Inpefa From Lexicon Pharmaceuticals, Inc.

The FDA has approved sotaglifozin (Inpefa) oral tablets from Lexicon Pharmaceuticals, Inc, to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure or chronic kidney disease, type 2 diabetes mellitus, and other cardiovascular risk factors.¹ Heart failure is the leading cause of hospitalizations for individuals aged 65 years and older, accounting for approximately 1.3 million hospitalizations each year. The highest risk of a heart failure event is in the first 30 days after hospital discharge, with 7% of patients dying and 25% rehospitalized within 1 month.²

Image credit: New Africa | stock.adobe.com

PHARMACOLOGY AND PHARMACOKINETICS

Sotagliflozin inhibits sodium-glucose cotransporter 1 (SGLT1) and sodium-glucose cotransporter 2 (SGLT2). Inhibition of SGLT1 reduces intestinal absorption of glucose and sodium. SGLT2 inhibition reduces renal reabsorption of glucose and sodium, which may lower both preload and afterload of the heart and downregulate sympathetic activity. The median time to maximum plasma concentration after a single oral dose is 1.25 to 3 hours, and the mean terminal half-life is 21 to 35 hours.¹

DOSAGE AND ADMINISTRATION

The recommended starting dose of sotagliflozin is 200 mg orally once daily, taken no more than 1 hour before the first meal of the day and swallowed whole. The dose should be increased to 400 mg orally once daily as tolerated after at least 2 weeks and may be decreased to 200 mg daily if not tolerated. Before patients begin treatment with sotagliflozin, renal function and volume status should be assessed. Patients with decompensated heart failure may begin treatment once hemodynamically stable.¹

CLINICAL TRIALS

Sotagliflozin was evaluated in the SOLOIST study (NCT03521934) and the SCORED study (NCT03315143). Both phase 3 double-blind, multicenter, parallel-group, placebo-controlled, randomized studies demonstrated that sotagliflozin significantly reduced risk of the composite end point of cardiovascular death, hospitalizations for heart failure, and urgent visits for heart failure as compared with placebo.^1,2

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Treatment with sotagliflozin is contraindicated in patients with a history of serious hypersensitivity to the medication.

Because sotagliflozin significantly increases the risk of diabetic ketoacidosis in patients with type 1 diabetes mellitus, ketones should be monitored in patients with type 1 diabetes mellitus and in those at risk for ketoacidosis, and the medication should be discontinued if ketoacidosis is suspected. Volume status should be assessed and corrected if necessary prior to starting treatment with sotagliflozin, and patients should be monitored for hypotension throughout treatment. Patients should also be monitored for signs and symptoms of pyelonephritis and urosepsis during therapy and treated promptly if either occurs.

A lower dose of insulin or insulin secretagogues may be required when used concomitantly with sotagliflozin. Because necrotizing fasciitis of the perineum has occurred in patients with diabetes mellitus receiving SGLT2 inhibitors, patients should be monitored for erythema, pain, swelling, or tenderness in the genital or perineal area, along with fever or malaise. If necrotizing fasciitis is suspected, sotagliflozin should be discontinued and treatment started. Sotagliflozin increases the risk of genital mycotic infections.

Coadministration with digoxin results in increased digoxin exposure. Sotagliflozin exposure is reduced when used concomitantly with uridine 5’-diphospho-glucuronosyltransferase inducers, such as rifampin (Rifadin; Sandoz). Concomitant use with lithium may decrease serum lithium concentrations.

Sotagliflozin should not be used during the second and third trimesters of pregnancy or while breastfeeding. Elderly patients and those with impaired renal function (eGFR < 30mL/min/1.73 m2) experienced a higher incidence of adverse reactions related to volume depletion.

The most common adverse reactions are diarrhea, hypoglycemia, urinary tract infection, and volume depletion.¹

About the Author

Monica Holmberg, PharmD, BCPS, is a pharmacist in Phoenix, Arizona, and a Pharmacy Times contributor.

References

1. Inpefa. Prescribing information. Lexicon Pharmaceuticals, Inc; 2023. Accessed June 28, 2023. https://www.lexpharma.com/inpefa-US-PI.pdf
2. Lexicon announces FDA approval of Inpefa (sotagliflozin) for treatment of heart failure. News release. Lexicon Pharmaceuticals, Inc. May 26, 2023. Accessed June 28, 2023. https://www.lexpharma.com/media-center/news/2023-05-26-lexicon-announces-fda-approval-of-inpefasotagliflozin-for-treatment-of-heart-failure