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Bexagliflozin (Brenzavvy): FDA Prescribing Information

Bexagliflozin (Brenzavvy)

type 2 diabetes medications list Bexagliflozin Brenzavvy

Bexagliflozin is a newly approved SGLT-2 inhibitor. It is marketed under the brand name, Brenzavvy, by TheracosBio, LLC. It got FDA approval on 20th January 2023.

Bexagliflozin, like all other SGLT2 inhibitors, acts on the renal tubules and inhibits glucose and sodium reabsorption.

Thus, in addition to being a potent diabetes medication, it also gets the body rid of excess fluid and salt.

It is associated with weight loss and improvement in blood pressure as well.

Bexagliflozin (Brenzavvy) FDA-approved indications [Ref]:

Brenzavvy has been approved for the treatment of individuals with Type 2 Diabetes Mellitus. It is not approved for the treatment of Type 1 Diabetes and individuals who are at risk of developing diabetic ketoacidosis.

In addition, it is not recommended in patients with a CrCl of less than 30 ml/minute (stage IV kidney disease). It is contraindicated in CKD patients who are on dialysis.

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Bexagliflozin (Brenzavvy) efficacy in Diabetes: A1C Lowering effect:

The A1C lowering effect of Bexagliflozin ranges from 0.4 – 0.6 %.

In a placebo-controlled clinical trial that lasted 24 weeks, the A1C lowered from a baseline of 8.1% to 7.6% [Ref]

Efficacy in Diabetes Brenzavvy Placebo
Change in A1C% 0.5% (8.1 to 7.6% 0.1% (7.9 to 7.8%)
Change in FPG (mg/dl) -16 (169 to 153) -3 (170 to 167)

When combined with metformin, the A1C dropped from 8.6 to 7.6% (1% reduction in the A1C) compared to a 0.5% reduction in the A1C.

When compared with Glimepiride, the A1C lowering effect Brenzavvy + Metformin was comparable to Glimepiride + Metformin (0.7% vs 0.6%)

When compared with Sitagliptin, the A1C-lowering effect of Brenzavvy + Metformin was comparable to Sitagliptin + Metformin (0.9% vs 0.8%)

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Bexagliflozin (Brenzavvy) effect on body weight:

Bexagliflozin (Brenzavvy) is associated with modest weight loss. In the clinical trials, Brenzavvy use was associated with 2.1 kg weight loss compared to 0.4 kg weight loss in the placebo group.

Bexagliflozin (Brenzavvy) Dosing Recommendations:

Brenzavvy is available as a 20 mg blue-colored Tablet. The recommended dose is 20 mg orally once a day after the morning meal.

It may be taken with or without food. However, the tablet should not be crushed or chewed before ingesting.

Dose in Kidney Disease:

The use of Brenzavvy in patients with kidney disease should be limited to those with an eGFR of more than 30 ml/minute. The dose adjustment in CKD is as follows:

  • ESRD and Dialysis: Contraindicated
  • eGFR of less than 30 ml/minute: Not recommended
  • eGFR of more than 30 ml/minute: No dose adjustment recommended.

Dose in Liver Disease:

Brenzavvy has not been studied in patients with liver disease. The manufacturer recommends using the usual dose in patients with mild to moderate liver impairment. However, it should be avoided in advanced liver disease.

Use in Pregnancy and Breastfeeding:

Brenzavvy is not recommended for use during pregnancy, especially during the 2nd and 3rd trimesters.

It has not been given a pregnancy risk category yet but likely falls in category C of pregnancy.

Similarly, the drug is not recommended during breastfeeding either because:

  • it has not been studied in breastfeeding mothers
  • it may cause volume depletion reducing the milk volume
  • it was found in animal milk and may cause side effects in infants.
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Bexagliflozin (Brenzavvy) Contraindications and Side effects:

It is contraindicated in patients who are allergic to the drug, or any component of the formulation.

In addition, it is contraindicated in patients who are on dialysis.

Euglycemic Ketoacidosis:

Like all other SGLT2 Inhibitors, Bexagliflozin is associated with euglycemic ketoacidosis. This means, the blood glucose may not be very high but the patient may still develop DKA.

It is therefore recommended to investigate any sick patient on Bexagliflozin for DKA if he/she develops abdominal pain, nausea, or shortness of breath.

In addition, all patients who are undergoing a major surgical procedure should stop the drug at least three days before the procedure.

Individuals who develop DKA should be treated in the hospital with intravenous fluids, intravenous insulin, and electrolyte solutions.

Individuals with a history of DKA or those who are at risk of developing DKA should not be started on any SGLT2 inhibitor including Brenzavvy.

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Amputation:

The risk of lower limb amputations is increased with Bexagliflozin (Brenzavvy), like all the SGLT-2 inhibitors.

The risk is greatest with Invokana (Canagliflozin), however, there is no exception.

In the clinical trial, there were 8.3 events of amputations per 1000 patient-years compared to 5.1 events of amputations per 1000 patient-years in the placebo group.

Most patients who had amputations done had infections of the lower limbs, gangrene, osteomyelitis, or ischemia.

It is recommended to assess the risk of amputations in patients who are started on Brenzavvy treatment.

This may include evaluation for diabetic neuropathy, peripheral arterial disease, and a history of previous lower limb amputation.

Patients should also be warned to report any new-onset symptoms of a boil, blackish discoloration of the toes or feet, swelling, redness, and pain in the feet.

Amputation risk Brenzavvy Placebo
Amputation 2% 1.2%
Amputation incidence rate (per 1000 patient-years) 8.3 5.1

 

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Dehydration:

Volume depletion is a common side effect of all SGLT2 inhibitors owing to the mechanism of action of SGLT2 inhibitors.

Patients may develop blackouts and symptomatic hypotension especially if they have one or more of the following conditions:

  • Elderly patients
  • Kidney disease with a CrCl of less than 60 ml/minute
  • those with a baseline low systolic blood pressure
  • those on diuretics
  • those with nausea, vomiting, or diarrhea.

All patients who may develop hypotension and volume depletion may be advised to take adequate fluids.

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Genital infections:

Genital infections especially genital mycotic infections and urinary tract infections are among the most common side effects of SGLT2 inhibitors including Bexagliflozin (Brenzavvy).

Urogenital infections are most common in females and those with a history of urogenital infections.

Patients should be asked to report if they develop frequent and burning micturition, nocturia, dysuria, and hesitancy.

The urogenital infections in clinical trials were reported as:

Urogenital infections Brenzavvy (372) Placebo (300)
Increased urination 7% 3%
Urinary tract infection 6% 4%
Female genital mycotic infection 6% 0%
Vaginal pruritis 3% 0%
Male genital mycotic infection 2% 1%

 

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Hypoglycemia:

Hypoglycemia is not a side effect of SGLT 2 inhibitors. However, the combined use of Brenzavvy and insulin or insulin secretagogues may increase the risk of hypoglycemia.

Patients may need a reduced dose of insulin or other diabetes medications to avoid the risks of hypoglycemia.

Fournier’s Gangrene:

Fournier’s gangrene is a serious and often life-threatening infection of the perineum and genital area. The incidence of Fournier’s gangrene has markedly increased with the use of SGLT2 inhibitors in the recent few years.

All patients who are on Brenzavvy treatment should be asked to report any symptoms of fever, redness, swelling, tenderness, or pain in the groin.

Patients usually need hospitalizations, intravenous antibiotics, fluids, frequent debridement, and surgeries.

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Other side effects associated with Brenzavvy:

Brenzavvy is also associated with an increase in:

  • Hemoglobin
  • Hematocrit
  • LDL levels

Bexagliflozin (Brenzavvy) Drug Interactions:

Brenzavvy Drug Interactions Impact What to do?
UGT enzyme inducers (Rifampicin, Phenobarbital) May reduce the efficacy of Brenzavvy. May need to switch to another diabetes medicine
Insulin or Insulin secretagogues The risk of hypoglycemia is increased May need to reduce the dose of insulin or other diabetes medicine
Lithium May reduce lithium concentration Monitor serum lithium concentration

 

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Bexagliflozin MOA (Mechanism of action):

Bexagliflozin is a potent SGLT2 inhibitor. It blocks the SGLT2 receptors present in the renal tubules and inhibits the reabsorption of glucose and sodium back into the plasma.

More glucose and sodium get excreted resulting in:

    • lowering of blood glucose and improvement in A1C.
    • loss of calories leading to weight loss.
    • loss of sodium and so improvement in blood pressure and heart failure
    • increased risk of genital and urinary tract infections
  • Effect on QTc:
    • no effect
  • Peak Plasma concentration after intake:
    • 2 to 4 hours
  • Protein-binding:
    • 93%
  • Metabolism:
    • It is primarily metabolized by UGT1A9 and partially by CYP3A
  • Terminal elimination half-life:
    • 12 hours
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Bexagliflozin brands and cost:

Brenzavvy (20 mg tablet) TheracosBio, LLC:

  • estimated price per 30 tablets is USD 300 to USD 600.
  • The cost will be updated soon

What do you think?

Written by Ahmed Farhan

I am an Internist practicing medicine for the last fifteen years. Over the years, I have learned that medicine is not about prescribing pills. True medical practice is helping people.
I do prescribe pills as well but the best results I get are when I motivate people to overcome their problems with little changes in their lifestyles.
Since most of my patients are obese and have diabetes, hypertension, and high cholesterol levels, I am writing at dibesity.com when free.
Dibesity, I know the correct word is diabesity. Ignore this! Be with us.
Also, you can contact me directly at dibesity.com@gmail.com

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