Drug Interaction Report

MONITOR: Coadministration with inducers of uridine diphosphate glucuronosyl transferase (UGT) enzymes may decrease the plasma concentrations of sotagliflozin, which is primarily metabolized by UGT1A9. When sotagliflozin (400 mg single dose) was coadministered with rifampin (multiple 600 mg doses), sotagliflozin peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 40% and 55%, respectively. Reduced efficacy of sotagliflozin may occur.

MANAGEMENT: Clinical and laboratory monitoring may be considered whenever a UGT inducer is added to or withdrawn from sotagliflozin therapy.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

ADJUST DOSING INTERVAL: Coadministration with a high-caloric meal may increase the bioavailability of sotagliflozin. When coadministered with a high-caloric breakfast, sotagliflozin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 149% and 50%, respectively, compared to fasting conditions. Multiple sotagliflozin doses (400 mg) administered immediately before breakfast, 30 minutes before breakfast, and 1 hour before breakfast in healthy subjects showed a consistent effect on urine glucose excretion, insulin, and postprandial glucose across all dose schedules.

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes.

MANAGEMENT: Sotagliflozin should be administered no more than 1 hour before the first meal of the day. Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.