bexagliflozin

Action and Spectrum

Mechanism of action 

The mechanism of action of bexagliflozin is that it selectively blocks the reabsorption of glucose by the kidney, which leads to increased glucose excretion in the urine and a reduction in blood glucose levels. The drug works by inhibiting SGLT2, a protein in the proximal tubules of the kidneys responsible for reabsorbing glucose from the filtered urine back into the bloodstream. By blocking SGLT2, bexagliflozin prevents glucose reabsorption, leading to increased glucose excretion in the urine 

Spectrum 

The spectrum of activity of bexagliflozin includes the treatment of type 2 diabetes. It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It is also used to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease 

Drug Interaction

Adverse Reaction

Frequency defined:  

1-10% 

Increased urination 

Female genital mycotic infections 

Thirst 

Sepsis 

Hypoglycemia 

Volume depletion adverse effects 

Urinary tract infection 

Increased LDL cholesterol 

Vaginal pruritis 

Male genital mycotic infections 

<1% 

Increased hemoglobin of more than 3g/dL from baseline 

Black Box Warning

Contraindication / Caution

Contraindications 

• Severe renal impairment: It is not recommended for use in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] less than 30 mL/min/1.73 m2) or end-stage renal disease (ESRD) requiring dialysis. 
• Hypersensitivity: It should not be used in patients with a known hypersensitivity to the drug or any ingredients. 
• Dehydration: Patients who are dehydrated or at risk of dehydration should not use bexagliflozin, as it can lead to an increased risk of volume depletion and hypotension. 
• Diabetic ketoacidosis: It should not be used in diabetic ketoacidosis (DKA) or patients with a history of DKA. 
• Concomitant use with other drugs: It should not be used concomitantly with other drugs that increase the risk of volume depletion and hypotension, such as diuretics, blood pressure-lowering medications, and lithium. 

Caution 

• Renal impairment: It should be used cautiously in patients with mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] 30 to 89 mL/min/1.73 m2), as it may lead to an increased risk of renal impairment. 
• Volume depletion: It can cause volume depletion, leading to dehydration and hypotension, so patients should be advised to drink adequate fluids and maintain a regular diet. 
• Amputations: It has been associated with an increased risk of lower limb amputations, mainly in the toes and feet, particularly in patients with prior amputations, peripheral vascular disease, and neuropathy. 
• Bone fractures: It have been associated with an increased risk of bone fractures, especially in women. 
• Vaginal yeast infection: It may increase women’s risk of vaginal yeast infections. 
• Interaction with other drugs: It can interact with other drugs, such as diuretics, blood pressure-lowering medications, lithium, and rifampin, increasing the risk of volume depletion and hypotension. 
• Lactic acidosis: It may cause lactic acidosis, a rare but serious metabolic complication that can occur due to the accumulation of lactic acid in the blood 

Pregnancy / Lactation

Pregnancy consideration: It should not be used during pregnancy or breastfeeding, as it may be harmful to a developing fetus or infant. 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology 

Sodium-glucose cotransporter 2 (SGLT2) is a protein located in the proximal tubules of the kidneys that is responsible for reabsorbing glucose from the filtered urine back into the bloodstream.  

Most of the glucose reabsorption in the kidney occurs via SGLT2. Inhibiting SGLT2, as bexagliflozin does, reduces the kidney’s filtered glucose reabsorption, which leads to an increase in urinary glucose excretion and a reduction in blood glucose levels. This mechanism of action is known as the “glucuretic” effect. 

In addition, the inhibition of SGLT2 also lowers the renal threshold for glucose, which means that glucose is excreted in urine at lower blood glucose levels. This results in a decrease in renal glucose reabsorption and increased glucose excretion in the urine, leading to reduced blood glucose levels. 

Pharmacodynamics 

The pharmacodynamics of bexagliflozin refers to the relationship between the drug’s concentration in the body and its biological effects. 

When bexagliflozin is taken orally, it is rapidly absorbed and reaches peak plasma concentrations within 1-2 hours. The drug then binds to the SGLT2 protein located in the proximal tubules of the kidneys, inhibiting its activity. This results in a reduction in the reabsorption of glucose by the kidneys, leading to increased glucose excretion in the urine and a reduction in blood glucose levels. 

It has a dose-dependent effect on glucose excretion and blood glucose levels. As the dosage increases, the amount of glucose excreted in the urine and the reduction in blood glucose levels also increase. 

In addition to its glucose-lowering effects, bexagliflozin promotes weight loss and may lower blood pressure. It can also reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease. 

It does not affect insulin secretion or insulin sensitivity and is thus considered a new class of glucose-lowering drugs for treating type 2 diabetes. 

Pharmacokinetics 

Absorption:  

It is rapidly absorbed after oral administration, reaching peak plasma concentrations within 2-4 hours. The absorption of bexagliflozin is not affected by food, but peak plasma time is delayed by 1 hour when taken with food. The peak plasma concentration is 134ng/ml 

Distribution:  

It is highly bound to plasma proteins which is 93%, mainly albumin and has a large volume of distribution of 262L. 

Metabolism: 

 It is metabolized in the liver by UGT1A9 and CYP3A4 enzymes. The primary metabolite is 3’-O-glucuronide, which is excreted in the urine.  

Elimination/Excretion:  

The elimination half-life of bexagliflozin is about 12-17 hours, allowing for once-daily dosing. The drug is excreted mainly in the urine (about 40.5%) and a smaller amount in feces (about 51.1%) 

Adminstartion

Administration 

Oral administration 

The recommended administration of bexagliflozin is to take it in the morning, with or without food. The tablet should be swallowed whole and not crushed or chewed. 

If a dose of bexagliflozin is missed, the patient should take it as soon as possible. It is important to advise patients not to double their next dose if they miss one, as this can lead to an overdose of the medication 

Storage 

It should be stored at a temperature between 20-25°C (68-77°F), with excursions permitted to 15-30°C (59-86°F). 

It is essential to keep the medication in its original container, with the cap tightly closed, and to protect it from moisture. Also, check the expiration date before using the medication and discard any expired medication. 

It is important to note that storing the medication outside the recommended temperature range or storing it improperly can affect its potency and effectiveness 

Patient Information Leaflet

Patient information leaflet 

Generic Name: bexagliflozin 

Pronounced: (bex-ag-li-floz-in) 

Why do we use bexagliflozin? 

It is an oral medication that is used to treat type 2 diabetes. Specifically, it improves glycemic control in adults with type 2 diabetes. 

The primary use of bexagliflozin is an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes. Additionally, bexagliflozin may promote weight loss, lower blood pressure, and reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease.