Version May 2024
Note: Hypovolemia, if present, should be corrected prior to initiating therapy. May require a gradual dose reduction of insulin and/or insulin secretagogues (sulfonylureas, meglitinides) to avoid hypoglycemia.
Cardiovascular risk reduction: Note: Cardiovascular benefits were demonstrated in patients with type 2 diabetes and chronic kidney disease (with or without albuminuria), along with other cardiovascular risk factors (Ref).
Oral: Initial: 200 mg once daily not more than 1 hour before first meal of the day; increase to 400 mg once daily after ≥2 weeks; may decrease to 200 mg once daily as necessary based on tolerability.
Heart failure: Note: Should be considered for use in combination with other evidence-based therapies as part of an optimal medical regimen for heart failure (Ref). Benefits were consistently demonstrated in patients with type 2 diabetes regardless of ejection fraction (Ref). For patients with decompensated heart failure, therapy may be initiated as soon as the patient is hemodynamically stable.
Oral: Initial: 200 mg once daily not more than 1 hour before first meal of the day; increase to 400 mg once daily after ≥2 weeks; may decrease to 200 mg once daily as necessary based on tolerability.
Missed dose: If dose is missed by >6 hours, skip dose and take the next dose as prescribed the next day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
eGFR ≥25 mL/minute/1.73 m2: No dosage adjustment necessary.
eGFR <25 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). In clinical trials, therapy was discontinued if eGFR decreased to <15 mL/minute/1.73 m2 during therapy.
Patients on dialysis: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). In clinical trials, therapy was discontinued in patients with decline in renal function requiring dialysis.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Pugh class B or C): Use is not recommended (has not been studied).
Refer to adult dosing.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors may cause events consistent with hypovolemia, including symptomatic hypotension, syncope, and dehydration (Ref). Overall, a reduction in both systolic and diastolic blood pressure (-4 to -6/-1 to -2 mm Hg) has been documented for SGLT2 inhibitors (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Inhibition of SGLT2 causes an increase in the excretion of glucose and sodium, thereby resulting in an osmotic diuresis and intravascular volume contraction (Ref).
Onset: Varied; timing is impacted by volume status (eg, reduced oral intake, fluid losses) and concomitant use of medications known to impact volume status or blood pressure (eg, diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs]) (Ref).
Risk factors:
• Kidney impairment (ie, eGFR <60 mL/minute/1.73 m2)
• Older adults
• Concomitant use of antihypertensives (eg, diuretics, ACE inhibitors, ARBs)
Sodium-glucose cotransporter 2 (SGLT2) inhibitors, including sotagliflozin, have been associated with an increased risk of genitourinary fungal infection (eg, vulvovaginal mycotic infection, vulvovaginal candidiasis, vulvovaginitis, candida balanitis, balanoposthitis). Urinary tract infections, including severe cases of urinary tract infection with sepsis and pyelonephritis requiring hospitalization have been associated with SGLT2 inhibitor therapy (Ref). These events are generally mild in intensity, respond to treatment, and do not lead to discontinuation (Ref). Additionally, rare but serious and potentially fatal cases of necrotizing fasciitis (perineum) (ie, Fournier gangrene) have been reported with SGLT2 inhibitors (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Patients with diabetes are more prone to urinary tract and genital infections, potentially due to glucosuria-induced bacterial growth, increased adherence of bacteria to the uroepithelium, and altered immune function (Ref). Because SGLT2 inhibitors increase urinary excretion of glucose, it has been hypothesized that these agents further increase the risk of these infections (Ref).
Onset: Varied; available literature suggests that the increased risk of genital infection may be apparent within the first month of SGLT2 inhibitor therapy and remain elevated throughout the course of therapy (Ref); Fournier gangrene may have an average onset of 9 months (range: 5 days to 49 months) (Ref).
Risk factors:
• Diabetes and/or uncontrolled hyperglycemia (Ref)
• Prior history of these types of infections
• Uncircumcised males (increased risk for genital infections) (Ref)
Cases of ketoacidosis have been reported in patients with type 1 and type 2 diabetes mellitus receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors, including sotagliflozin (Ref).
In some cases, patients have presented with normal or only modestly elevated blood glucose (<250 mg/dL), which can lead to misdiagnosis, prevent timely initiation of treatment, and negatively influence duration of illness (Ref). In addition, SGLT2 inhibitor-mediated increases in urinary glucose loss may persist for several days after discontinuation which may impact duration of illness in patients who develop ketoacidosis (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Several mechanisms have been proposed centered on increased ketone body production and reabsorption. Because SGLT2 inhibitors decrease urinary excretion of ketone bodies and decrease blood glucose in an insulin-independent manner, plasma glucose and urine ketone concentrations may be lower than what is typically expected in classic presentations of diabetic ketoacidosis (Ref).
Onset: Varied; timing is often impacted by the onset of metabolically stressful events (eg, surgery, extensive exercise, myocardial infarction, stroke, severe infections, prolonged fasting) (Ref).
Risk factors:
• Patients with diabetes who are insulin deficient (eg, latent autoimmune diabetes in adults, type 1 diabetes, or some patients with long-standing type 2 diabetes) (Ref)
• Metabolically stressful events (eg, surgery, extensive exercise, myocardial infarction, stroke, severe infections, prolonged fasting) (Ref)
• Presence of other risk factors that may predispose a patient to ketoacidosis (eg, pancreatic insulin deficiency, dose decreases of insulin, caloric restriction, alcohol abuse, acute febrile illness, surgery, or any other extreme stress event)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%: Genitourinary: Urinary tract infection (9% to 12%) (table 1)
|
Drug (Sotagliflozin) |
Placebo |
Indication |
Number of Patients (Sotagliflozin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
12% |
11% |
Type 2 diabetes mellitus and chronic kidney disease |
5,291 |
5,286 |
|
9% |
7% |
Type 2 diabetes mellitus and worsening heart failure |
605 |
611 |
1% to 10%:
Endocrine & metabolic: Hypoglycemia (4%), hypovolemia (5% to 9%) (table 2)
|
Drug (Sotagliflozin) |
Placebo |
Indication |
Number of Patients (Sotagliflozin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
5% |
4% |
Type 2 diabetes mellitus and chronic kidney disease |
5,291 |
5,286 |
|
9% |
9% |
Type 2 diabetes mellitus and worsening heart failure |
605 |
611 |
Gastrointestinal: Diarrhea (7% to 8%)
Genitourinary: Genitourinary fungal infection (0.8% to 2%) (table 3)
|
Drug (Sotagliflozin) |
Placebo |
Indication |
Number of Patients (Sotagliflozin) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
2% |
0.9% |
Type 2 diabetes mellitus and chronic kidney disease |
5,291 |
5,286 |
|
0.8% |
0.2% |
Type 2 diabetes mellitus and worsening heart failure |
605 |
611 |
Frequency not defined:
Endocrine & metabolic: Ketoacidosis (Bhatt 2021)
Renal: Decreased estimated GFR (eGFR), increased serum creatinine
Postmarketing:
Genitourinary: Urinary tract infection with sepsis
Renal: Pyelonephritis
Hypersensitivity to sotagliflozin or any component of the formulation.
Concerns related to adverse effects:
• Hypoglycemia: May increase the risk of hypoglycemia when used concomitantly with insulin or insulin secretagogues; consider insulin or insulin secretagogue dose reduction when used in combination with sotagliflozin.
• Renal effects: Increased serum creatinine and decreased eGFR may occur following sotagliflozin initiation. Most changes in renal function occur within 4 weeks of therapy initiation and then stabilize.
Disease-related concerns:
• Bariatric surgery:
– Altered absorption: Absorption may be altered given the anatomic and transit changes created by gastric bypass and sleeve gastrectomy surgery (Mechanick 2020; Melissas 2013).
– Dehydration: Evaluate, correct, and maintain postsurgical fluid requirements and volume status prior to initiating therapy and closely monitor the patient for the duration of therapy; volume depletion and related adverse events (eg, hypotension, orthostatic hypotension, syncope) have occurred. Fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band (Mechanick 2020).
– Euglycemic diabetic ketoacidosis: Discontinue therapy ≥3 days prior to surgery. Ketoacidosis has been reported in patients with type 1 and type 2 diabetes on SGLT2 inhibitors. In some cases, normal or only modestly elevated blood glucose was present (<250 mg/dL). Risk factors include significant reduction in insulin, caloric restriction, stress of surgery, and infection occurred. Fluid intake may be more difficult after gastric bypass, sleeve gastrectomy, and gastric band.
Special populations:
• Older adults: Older adults may be predisposed to symptoms related to intravascular volume depletion (eg, hypotension, orthostatic hypotension, dizziness, syncope, dehydration).
Other warnings/precautions:
• Surgical procedures: Temporarily discontinue ≥3 days prior to surgery; ensure patient is clinically stable and has resumed oral intake prior to reinitiating therapy.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Inpefa: 200 mg [contains fd&c blue #2 (indigo carm) aluminum lake]
Inpefa: 400 mg
No
Tablets (Inpefa Oral)
200 mg (per each): $23.92
400 mg (per each): $23.92
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer no more than 1 hour before the first meal of the day; swallow tablets whole, do not cut, crush, or chew.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Inpefa: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216203s000lbl.pdf#page=24
Cardiovascular risk reduction: Risk reduction of cardiovascular mortality, hospitalization for heart failure, and urgent heart failure visits in adults with type 2 diabetes, chronic kidney disease, and other cardiovascular risk factors.
Heart failure: Risk reduction of cardiovascular mortality, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure.
Beers Criteria: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients ≥65 years of age due to increased risk of urogenital infections, especially in women during the first month of use. In addition, a higher risk of euglycemic diabetic ketoacidosis has been observed in older adults (Beers Criteria [AGS 2023]).
Substrate of CYP3A4 (minor), OAT1/3, OATP1B1/1B3 (SLCO1B1/1B3), UGT1A9; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits P-glycoprotein/ABCB1; Induces CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Risk D: Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: Monitor therapy
Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Atogepant: Sotagliflozin may decrease the serum concentration of Atogepant. Sotagliflozin may increase the serum concentration of Atogepant. Management: For treatment of episodic migraine, the recommended dose of atogepant is 30 mg once daily or 60 mg once daily when combined with sotagliflozin. When used for treatment of chronic migraine, use of atogepant with sotagliflozin should be avoided. Risk D: Consider therapy modification
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Beta-Blockers (Beta1 Selective): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Beta-Blockers (Nonselective): May enhance the hypoglycemic effect of Antidiabetic Agents. Beta-Blockers (Nonselective) may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Bortezomib: May enhance the therapeutic effect of Antidiabetic Agents. Bortezomib may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
CarBAMazepine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: Monitor therapy
CloZAPine: CYP3A4 Inducers (Weak) may decrease the serum concentration of CloZAPine. Risk C: Monitor therapy
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider therapy modification
CycloSPORINE (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Risk D: Consider therapy modification
Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Etilefrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Glecaprevir and Pibrentasvir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hormonal Contraceptives: CYP3A4 Inducers (Weak) may decrease the serum concentration of Hormonal Contraceptives. Management: Advise patients to use an alternative method of contraception or a back-up method during coadministration, and to continue back-up contraception for 28 days after discontinuing a weak CYP3A4 inducer to ensure contraceptive reliability. Risk D: Consider therapy modification
Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy
Insulins: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors may enhance the hypoglycemic effect of Insulins. Management: Consider a decrease in insulin dose when initiating therapy with a sodium-glucose cotransporter 2 inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Risk D: Consider therapy modification
Lithium: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors may decrease the serum concentration of Lithium. Risk C: Monitor therapy
Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inducers (Weak) may decrease the serum concentration of NiMODipine. Risk C: Monitor therapy
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider therapy modification
Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider therapy modification
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider therapy modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider therapy modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy
Selpercatinib: CYP3A4 Inducers (Weak) may decrease the serum concentration of Selpercatinib. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Sirolimus (Conventional): Sotagliflozin may decrease the serum concentration of Sirolimus (Conventional). Sotagliflozin may increase the serum concentration of Sirolimus (Conventional). Management: Avoid concurrent use of sirolimus with sotagliflozin when possible. If combined, monitor for increases or decreases in sirolimus concentrations and increased sirolimus toxicities. Sirolimus dose adjustments may be required. Risk D: Consider therapy modification
Sirolimus (Protein Bound): Sotagliflozin may decrease the serum concentration of Sirolimus (Protein Bound). Sotagliflozin may increase the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sulfonylureas: Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors may enhance the hypoglycemic effect of Sulfonylureas. Management: Consider a decrease in sulfonylurea dose when initiating therapy with a sodium-glucose cotransporter 2 (SGLT2) inhibitor and monitor patients for hypoglycemia. Risk D: Consider therapy modification
Tacrolimus (Systemic): Sotagliflozin may decrease the serum concentration of Tacrolimus (Systemic). Sotagliflozin may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Ubrogepant: Sotagliflozin may decrease the serum concentration of Ubrogepant. Sotagliflozin may increase the serum concentration of Ubrogepant. Management: Consider avoiding this combination if possible. Ubrogepant dose increases are recommended during coadministration with weak CYP3A4 inducers, and dose increases are recommended with P-gp inhibitors. The net effect of sotagliflozin is unknown. Risk D: Consider therapy modification
UGT1A9 Inducers: May decrease the serum concentration of Sotagliflozin. Risk C: Monitor therapy
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Administration with a high-calorie meal increases Cmax and AUC by 149% and 50%, respectively. Sotagliflozin should be administered no more than 1 hour before the first meal of the day.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are not recommended for the treatment of heart failure in patients planning to become pregnant (AHA/ACC/HFSA [Heidenreich 2022]).
Based on data from animal reproduction studies, in utero exposure to sotagliflozin may cause fetal harm; adverse renal changes were observed in rats exposed during the period of renal development. According to the manufacturer, use during the second and third trimesters is not recommended.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are not recommended for the treatment of heart failure during pregnancy (AHA/ACC/HFSA [Heidenreich 2022]).
It is not known if sotagliflozin is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer.
Blood glucose; renal function (baseline and periodically during treatment); monitor for genital mycotic infections and urinary tract infection; monitor for signs/symptoms of necrotizing fasciitis (eg, fever and malaise along with genital or perianal pain, tenderness, erythema, swelling), hypersensitivity reactions; volume status (eg, weight, BP, hematocrit, electrolytes; baseline and periodically during treatment) and signs/symptoms of hypotension; if signs/symptoms of ketoacidosis (eg, nausea/vomiting, abdominal pain, malaise, shortness of breath), confirm diagnosis by direct measurement of blood ketones and arterial pH (measurement of serum bicarbonate or urinary ketones may not be adequate) (AACE [Handelsman 2016]).
Sotagliflozin is an inhibitor of sodium-glucose cotransporter (SGLT) 1 and 2. SGLT2 inhibition reduces renal reabsorption of glucose and sodium, which may decrease cardiac preload/afterload and downregulate sympathetic activity. SGLT1 inhibition reduces intestinal absorption of glucose and sodium. The mechanism for sotagliflozin’s cardiovascular benefits has not been established.
Duration: 5 to 10 hours (effective half-life).
Protein binding: >93%.
Metabolism: Primarily metabolized by UGT1A9, and to a lesser extent CYP3A4, to metabolite sotagliflozin 3-O-glucoronide.
Bioavailability: ~25%; significant (~50%) contribution to overall exposure from enterohepatic circulation.
Half-life elimination: Terminal half-life: sotagliflozin: 21 to 35 hours; sotagliflozin 3-O-glucoronide: 19 to 26 hours.
Time to peak: Median: 2.5 to 4 hours.
Excretion: Urine (57%); feces (37%).
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