Drug Interactions between conivaptan and selpercatinib

GENERALLY AVOID: Coadministration with moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of selpercatinib, which is primarily metabolized by the isoenzyme. Based on pharmacokinetic modeling, administration of multiple doses of selpercatinib (160 mg twice daily) with multiple doses of the moderate CYP450 3A4 inhibitors diltiazem (60 mg three times daily), fluconazole (200 mg once daily), or verapamil (80 mg three times daily) is predicted to increase selpercatinib peak plasma concentration (Cmax) by 46% to 76% and systemic exposure (AUC) by 60% to 99%. Increased exposure to selpercatinib may increase the risk of serious adverse effects such as QT interval prolongation, liver transaminase and bilirubin elevations, hypertension, hemorrhage, edema, and hypersensitivity reactions (e.g., fever, rash, arthralgias/myalgias with concurrent decreased platelets or transaminitis). In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.


MANAGEMENT: Concomitant use of selpercatinib with moderate CYP450 3A4 inhibitors should be avoided when possible. However, if coadministration is required, a dosage reduction of selpercatinib is advised. The manufacturer's product labeling should be consulted for specific dosage modification recommendations for concomitant use of selpercatinib with moderate CYP450 3A4 inhibitors. Close monitoring for adverse effects is advisable, including more frequent ECGs and laboratory monitoring of liver enzymes, bilirubin, electrolytes, glucose, and blood counts. Selpercatinib treatment should be discontinued, interrupted, or dosage reduced in patients with serious or life-threatening toxicities in accordance with the product labeling. After the inhibitor has been discontinued for 3 to 5 elimination half-lives, the selpercatinib dosage that was taken prior to initiating the inhibitor may be resumed.