Drug Interactions between encorafenib and Sovuna

GENERALLY AVOID: Hydroxychloroquine (HCQ) can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such advanced age, congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). In a retrospective study of electronic health records analyzing QTc prolongation risk in patients on HCQ alone or with other QT-prolonging drugs, a statistically significant QTc interval increase of 18 msec was observed in the HCQ monotherapy group. No significant QTc increase was found in patients taking HCQ with the evaluated QT-prolonging medications. However, this result may have been influenced by factors such as varying patient sensitivity to QT-prolonging drugs across treatment sites, and differences in HCQ exposure duration prior to QTc measurement in combination therapy cases.

MANAGEMENT: Coadministration of hydroxychloroquine with other drugs that can prolong the QT interval should generally be avoided, particularly in patients with baseline QT prolongation (e.g., QTc greater than or equal to 500 msec) or congenital long QT syndrome. Close monitoring of QTc interval, electrolyte levels, and renal and hepatic function is recommended if concomitant use is required, and benefits are anticipated to outweigh the risks. Electrolyte abnormalities should be corrected prior to initiating treatment with hydroxychloroquine. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Because hydroxychloroquine is eliminated slowly from the body (terminal half-life: 40-50 days), potential drug interactions may persist for several weeks to months after its discontinuation.

MONITOR CLOSELY: Coadministration with strong inducers of CYP450 3A4 or 2C8 may decrease the plasma concentrations and therapeutic effects of hydroxychloroquine (HCQ), which is partially metabolized by the isoenzyme. When rifampin, a potent CYP450 3A4 and moderate CYP450 2C8 inducer, was administered concomitantly with hydroxychloroquine, a lack of efficacy of hydroxychloroquine was reported.

MANAGEMENT: Caution and close monitoring are recommended whenever hydroxychloroquine is used concomitantly with strong CYP450 3A4 or 2C8 inducers. Clinical and laboratory monitoring should be considered whenever a strong CYP450 3A4 or 2C8 inducer is added to or withdrawn from therapy with hydroxychloroquine, and the dosage adjusted as necessary.