Drug Interactions between losartan and Promacta

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use potassium-containing salt substitutes or over-the-counter potassium supplements without consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum potassium levels is recommended. Patients should also be advised to seek medical attention if they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion, tingling of the extremities, or feelings of heaviness in the legs.

MONITOR: Grapefruit juice may modestly decrease and delay the conversion of losartan to its active metabolite, E3174. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The clinical significance is unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Patients who regularly consume grapefruits and grapefruit juice should be monitored for altered efficacy of losartan. Grapefruits and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact.

ADJUST DOSING INTERVAL: Food may reduce the oral bioavailability of eltrombopag. In healthy volunteers, a standard high-fat breakfast significantly decreased plasma eltrombopag peak plasma concentration (Cmax) by 65% and systemic exposure (AUC) by 59% and delayed Tmax by one hour. The calcium content of this meal may have also contributed to this decrease in exposure. In another study, adult subjects administered a single 25 mg dose of eltrombopag for oral suspension with a high-calcium, moderate-fat, moderate-calorie meal exhibited a 79% decrease in Cmax and 75% decrease in AUC of eltrombopag. Administration of eltrombopag 2 hours after the high-calcium meal decreased eltrombopag Cmax by 48% and AUC by 47%, while administration 2 hours before the high-calcium meal decreased eltrombopag Cmax by 14% and AUC by 20%.

ADJUST DOSING INTERVAL: Polyvalent cations such as aluminum, calcium, iron, magnesium, and zinc can significantly reduce the gastrointestinal absorption of eltrombopag due to chelation. In one clinical trial, administration of a single 75 mg dose of eltrombopag with an antacid containing 1524 mg aluminum hydroxide and 1425 mg magnesium carbonate resulted in an approximately 70% decrease in eltrombopag Cmax and AUC.

MANAGEMENT: Eltrombopag should be taken on an empty stomach one hour before or two hours after a meal. Additionally, eltrombopag should be taken at least 2 hours before or 4 hours after any products that contain polyvalent cations such as antacids, mineral supplements, dairy products, and fortified juices.