Sodium-Glucose Cotransporter 2 Inhibitor

Inpefa

Approved 26 May 2023OralTablet

The FDA lists this product in 2 strengths and forms.

Indications

INPEFA is indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors INPEFA is a sodium-glucose cotransporter 2 (SGLT2) inhibitor indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with: heart failure ( 1 ) or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors ( 1 )

Contraindications

INPEFA is contraindicated in patients with a history of serious hypersensitivity reaction to INPEFA. History of serious hypersensitivity reaction to INPEFA. ( 4 )

Warnings and precautions

Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis: Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis, as indicated. Assess for ketoacidosis regardless of presenting blood glucose levels and discontinue INPEFA if ketoacidosis is suspected. Monitor patients for resolution of ketoacidosis before restarting.

( 5.1 ) Volume Depletion: Before initiating, correct volume status. Monitor for signs and symptoms of hypotension during therapy. ( 5.2 ) Urosepsis and Pyelonephritis: Monitor for signs and symptoms during therapy and treat promptly. ( 5.3 ) Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues: Lower dose of insulin or insulin secretagogue may be required. ( 5.4 ) Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) : Monitor for pain, tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise.

Discontinue INPEFA and treat urgently. ( 5.5 ) Genital Mycotic Infections : Monitor and treat as appropriate. ( 5.6 )

5.1Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Indications

Warnings and precautions

Discontinue INPEFA and treat urgently. ( 5.5 ) Genital Mycotic Infections : Monitor and treat as appropriate. ( 5.6 )

5.1Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

on animal data showing renal effects, INPEFA is not recommended during the second and third trimesters of pregnancy. Available data with INPEFA in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with untreated heart failure in pregnancy [see Clinical Considerations ] .

In rats, renal changes were observed when sotagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy. Exposure approximately 5 times the clinical exposure at the maximum recommended human dose (MRHD) of 400 mg once daily caused increased kidney weights and renal pelvis and tubule dilatations that were partially reversible [see Data ] . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated Maternal and/or Embryo-fetal Risk Pregnant women with congestive heart failure are at increased risk for preterm birth.

Clinical classification of heart disease may worsen with pregnancy and lead to maternal death. Data Animal Data In embryo-fetal development studies in rats and rabbits, sotagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. Sotagliflozin was not teratogenic when administered at doses up to 100 mg/kg/day in pregnant rats during embryonic organogenesis (40 times the human exposure at the MRHD).

Higher exposures (350 mg/kg or 161 times the human exposure at the MRHD) resulted in embryo-lethality, effects on fetal growth, and cardiovascular and skeletal fetal abnormalities commensurate with maternal toxicity. Sotagliflozin was not teratogenic when administered at doses up to 200 mg/kg/day in pregnant rabbits (9 times the human exposure at the MRHD). In a prenatal and postnatal development study in pregnant and lactating rats, sotagliflozin was administered at oral doses up to 100 mg/kg/day from gestation Day 6 through to lactation Day 20 (weaning).

An increased incidence of dilated kidneys with discoloration and dilated ureters was observed at doses ≥ 30 mg/kg (≥ 4 times the human exposure at the MRHD). Sotagliflozin did not adversely affect developmental landmarks, sexual maturation, or reproductive performance of the offspring at doses up to 40 times the human exposure at the MRHD. Sotagliflozin dosed directly to juvenile rats from postnatal Day (PND) 21 until PND 90 at doses of 3, 10, 30, and 75 mg/kg/day caused dose-related increased kidney weights for males given ≥ 10 mg/kg/day and females given ≥ 30 mg/kg/day and was correlated with renal tubular and pelvis dilation for animals given ≥ 30 mg/kg/day.

These findings were fully or partially reversed after a 29-day recovery period. These outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimesters of human development.

Adverse reactions

The following important adverse reactions are described elsewhere in the labeling: Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis [see Warnings and Precautions ( 5.1 )] Volume Depletion [see Warnings and Precautions ( 5.2 )] Urosepsis and Pyelonephritis [see Warnings and Precautions ( 5.3 )] Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [see Warnings and Precautions ( 5.4 )] Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) [see Warnings and Precautions ( 5.5 )] Genital Mycotic Infections [see Warnings and Precautions ( 5.6 )] Most common adverse reactions (incidence ≥ 5%) are urinary tract infection, volume depletion, diarrhea, and hypoglycemia.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Lexicon at 1-855-330-2573 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In the phase 3 (SOLOIST [see Clinical Studies ( 14.1 )] and SCORED [see Clinical Studies ( 14.2 )] ) placebo-controlled trials, 5,896 subjects received INPEFA.

In the SOLOIST study, 336 patients (56%) reached the 400 mg dose. In the SCORED study, 3,934 patients (74%) reached the 400 mg dose. In the SOLOIST study, 5.6% of patients in the INPEFA group and 5.4% of patients in the placebo group discontinued therapy due to adverse events (AEs). In the SCORED study, 5.0% of patients in the INPEFA group and 4.5% of patients in the placebo group discontinued therapy due to AEs. Table 1 Adverse Reactions Reported in ≥ 2% of Patients Treated with INPEFA and Greater Than Placebo in Either SOLOIST or SCORED Adverse Reaction SOLOIST N = 1,216 SCORED N = 10,577 Placebo (%) N = 611 INPEFA (%) N = 605 Placebo (%) N = 5,286 INPEFA (%) N = 5,291 Urinary tract infection 7.2 8.6 11.0

11.5 Volume depletion 8.8 9.3 4.0

5.2 Diarrhea 4.1 6.9 6.0

8.4 Hypoglycemia 2.8 4.3 7.9

7.7 Dizziness 2.5 2.6 2.8

3.3 Genital mycotic infection 0.2 0.8 0.9

2.4Changes in Laboratory Test Values During Treatment Increase in Serum Creatinine and Decrease

in eGFR Initiation of SGLT2 inhibitors, including INPEFA, causes a small increase in serum creatinine and decrease in eGFR. These changes in serum creatinine and eGFR generally occur within 4 weeks of starting therapy and then stabilize regardless of baseline kidney function. Changes that do not fit this pattern should prompt further evaluation to exclude the possibility of acute kidney injury. In studies that included patients with type 2 diabetes mellitus with moderate renal impairment, the acute effect on eGFR reversed after treatment discontinuation, suggesting acute hemodynamic changes may play a role in the renal function changes observed with INPEFA [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.6 )] .

Inpefa

Indications

Contraindications

Warnings and precautions

5.1Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Two medicines in one question?

Inpefa

Indications

Contraindications

Warnings and precautions

5.1Diabetic Ketoacidosis in Patients with Type 1 Diabetes Mellitus and Other Ketoacidosis

Two medicines in one question?

5.2Volume Depletion

5.4Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin

5.5Necrotizing Fasciitis of the Perineum (Fournier's Gangrene) Reports

5.6Genital Mycotic Infections

5.7Positive Urine Glucose Test

5.8Interference with 1,5-anhydroglucitol (1,5-AG) Assay

Interactions

7.1Digoxin

7.2Uridine 5'-diphospho-glucuronosyltransferase (UGT) Inducer Glucuronidation by UGT1A9,

7.3Lithium

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

Adverse reactions

6.1Clinical Trials Experience

2.4Changes in Laboratory Test Values During Treatment Increase in Serum Creatinine and Decrease

Composition

Strengths and forms

Official product information

At a glance

Guidelines