on diuretics, or who are elderly; before initiating treatment in patients with one or more of risk factors, assess volume status and renal function
Renal impairment may occur owing to intravascular volume contraction; before initiating, consider factors that may predispose patients to acute kidney injury, including hypovolemia, chronic renal insufficiency, CHF, and concomitant medications (eg, diuretics, ACE inhibitors, ARBs, NSAIDs); consider temporarily discontinuing ertugliflozin in any setting of reduced oral intake or fluid loss; monitor for signs and symptoms of acute kidney injury, and, if evident, discontinue drug promptly and institute treatment
Genital mycotic infections may occur; patients with history of genital mycotic infections and uncircumcised males are more susceptible
Serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization reported in patients receiving SGLT2 inhibitors
Increases risk of urinary tract infections (UTIs), including life-threatening urosepsis and pyelonephritis that started as UTIs
Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4°F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary
Dose-related increases in LDL-C reported
No conclusive evidence of macrovascular risk reduction with empagliflozin or any other antidiabetic agent
Lower limb amputations
- An increased risk for lower limb amputation (primarily of the toe) has been observed in clinical studies with another SGLT2 inhibitor; before initiating, consider factors that may predispose patient to increased risk of amputations (eg, history of prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers)
- Counsel patients about importance of routine preventative foot care; monitor patients receiving drug for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue therapy if these complications occur
Ketoacidosis
- Not indicated for patients with type 1 diabetes mellitus (T1DM); in placebo-controlled trials, risk of ketoacidosis was increased in patients with T1DM who received SGLT2 inhibitors
- Risk of ketoacidosis may be greater with higher doses
- Before initiating therapy, consider factors in patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
- Consider temporarily discontinuing therapy for at least 3 days for patients who undergo scheduled surgery
- Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or post-surgery); ensure risk factors for ketoacidosis are resolved prior to restarting therapy
- Restart once the patient’s oral intake is back to baseline and any other risk factors for ketoacidosis (blood acid buildup) are resolved
- Type 2 diabetes mellitus and pancreatic disorders (eg, history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors.
- Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse
- Ketoacidosis and glucosuria may persist longer than typically expected; urinary glucose excretion persists for 3 days after discontinuing therapy; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors
- Consider ketone monitoring in patients at risk for ketoacidosis if indicated by the clinical situation; assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis; if ketoacidosis is suspected, discontinue therapy, promptly evaluate, and treat ketoacidosis, if confirmed; monitor patients for resolution of ketoacidosis before restarting therapy
- Educate all patients on signs and symptoms of ketoacidosis and instruct patients to discontinue therapy and seek medical attention immediately if signs and symptoms occur
Drug interactions overview
- Hypoglycemia risk increased with insulin and insulin secretagogues (eg, sulfonylureas); a lower dose of insulin or insulin secretagogue may be required
Laboratory testing
- Urine glucose tests is not recommended in patients taking SGLT2 inhibitors, as SGLT2 inhibitors, increase urinary glucose excretion and lead to positive urine glucose tests; use alternative methods to monitor glycemic control
- 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
Pregnancy
Pregnancy
Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy
Data are limited in pregnant women and 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
Animal data
- 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 ~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 fetal harm in rats or rabbits at exposures of ertugliflozin ~300 times higher than the maximal clinical dose of 15 mg/day when administered during organogenesis
Lactation
Not recommended while breastfeeding
Unknown if distributed in human breast milk
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 ertugliflozin is not recommended while breastfeeding
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Selective sodium-glucose transporter-2 (SGLT2) inhibitor
SGLT-2 inhibition lowers the renal glucose threshold (ie, the plasma glucose concentration, which exceeds the maximum glucose reabsorption capacity of the kidney); lowering the renal glucose threshold results in increased urinary glucose excretion
Absorption
Peak plasma time: 1 hr (fasting); 2 hr (high-fat, high-caloric meal)
Peak plasma concentration, steady-state: 81.3 ng/mL (5 mg qDay); 268 ng/mL (15 mg qDay)
AUC, steady-state: 398 ng⋅hr/mL (5 mg qDay); 1,193 ng⋅hr/mL (15 mg qDay)
Steady-state is reached after 4-6 days
Bioavailability, 15 mg dose: ~100%
Distribution
Vd, steady-state: 85.5 L
Protein binding: 93.6%
Blood-to-plasma concentration ratio of ertugliflozin: 0.66
Metabolism
Major metabolic pathway for ertugliflozin is UGT1A9 and UGT2B7-mediated O-glucuronidation to 2 glucuronides (pharmacologically inactive at clinically relevant concentrations)
YP-mediated (oxidative) metabolism of ertugliflozin is minimal (12%)
Excretion
Half-life: 16.6 hr
Clearance: 11.2 L/hr
Excretion, oral [14C]-ertugliflozin solution: Feces (40.9%); urine (50.2%)
Excretion, unchanged ertugliflozin: Feces (33.8%); urine (1.5%)
Administration
Oral administration
Take in the morning qDay, with or without food
Missed dose
- Take it as soon as possible
- If it is almost time for next scheduled dose, skip missed dose and take the next regularly scheduled time
- Do not take 2 doses of ertugliflozin at the same time
Storage
Store at room temperature between 68-77°F (20-25°C)
Keep tablets dry
Store blister packs in the original package
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Steglatro oral - | 5 mg tablet |  | |
| Steglatro oral - | 15 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
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