Bexagliflozin
FDA Drug Information • Also known as: Bexagliflozin, Brenzavvy
- Brand Names
- Bexagliflozin, Brenzavvy
- Drug Class
- Sodium-Glucose Cotransporter 2 Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- TABLET
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION Bexagliflozin tablets for oral use contain bexagliflozin, an SGLT2 inhibitor. The chemical name of bexagliflozin is (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-cyclopropoxyethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol. The molecular formula is C 24 H 29 ClO 7 and the molecular weight is 464.94 g/mol. The structural formula is: Bexagliflozin is a white/off-white to pale yellow powder. It is very slightly soluble in water and freely soluble in methanol, acetone, ethylene glycol, and propylene glycol. It is slightly soluble in heptane, cyclohexane, and toluene. Crystalline bexagliflozin is not hygroscopic. Each film-coated tablet contains 20 mg of bexagliflozin and the inactive ingredients colloidal silicon dioxide, glyceryl dibehenate, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene oxide, and poloxamer 188. In addition, the film coating ingredient, Opadry ® II Blue 85F99153, contains the inactive ingredients FD&C Blue #1/Brilliant Blue FCF Aluminum Lake, FD&C Blue #2/Indigo Carmine Aluminum Lake, macrogol 3350, partially hydrolyzed polyvinyl alcohol, talc, and titanium dioxide. bexagliflozin-structure
What Is Bexagliflozin Used For?
1 INDICATIONS AND USAGE Bexagliflozin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Limitations of Use Bexagliflozin is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. [see Warnings and Precautions ( 5.1 )] . Bexagliflozin 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. ( 1 ) Limitation of Use: Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. ( 1 )
Dosage and Administration
2 DOSAGE AND ADMINISTRATION
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following important adverse reactions are described below and elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions ( 5.1 )] Lower Limb Amputation [see Warnings and Precautions ( 5.2 ) ] Volume Depletion [see Warnings and Precautions ( 5.3 )] Urosepsis and Pyelonephritis [see Warnings and Precautions ( 5.4 )] Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions ( 5.5 )] Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) [see Warnings and Precautions ( 5.6 )] Genital Mycotic Infections [see Warnings and Precautions ( 5.7 )] Most common adverse reactions (incidence > 5%) are female genital mycotic infections, urinary tract infection and increased urination ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact the bexagliflozin information line at 1-855-273-6928 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. Pool of Placebo-Controlled Trials Evaluating Bexagliflozin Tablets, 20 m g The data in Table 1 are derived from three trials in adults with type 2 diabetes mellitus: two 24-week placebo-controlled trials (one as monotherapy and another as add-on to metformin therapy; Trials 1 and 2, respectively) [see Clinical Studies ( 14.2 , 14.3 )] and a 12-week, placebo-controlled, dose-ranging, monotherapy trial (only the data from the 20 mg dosage of bexagliflozin tablets per day were included in this pool). In these pooled trials, patients received placebo (N = 300) or bexagliflozin 20 mg (N = 372), once daily. The mean age of the population was 56 years and 5% of the patients were older than 75 years of age. Fifty-seven percent (57%) were male and 45% were White, 38% Asian, 15% Black and 2% other races. At baseline, the mean duration of type 2 diabetes mellitus was 7.7 years and the mean hemoglobin A1c (HbA1c) was 8.2%. Established microvascular complications of type 2 diabetes mellitus at baseline included diabetic nephropathy (0.8%), retinopathy (24%), and peripheral neuropathy (33%). Baseline renal function was eGFR ≥ 60 mL/min/1.73 m 2 in 98% of patients and eGFR 45 to < 60 mL/min/1.73 m 2 in 2% of patients (mean eGFR 92 mL/min/1.73 m 2 ). Table 1 shows common adverse reactions associated with the use of bexagliflozin tablets in these trials. These adverse reactions occurred more commonly in bexagliflozin-treated patients than placebo-treated patients, and occurred in at least 2% of bexagliflozin-treated patients. Table 1. Adverse Reactions in Adults with Type 2 Diabetes Mellitus - Monotherapy or in Combination with Metformin* Percentage of Patients Placebo N = 300 Bexagliflozin N = 372 Increased urination a 3 7 Urinary tract infection b 4 6 Female genital mycotic infections c 0 6 Thirst d 2 3 Vaginal pruritus e 0 3 Male genital mycotic infection f 1 2 Hypoglycemia 1 2 * The three placebo-controlled trials included two monotherapy trials and one add-on combination trial with metformin in adults with type 2 diabetes mellitus (Trials 1, 2, and a 12-week dose ranging trial). Adverse reactions were those that occurred more commonly in bexagliflozin-treated patients than placebo-treated patients and occurred in at least 2% of bexagliflozin-treated patients. a Includes: polyuria, pollakiuria, micturition urgency, nocturia. b Includes: dysuria, urinary tract infection, nitrite urine present, streptococcal urinary tract infection, cystitis. c Includes: vulvovaginal mycotic infection, vaginal infection, genital infection fungal, vulvovaginal candidiasis. Percentages calculated with the number of female patients in each group as denominator: placebo (N = 130), bexagliflozin...
Drug Interactions
7 DRUG INTERACTIONS See Table 4 for clinically significant interactions with bexagliflozin tablets. Table 4. Clinically Significant Interactions with Bexagliflozin Tablets UGT Enzyme Inducers Clinical Impact UGT Enzyme Inducers may significantly reduce exposure to bexagliflozin and lead to a decreased efficacy [ see Clinical Pharmacology ( 12.3 )]. Intervention Consider adding another antihyperglycemic agent in patients who require additional glycemic control. Concomitant Use with Insulin and Insulin Secretagogues Clinical Impact The risk of hypoglycemia is increased when bexagliflozin tablets are used in combination with insulin and/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 bexagliflozin tablets. Lithium Clinical Impact Concomitant use with SGLT2 inhibitors such as bexagliflozin tablets may decrease serum lithium concentrations. Intervention Monitor serum lithium concentration more frequently upon bexagliflozin tablets initiation and discontinuation. 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.
Contraindications
4 CONTRAINDICATIONS Bexagliflozin tablets are contraindicated in patients: With hypersensitivity to bexagliflozin or any excipient in bexagliflozin tablets. Anaphylaxis and angioedema have been reported with sodium-glucose co-transporter 2 (SGLT2) inhibitors.
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary Based on animal data showing adverse renal effects, bexagliflozin is not recommended during the second and third trimesters of pregnancy. The available data on use of bexagliflozin tablets during pregnancy are insufficient to determine a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations ) . In animal studies, adverse renal pelvic and tubule dilatations that were not fully reversible were observed in rats when bexagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy at exposures 11 times the 20 mg clinical dose (see Data ) . The estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a peri-conceptional HbA1c > 7% and has been reported to be as high as 20% to 25% in women with a peri-conceptional 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% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Data Animal Data Bexagliflozin administered to juvenile rats at 0.3, 3 or 30 mg/kg/day by oral gavage from postnatal days 21 to 90 caused a dose dependent increase in the incidence and...
Overdosage
10 OVERDOSAGE In the event of an overdose of bexagliflozin tablets, consider contacting 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. Removal of bexagliflozin by hemodialysis has not been studied.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Bexagliflozin 20 mg tablets are blue, caplet-shaped, biconvex, bevel-edged, film-coated debossed with “2” and inverted “2” on one side.
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.