Drug Interactions between Adderall and finerenone

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.

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GENERALLY AVOID: Alcohol may potentiate the cardiovascular effects of amphetamines. The exact mechanism of interaction is unknown. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state. The interaction was suspected in a case report of a 20-year-old male who experienced retrosternal chest pain shortly after drinking alcohol and taking a double dose of his amphetamine/dextroamphetamine medication (Adderall 15 mg X 2) to stay alert. The patient had no family history of cardiovascular diseases, and his past medical history was remarkable only for ADHD. Prior to the episode, the patient had not taken his medication for weeks and had been drinking whiskey the previous three nights before going to bed. The patient was diagnosed with myocardial infarction likely secondary to amphetamine-induced coronary vasospasm.

MANAGEMENT: Concomitant use of amphetamines and alcohol should be avoided if possible, especially in patients with a history of heart disease.

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GENERALLY AVOID: Alcohol may potentiate the cardiovascular effects of amphetamines. The exact mechanism of interaction is unknown. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state. The interaction was suspected in a case report of a 20-year-old male who experienced retrosternal chest pain shortly after drinking alcohol and taking a double dose of his amphetamine/dextroamphetamine medication (Adderall 15 mg X 2) to stay alert. The patient had no family history of cardiovascular diseases, and his past medical history was remarkable only for ADHD. Prior to the episode, the patient had not taken his medication for weeks and had been drinking whiskey the previous three nights before going to bed. The patient was diagnosed with myocardial infarction likely secondary to amphetamine-induced coronary vasospasm.

MANAGEMENT: Concomitant use of amphetamines and alcohol should be avoided if possible, especially in patients with a history of heart disease.

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