Drug Interaction Report

MONITOR: The use of mTOR (mammalian target of rapamycin) inhibitors has been associated with the development of angioedema, and coadministration with amlodipine may increase the risk. The mechanism of this interaction has not been established. The onset of angioedema may sometimes be delayed up to two months following initiation of therapy. In addition, amlodipine, a weak CYP450 3A4 inhibitor, may increase the plasma concentrations of mTOR inhibitors, which are primarily metabolized by the isoenzyme.

MANAGEMENT: Caution is advised if amlodipine is administered with mTOR inhibitors. Clinicians and patients should be aware of the potential for increased plasma levels as well as the risk of angioedema when mTOR inhibitors are prescribed with amlodipine. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever amlodipine is added to or withdrawn from therapy. Patients should be advised to promptly discontinue these medications and seek medical attention if they develop signs or symptoms suggestive of angioedema such as swelling of the face, extremities, eyes, lips, or tongue, and difficulty swallowing or breathing. Patients should be monitored for development of other adverse effects including hypertension, hyperlipidemia, renal impairment, proteinuria, infections, and various types of malignancies.

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered everolimus. The mechanism is inhibition of CYP450 3A4 and P-glycoprotein activity in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with everolimus should avoid consumption of grapefruit and grapefruit juice.