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Ertugliflozin And Sitagliptin

FDA Drug Information • Also known as: Steglujan

Brand Names
Steglujan
Dosage Form
TABLET, FILM COATED
Product Type
DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION STEGLUJAN (ertugliflozin and sitagliptin) tablet for oral use contains ertugliflozin L-pyroglutamic acid, a SGLT2 inhibitor, and sitagliptin phosphate, a DPP-4 inhibitor. Ertugliflozin The chemical name of ertugliflozin L-pyroglutamic acid is (1 S ,2 S ,3 S ,4 R ,5 S )-5-(4-chloro-3-(4-ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8-dioxabicyclo[3.2.1]octane-2,3,4-triol, compound with (2 S )-5-oxopyrrolidine-2-carboxylic acid. The molecular formula is C 27 H 32 ClNO 10 and the molecular weight is 566.00. The chemical structure is: Ertugliflozin L-pyroglutamic acid is a white to off-white powder that is soluble in ethyl alcohol and acetone, slightly soluble in ethyl acetate and acetonitrile and very slightly soluble in water. Sitagliptin Sitagliptin phosphate monohydrate is described chemically as 7-[(3 R )-3-amino-1-oxo-4-(2,4,5-trifluorophenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-1,2,4-triazolo[4,3- a ]pyrazine phosphate (1:1) monohydrate. The empirical formula is C 16 H 15 F 6 N 5 O∙H 3 PO 4 ∙H 2 O and the molecular weight is 523.32. The structural formula is: Sitagliptin phosphate monohydrate is a white to off-white, crystalline, non-hygroscopic powder. It is soluble in water and N,N-dimethyl formamide; slightly soluble in methanol; very slightly soluble in ethanol, acetone, and acetonitrile; and insoluble in isopropanol and isopropyl acetate. STEGLUJAN is available for oral use as film-coated tablets containing: 6.48 mg ertugliflozin L-pyroglutamic acid equivalent to 5 mg of ertugliflozin and 128.5 mg sitagliptin phosphate monohydrate equivalent to 100 mg sitagliptin (STEGLUJAN 5/100) 19.43 mg ertugliflozin L-pyroglutamic acid equivalent to 15 mg of ertugliflozin and 128.5 mg sitagliptin phosphate monohydrate equivalent to 100 mg sitagliptin (STEGLUJAN 15/100) Inactive ingredients are microcrystalline cellulose, dibasic calcium phosphate anhydrous, croscarmellose sodium, sodium stearyl fumarate, magnesium stearate, and propyl gallate. The...

What Is Ertugliflozin And Sitagliptin Used For?

1 INDICATIONS AND USAGE STEGLUJAN ® is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see Warnings and Precautions (5.1) ]. Has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk for the development of pancreatitis while using STEGLUJAN [see Warnings and Precautions (5.2) ] . STEGLUJAN is a combination of ertugliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, and sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use: Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. ( 1 ) Has not been studied in patients with a history of pancreatitis. ( 1 , 5.2 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Assess renal function before initiating and as clinically indicated. ( 2.1 ) Correct volume depletion before initiating. ( 2.1 ) Recommended starting dosage is 5 mg ertugliflozin/100 mg sitagliptin orally once daily, taken in the morning, with or without food. ( 2.2 ) Increase dosage to 15 mg ertugliflozin/100 mg sitagliptin orally once daily in those tolerating STEGLUJAN and needing additional glycemic control. ( 2.2 ) Use is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m 2 . ( 2.2 ) Withhold STEGLUJAN for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting. ( 2.3 ) 2.1 Prior to Initiation of STEGLUJAN Assess renal function before initiating STEGLUJAN and as clinically indicated [see Warnings and Precautions (5.4) ] . Assess volume status. In patients with volume depletion, correct this condition before initiating STEGLUJAN [see Warnings and Precautions (5.5) and Use in Specific Populations (8.5 , 8.6) ]. 2.2 Recommended Dosage The recommended starting dosage of STEGLUJAN is 5 mg ertugliflozin/100 mg sitagliptin orally once daily, taken in the morning, with or without food. For patients treated with ertugliflozin who are being switched to STEGLUJAN, the dosage of ertugliflozin can be maintained. For additional glycemic control, the dosage may be increased to 15 mg ertugliflozin/100 mg sitagliptin orally once daily in patients tolerating STEGLUJAN. Use is not recommended in patients with an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m 2 . Use of STEGLUJAN is contraindicated in patients with severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease (ESRD) or on dialysis [see Contraindications (4) ] . 2.3 Temporary Interruption for Surgery Withhold STEGLUJAN for at least 4 days, if possible, prior to surgery or procedures associated with prolonged fasting. Resume STEGLUJAN when the patient is clinically stable and has resumed oral intake [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ].

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following important adverse reactions are described elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes and Other Ketoacidosis [see Warnings and Precautions (5.1) ] Pancreatitis [see Warnings and Precautions (5.2) ] Lower Limb Amputation [see Warnings and Precautions (5.3) ] Acute Renal Failure [see Warnings and Precautions (5.4) ] Volume Depletion [see Warnings and Precautions (5.5) ] Urosepsis and Pyelonephritis [see Warnings and Precautions (5.6) ] Heart Failure [see Warnings and Precautions (5.7) ] Hypoglycemia with Concomitant Use with Insulin or Insulin Secretagogues [see Warnings and Precautions (5.8) ] Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) [see Warnings and Precautions (5.9) ] Genital Mycotic Infections [see Warnings and Precautions (5.10) ] Hypersensitivity Reactions [see Warnings and Precautions (5.11) ] Severe and Disabling Arthralgia [see Warnings and Precautions (5.12) ] Bullous Pemphigoid [see Warnings and Precautions (5.13) ] Most common adverse reactions associated with ertugliflozin (incidence ≥5%): female genital mycotic infections. ( 6.1 ) Most common adverse reactions associated with sitagliptin (incidence ≥5%): upper respiratory tract infection, nasopharyngitis and headache. In the add-on to sulfonylurea and add-on to insulin studies, hypoglycemia was also more commonly reported in patients treated with sitagliptin compared to placebo. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Ertugliflozin and Sitagliptin The safety of concomitantly administered ertugliflozin and sitagliptin has been evaluated in 990 patients with type 2 diabetes mellitus treated for 26 weeks in three studies; a factorial study of ertugliflozin 5 mg or 15 mg in combination with sitagliptin 100 mg once daily compared to the individual components, a placebo-controlled study of ertugliflozin 5 mg or 15 mg as add-on therapy to sitagliptin 100 mg and metformin HCl once daily, and a placebo-controlled study of initial therapy with ertugliflozin 5 mg or 15 mg once daily in combination with sitagliptin 100 mg once daily [see Clinical Studies (14) ] . The incidence and type of adverse reactions in these three studies were similar to the adverse reactions seen with ertugliflozin and described below in Table 1 . Ertugliflozin Pool of Placebo-Controlled Trials The data in Table 1 are derived from 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 Clinical Studies (14) ] . 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 mean age of the population was 57 years and 2% were older than 75 years of age. Fifty-three percent (53%) of the population was male and 73% were White, 15% were Asian, and 7% were Black or African American. At baseline the population had diabetes for an average of 7.5 years, had a mean HbA1c of 8.1%, and 19.4% had established microvascular complications of diabetes. Baseline renal function (mean eGFR 88.9 mL/min/1.73 m 2 ) was normal or mildly impaired in 97% of patients and moderately impaired in 3% of patients. Table 1 shows common adverse reactions associated with the use of ertugliflozin. These adverse reactions were not present at baseline, occurred more commonly on ertugliflozin than on placebo, and occurred in at least 2% of patients treated with either ertugliflozin 5 mg or ertugliflozin...

Drug Interactions

7 DRUG INTERACTIONS Table 3: Clinically Significant Drug Interactions with STEGLUJAN Insulin or Insulin Secretagogues Clinical Impact: The risk of hypoglycemia is increased when STEGLUJAN is used in combination with insulin or an insulin secretagogue. Intervention: A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with STEGLUJAN. Lithium Clinical Impact: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations. Intervention: Monitor serum lithium concentration more frequently during STEGLUJAN initiation and dosage changes. Positive Urine Glucose Test Clinical Impact: SGLT2 inhibitors increase urinary glucose excretion and will lead to positive urine glucose tests. Intervention: Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control. Interference with 1,5-anhydroglucitol (1,5-AG) Assay Clinical Impact: Measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Intervention: Monitoring glycemic control with 1,5-AG assay is not recommended. Use alternative methods to monitor glycemic control. See full prescribing information for information on drug interactions and interference of STEGLUJAN with laboratory tests. ( 7 )

Contraindications

4 CONTRAINDICATIONS STEGLUJAN is contraindicated in patients with: Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease (ESRD), or on dialysis [see Warnings and Precautions (5.4) and Use in Specific Populations (8.6) ] . Hypersensitivity to sitagliptin, ertugliflozin, or any excipient, in STEGLUJAN. Reactions such as anaphylaxis or angioedema have occurred [see Warnings and Precautions (5.11) and Adverse Reactions (6.2) ]. Severe renal impairment (eGFR less than 30 mL/min/1.73 m 2 ), end-stage renal disease, or dialysis. ( 4 ) Hypersensitivity to sitagliptin, ertugliflozin, or any excipient in STEGLUJAN. ( 4 , 5.11 , 6.2 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects, from ertugliflozin, STEGLUJAN is not recommended during the second and third trimesters of pregnancy. The limited available data with ertugliflozin and sitagliptin use during pregnancy 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 (see Clinical Considerations ) . 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 fetal 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 (see Data ) . In rats and rabbits, sitagliptin doses of 250 and 125 mg/kg, respectively (approximately 30 and 20 times the human exposure at the maximum recommended human dose) did not adversely affect development outcomes of either species. The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with a HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Overdosage

10 OVERDOSAGE STEGLUJAN In the event of an overdose with STEGLUJAN, contact the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Employ the usual supportive measures as dictated by the patient's clinical status. Ertugliflozin Removal of ertugliflozin by hemodialysis has not been studied. Sitagliptin In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., remove unabsorbed material from the gastrointestinal tract, employ clinical monitoring (including obtaining an electrocardiogram), and institute supportive therapy as dictated by the patient's clinical status. Sitagliptin is modestly dialyzable. In clinical studies, approximately 13.5% of the dose was removed over a 3- to 4-hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known if sitagliptin is dialyzable by peritoneal dialysis.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING STEGLUJAN (ertugliflozin and sitagliptin) tablets are available in the strengths listed below: Strength Description How Supplied NDC 5 mg/100 mg tablets beige, almond-shaped, debossed with “554” on one side and plain on the other side. unit-of-use bottles of 30 0006-5367-03 unit-of-use bottles of 90 0006-5367-06 15 mg/100 mg tablets brown, almond-shaped, debossed with “555” on one side and plain on the other side. unit-of-use bottles of 30 0006-5368-03 unit-of-use bottles of 90 0006-5368-06 Store at 20°C-25°C (68°F-77°F), excursions permitted between 15°C-30°C (between 59°F-86°F) [see USP Controlled Room Temperature]. Protect from moisture. Store in a dry place.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.