t QT interval and are metabolized by CYP3A4, such as dolasetron. Both dolasetron and itraconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of itraconazole (a potent CYP3A4 inhibitor) with dolasetron (a CYP3A4 substrate) may result in elevated dolasetron plasma concentrations and an increased risk for adverse events, including QT prolongation. If itraconazole therapy is stopped, it may be prudent to continue close monitoring for up to 2 weeks after discontinuing itraconazole. Once discontinued, the plasma concentration of itraconazole decreases to almost undetectable concentrations within 7 to 14 days. The decline in plasma concentrations may be even more gradual in patients with hepatic cirrhosis or who are receiving concurrent CYP3A4 inhibitors.
Ivacaftor: Use caution when administering ivacaftor and dolasetron concurrently. Ivacaftor is an inhibitor of CYP3A and dolasetron is partially metabolized by CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as dolasetron, can theoretically increase dolasetron exposure leading to increased or prolonged therapeutic effects and adverse events; however, the clinical impact of this has not yet been determined.
Ketoconazole: Caution is advised when administering ketoconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as dolasetron. Both dolasetron and ketoconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of ketoconazole (a potent CYP3A4 inhibitor) with dolasetron (a CYP3A4 substrate) may result in elevated dolasetron plasma concentrations and an increased risk for adverse events, including QT prolongation.
Lapatinib: Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and lapatinib should be used together cautiously. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. In vitro, lapatinib, at clinically relevant concentrations, inhibits CYP3A4 and CYP2C8. If lapatinib will be coadministered with a CYP3A4 substrate, exercise caution and consider dose reduction of the concomitant substrate drug. Use lapatinib with extreme caution, if at all, in patients taking CYP3A4 substrates that also have potential to induce QT prolongation such dolasetron.
Lenvatinib: Lenvatinib should be used cautiously and with close monitoring with dolasetron. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. QT prolongation was reported in patients with radi |
