Dosing & Uses
Dosage Forms & Strengths
tablet
- 20mg
Type 2 Diabetes Mellitus
Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
20 mg PO qAM
Dosage Modifications
Renal impairment
- Mild-to-moderate (eGFR 30-89 mL/min/1.73 m2): No dosage adjustment required
- Severe (eGFR <30 mL/min/1.73 m2): Not recommended owing to decline of glucose-lowering effect and reduction in urine output
- Dialysis: Contraindicated
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): No dosage adjustment required
- Severe (Child-Pugh C): Not studied
Dosing Considerations
Assess renal function before initiating and periodically thereafter as clinically indicated
Assess volume status; in patients with volume depletion, correct condition before initiating
Before initiating therapy, consider patient history that may predispose to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
Before initiating, consider patient history that may predispose need for amputations (eg, history of prior amputation, peripheral vascular disease, neuropathy, diabetic foot ulcers)
Limitation of use
- Not recommended in patients with type 1 diabetes mellitus
- May increase risk of diabetic ketoacidosis in patients with type 1 diabetes mellitus
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (32)
- carbamazepine
carbamazepine will decrease the level or effect of bexagliflozin by Other (see comment). Modify Therapy/Monitor Closely. Bexagliflozin is a major substrate of UGT1A9. If coadministered with a UGT1A9 inducer, consider adding another antihyperglycemic agent in patients requiring additional glycemic control.
- chlorpropamide
bexagliflozin, chlorpropamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
- glimepiride
bexagliflozin, glimepiride. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
- glipizide
bexagliflozin, glipizide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
- glyburide
bexagliflozin, glyburide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin aspart
bexagliflozin increases effects of insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin aspart protamine/insulin aspart
bexagliflozin increases effects of insulin aspart protamine/insulin aspart by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin degludec
bexagliflozin increases effects of insulin degludec by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin degludec/insulin aspart
bexagliflozin, insulin degludec/insulin aspart. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin detemir
bexagliflozin increases effects of insulin detemir by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin glargine
bexagliflozin increases effects of insulin glargine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin glulisine
bexagliflozin increases effects of insulin glulisine by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin inhaled
bexagliflozin increases effects of insulin inhaled by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin isophane human/insulin regular human
bexagliflozin increases effects of insulin isophane human/insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin lispro
bexagliflozin increases effects of insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin lispro protamine/insulin lispro
bexagliflozin increases effects of insulin lispro protamine/insulin lispro by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin NPH
bexagliflozin increases effects of insulin NPH by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- insulin regular human
bexagliflozin increases effects of insulin regular human by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin to avoid hypoglycemia when coadministered with bexagliflozin.
- lithium
bexagliflozin decreases effects of lithium by Other (see comment). Use Caution/Monitor. Comment: Concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations; monitor serum lithium concentration more frequently during therapy initiation and dosage changes.
- lonapegsomatropin
lonapegsomatropin decreases effects of bexagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- mecasermin
mecasermin decreases effects of bexagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- nateglinide
bexagliflozin, nateglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
- phenobarbital
phenobarbital will decrease the level or effect of bexagliflozin by Other (see comment). Modify Therapy/Monitor Closely. Bexagliflozin is a major substrate of UGT1A9. If coadministered with a UGT1A9 inducer, consider adding another antihyperglycemic agent in patients requiring additional glycemic control.
- phenytoin
phenytoin will decrease the level or effect of bexagliflozin by Other (see comment). Modify Therapy/Monitor Closely. Bexagliflozin is a major substrate of UGT1A9. If coadministered with a UGT1A9 inducer, consider adding another antihyperglycemic agent in patients requiring additional glycemic control.
- repaglinide
bexagliflozin, repaglinide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
- rifampin
rifampin will decrease the level or effect of bexagliflozin by Other (see comment). Modify Therapy/Monitor Closely. Bexagliflozin is a major substrate of UGT1A9. If coadministered with a UGT1A9 inducer, consider adding another antihyperglycemic agent in patients requiring additional glycemic control.
- ritonavir
ritonavir will decrease the level or effect of bexagliflozin by Other (see comment). Modify Therapy/Monitor Closely. Bexagliflozin is a major substrate of UGT1A9. If coadministered with a UGT1A9 inducer, consider adding another antihyperglycemic agent in patients requiring additional glycemic control.
- somapacitan
somapacitan decreases effects of bexagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatrogon
somatrogon decreases effects of bexagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- somatropin
somatropin decreases effects of bexagliflozin by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Growth hormone products may decrease insulin sensitivity, particularly at higher doses. Antidiabetic agents may require dose adjustment after initiating growth hormone.
- tolazamide
bexagliflozin, tolazamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
- tolbutamide
bexagliflozin, tolbutamide. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Consider a lower dose of insulin secretagogue to avoid hypoglycemia when coadministered with bexagliflozin.
Minor (0)
Adverse Effects
1-10%
Volume depletion adverse effects (8.9%)
Increased urination (7%)
Urinary tract infection (6%)
Female genital mycotic infections (6%)
Increased LDL-C by 3 mg/dL (4.1%)
Thirst (3%)
Vaginal pruritus (3%)
Sepsis (2.3%)
Male genital mycotic infection (2%)
Hypoglycemia; monotherapy or plus metformin (2%)
Amputation (2%)
<1%
Increased hemoglobin >3 g/dL from baseline (0.7%)
Warnings
Contraindications
Hypersensitivity to bexagliflozin or excipients
Dialysis
Cautions
Serious hypersensitivity reactions (eg, angioedema) reported; if a hypersensitivity reaction occurs, discontinue treatment; treat promptly per standard of care, and monitor until signs and symptoms resolve
Serious urinary tract infections, including urosepsis and pyelonephritis, reported; evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated
Ketoacidosis
- Ketoacidosis, a serious, life-threatening condition resulting in urgent hospitalization or death, reported in patients treated with sodium-gluose cotransporter 2 (SGLT2) inhibitors
- Not indicated for treatment of type 1 diabetes mellitus
- Assess for ketoacidosis in patients who present with signs and symptoms consistent with severe metabolic acidosis, regardless of blood glucose levels
- Ketoacidosis may be present even if blood glucose levels are <250 mg/dL
- Treatment may require insulin, fluid, and carbohydrate replacement
- Consider temporarily discontinuing therapy for at least 3 days for patients who undergo scheduled surgery
- Consider monitoring for ketoacidosis and temporarily discontinuing therapy in other clinical situations known to predispose to ketoacidosis (eg, prolonged fasting due to acute illness or postsurgery); ensure risk factors for ketoacidosis are resolved prior to restarting therapy
- Restart once patient’s oral intake is back to baseline and any other risk factors for ketoacidosis (eg, blood acid build-up) are resolved
Lower limb amputation
- Increased incidence of lower limb amputations occurred in bexagliflozin-treated patients compared with placebo-treated patients in a randomized, placebo-controlled trial evaluating patients with type 2 diabetes mellitus who either had established cardiovascular disease (CVD) or were at risk for CVD
- Risk of amputation was highest in patients with baseline history of prior amputation, peripheral vascular disease, and neuropathy
Volume depletion
- Intravascular volume depletion, which may manifest as symptomatic hypotension or acute changes in creatinine, occurred
- Acute kidney injury reported, some required hospitalization and dialysis
- Patients with impaired renal function (eGFR <60 mL/min/1.73 m2), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension
- Before initiating therapy 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 treatment; monitor for signs and symptoms of volume depletion and renal function, after initiating therapy
Necrotizing fasciitis
- Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors
- Signs and symptoms include pain or tenderness, erythema, or swelling in genital or perineal area, along with fever or malaise
- If suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad spectrum antibiotics and surgical débridement if necessary
Mycotic infections
- Genital mycotic infections may occur
- Patients with history of genital mycotic infections and uncircumcised males are more susceptible
- Inform male patients that yeast infections of the penis (eg, balanitis or balanoposthitis) may occur; provide them with information regarding signs and symptoms (rash or redness of the glans or foreskin of the penis); advise them of treatment options and when to seek medical advice
Drug interaction overview
-
UGT enzyme inducers
- Consider adding another antihyperglycemic agent in patients requiring additional glycemic control
- UGT inducers may significantly reduce systemic exposure to bexagliflozin and lead to decreased efficacy
-
Insulin and insulin secretagogues
- Dosage modification
- Hypoglycemia risk increased with insulin and insulin secretagogues (eg, sulfonylureas); a lower dose of insulin or insulin secretagogue may be required
-
Lithium
- Monitor lithium levels more frequently upon SGLT2 inhibitor initiation and discontinuation
- SGLT2 inhibitors may decrease serum lithium concentrations
-
Laboratory testing
- Urine glucose tests are not recommended in patients taking SGLT2 inhibitors, as SGLT2 inhibitors increase urinary glucose excretion and lead to positive urine glucose tests; use alternative methods to monitor glycemic control
- 1,5-anhydroglucitol (AG) assay is not recommended, as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors; use alternative methods to monitor glycemic control
Pregnancy & Lactation
Pregnancy
Based on animal data showing adverse renal effects, not recommended during second and third trimesters of pregnancy
Limited data available in pregnant females are insufficient to determine a drug-associated risk for major birth defects and miscarriage
There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy
Animal studies
- Adverse renal pelvic and tubule dilatations that were not fully reversible were observed in rats when bexagliflozin was administered during renal development corresponding to the late second and third trimesters of human pregnancy at exposures 11 times the 20 mg clinical dose
Clinical considerations
- Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, stillbirth, and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity
Lactation
There is no information regarding drug presence in human milk, including the effects on breastfed infants or on milk production
Present in the milk of lactating rats at milk:plasma ratio of ~2
Since human kidney maturation occurs in utero and during the first 2 years of life, when lactation exposure may occur, there may be risk to the developing human kidney
Advise females of reproductive potential that bexagliflozin is not recommended while breastfeeding
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Sodium-glucose cotransporter 2 (SGLT2) is the transporter responsible for reabsorption of the majority of glucose from the renal glomerular filtrate in the renal proximal tubule
Inhibiting SGLT2 reduces renal reabsorption of filtered glucose and lowers the renal threshold for glucose, thereby increasing urinary glucose excretion
Absorption
Peak plasma time: 2-4 hr; 5 hr (with food)
Peak plasma concentration: 134 ng/mL
AUC: 1,152 ng⋅h/mL
Distribution
Protein bound: ~93%
Vd: 262 L
Metabolism
UGT1A9 (major); CYP3A (minor)
Elimination
Half-life: ~12 hr
Oral clearance: 19.1 L/hr
Excretion (mainly as 3’-O-glucuronide): Feces 51.1%; urine 40.5%
Administration
Oral Administration
Take in morning, with or without food
Swallow tablet whole; do not crush or chew
Missed dose: Take as soon as possible; advise patients not to double their next dose
Storage
Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)
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