Drug Interactions between Grafapex and mavorixafor

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Coadministration with P-glycoprotein (P-gp) and/or moderate CYP450 3A4 inhibitors may increase the plasma concentrations and effects of mavorixafor, which is both a substrate of the P-gp efflux transporter and primarily metabolized by CYP450 3A4. When a single dose of mavorixafor (200 mg) was coadministered with the strong CYP450 3A4 and P-gp inhibitor itraconazole (200 mg at steady state), mavorixafor's systemic exposure (AUC) increased approximately 2-fold. The resulting AUC was similar to that expected from a single dose of 400 mg given alone to healthy subjects. Clinical data with drugs that are less potent inhibitors or only inhibit CYP450 3A4 or P-gp are not available. As mavorixafor causes concentration-dependent QT interval prolongation, an increase in its AUC could increase the possibility of experiencing this adverse effect. Likewise, this risk may be further increased if the P-gp and/or CYP450 3A4 inhibitor being used also carries a risk of QT prolongation (e.g., amiodarone, azithromycin, bepridil, ciprofloxacin, clofazimine, crizotinib, dronedarone, erythromycin, fluconazole, lapatinib, oral lefamulin, nilotinib, osimertinib, pacritinib, quinidine, quinine, ranolazine, ribociclib).

MANAGEMENT: Caution and close clinical monitoring for adverse effects associated with mavorixafor, such as QT prolongation, are advised if concurrent use with a P-gp and/or moderate CYP450 3A4 inhibitor is required. Any modifiable risk factors for QT prolongation, such as electrolyte abnormalities, should be corrected. The QTc (QT interval corrected for heart rate) should be assessed at baseline and as clinically indicated during concomitant therapy. If adverse reactions associated with mavorixafor develop, its daily dose should be reduced by steps of 100 mg, as described in the labeling, but not to a dose less than 200 mg. If the P-gp and/or CYP450 3A4 inhibitor also carries a risk of QTc prolongation, its labeling should be consulted as well for more specific guidance on monitoring and potential adjustments to treatment should this adverse effect occur.