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.

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.