Sotagliflozin (Monograph)

Brand name: Inpefa
Drug class: Sodium-glucose (SGLT) Cotransporter Inhibitors

Medically reviewed by Drugs.com on Apr 10, 2025. Written by ASHP.

Introduction

Sodium-glucose cotransporter 2 (SGLT2) inhibitor.

Uses for Sotagliflozin

Heart Failure

Used to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adult patients with heart failure or in patients with type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors.

Current guidelines on heart failure recommend guideline-directed medical therapy with a combination of the following drugs to reduce morbidity and mortality: angiotensin-converting enzyme (ACE) inhibitors, SGLT2 inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors (ARNIs), β-adrenergic blocking agents, and mineralocorticoid receptor antagonists. SGLT2 inhibitors are recommended in all patients with heart failure (either reduced ejection fraction or preserved ejection fraction), irrespective of the presence of type 2 diabetes mellitus, in the absence of contraindications.

Sotagliflozin Dosage and Administration

General

Pretreatment Screening

• Assess volume status and, if necessary, correct volume depletion.

• Assess renal function.

Patient Monitoring

• Assess renal function as clinically indicated.

• Monitor for signs and symptoms of urinary tract and genital mycotic infections.

• Monitor for signs and symptoms of hypotension.

Other General Considerations

• For patients with decompensated heart failure, sotagliflozin may be initiated as soon as the patient is hemodynamically stable, including during hospitalization or urgent outpatient treatment or immediately upon discharge.

• Withhold sotagliflozin therapy for at least 3 days, if possible, prior to major surgery or procedures associated with prolonged fasting. Resume sotagliflozin when the patient is clinically stable and has resumed oral intake.

Administration

Administer orally once daily not more than one hour prior to first meal of the day.

Swallow tablets whole; do not cut, crush, or chew.

If a dose is missed by more than 6 hours, instruct patient to take next dose as prescribed the next day.

Dosage

Adults

Heart Failure

Recommended Dosage

Oral

Initially, 200 mg once daily.

May increase dosage after at least 2 weeks to 400 mg once daily as tolerated. Down-titrate to 200 mg as necessary.

Special Populations

Hepatic Impairment

Mild hepatic impairment (Child-Pugh class A): No dosage adjustment necessary.

Moderate or severe hepatic impairment (Child-Pugh class B or C): Use not recommended.

Renal Impairment

No specific population dosage recommendations at this time.

Geriatric Patients

No specific population dosage recommendations at this time; greater sensitivity cannot be ruled out.

Cautions for Sotagliflozin

Contraindications

• History of serious hypersensitivity reaction to sotagliflozin.

Warnings/Precautions

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Ketoacidosis requiring hospitalization reported in patients with type 1 or type 2 diabetes mellitus receiving SGLT2 inhibitors; may occur without markedly elevated blood glucose concentration (e.g., <250 mg/dL). Sotagliflozin not indicated for glycemic control.

Evaluate for presence of ketoacidosis in patients experiencing severe metabolic acidosis regardless of patient's blood glucose concentration; discontinue sotagliflozin and initiate appropriate treatment if confirmed. Monitor for resolution prior to restarting the drug.

Prior to initiating sotagliflozin therapy, consider factors that may predispose patients to ketoacidosis (e.g., pancreatic disorders, insulin deficiency, reduced caloric intake, acute febrile illness, ketogenic diet, surgery, volume depletion, alcohol abuse).

Educate patients on signs and symptoms of ketoacidosis (e.g., nausea, vomiting, abdominal pain, tiredness, trouble breathing) and instruct patients to discontinue sotagliflozin and seek medical attention immediately if signs and symptoms occur.

Withhold sotagliflozin, if possible, in temporary clinical situations that may predispose patients to ketoacidosis; resume therapy once patient is clinically stable and has resumed oral intake.

Consider ketone monitoring in patients with type 1 diabetes mellitus and in other patients at risk for ketoacidosis if indicated by the clinical situation.

Volume Depletion

May cause intravascular volume depletion, which may manifest as symptomatic hypotension or acute transient changes in creatinine. Patients with impaired renal function (eGFR <60 mL/minute per 1.73 m²), elderly patients, or patients on loop diuretics may be at increased risk.

Prior to initiation in patients with one or more of these characteristics, assess volume status and renal function. Correct volume depletion prior to initiating sotagliflozin.

Monitor for signs and symptoms of hypotension; assess renal function after initiating therapy.

Urosepsis and Pyelonephritis

Treatment with SGLT2 inhibitors increases risk for urinary tract infections.

Prior to initiating sotagliflozin, consider factors that may predispose patients to serious urinary tract infections (e.g., history of difficulty urinating or infections of the bladder, kidneys, or urinary tract).

Monitor patients for signs and symptoms of urinary tract infections and initiate treatment, if indicated.

Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues

When adding sotagliflozin to therapy with an insulin secretagogue or insulin, consider reducing dosage of concomitant insulin secretagogue or insulin to reduce risk of hypoglycemia.

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

Necrotizing fasciitis of the perineum (Fournier's gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, reported during postmarketing surveillance in males and females with type 2 diabetes mellitus receiving an SGLT2 inhibitor.

Assess patient for necrotizing fasciitis if pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, occurs.

If Fournier's gangrene suspected, discontinue sotagliflozin and initiate treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Alternate therapy for heart failure should be provided.

Genital Mycotic Infections

Increases risk of genital mycotic infections; more likely to develop in patients with history of these infections.

Monitor for genital mycotic infections and institute appropriate treatment if these infections occur.

Laboratory Test Interferences

SGLT2 inhibitors, including sotagliflozin, increase urinary glucose excretion and result in false-positive urine glucose tests. Manufacturer states that urinary glucose tests should not be used. Manufacturer states that 1,5-anhydroglucitol assay is unreliable for monitoring glucose levels in patients taking SGLT2 inhibitors. Alternate methods to monitor glucose levels should be used.

Specific Populations

Pregnancy

Insufficient evidence to evaluate drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Untreated heart failure in pregnancy is associated with risks to pregnant woman and fetus; clinical classification of heart failure may worsen with pregnancy and lead to maternal death. Based on findings in animal studies showing renal effects, sotagliflozin not recommended during second and third trimesters of pregnancy.

Lactation

No data on presence of sotagliflozin in human milk, effects on breast-fed infant, or effects on milk production. Distributed into milk in rats. Breast-feeding not recommended while taking sotagliflozin due to potential for serious adverse reactions in breast-fed infants.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in efficacy determined between older and younger patients based on clinical trials and experience; greater sensitivity of some older individuals cannot be ruled out. In patients ≥65 years of age, a higher proportion of patients treatment with sotagliflozin had adverse reactions of volume depletion. Elderly patients may be at increased risk for volume depletion adverse reactions, including hypotension.

Hepatic Impairment

No dosage adjustment necessary in mild hepatic impairment (Child-Pugh class A). Safety and efficacy not established in moderate or severe hepatic impairment (Child-Pugh class B or C); use not recommended in such patients.

Renal Impairment

Safety profile of sotagliflozin in patients with chronic kidney disease across eGFR subgroups (ranging from 25 to 60 mL/minute per 1.73 m²) in clinical studies was consistent with known safety profile. There was an increase in volume-related adverse effects (e.g., hypotension, dizziness) in patients with eGFR <30 mL/minute per 1.73 m² relative to overall safety population. Efficacy and safety studies did not enroll patients with eGFR <25 mL/minute per 1.73 m² or those on dialysis. After starting therapy in these studies, patients were discontinued if eGFR fell below 15 mL/minute per 1.73 m² or were initiated on chronic dialysis.

Common Adverse Effects

Most common adverse effects (≥5%): Urinary tract infection, volume depletion, diarrhea, hypoglycemia.

Drug Interactions

Extensively metabolized, primarily by uridine diphosphate-glucuronosyl transferase (UGT) 1A9 and to a lesser extent by CYP3A4.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Major metabolite, sotagliflozin 3-O-glucuronide, shown to have in vitro potential to inhibit CYP3A4 and CYP2D6, and induce CYP3A4.

Drugs Affecting or Affected by Transport Systems

Substrate of organic anion transporter (OAT) 3, organic anion transporter polypeptide (OATP) 1B1, and OATP1B3, but not OAT1 and organic cation transporter (OCT) 2; does not inhibit any of these uptake transporters at clinically relevant plasma concentrations.

Has been shown to have an inhibitory effect on P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).

Specific Drugs

Sotagliflozin Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability approximately 25%; enterohepatic circulation contributes to approximately 50% of overall exposure.

Maximum plasma concentration and AUC increase in dose-proportional manner in therapeutic dosage range (200—400 mg once daily).

Effect of Food

High-caloric breakfast increases maximum plasma concentration and AUC by 149% and 50%, respectively.

Special Populations

Exposure following single dose of sotagliflozin 400 mg is approximately 70% higher in mild renal impairment (eGFR 60 to <90 mL/minute per 1.73 m²) and 170% higher in patients with moderate renal impairment (eGFR 30 to <60 mL/minute per 1.73 m²) compared to those with normal renal function (eGFR ≥90 mL/minute per 1.73 m²).

AUC not increased in mild (Child-Pugh class A) hepatic impairment but is increased approximately 3-fold in moderate (Child-Pugh class B) hepatic impairment and approximately 6-fold in severe (Child-Pugh class C) hepatic impairment compared to normal hepatic function.

Distribution

Extent

Distributed into rat milk; unknown if distributed into human milk.

Plasma Protein Binding

Sotagliflozin and its major metabolite, sotagliflozin 3-O-glucuronide: >93%.

Elimination

Metabolism

Extensively metabolized predominantly to sotagliflozin 3-O-glucuronide primarily by uridine diphosphate-glucuronosyl transferase (UGT) 1A9 and to lesser extent by CYP3A4.

Predominant metabolite is sotagliflozin 3-O-glucuronide, representing mean of 33% of administered dose.

Elimination Route

Recovered in urine (57%) and feces (37%).

Half-life

Sotagliflozin mean half-life 21—35 hours; sotagliflozin 3-O-glucuronide mean half-life 19—26 hours.

Sotagliflozin effective half-life ranges from 5—10 hours.

Special Populations

Pharmacokinetics not affected by age, body weight, sex, and race.

Stability

Storage

Oral

Tablets, film-coated

Store at 20—25°C; excursions permitted to 15—30°C.

Actions

• Inhibitor of sodium-glucose cotransporter (SGLT) 2 and SGLT1.

• Inhibition of SGLT2 reduces renal absorption of glucose and sodium, which may influence several physiologic functions such as lowering both pre- and afterload of the heart and downregulating sympathetic activity.

• Inhibition of SGLT1 reduces intestinal absorption of glucose and sodium.

• Mechanism of cardiovascular benefits have not been established.

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).

• Inform patients with type 1 diabetes mellitus that using sotagliflozin can increase their risk of life-threatening diabetic ketoacidosis. For all other patients, inform them that sotagliflozin can cause potentially fatal ketoacidosis and that type 2 diabetes mellitus is a risk factor. Educate all patients on precipitating factors (such as infection, reduced caloric intake, ketogenic diet, surgery, insulin dose reduction, dehydration, and alcohol abuse) and symptoms of ketoacidosis (including nausea, vomiting, abdominal pain, tiredness, and labored breathing). Inform patients that blood glucose may be normal even in the presence of ketoacidosis. Advise patients that they may be asked to monitor ketones. If symptoms of ketoacidosis occur, instruct patients to discontinue sotagliflozin and seek medical attention immediately.

• Inform patients that symptomatic hypotension may occur with sotagliflozin and advise them to contact their clinician if they experience such symptoms. Inform patients that dehydration may increase the risk for hypotension, and to have adequate fluid intake.

• Inform patients of the potential for urinary tract infections, which may be serious. Provide patients with information on the symptoms of urinary tract infections. Advise patients to seek medical advice promptly if such symptoms occur.

• Inform patients that the incidence of hypoglycemia is increased when sotagliflozin is used in combination with insulin and that a lower dose of insulin may be required to reduce the risk of hypoglycemia.

• Inform patients that necrotizing infections of the perineum (Fournier's Gangrene) have occurred with sotagliflozin in patients with diabetes mellitus. Counsel patients to promptly seek medical attention if they develop pain, tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, along with a fever above 38°C or malaise.

• Inform female patients that vaginal yeast infections may occur and provide them with information on the signs and symptoms of vaginal yeast infections. Inform male patients that yeast infections of the penis (e.g., balanitis or balanoposthitis) may occur, especially in patients with prior history. Provide patients with information on the signs and symptoms of balanitis and balanoposthitis (rash or redness of the glans or foreskin of the penis). Advise patients of treatment options and when to seek medical advice.

• Inform patients that hypersensitivity reactions (e.g., urticaria, anaphylactic reactions, and angioedema) have been reported with other SGLT2 inhibitors. Advise patients to immediately report any signs or symptoms suggesting allergic reaction or angioedema and to discontinue the drug until they have consulted their clinician.

• Advise pregnant patients of the potential risk to a fetus with treatment with sotagliflozin. Instruct patients to immediately inform their healthcare provider if pregnant or planning to become pregnant. Advise patients that use of sotagliflozin is not recommended while breastfeeding.

• Inform patients that they will test positive for glucose in the urine due to the mechanism of action of sotagliflozin.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.

• Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Medical Disclaimer