Drug Interactions between amoxicillin / clarithromycin / vonoprazan and mavorixafor

ADJUST DOSE: Coadministration with potent CYP450 3A4 inhibitors may significantly increase the plasma concentrations and effects of mavorixafor, which is primarily metabolized by the isoenzyme. When a single dose of mavorixafor (200 mg) was coadministered with the strong CYP450 3A4 and P-glycoprotein (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. Mavorixafor is also a substrate of P-gp, so itraconazole's ability to inhibit this efflux transporter may have contributed to the increase in AUC. Clinical data with potent CYP450 3A4 inhibitors that do not also inhibit P-gp are not available. As mavorixafor causes concentration-dependent QT interval prolongation, an increase in its AUC may increase the risk of experiencing this adverse effect. Likewise, this risk may be further increased if the CYP450 3A4 inhibitor being used also carries a risk of QT prolongation (e.g., adagrasib, ceritinib, clarithromycin, ketoconazole, levoketoconazole, mifepristone, posaconazole, saquinavir, telithromycin, voriconazole).

MANAGEMENT: If mavorixafor must be used concurrently with a potent CYP450 3A4 inhibitor, the daily dose should be reduced to 200 mg. Close monitoring for an increase in adverse effects, such as QT prolongation, is also advised. 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. In addition, the labeling for each medication should be consulted as changes in the QTc interval may require dose adjustments or discontinuation of the drug(s) suspected to be at fault.

MONITOR: Coadministration with P-glycoprotein (P-gp) and/or CYP450 3A4 inhibitors may increase the plasma concentrations and effects of mavorixafor, which is both a substrate of the P-gp 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 of CYP450 3A4 and/or P-gp are not available. As mavorixafor causes concentration-dependent QT interval prolongation, an increase in its AUC could increase the risk of experiencing this adverse effect.

MANAGEMENT: Caution and monitoring for adverse effects associated with mavorixafor, such as QT prolongation, are advised if concurrent use with a P-gp and/or 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. In addition, the labeling for each medication should be consulted as changes in the QTc interval may require dose adjustments or discontinuation of the drug(s) suspected to be at fault.

Although some in vitro data indicate synergism between macrolide antibiotics and penicillins, other in vitro data indicate antagonism. When these drugs are given together, neither has predictable therapeutic efficacy. Data are available for erythromycin, although theoretically this interaction could occur with any macrolide. Except for monitoring of the effectiveness of antibiotic therapy, no special precautions appear to be necessary.