Drug Interaction Report

MONITOR CLOSELY: Coadministration with potent CYP450 3A4 inhibitors may increase the plasma concentrations and effects of unconjugated DM4, the microtubule inhibitor component of mirvetuximab soravtansine. Mirvetuximab soravtansine is a folate receptor alpha (FR-alpha)-directed antibody-drug conjugate (ADC) that releases DM4 via proteolytic cleavage, and DM4 has been shown to be primarily metabolized by CYP450 3A4. Increased concentrations of unconjugated DM4 may increase the risk of adverse effects including ocular toxicity (e.g., visual impairment, corneal disorders, dry eye, photophobia, eye pain, and uveitis), pneumonitis, and peripheral neuropathy. Clinical data are not available. Other, less potent CYP450 3A4 inhibitors are not expected to interact.

MANAGEMENT: Caution is recommended if mirvetuximab soravtansine is administered in combination with potent CYP450 3A4 inhibitors. Close monitoring for adverse reactions including ocular toxicity, pneumonitis, and peripheral neuropathy is advised. Mirvetuximab soravtansine treatment may need to be discontinued, interrupted, or dosage reduced in patients with serious or life-threatening toxicities in accordance with the product labeling. Alternative treatment that does not interfere with mirvetuximab soravtansine metabolism should be considered whenever possible.

ADJUST DOSING INTERVAL: Food may significantly increase the plasma concentrations of mifepristone.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mifepristone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: When mifepristone is used daily to control hyperglycemia secondary to hypercortisolism in patients with endogenous Cushing's syndrome, it should be taken with food to achieve consistent plasma drug levels. Patients should be advised to avoid consuming grapefruit or grapefruit juice during treatment with mifepristone, as it may cause increased adverse effects such as headache, dizziness, fatigue, nausea, vomiting, cramping, diarrhea, hypokalemia, adrenal insufficiency, vaginal bleeding, arthralgia, peripheral edema, and hypertension. Because mifepristone is eliminated slowly from the body, the interaction with grapefruit juice may be observed for a prolonged period.