Drug Interactions between finerenone and Rifadin IV

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of finerenone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. Pharmacokinetic modeling simulations suggest that concomitant use of finerenone with 200 mg twice daily itraconazole, a potent CYP450 3A4 inhibitor, increases finerenone peak plasma concentration (Cmax) and systemic exposure (AUC) by 137% and 531%, respectively. Clarithromycin, another potent CYP450 3A4 inhibitor, given at 500 mg twice daily is predicted to increase finerenone Cmax by 125% and AUC by 428%. Additionally, drug interaction studies showed that concomitant use of finerenone with 500 mg thrice daily erythromycin, a moderate CYP450 3A4 inhibitor, increased mean finerenone Cmax and AUC by 88% and 248%, respectively. Verapamil, another moderate CYP450 3A4 inhibitor, given as a 240 mg controlled-release tablet once daily increased mean finerenone Cmax by 120% and AUC by 170%. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. High exposure to finerenone may potentiate the risk of hyperkalemia, and the risk may be further increased with decreasing kidney function and higher baseline potassium levels.

MONITOR CLOSELY: Dietary intake of excess potassium, especially via salt substitutes, may increase the risk of hyperkalemia in patients who are using finerenone. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

Administration of finerenone with high-fat, high-calorie food decreased finerenone Cmax by 19%, increased AUC by 21%, and prolonged the time to reach Cmax to 2.5 hours. These changes are not considered clinically relevant.

MANAGEMENT: Patients receiving finerenone therapy should be instructed to avoid consumption of grapefruit or grapefruit juice. In addition, patients should receive dietary counseling and be advised not to use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes or supplements are used concurrently, more frequent monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience signs and symptoms of hyperkalemia such as nausea, vomiting, weakness, listlessness, tingling of the extremities, paralysis, confusion, weak pulse, and a slow or irregular heartbeat. Finerenone may be taken with or without food.

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.