FOR HEALTHCARE PROFESSIONALS

BRENZAVVY Clinical Data

How to get Brenzavvy page
stay connected button image 502x124 1

The safety and efficacy of BRENZAVVY (bexagliflozin) were evaluated in 23 clinical studies. Highlighted below are some of the key Phase 3 studies.

BRENZAVVY® (bexagliflozin) Safety and Effectiveness in Patients with Stage 3 Chronic Kidney Disease (CKD)

Study Design
A phase 3, randomized, double-blind, placebo-controlled trial evaluated the effectiveness and safety of BRENZAVVY, 20 mg, in adults with type 2 diabetes mellitus, moderate renal impairment (stage 3 CKD) and inadequate glycemic control. 312 adults received BRENZAVVY, 20 mg, or placebo in addition to ongoing hypoglycemic medications for 24 weeks. Eligible patients were stratified based on their estimated glomerular filtration rate (eGFR; either 30 to < 45 mL min-1 per 1.73 m2, stage 3b CKD, or 45 to < 60 mL min-1 per 1.73 m2, stage 3a CKD), baseline HbA1c (> 8.5% or not) or use of insulin. The primary endpoint was the change in HbA1c from baseline to week 24.

Study Population

At baseline, 166 patients had CKD stage 3a while 146 had CKD stage 3b. The average age was 69.6 years. Enrolled patients had an average duration of diabetes of approximately 16 years, a mean baseline HbA1c level of 7.98%, and a mean BMI of 30.2 kg m-2. Approximately 56% of patients were prescribed insulin prior to study participation and were instructed to continue their insulin dosing throughout their participation in the study. 37% of patients had normal albuminuria (UACR < 30 mg g-1), 38% had moderately increased albuminuria (UACR 30-299 mg g-1) and 25% had severely increased albuminuria (UACR ≥ 300 mg g-1).

Body Mass

247 adults in the randomized population had a baseline BMI ≥ 25 kg m-2. Following 24 weeks of treatment with BRENZAVVY or placebo, a reduction in the mean body weight was observed in both arms. The placebo-adjusted change in the BRENZAVVY arm was −1.76 kg and was statistically significant.

HbA1c

BRENZAVVY treatment improved glycemic control in patients with moderate renal impairment. The reduction of 0.61% from baseline HbA1c and the placebo-corrected treatment effect of −0.37% was clinically meaningful and statistically significant. Rescue medication was provided to 26 patients (9 in the BRENZAVVY arm and 17 in the placebo arm). Including observed values after treatment with rescue medication showed a reduction of 0.59% from baseline HbA1c and a placebo-corrected treatment effect of −0.28%.

Urine Albumin to Creatinine Ratio (UACR)
Decreased albuminuria was observed in patients treated with BRENZAVVY. A statistically significant placebo-adjusted geometric mean ratio reduction in the UACR of 20.1% was observed in the BRENZAVVY arm.
  1. Allegretti AS, Zhang W, Zhou W, et al. Safety and Effectiveness of Bexagliflozin in Patients With Type 2 Diabetes Mellitus and Stage 3a/3b CKD. Am J Kidney Dis. 2019;74(3):328-337. doi:10.1053/j.ajkd.2019.03.417; PMID: 31101403; PMCID: PMC10077840.

BRENZAVVY® (bexagliflozin) Safety and Effectiveness in Patients as an Adjunct to Metformin

Study Design
A phase 3, randomized, double-blind, placebo-controlled trial evaluated the effectiveness and safety of BRENZAVVY, 20 mg, in adults with type 2 diabetes mellitus as an adjunct to metformin. 317 adults received BRENZAVVY, 20 mg, or placebo in addition to ongoing metformin treatment for 24 weeks. Eligible patients were stratified based on baseline HbA1c (> 8.5% or not) and country of residence. The primary endpoint was the change in HbA1c from baseline to week 24.

An open label group enrolled an additional 34 patients with HbA1c > 10.5 and ≤ 12.0% and was analyzed separately.

Study Population

The average age in the double-blind group was 55.8 years. Enrolled patients had an average duration of diabetes of approximately 9.1 years, a mean baseline HbA1c level of 8.6%, fasting plasma glucose (FPG) of 189 mg dL-1 and systolic blood pressure (SBP) of 129 mm Hg. 52.1% of patients had a baseline HbA1c < 8.5% at baseline while 47.9% had baseline HbA1c between 8.5 and 10.5%. 47.6% of study patients were from Japan while 52.4% of patients resided in the United States.

The majority of the open label group resided in the United States (79.4%) and the average age was 52.1 years. The average duration of diabetes was approximately 9.2 years and the mean baseline values for HbA1c, FPG, and SBP were 11.1%, 239.6 mg dL1 and 131 mm Hg, respectively.

Fasting Plasma Glucose
BRENZAVVY treatment decreased fasting plasma glucose levels in patients. The change from baseline FPG in the BRENZAVVY arm was −45.2 mg dL-1 with a placebo-adjusted change of −24.3 mg dL-1.
HbA1c

BRENZAVVY treatment improved glycemic control in patients. The reduction of 1.09% from baseline HbA1c and the placebo-corrected treatment effect of −0.53% was clinically meaningful and statistically significant. Rescue medication was provided to 38 patients (6 in the BRENZAVVY arm and 32 in the placebo arm). Exclusion of values observed after treatment with rescue medication gave a reduction of 1.07% from baseline HbA1c and a placebo-corrected treatment effect of −0.67%.

The open label group had a mean change in HbA1c of −2.82% after 24 weeks of BRENZAVVY treatment.

Systolic Blood Pressure

BRENZAVVY treatment decreased systolic blood pressure. The change from baseline SBP in the BRENZAVVY arm was −5.03 mm Hg with a placebo-adjusted reduction of −7.07 mm Hg as patients in the placebo arm had an overall increase from baseline of 1.67 mm Hg.

The open label group had a mean change in SBP of −8.19 mm Hg after 24 weeks of BRENZAVVY treatment.

  1. Halvorsen YD, Conery AL, Lock JP, Zhou W, Freeman MW. Bexagliflozin as an adjunct to metformin for the treatment of type 2 diabetes in adults: A 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab. 2023; 1- 9. doi: 10.1111/dom.15192. PMID: 37409573.

BRENZAVVY® (bexagliflozin) Safety and Effectiveness Compared to Glimepiride as an Adjunct to Metformin for Treatment of Type 2 Diabetes Mellitus in Adults

Study Design
A phase 3, randomized, double-blind, active-controlled, parallel-group designed trial compared the safety and effectiveness of BRENZAVVY, 20 mg, to glimepiride, optimally titrated up to 6 mg, in adults with type 2 diabetes mellitus medicated with metformin (≥ 1500 mg day-1) for at least 8 weeks prior to the screening visit. Patients were eligible if their antidiabetic regimen included another oral hypoglycemic agent (OHA), if they discontinued the second agent for at least 6 weeks prior to entering the 2-week, single blind placebo run-in period that all subjects underwent. 426 adults received BRENZAVVY or glimepiride in addition to ongoing metformin for up to 96 weeks. Eligible patients were stratified based on their baseline HbA1c (> 8.5% or not), treatment history (metformin only or metformin plus another OHA), and their renal function at the screening visit (eGFR 60 to < 90 mL min-1 per 1.73 m2 or ≥ 90 mL min-1 per 1.73 m2). The primary endpoint was the intergroup difference in HbA1c from baseline to week 60. Participants remained enrolled through a safety monitoring period of an additional 36 weeks to allow for assessment of the durability of the treatment effect and the identification of any adverse treatment-related sequelae.

Study Population

The study population had a mean age of 59.6 years, a mean duration of disease of 8.7 years and body mass of 89.1 kg. The mean HbA1c at baseline was 8.01% and a majority had a treatment history of metformin only (64.3%) while the remainder had received metformin and another OHA prior to randomization (35.7%). Most of the population had near-normal renal function with a mean eGFR of 91.4 mL min-1 per 1.73 m2. 70% of subjects resided in Europe while 30% were from the United States.

Body Mass

BRENZAVVY was superior to glimepiride for the reduction in body mass from baseline to week 60 for study participants with a BMI ≥ 25 kg m-2 at baseline (94.6% of the study population). Following 60 weeks of treatment with BRENZAVVY, the intergroup model-adjusted difference for those treated with glimepiride was −4.31 kg.

Hypoglycemia Events
BRENZAVVY was superior to glimepiride for the proportion of patients experiencing documented symptomatic hypoglycemia (symptoms accompanied by a measured plasma glucose concentration ≤ 70 mg dL1) and no patients experienced severe hypoglycemia in either treatment arm. 7 patients (3.3%) in the BRENZAVVY arm experienced documented symptomatic hypoglycemia compared to 44 patients (20.8%) in the glimepiride arm.
HbA1c

BRENZAVVY was noninferior to glimepiride for the management of type 2 diabetes mellitus in a population poorly controlled by metformin or metformin plus one other OHA. The model-adjusted mean change in HbA1c from baseline to week 60 was −0.70% in the BRENZAVVY arm and −0.66% in the glimepiride arm. The improvement in glycemic control was clinically meaningful. At week 60, 70 adults in the BRENZAVVY arm (36.3%) and 65 subjects in the glimepiride arm (34.0%) had achieved an HbA1c < 7.0%.

Systolic Blood Pressure

BRENZAVVY was superior to glimepiride for the reduction in systolic blood pressure from baseline to week 60 for study participants with an SBP ≥ 140 mmHg at baseline. Patients in the BRENZAVVY-treated arm had a change in SBP of −13.48 mmHg compared to −6.95 mmHg in the glimepiride-treated arm. The intergroup difference of −6.53 mmHg favoring the BRENZAVVY arm was statistically significant.

Renal Function

The mean change from baseline eGFR for BRENZAVVY minus the mean change from baseline for glimepiride was 3.14 mL min-1 per 1.73m2 at 96 weeks. During the treatment period, participants in the BRENZAVVY arm experienced a change in eGFR of −1.33 mL min-1 per 1.73 m2 whereas those in the glimepiride arm experienced a change of −4.47 mL min-1 per 1.73m2. At the follow-up visit conducted 2 weeks after last dose, BRENZAVVY-treated patients exhibited a mean increase in eGFR of 1.38 mL min-1 per 1.73 m2 from the baseline value whereas glimepiride-treated patients exhibited a mean decrease of 4.67 mL min-1 per 1.73 m2 from baseline.

  1. Halvorsen YD, Lock JP, Frias JP, et al. A 96-week, double-blind, randomized controlled trial comparing bexagliflozin to glimepiride as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2023;25(1):293-301. doi:10.1111/dom.14875; PMID: 36178197.

BRENZAVVY® (bexagliflozin) Safety and Effectiveness Compared to Sitagliptin as an Adjunct to Metformin for Treatment of Type 2 Diabetes Mellitus in Adults

Study Design
A phase 3, randomized, double-blind, active-controlled, parallel-group trial compared the safety and effectiveness of BRENZAVVY, 20 mg, to sitagliptin, 100 mg, in adults with type 2 diabetes mellitus and medicated with metformin (≥ 1500 mg day-1) for at least 8 weeks prior to the screening visit. 386 adults received BRENZAVVY or sitagliptin in addition to ongoing metformin for 24 weeks. Eligible patients were stratified based on their baseline HbA1c (> 8.5% or not). The primary endpoint was the intergroup difference in the change in HbA1c from baseline to week 24.

Study Population

The study population had a mean age of 59.4 years, a mean duration of disease of 8.8 years and mean body mass of 89.9 kg. The mean HbA1c at baseline was 7.99%.

HbA1c

BRENZAVVY was noninferior to sitagliptin for the management of type 2 diabetes mellitus in a population poorly controlled by metformin alone. The model-adjusted mean change in HbA1c from baseline to week 24 was −0.74% in the BRENZAVVY arm and −0.82% in the sitagliptin arm. The improvement in glycemic control was clinically meaningful. At week 24, 75 of the BRENZAVVY treated patients (41.7%) achieved a treatment goal of HbA1c < 7.0%.

Body Mass

BRENZAVVY was superior to sitagliptin for the reduction in body mass from baseline to week 24 for study participants with a BMI ≥ 25 kg m-2 at baseline measurement. Following 24 weeks of treatment with BRENZAVVY, the intergroup model-adjusted difference from those treated with sitagliptin was −2.54 kg.

Fasting Plasma Glucose

BRENZAVVY was superior to sitagliptin for reduction of fasting plasma glucose concentration from baseline to week 24. A decrease by 32.8 mg dL-1 was observed in the BRENZAVVY arm compared to 26.1 mg dL-1 in the sitagliptin arm.

  1. Halvorsen YD, Lock JP, Zhou W, Zhu F, Freeman MW. A 24-week, randomized, double-blind, active-controlled clinical trial comparing bexagliflozin with sitagliptin as an adjunct to metformin for the treatment of type 2 diabetes in adults. Diabetes Obes Metab. 2019;21(10):2248-2256. doi:10.1111/dom.13801; PMID: 31161692.

BRENZAVVY® (bexagliflozin) Cardiovascular Safety Profile

Meta-Analysis Design
In 2008, FDA published a Guidance for Industry that required sponsors to comply with standards to ensure the cardiovascular safety of products designed to treat diabetes. The Agency established two criteria: a pre-market threshold and a post-approval threshold. To satisfy the first criterion, the upper bound of the 95% confidence interval for the hazard ratio for major adverse cardiovascular events (MACE) caused by the product had to be less than 1.8. For the second criterion, the sponsor had to demonstrate that the upper bound was less than 1.3. The endpoint for the pre-approval standard could include more events than the endpoint for the post-approval standard. 

The pre-specified analysis included all BRENZAVVY double-blind, controlled, phase 2 and phase 3 studies. The largest number of events were provided by phase 3 study THR-1442-C-476, which evaluated the safety and efficacy of BRENZAVVY in a population at increased risk for major adverse cardiovascular events. TheracosBio planned THR-1442-C-476 to meet the 1.8 criterion and intended to follow up with a second study if necessary. As a result, THR-1442-C-476 was relatively small, with 1699 evaluated subjects, compared to other SGLT2 inhibitor programs, which had up to 17160 participants. The trial was event-driven and planned to be continued until at least 134 events were recorded. 

The primary objective of the meta-analysis was to demonstrate the upper limit of the two-sided 95% confidence interval of the hazard ratio of BRENZAVVY to placebo was below 1.8, for a composite endpoint consisting of cardiovascular death, non-fatal stroke, non-fatal myocardial infarction and hospitalization for unstable angina (MACE+). The first key secondary objective was to demonstrate that the upper limit of the two-sided 95% confidence interval of the hazard ratio of BRENZAVVY to placebo was below 1.3 for a composite endpoint consisting of cardiovascular death, non-fatal stroke and non-fatal myocardial infarction (MACE).

Study Population
The average age of patients included in the meta-analysis at baseline was 61.7 years with 41.3% of patients ≥ 65 years and 9.0% of patients ≥75 years. Patients had an average duration of diabetes of approximately 11.6 years, a mean baseline HbA1c level of 8.13%, and most patients (82.8%) had eGFR at baseline ≥ 60 mL min-1 per 1.73 m2 . Some patients reported a cardiovascular disease history including myocardial infarction (22.7%), arterial revascularization (22.8%), congestive heart failure (12.4%), and/or stroke (5.4%). Patients resided in North America (50.1%), Europe (33.3%), Asia (15.1%), and South America (1.5%).
Time to First Adjudicated MACE+ (4-event composite endpoint)

The hazard ratio for MACE+ for patients in the BRENZAVVY arm compared to patients in the placebo arm was 0.795 (95% CI 0.578, 1.094; p-value for noninferiority at 1.8 < 0.0001). Since the upper limit of the two-sided 95% confidence interval was below 1.8, the noninferiority of BRENZAVVY to placebo for the pre-approval criterion was demonstrated.

Time to First Adjudicated MACE (3-event composite endpoint)

The hazard ratio for MACE for patients in the BRENZAVVY arm was 0.815 (95% CI 0.590, 1.125; p-value for noninferiority at 1.3 of 0.0023). Since the upper limit of the two-sided 95% confidence interval of the hazard ratio of BRENZAVVY to placebo was below 1.3, the hypothesis that BRENZAVVY would increase the risk of MACE by a factor of 1.3 or more was rejected.

Conclusions of the Meta-Analysis

A meta-analysis of major adverse cardiovascular events in the pre-approval program showed that both the pre-approval and post-approval requirements were met for BRENZAVVY. This was possible because the point estimates were substantially less than the value of 1.0 chosen for study planning purposes.

  1. McMurray JJV, Solomon SD, Lock JP, et al. Meta-analysis of risk of major adverse cardiovascular events in adults with type 2 diabetes treated with bexagliflozin. Diabetes Obes Metab. 2024;26(3):971-979.

BRENZAVVY® (bexagliflozin) Safety and Effectiveness Compared to Dapagliflozin as an Adjunct to Metformin for Treatment of Type 2 Diabetes Mellitus in Adults

Study Design A phase 3, randomized, double-blind, active-controlled trial compared the safety and effectiveness of BRENZAVVY, 20 mg, to dapagliflozin, 10 mg, as an adjunct to metformin for the treatment of type 2 diabetes mellitus in adults. The study population consisted of 406 participants who received BRENZAVVY or dapagliflozin in addition to ongoing metformin treatment for 24 weeks. The primary endpoint was the change in HbA1c  from baseline to week 24. This clinical trial was the first to directly compare any two SGLT2 inhibitors using a randomized, double-blind, controlled design evaluating effectiveness and safety.
Study Population
The average age in the study population was 56.0 years. Enrolled patients had an average duration of diabetes of approximately 6.45 years, a mean baseline HbA1c level of 8.53%, fasting plasma glucose (FPG) of 9.59 mmol L-1 , body mass of 70.2 kg, systolic blood pressure of 128 mm Hg, and 2-hour postprandial blood glucose (PPG) concentration of 14.72 mmol L-1 . Study patients were predominantly Asian (99.3%) and all resided in China.
HbA1c

BRENZAVVY treatment was noninferior to dapagliflozin for the management of type 2 diabetes mellitus in a population poorly controlled by metformin alone. The least-squares mean change in HbA1c  from baseline to week 24 was -1.08% in the BRENZAVVY arm and -1.10% in the dapagliflozin arm. The improvement in glycemic control was considered clinically meaningful.

At week 24, 61 patients in the BRENZAVVY arm (32.3%) and 59 patients in the dapagliflozin arm (31.6%) had achieved HbA1c < 7.0%, while 23 patients in the BRENZAVVY arm (12.2%) and 21 patients in the dapagliflozin arm (11.2%) had achieved HbA1c  < 6.5%. 

Fasting Plasma Glucose

BRENZAVVY or dapagliflozin treatment decreased fasting plasma glucose levels in patients from baseline to week 24. The change from baseline FPG in the BRENZAVVY arm was -1.95 mmol L-1  compared to -1.87 mmol L-1 in the dapagliflozin arm.

Body Mass

BRENZAVVY or dapagliflozin treatment decreased body mass in patients from baseline to week 24. The change from baseline body mass in the BRENZAVVY arm was -2.52 kg compared to -2.22 kg in the dapagliflozin arm.

Systolic Blood Pressure

BRENZAVVY or dapagliflozin treatment decreased systolic blood pressure from baseline to week 24. The change from baseline SBP in the BRENZAVVY arm was -6.4 mm Hg whereas patients in the dapagliflozin arm saw a change of -6.3 mm Hg.

2-h Postprandial Plasma Glucose
BRENZAVVY or dapagliflozin treatment decreased 2-hour postprandial plasma glucose from baseline to week 24. The change from baseline PPG in the BRENZAVVY arm was -3.19 mmol L-1 whereas patients in the dapagliflozin arm saw a change of -3.05 mmol L-1 .
Safety

The number of patients that experienced adverse events was comparable between the BRENZAVVY and dapagliflozin arms. 62.6% of patients treated with BRENZAVVY and 65.0% of patients treated with dapagliflozin reported events during the trial with 4.4% and 3.5% of patients reporting serious adverse events in the BRENZAVVY and dapagliflozin arms, respectively.

  1. Xie L, Han J, Cheng Z, Liu D, Liu, J, Xu C, Sun W, Li Q, Bian F, Zhang W, Chen, J, Zhu Q, Thurber TK, Lock JP. Efficacy and safety of Bexagliflozin compared with Dapagliflozin as an adjunct to metformin in Chinese patients with type 2 diabetes mellitus: a 24 week, randomized, double blind, active-controlled, phase 3 trial. Journal of Diabetes. 2024; 16(4):e13526. doi:10.1111/1753-0407.13526
Important Safety Information

Limitation of Use: BRENZAVVY (bexagliflozin) is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. 

Contraindications
BRENZAVVY is contraindicated in patients with hypersensitivity to bexagliflozin or any excipient in BRENZAVVY. Anaphylaxis and angioedema have been reported with sodium-glucose co-transporter 2 (SGLT2) inhibitors. 

Warnings and Precautions 

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis
BRENZAVVY increases the risk of life-threatening ketoacidosis in patients with type 1 diabetes. Type 2 diabetes and pancreatic disorders are also risk factors for ketoacidosis and fatal events of ketoacidosis have been reported in patients with type 2 diabetes 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. Signs and symptoms of diabetic ketoacidosis are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Assess patients who present with signs and symptoms of metabolic ketoacidosis, regardless of blood glucose levels. If suspected, discontinue BRENZAVVY, treat promptly and monitor for resolution before restarting. Consider ketone monitoring in patients with type 1 diabetes mellitus as well as in others at risk for ketoacidosis. Withhold BRENZAVVY in clinical situations known to predispose to ketoacidosis and resume when clinically stable. Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue BRENZAVVY and seek medical attention immediately if signs and symptoms occur. 

Lower Limb Amputation
Lower limb amputations have been observed in patients treated with BRENZAVVY in a study of patients with type 2 diabetes who had either established cardiovascular disease (CVD) or were at risk for CVD. Of the 23 BRENZAVVY-treated patients who had amputations, 15 were amputations of the toe and midfoot and 8 were amputations above and below the knee. Some patients had multiple amputations. Lower limb infections, gangrene, ischemia, and osteomyelitis were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy. 

Before initiating BRENZAVVY, consider factors in the patient’s history that may predispose to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients receiving BRENZAVVY about the importance of routine preventative foot care and monitor for signs and symptoms of diabetic foot infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.  

Volume Depletion
BRENZAVVY can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors. Before initiating, assess volume status and renal function in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, patients with low systolic blood pressure, or patients on loop diuretics. In patients with volume depletion, correct this condition. After initiating, monitor for signs and symptoms of volume depletion and renal function. 

Urosepsis and Pyelonephritis
Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been identified in patients receiving SGLT2 inhibitors, including BRENZAVVY. Treatment with BRENZAVVY increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat them promptly. 

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues
Insulin and insulin secretagogues (e.g., sulfonylureas) are known to cause hypoglycemia. BRENZAVVY may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with BRENZAVVY. 

Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)
Serious, life-threatening cases requiring urgent surgical intervention have been identified in postmarketing surveillance in both males and females with diabetes mellitus receiving SGLT2 inhibitors. Serious outcomes have included hospitalization, multiple surgeries, and death. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal areas, along with fever or malaise. If suspected, start treatment, and discontinue BRENZAVVY. 

Genital Mycotic Infections
BRENZAVVY increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately. 

MOST COMMON ADVERSE REACTIONS (>5%): Female genital mycotic infections, urinary tract infection and increased urination. 

USE IN SPECIFIC POPULATIONS
• Pregnancy: BRENZAVVY is not recommended during the second and third trimesters.
• Lactation: BRENZAVVY is not recommended when breastfeeding.
• Geriatric patients: There is a higher incidence of adverse reactions related to volume depletion.
• Renal Impairment: There is a higher incidence of adverse reactions related to reduced renal function.
• Hepatic Impairment: BRENZAVVY is not recommended for patients with severe hepatic impairment. 

DRUG INTERACTIONS:
Inducers of UGT1A9 could result in more rapid clearance of BRENZAVVY by metabolism. Doses of insulin and sulfonylureas may need to be reduced to offset the action of BRENZAVVY. The safety of BRENZAVVY is compromised when it is coupled with insulin or an insulin secretagogue (sulfonylureas and meglitinides – the latter rarely used in the US). Lithium carbonate is used as a mood stabilizer in bipolar disorder. Lithium ions might be preferentially (compared to sodium ions) taken up with glucose in the kidney. Empirical evidence has shown that lithium levels can be lower when SGLT2 inhibitors are administered. SGLT2 inhibitors produce pronounced glucosuria, which makes urine testing for glucose diagnostically useless. Measurements of 1,5 anhydroglucitol are also compromised. 

For additional important safety information about BRENZAVVY, please see the full Prescribing Information. 

Important Safety Information

Limitation of Use: BRENZAVVY (bexagliflozin) is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. 

Contraindications 
BRENZAVVY is contraindicated in patients

Scroll to Top

Important Safety Information

Limitation of Use: BRENZAVVY (bexagliflozin) is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients. 

Contraindications
BRENZAVVY is contraindicated in patients with hypersensitivity to bexagliflozin or any excipient in BRENZAVVY. Anaphylaxis and angioedema have been reported with sodium-glucose co-transporter 2 (SGLT2) inhibitors. 

Warnings and Precautions 

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis
BRENZAVVY increases the risk of life-threatening ketoacidosis in patients with type 1 diabetes. Type 2 diabetes and pancreatic disorders are also risk factors for ketoacidosis and fatal events of ketoacidosis have been reported in patients with type 2 diabetes 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. Signs and symptoms of diabetic ketoacidosis are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Assess patients who present with signs and symptoms of metabolic ketoacidosis, regardless of blood glucose levels. If suspected, discontinue BRENZAVVY, treat promptly and monitor for resolution before restarting. Consider ketone monitoring in patients with type 1 diabetes mellitus as well as in others at risk for ketoacidosis. Withhold BRENZAVVY in clinical situations known to predispose to ketoacidosis and resume when clinically stable. Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue BRENZAVVY and seek medical attention immediately if signs and symptoms occur. 

Lower Limb Amputation
Lower limb amputations have been observed in patients treated with BRENZAVVY in a study of patients with type 2 diabetes who had either established cardiovascular disease (CVD) or were at risk for CVD. Of the 23 BRENZAVVY-treated patients who had amputations, 15 were amputations of the toe and midfoot and 8 were amputations above and below the knee. Some patients had multiple amputations. Lower limb infections, gangrene, ischemia, and osteomyelitis were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy. 

Before initiating BRENZAVVY, consider factors in the patient’s history that may predispose to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients receiving BRENZAVVY about the importance of routine preventative foot care and monitor for signs and symptoms of diabetic foot infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and institute appropriate treatment.  

Volume Depletion
BRENZAVVY can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. Acute kidney injury requiring hospitalization and dialysis has been reported in patients with type 2 diabetes receiving SGLT2 inhibitors. Before initiating, assess volume status and renal function in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, patients with low systolic blood pressure, or patients on loop diuretics. In patients with volume depletion, correct this condition. After initiating, monitor for signs and symptoms of volume depletion and renal function. 

Urosepsis and Pyelonephritis
Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been identified in patients receiving SGLT2 inhibitors, including BRENZAVVY. Treatment with BRENZAVVY increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat them promptly. 

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues
Insulin and insulin secretagogues (e.g., sulfonylureas) are known to cause hypoglycemia. BRENZAVVY may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with BRENZAVVY. 

Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)
Serious, life-threatening cases requiring urgent surgical intervention have been identified in postmarketing surveillance in both males and females with diabetes mellitus receiving SGLT2 inhibitors. Serious outcomes have included hospitalization, multiple surgeries, and death. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal areas, along with fever or malaise. If suspected, start treatment, and discontinue BRENZAVVY. 

Genital Mycotic Infections
BRENZAVVY increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately. 

MOST COMMON ADVERSE REACTIONS (>5%): Female genital mycotic infections, urinary tract infection and increased urination. 

USE IN SPECIFIC POPULATIONS
• Pregnancy: BRENZAVVY is not recommended during the second and third trimesters.
• Lactation: BRENZAVVY is not recommended when breastfeeding.
• Geriatric patients: There is a higher incidence of adverse reactions related to volume depletion.
• Renal Impairment: There is a higher incidence of adverse reactions related to reduced renal function.
• Hepatic Impairment: BRENZAVVY is not recommended for patients with severe hepatic impairment. 

DRUG INTERACTIONS:
Inducers of UGT1A9 could result in more rapid clearance of BRENZAVVY by metabolism. Doses of insulin and sulfonylureas may need to be reduced to offset the action of BRENZAVVY. The safety of BRENZAVVY is compromised when it is coupled with insulin or an insulin secretagogue (sulfonylureas and meglitinides – the latter rarely used in the US). Lithium carbonate is used as a mood stabilizer in bipolar disorder. Lithium ions might be preferentially (compared to sodium ions) taken up with glucose in the kidney. Empirical evidence has shown that lithium levels can be lower when SGLT2 inhibitors are administered. SGLT2 inhibitors produce pronounced glucosuria, which makes urine testing for glucose diagnostically useless. Measurements of 1,5 anhydroglucitol are also compromised. 

For additional important safety information about BRENZAVVY, please see the full Prescribing Information. 

Important Safety Information

Limitation of Use: BRENZAVVY is not recommended in patients with type 1 diabetes mellitus. It may increase the risk of diabetic ketoacidosis in these patients.

Contraindications
BRENZAVVY (bexagliflozin) is contraindicated in patients:
• With hypersensitivity to bexagliflozin or any excipient in BRENZAVVY. Anaphylaxis and angioedema have been reported with sodium-glucose co-transporter 2 (SGLT2) inhibitors.
• On dialysis

Warnings And Precautions

Ketoacidosis
Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, have been identified in clinical trials and postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus who received SGLT2 inhibitors, including BRENZAVVY (bexagliflozin). Fatal cases of ketoacidosis have been reported for patients taking SGLT2 inhibitors. In placebo-controlled trials of patients with type 1 diabetes, the risk of ketoacidosis was increased in patients who received SGLT2 inhibitors compared to patients who received placebo. BRENZAVVY is not indicated for the treatment of patients with type 1 diabetes mellitus.

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

In many of the reported cases, and particularly in patients with type 1 diabetes, the presence of ketoacidosis was not immediately recognized, and the institution of treatment was delayed because the presenting blood glucose levels were below those typically expected for diabetic ketoacidosis (often less than 250 mg/dL). Signs and symptoms at presentation were consistent with dehydration and severe metabolic acidosis and included nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. In some but not all cases, factors predisposing to ketoacidosis, such as insulin dose reduction, acute febrile illness, reduced caloric intake, surgery, pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery), and alcohol abuse were identified.

Before initiating BRENZAVVY (bexagliflozin), consider factors in the patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse.

For patients who undergo scheduled surgery, consider temporarily discontinuing BRENZAVVY (bexagliflozin) for at least 3 days prior to surgery. Consider monitoring for ketoacidosis and temporarily discontinuing BRENZAVVY in clinical situations known to predispose to ketoacidosis (e.g., prolonged fasting due to acute illness or post-surgery). Ensure risk factors for ketoacidosis are resolved prior to restarting BRENZAVVY. Educate patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue BRENZAVVY and seek medical attention immediately if signs and symptoms occur.

Lower Limb Amputation
An increased incidence of lower limb amputations occurred in BRENZAVVY (bexagliflozin)-treated patients compared to placebo-treated patients (8.3 versus 5.1 events per 1,000 patient-years) in a randomized, placebo-controlled trial evaluating patients with type 2 diabetes who had either established cardiovascular disease (CVD) or were at risk for CVD.

Of the 23 BRENZAVVY (bexagliflozin)-treated patients who had amputations, 15 were amputations of the toe and midfoot and 8 were amputations above and below the knee. Some patients had multiple amputations.

Lower limb infections, gangrene, ischemia, and osteomyelitis were the most common precipitating medical events leading to the need for an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy.

Before initiating BRENZAVVY (bexagliflozin), consider factors in the patient history that may predispose to the need for amputations, such as a history of prior amputation, peripheral vascular disease, neuropathy, and diabetic foot ulcers. Counsel patients about the importance of routine preventative foot care. Monitor patients receiving BRENZAVVY for signs and symptoms of infection (including osteomyelitis), new pain or tenderness, sores or ulcers involving the lower limbs, and discontinue BRENZAVVY if these complications occur.

Volume Depletion
BRENZAVVY (bexagliflozin) can cause intravascular volume contraction which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been postmarketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors. Patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), elderly patients, patients with low systolic blood pressure, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating BRENZAVVY in patients with one or more of these characteristics, assess volume status and renal function. In patients with volume depletion, correct this condition before initiating BRENZAVVY. Monitor for signs and symptoms of volume depletion and renal function after initiating therapy.

Urosepsis and Pyelonephritis
There have been reports of serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization in patients receiving SGLT2 inhibitors, including BRENZAVVY (bexagliflozin). Treatment with SGLT2 inhibitors, including BRENZAVVY, increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated.

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues
Insulin and insulin secretagogues (e.g., sulfonylureas) are known to cause hypoglycemia. BRENZAVVY (bexagliflozin) may increase the risk of hypoglycemia when used in combination with insulin and/or an insulin secretagogue. A lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when used in combination with BRENZAVVY.

Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene)
Reports of necrotizing fasciitis of the perineum (Fournier’s Gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors. Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death.

Patients treated with BRENZAVVY (bexagliflozin) presenting with pain or tenderness, erythema, or swelling in the genital or perineal areas, along with fever or malaise, should be assessed for necrotizing fasciitis. If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue BRENZAVVY, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.

Genital Mycotic Infections
BRENZAVVY (bexagliflozin) increases the risk of genital mycotic infections. Patients who have a history of genital mycotic infections or who are uncircumcised are more likely to develop genital mycotic infections. Monitor and treat appropriately.

Adverse Reactions
The most common adverse reactions (incidence > 5%) were female mycotic infections, urinary tract infection, and increased urination.

Use in Specific Populations
• Pregnancy: Advise females of the potential risk to a fetus especially during the second and third trimesters. BRENZAVVY (bexagliflozin) is not recommended during the second and third trimesters of pregnancy.
• Lactation: Not recommended when breastfeeding
• Geriatric patients: Higher incidence of adverse reactions related to volume depletion
• Renal Impairment: Higher incidence of adverse reactions related to reduced renal function
• Hepatic Impairment: Not recommended for patient with severe hepatic impairment

Drug Interactions

UGT Enzyme Inducers

Clinical Impact
UGT Enzyme Inducers may significantly reduce exposure to BRENZAVVY and lead to decreased efficacy.
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 BRENZAVVY is 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 BRENZAVVY.
Lithium
Clinical Impact
Concomitant use with SGLT2 inhibitors such as BRENZAVVY may decrease serum lithium concentrations.
Intervention
Monitor serum lithium concentration more frequently upon BRENZAVVY 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.
For additional important safety information about BRENZAVVY, please see the Prescribing Information.

Are you a healthcare professional?

This section contains information intended for healthcare professionals in the United States only and is not intended for the general public.

No, I am not. Please take me back.

Yes, I am.

This site is intended only for users in the United States.
© 2023 TheracosBio, LLC

TERMS OF USE

Last Updated on March 16, 2023

PLEASE READ THESE TERMS OF USE (the “Terms of Use”) CAREFULLY BEFORE ACCESSING HTTPS://WWW.BRENZAVVY.COM AND ITS RELATED ADDRESSES IN THE BRENZAVVY.COM DOMAIN (THE “SITE”) AS THEY CONSTITUTE A LEGALLY BINDING AGREEMENT BETWEEN YOU AND THERACOSBIO, LLC (TOGETHER WITH ITS AFFILIATES, REFERRED TO HEREIN COLLECTIVELY AS “THERACOSBIO” OR “US” OR “WE”) AND GOVERN YOUR ACCESS TO AND USE OF THE SITE. IF YOU DO NOT AGREE TO THESE TERMS OF USE, PLEASE DO NOT USE THE SITE. YOUR CONTINUED USE OF THE SITE WILL INDICATE YOUR ACCEPTANCE OF THESE TERMS OF USE.

NO MEDICAL ADVICE. The Site is provided for informational purposes only and is not medical advice or a substitute for professional medical advice, diagnosis, treatment or care. Only a healthcare professional can determine if a product described on the Site is appropriate for you. Use of the Site is not a substitute for consultation with a healthcare professional. YOU SHOULD NEVER DISREGARD OR DELAY SEEKING MEDICAL ADVICE BECAUSE OF SOMETHING THAT YOU HAVE SEEN ON THE SITE. PLEASE CONSULT A QUALIFIED HEALTHCARE PROFESSIONAL BEFORE USING ANY PRODUCT DISCUSSED ON THE SITE.

PRIVACY. Our Privacy Policy is located at (“Privacy Policy”) and describes our collection, use and disclosure of data and information in connection with the Site. Our Privacy Policy is expressly incorporated into these Terms of Use, and by using the Site you agree to the collection, use and disclosure practices described in the Privacy Policy.

  1. CONTENT MADE AVAILABLE ON OR THROUGH THE SITE AND YOUR USE OF CONTENT.
    1. Description of Content. The Site contains a variety of Content (defined below), whether (1) proprietary to TheracosBio, or (2) proprietary to third parties. “Content” includes, but is not limited to text, data, files, documents, reports, software, scripts, layout, design, function and “look and feel,” graphics, images, audio, videos, audiovisual combinations, interactive features and any other materials that you may view or access through the Site.
    2. Proprietary Rights. You acknowledge and agree that all Content, whether publicly posted or privately transmitted, as well as all derivative works thereof, are owned by TheracosBio or other parties that have licensed their material to TheracosBio, and are protected by copyright, trademark, and other intellectual property laws.
    3. Disclaimer. Content is provided to you AS IS. You understand that we do not guarantee the accuracy, safety, completeness, currency, integrity or quality of Content and you hereby agree that you must evaluate and bear all risks associated with your use of any Content.
  2. RESTRICTIONS ON YOUR USE OF THE SITE You agree that you shall not (and shall not allow any third party to): (i) access or use the Site in an unlawful way or for an unlawful or illegitimate purpose or in any manner that contravenes these Terms of Use or our Privacy Policy; (ii) attempt to disrupt the operation of the Site, divert visitors from the Site and/or attempt to control visitors to the Site or present information on the Site, for example through use of methods such as installation of malware, presentation of information or advertising, collection of visitor information, or launch of denial of service attacks; (iii) attempt, through any means, to gain unauthorized access to the Site and/or the computer systems or networks of TheracosBio; (iv) impersonate any person or entity, or falsely state or otherwise misrepresent your affiliation with a person or entity; or (v) use any robot, spider, scraping or framing technique in violation of trademark, copyright or other proprietary rights of TheracosBio.
  3. TRADEMARKS/SERVICE MARKS, LOGOS, SLOGANS AND TAGLINES. All trademarks, service marks, logos, slogans and taglines displayed on the Site (collectively, “Marks”) are the property of TheracosBio or their respective owners and nothing contained herein should be construed as granting any license or right to use any Marks displayed on the Site without the express written permission of TheracosBio, or such third party as may own the Mark.
  4. OPERATION/RECORDS RETENTION. You understand that the Site is provided as a courtesy to you and that we may modify, suspend or terminate all or a portion of the Site at any time in our discretion without prior notice to you.
  5. TERMINATION/EXCLUSION. We reserve the right, in our sole discretion, to revoke, terminate or suspend any privileges associated with accessing our Site for any reason or for no reason whatsoever, including improper use of the Site or failure to comply with these Terms of Use.
  6. VISITOR/USER SUGGESTIONS. You acknowledge and agree that any questions, comments, suggestions, ideas, feedback, or other information provided by you to TheracosBio (“Comments”) are not confidential and you hereby grant to TheracosBio a worldwide, perpetual, irrevocable, royalty-free license to reproduce, display, perform, distribute, publish, modify, edit or otherwise use such Comments as it deems appropriate, for any and all commercial or non-commercial purposes, in its sole discretion.
  7. The Site may contain links to other websites under the control of third parties. TheracosBio’s provision of links to other websites on the Site is for your convenience and does not signify TheracosBio’s endorsement, approval of the contents, or assurance regarding the safety of such other sites or their contents. TheracosBio has no control over and is not responsible for any third-party websites or their content.
  8. ELECTRONIC COMMUNICATIONS. When you enter information on the Site, send emails to us or otherwise communicate with us electronically, you consent to receive communications from us electronically. We will communicate with you by email or by posting notices on the Site. You agree that all such communications constitute communications in writing and are effective immediately.
  9. YOUR INFORMATION. You grant TheracosBio a non-exclusive license to copy, use and display any and all data, information or communications (including personally identifiable data (“Personal Information”)) sent to TheracosBio or entered by you or on your behalf, while accessing the Site to the extent necessary for TheracosBio to operate the Site, its business and/or to facilitate interactions or transactions with you. You acknowledge that TheracosBio has no control whatsoever over the content of any Personal Information as it is provided to us, and that it is your sole responsibility, at your own expense, to provide the Personal Information and to ensure that the Personal Information you transmit complies with applicable laws and regulations. TheracosBio is under no obligation to review your Personal Information for accuracy, potential liability or for any other reason.You represent and warrant to us that you have the right to provide any Personal Information that you provide to us. By providing Personal Information on the Site, you grant us the right and license to use, display, reproduce, adapt, modify, re-arrange and distribute the Personal Information in order to respond to your communication through the Site. You understand that your Personal Information may be transferred unencrypted over public networks.
  10. DISCLAIMER OF WARRANTY. ACCESS TO THE SITE IS PROVIDED “AS IS” AND “AS AVAILABLE” “WITH ALL FAULTS” AND WITHOUT ANY WARRANTY OF ANY KIND, EXPRESS OR IMPLIED. NEITHER THERACOSBIO NOR ITS LICENSORS WARRANT THAT ACCESS TO THE SITE WILL BE UNINTERRUPTED OR ERROR-FREE, OR THAT DEFECTS, IF ANY, WILL BE CORRECTED; NOR DOES THERACOSBIO MAKE ANY REPRESENTATIONS ABOUT THE ACCURACY, RELIABILITY, CURRENCY, QUALITY, COMPLETENESS, USEFULNESS, PERFORMANCE, SECURITY, LEGALITY OR SUITABILITY OF THE SITE.  IF YOU USE THE SITE FROM OUTSIDE THE UNITED STATES OF AMERICA, YOU ARE SOLELY RESPONSIBLE FOR COMPLIANCE WITH ALL APPLICABLE LAWS.
  11. EXCLUSIVE REMEDY. IN THE EVENT OF ANY PROBLEM WITH THE SITE, YOU AGREE THAT YOUR SOLE AND EXCLUSIVE REMEDY IS TO CEASE USING THE SITE.
  12. INDEMNIFICATION. You agree to indemnify, hold harmless, and defend TheracosBio and its licensors, suppliers, officers, directors, employees, agents, affiliates, subsidiaries, successors and assigns (collectively “Indemnified Parties”) from and against any and all liability, loss, claim, damages, expense, or cost (including but not limited to attorneys’ fees), incurred by or made against the Indemnified Parties in connection with any claim arising from or related to your use of the Site, or any breach or violation of these Terms of Use by you.
  13. MISCELLANEOUS. THE FORMATION, INTERPRETATION AND PERFORMANCE OF THIS AGREEMENT AND ANY DISPUTES ARISING OUT OF IT SHALL BE GOVERNED BY THE SUBSTANTIVE AND PROCEDURAL LAWS OF THE COMMONWEALTH OF MASSACHUSETTS WITHOUT REGARD TO ITS RULES ON CONFLICTS OR CHOICE OF LAW AND, TO THE EXTENT APPLICABLE, THE LAWS OF THE UNITED STATES OF AMERICA.
  14. COMMENTS AND CONCERNS. All feedback, questions or other communications relating to the Site should be submitted to us using our “Contact” feature on https://www.theracosbio.com/.

PRIVACY POLICY

Last Updated on March 16, 2023

SUMMARY

This privacy policy (the “Privacy Policy”) is intended to inform you of the policies and practices of TheracosBio and its affiliates (referred to herein as “TheracosBio” or pronouns we/us/our) regarding the collection, use and disclosure of information that you provide when you visit https://www.brenzavvy.com and its related addresses in the brenzavvy.com domain (the “Site”). By using the Site, you indicate that you agree to this Privacy Policy. If you do not agree with this Privacy Policy, you should not use the Site. This Privacy Policy may change from time to time. Changes are effective the date that they are published, so please check periodically to ensure that you have reviewed the most current version of the Privacy Policy. If you have questions, comments, suggestions or concerns about the Privacy Policy, please contact us by using our “Contact” feature on https://www.theracosbio.com.

DEFINITIONS

“Personal Information” is information about you that is personally identifiable to you like your name, state of residence, and e-mail address.

“Anonymous Information” means information that is not associated with or linked to you or your Personal Information. We construe potentially informative data such as internet protocol addresses, browser configurations and other information conveyed in an https request to the site as Anonymous Information.

INFORMATION YOU PROVIDE TO US

We collect Personal Information that you voluntarily provide to us when you use the Site. For example, you may provide us with your contact information such as your email address, first and last name, phone number or other Personal Information that you choose to submit through email, an online form or other method, such as through the “Contact” feature on https://www.theracosbio.com. Please do not submit any personal health information or other sensitive Personal Information. TheracosBio is not a healthcare provider, and any questions related to healthcare or clinical treatment should be directed to a qualified healthcare provider.

INFORMATION WE AUTOMATICALLY COLLECT

Log Files

The Site gathers certain Anonymous Information automatically (as do many websites) and stores it in web server log files. This information includes the internet protocol (IP) address, browser type, internet service provider (ISP), referring pages, operating system, date/time stamp, and page access/user action data. TheracosBio or those working on its behalf may use this information to improve the Site, analyze trends, administer the Site, identify sequences of user actions around the Site, and gather general information about Site use.

Cookies

A cookie is a small text file that is stored on a user’s device for record-keeping purposes. It can also help TheracosBio understand how Site visitors arrive at the Site and what pages they view during their visit. Similar to many websites, the Site uses a standard technology called a “session cookie” to enable the Site to recognize your device during a visit to the Site. The session cookie is not retained after you close your browser. You can configure your browser to disable cookies. If you disable cookies, you will still be able to view the Site, but some functionality of the Site may be lost.

HOW WE USE YOUR INFORMATION

In general, we collect Anonymous Information and Personal Information so that we can ensure the secure functioning of the Site, support the mission of our company, and provide information that you request from us. The most important (but not the sole) uses of the Information are to:

  • Provide, operate, improve, maintain, and protect the Site
  • Provide you with technical and other support
  • Conduct research, monitor and analyze trends and usage
  • Contact you to respond to your inquiries
  • Enhance or improve the user experience, our business, or the Site, including the safety and security of the Site
  • Personalize the Site for your convenience
  • Comply with any applicable law, regulation, subpoena, legal process, or governmental request as necessary

HOW WE SHARE YOUR PERSONAL INFORMATION

We do not rent or sell your Personal Information.

Like most companies, we share information, including Personal Information, in certain circumstances with third parties through operation of our Site and our business. Below we explain those circumstances.

SERVICE PROVIDERS

To the extent that we have collected Personal Information from you, we may transfer Personal Information to third parties for the purpose of operating our business. For example, we may transfer your Personal Information to a third-party service provider to assist with a response to a request.

REQUIRED TRANSFERS

We may also transfer your Personal Information to third parties under the following circumstances: (i) to comply with a legal requirement, subpoena, judicial proceeding, court order, governmental request, or legal process; (ii) to support the investigation of possible criminal activity, such as fraud or identity theft; (iii) in connection with the sale, purchase, merger, asset sale, financing, reorganization, liquidation or dissolution of TheracosBio including the evaluation thereof; (iv) when we believe it is necessary to protect the rights, property, or safety of TheracosBio or other persons, or (v) as otherwise required or permitted by law, including any contractual obligations of TheracosBio.

AS DIRECTED BY YOU AND WITH YOUR CONSENT

Except as otherwise provided in this Privacy Policy, we share Personal Information with companies, organizations or individuals outside of TheracosBio only at your direction or when we have your consent to do so.

CURRENCY AND ACCURACY OF INFORMATION

TheracosBio endeavors to keep the Site current but there can be no guarantee that Site information is complete or accurate at any given time.

OTHER WEBSITES

The Site may contain links to other websites under the control of third parties. TheracosBio’s provision of links to other websites on the Site is for your convenience and does not signify TheracosBio’s endorsement or assurance regarding the safety of such other sites or their contents. TheracosBio has no control over and is not responsible for any third-party websites or their content. The terms of this Privacy Policy do not apply to third party websites.

SECURITY

TheracosBio uses standard measures to maintain the security of the Site, consistent with the nature of the information collected on the Site. Despite these safeguards, we cannot guarantee that unauthorized third parties will not be able to defeat our security and improperly collect, access, steal or modify any Personal Information that we may have collected from you.

NOTICE FOR VISITORS FROM OUTSIDE OF THE UNITED STATES

The Site is intended for users in the United States. The United States and other countries have not harmonized their privacy regulations. TheracosBio servers are located in the United States and TheracosBio has written its Privacy Policy to satisfy United States regulations. By using the Site, you agree to the level of privacy protection set forth in this policy.

CHILDREN UNDER 13 YEARS OF AGE

The Site is not intended for, or designed to attract, children under the age of 13, and TheracosBio does not intentionally gather Personal Information about visitors who are under the age of 13. TheracosBio would be pleased to work with parents and guardians to delete from its records any Personal Information a child may improperly disclose. If you believe that TheracosBio has been provided with Personal Information about a child who is under the age of 13, please contact us by using our “Contact” feature on https://www.theracosbio.com so that we may delete such Personal Information.

Are you a healthcare professional?

This section contains information intended for healthcare professionals in the United States only and is not intended for the general public.

No, I am not. Please take me back.
Yes, I am.

This site is intended only for users in the United States.
© 2023 TheracosBio, LLC

Important Safety Information

Do not take BRENZAVVY (bexagliflozin) if you:
• Are allergic to bexagliflozin or any ingredients in BRENZAVVY

BRENZAVVY can cause serious side effects, including:

Diabetic Ketoacidosis: (increased ketones in your blood or urine) in people with type 1 diabetes and other ketoacidosis. BRENZAVVY can cause ketoacidosis that can be life-threatening and may lead to death. Ketoacidosis is a serious condition which needs to be treated in a hospital. People with type 1 diabetes have a high risk of getting ketoacidosis. People with type 2 diabetes or pancreas problems also have an increased risk of getting ketoacidosis. Ketoacidosis can also happen in people who: are sick, cannot eat or drink as usual, skip meals, are on a diet high in fat and low in carbohydrates (ketogenic diet), take less than the usual amount of insulin or miss insulin doses, drink too much alcohol, have a loss of too much fluid from the body (volume depletion), or who have surgery. Ketoacidosis can happen even if your blood sugar is less than 250 mg/dL. Your healthcare provider may ask you to periodically check ketones in your urine or blood.

Stop taking BRENZAVVY and call your healthcare provider or get medical help right away if you get any of the following. If possible, check for ketones in your urine or blood, even if your blood sugar is less than 250 mg/dL.

• nausea
• vomiting
• stomach-area (abdominal) pain
• tiredness
• trouble breathing
• ketones in your urine or blood
 

Amputations: BRENZAVVY may increase your risk of lower limb amputations. Amputations mainly involve removal of the toe or part of the foot, however, amputations involving the leg, below and above the knee, have also occurred. Some people had more than one amputation.

You may be at a higher risk of lower limb amputation if you:

• have a history of amputation
• have heart disease or are at risk for heart disease
• have had blocked or narrowed blood vessels, usually in your leg, or have damage to the nerves (neuropathy) in your leg
• have had diabetic foot ulcers or sores

Call your healthcare provider right away if you have new pain or tenderness or any sores, ulcers, or infections in your leg or foot. Your healthcare provider may decide to stop your BRENZAVVY treatment for a while if you have these signs or symptoms. Talk to your healthcare provider about proper foot care.

Dehydration: BRENZAVVY can cause some people to become dehydrated (the loss of body water and salt). Dehydration can make you feel dizzy, faint, light-headed, or weak, especially when you stand up (orthostatic hypotension). There have been reports of sudden worsening of kidney function in people who are taking BRENZAVVY.

You may be at higher risk of dehydration if you:

• have low blood pressure
• take medicines that lower your blood pressure, including diuretics (water pills), or are on a low-sodium (salt) diet
• have kidney problems
• are 65 years of age or older

Talk to your healthcare provider about what you can do to prevent dehydration including how much fluid you should drink on a daily basis. Call your healthcare provider right away if you reduce the amount of food or liquid you drink, for example if you are sick and cannot eat, or start to lose liquids from your body due to conditions like vomiting or diarrhea.

Vaginal yeast infection: Women who take BRENZAVVY may get vaginal yeast infections.

Yeast infections can be a serious but common side effect of taking BRENZAVVY. Symptoms of a vaginal yeast infection include:

• vaginal odor
• white or yellowish vaginal discharge (discharge may be lumpy or look like cottage cheese)
• vaginal itching

Yeast infection of the penis (balanitis or balanoposthitis): Men who take BRENZAVVY may get a yeast infection of the skin around the penis. Men who are not circumcised may have swelling of the penis that makes it difficult to pull back the skin around the tip of the penis.

Other symptoms of yeast infection of the penis include:

• redness, itching, or swelling of the penis
• rash of the penis
• foul smelling discharge from the penis
• pain in the skin around penis
 

Talk to your healthcare provider about what to do if you get symptoms of a yeast infection of the vagina or penis. Your healthcare provider may suggest you use an over-the-counter antifungal medicine. Talk to your healthcare provider as soon as possible if you use an over-the-counter antifungal medication and your symptoms do not go away.

The most common side effects of BRENZAVVY (bexagliflozin) include:

• vaginal yeast infections
• urinary tract infection
• changes in urination including an urgent need to urinate more often, in larger amounts, or at night.

Before you take BRENZAVVY, tell your healthcare provider about all of your medical conditions, including if you:

• have type 1 diabetes or have had diabetic ketoacidosis
• have a decrease in your insulin dose
• have a serious infection
• have a history of infection of the vagina or penis
• have a history of amputation
• have had blocked or narrowed blood vessels, usually in your leg
• have damage to the nerves (neuropathy) in your leg
• have had diabetic foot ulcers or sores
• have kidney problems
• have liver problems
• have a history of urinary tract infections or problems with urination
• have or have had problems with your pancreas, including pancreatitis or surgery on your pancreas
• are on a low sodium (salt) diet. Your healthcare provider may change your diet or your dose.
• are going to have surgery. Your healthcare provider may stop your BRENZAVVY before you have surgery. Talk to your healthcare provider if you are having surgery about when to stop taking BRENZAVVY and when to start it again.
• are eating less or there is a change in your diet
• are dehydrated
• drink alcohol very often or drink a lot of alcohol in the short term (“binge” drinking).
• have ever had an allergic reaction to BRENZAVVY
• are pregnant or planning to become pregnant. BRENZAVVY may harm your unborn baby. If you become pregnant while taking BRENZAVVY, tell your healthcare provider as soon as possible. Talk with your healthcare provider about the best way to control your blood sugar while you are pregnant.
• are breastfeeding or plan to breastfeed. BRENZAVVY may pass into your breast milk and may harm your baby. Talk with your healthcare provider about the best way to feed your baby if you take BRENZAVVY. Do not breastfeed while taking BRENZAVVY.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

BRENZAVVY may affect the way other medicines work, and other medicines may affect how BRENZAVVY works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

What are the possible side effects of BRENZAVVY?

Serious urinary tract infections. Serious urinary tract infections that may lead to hospitalization have happened in people who are taking BRENZAVVY. Tell your healthcare provider if you have signs or symptoms of a urinary tract infection such as a burning feeling when passing urine, a need to urinate often, the need to urinate right away, pain in the lower part of your stomach (pelvis), or blood in the urine. Sometimes people also may have a fever, back pain, nausea or vomiting.

Low blood sugar (hypoglycemia). If you take BRENZAVVY with another medicine that can cause low blood sugar such as a sulfonylurea or insulin, your risk of getting low blood sugar is higher. The dose of your sulfonylurea or insulin may need to be lowered while you take BRENZAVVY. Signs or symptoms of low blood sugar may include:

• headache
• confusion
• hunger
• shaking or feeling jittery
• drowsiness
• dizziness
• fast heartbeat
• weakness
• sweating
• irritability
 

A rare but serious bacterial infection that causes damage to the tissue under the skin (necrotizing fasciitis) in the area between and around the anus and genitals (perineum). Necrotizing fasciitis of the perineum has happened in people who take BRENZAVVY. Necrotizing fasciitis of the perineum may lead to hospitalization, may require multiple surgeries, and may lead to death. Seek medical attention immediately if you have a fever or you are feeling very weak, tired or uncomfortable (malaise) and you develop any of the following symptoms in the area between and around your anus and genitals:

• pain or tenderness
• swelling
• redness of the skin (erythema)
 

Serious allergic reaction. If you have any symptoms of a serious allergic reaction, stop taking BRENZAVVY and call your healthcare provider right away or go to the nearest hospital emergency room. Symptoms of a serious allergic reaction to BRENZAVVY may include:

• skin rash
• raised red patches on your skin (hives)
• swelling of the face, lips, tongue, and throat that may cause difficulty in breathing or swallowing

Your healthcare provider may give you a medicine for your allergic reaction and prescribe a different medicine for your diabetes.

You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.

For additional important safety information about BRENZAVVY, please see the Medication Guide.