Drug Interactions between oxaliplatin and trilaciclib

MONITOR: Coadministration with trilaciclib may increase the plasma concentrations of drugs that are substrates of organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporters 1 (MATE1) and 2K (MATE-2K). Trilaciclib is an inhibitor of these transporters and may reduce the renal clearance of drugs that undergo active tubular secretion mediated by these transporters. When metformin, a known substrate of OCT2, MATE1 and MATE-2K, was administered in combination with trilaciclib, metformin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 81% and 65%, respectively, while renal clearance decreased by 37%. No clinically significant differences in the pharmacokinetics of topotecan, a MATE1 and MATE-2K substrate, were observed when given with trilaciclib.

MANAGEMENT: Caution is advised when trilaciclib is used concomitantly with drugs that are OCT2, MATE1 and MATE-2K substrates, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever trilaciclib is added to or withdrawn from therapy. Patients should be monitored for the development of adverse effects. The prescribing information recommends avoiding concomitant use of trilaciclib with certain OCT2, MATE1, and MATE-2K substrates where minimal concentration changes may lead to serious or life-threatening toxicities. The prescribing information for concomitant medications should be consulted to assess the benefits versus risks of concomitant use of trilaciclib.

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